Drugs Details

Drugs Info of Intron A
Drugs Details
  • Drugs Type  : Multum
  • Date : 18th Feb 2015 02:45 am
  • Brand Name : Intron A
  • Generic Name :  interferon alfa-2b (Pronunciation: IN ter FEAR on AL fa 2b)
Descriptions

INTRON® A (Interferon alfa-2b) for intramuscular, subcutaneous, intralesional, or intravenous injection is a purified sterile recombinant interferon product.

INTRON A recombinant for Injection has been classified as an alpha interferon and is a water-soluble protein with a molecular weight of 19,271 daltons produced by recombinant DNA techniques. It is obtained from the bacterial fermentation of a strain of Escherichia coli bearing a genetically engineered plasmid containing an interferon alfa2b gene from human leukocytes. The fermentation is carried out in a defined nutrient medium containing the antibiotic tetracycline hydrochloride at a concentration of 5 to 10 mg/L; the presence of this antibiotic is not detectable in the final product. The specific activity of interferon alfa-2b, recombinant is approximately 2.6 x 108 IU/mg protein as measured by the HPLC assay.

Powder for Injection

Vial Strength Million IU mL Diluent Final Concentration after Reconstitution million IU/mL* mg INTRON A† per vial Route of Administration
10 1 10 0.038 IM, SC, IV, IL
18 1 18 0.069 IM, SC, IV
50 1 50 0.192 IM, SC, IV
* Each mL also contains 20 mg glycine, 2.3 mg sodium phosphate dibasic, 0.55 mg sodium phosphate monobasic, and 1.0 mg human albumin.
† Based on the specific activity of approximately 2.6 x 108 IU/mg protein, as measured by HPLC assay.

Prior to administration, the INTRON A Powder for Injection is to be reconstituted with the provided Diluent for INTRON A (Sterile Water for Injection USP) (see DOSAGE AND ADMINISTRATION). INTRON A Powder for Injection is a white to cream-colored powder.

Solution Vials for Injection

Vial Strength Concentration* mg INTRON A+ per vial Route of Administration
18‡ MIU multidose 3 million IU/0.5 mL 0.088 IM, SC
25¶ MIU multidose 5 million IU/0.5 mL 0.123 IM, SC, IL
* Each mL contains 7.5 mg sodium chloride, 1.8 mg sodium phosphate dibasic, 1.3 mg sodium phosphate monobasic, 0.1 mg edetate disodium, 0.1 mg polysorbate 80, and 1.5 mg m-cresol as a preservative.
† Based on the specific activity of approximately 2.6 x 108 IU/mg protein as measured by HPLC assay.
‡ This is a multidose vial which contains a total of 22.8 million IU of interferon alfa-2b, recombinant per 3.8 mL in order to provide the delivery of six 0.5-mL doses, each containing 3 million IU of INTRON A (for a label strength of 18 million IU).
¶ This is a multidose vial which contains a total of 32.0 million IU of interferon alfa-2b, recombinant per 3.2 mL in order to provide the delivery of five 0.5-mL doses, each containing 5 million IU of INTRON A (for a label strength of 25 million IU).

These packages do not require reconstitution prior to administration (see DOSAGE AND ADMINISTRATION). INTRON A Solution for Injection is a clear, colorless solution.

What are the possible side effects of interferon alfa-2b (Intron A)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using interferon alfa-2b and call your doctor at once if you have a serious side effect such as:

  • severe depression, aggressive behavior, or thoughts of hurting yourself or others;
  • fast, slow, or uneven heart rate, feeling like you might pass out;
  • fever, chills, body aches, flu symptoms, pale skin, easy bruising or bleeding, unusual weakness;
  • vision or hearing...

Read All Potential Side Effects and See Pictures of Intron A »

What are the precautions when taking interferon alfa-2b, recombinant for injection (Intron A)?

See also Warning section.

Before using interferon alfa, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients (such as albumin), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: severe liver conditions (e.g., autoimmune hepatitis, decompensated liver disease).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: blood cell disorders (e.g., anemia, neutropenia, thrombocytopenia), cancer, diabetes, eye problems, heart disease (e.g., angina,...

Read All Potential Precautions of Intron A »


This monograph has been modified to include the generic and brand name in many instances.

Indications

Hairy Cell Leukemia

INTRON® A is indicated for the treatment of patients 18 years of age or older with hairy cell leukemia.

Malignant Melanoma

INTRON A is indicated as adjuvant to surgical treatment in patients 18 years of age or older with malignant melanoma who are free of disease but at high risk for systemic recurrence, within 56 days of surgery.

Follicular Lymphoma

INTRON A is indicated for the initial treatment of clinically aggressive (see CLINICAL PHARMACOLOGY) follicular Non-Hodgkin's Lymphoma in conjunction with anthracycline-containing combination chemotherapy in patients 18 years of age or older. Efficacy of INTRON A therapy in patients with low-grade, lowtumor burden follicular Non-Hodgkin's Lymphoma has not been demonstrated.

Condylomata Acuminata

INTRON A is indicated for intralesional treatment of selected patients 18 years of age or older with condylomata acuminata involving external surfaces of the genital and perianal areas (see DOSAGE AND ADMINISTRATION).

The use of this product in adolescents has not been studied.

AIDS-Related Kaposi's Sarcoma

INTRON A is indicated for the treatment of selected patients 18 years of age or older with AIDS-Related Kaposi's Sarcoma. The likelihood of response to INTRON A therapy is greater in patients who are without systemic symptoms, who have limited lymphadenopathy and who have a relatively intact immune system as indicated by total CD4 count.

Chronic Hepatitis C

INTRON A is indicated for the treatment of chronic hepatitis C in patients 18 years of age or older with compensated liver disease who have a history of blood or blood-product exposure and/or are HCV antibody positive. Studies in these patients demonstrated that INTRON A therapy can produce clinically meaningful effects on this disease, manifested by normalization of serum alanine aminotransferase (ALT) and reduction in liver necrosis and degeneration.

A liver biopsy should be performed to establish the diagnosis of chronic hepatitis. Patients should be tested for the presence of antibody to HCV. Patients with other causes of chronic hepatitis, including autoimmune hepatitis, should be excluded. Prior to initiation of INTRON A therapy, the physician should establish that the patient has compensated liver disease. The following patient entrance criteria for compensated liver disease were used in the clinical studies and should be considered before INTRON A treatment of patients with chronic hepatitis C:

  • No history of hepatic encephalopathy, variceal bleeding, ascites, or other clinical signs of decompensation
  • Bilirubin : Less than or equal to 2 mg/dL
  • Albumin : Stable and within normal limits
  • Prothrombin Time : Less than 3 seconds prolonged
  • WBC : Greater than or equal to 3000/mm³
  • Platelets : Greater than or equal to 70,000/mm³

Serum creatinine should be normal or near normal.

Prior to initiation of INTRON A therapy, CBC and platelet counts should be evaluated in order to establish baselines for monitoring potential toxicity. These tests should be repeated at Weeks 1 and 2 following initiation of INTRON A therapy, and monthly thereafter. Serum ALT should be evaluated at approximately 3-month intervals to assess response to treatment (see DOSAGE AND ADMINISTRATION).

Patients with preexisting thyroid abnormalities may be treated if thyroidstimulating hormone (TSH) levels can be maintained in the normal range by medication. TSH levels must be within normal limits upon initiation of INTRON A treatment and TSH testing should be repeated at 3 and 6 months (see PRECAUTIONS, Laboratory Tests).

INTRON A in combination with REBETOL® is indicated for the treatment of chronic hepatitis C in patients 3 years of age and older with compensated liver disease previously untreated with alpha interferon therapy and in patients 18 years of age and older who have relapsed following alpha interferon therapy. See REBETOL prescribing information for additional information.

Chronic Hepatitis B

INTRON A is indicated for the treatment of chronic hepatitis B in patients 1 year of age or older with compensated liver disease. Patients who have been serum HBsAg positive for at least 6 months and have evidence of HBV replication (serum HBeAg positive) with elevated serum ALT are candidates for treatment. Studies in these patients demonstrated that INTRON A therapy can produce virologic remission of this disease (loss of serum HBeAg) and normalization of serum aminotransferases. INTRON A therapy resulted in the loss of serum HBsAg in some responding patients.

Prior to initiation of INTRON A therapy, it is recommended that a liver biopsy be performed to establish the presence of chronic hepatitis and the extent of liver damage. The physician should establish that the patient has compensated liver disease. The following patient entrance criteria for compensated liver disease were used in the clinical studies and should be considered before INTRON A treatment of patients with chronic hepatitis B:

  • No history of hepatic encephalopathy, variceal bleeding, ascites, or other signs of clinical decompensation
  • Bilirubin : Normal
  • Albumin : Stable and within normal limits
  • Prothrombin Time : Adults less than 3 seconds prolonged
    Pediatrics less than or equal to 2 seconds prolonged
  • WBC : Greater than or equal to 4000/mm³
  • Platelets : Adults greater than or equal to 100,000/mm³
    Pediatrics greater than or equal to 150,000/mm³

Patients with causes of chronic hepatitis other than chronic hepatitis B or chronic hepatitis C should not be treated with INTRON A. CBC and platelet counts should be evaluated prior to initiation of INTRON A therapy in order to establish baselines for monitoring potential toxicity. These tests should be repeated at treatment Weeks 1, 2, 4, 8, 12, and 16. Liver function tests, including serum ALT, albumin, and bilirubin, should be evaluated at treatment Weeks 1, 2, 4, 8, 12, and 16. HBeAg, HBsAg, and ALT should be evaluated at the end of therapy, as well as 3- and 6-months posttherapy, since patients may become virologic responders during the 6-month period following the end of treatment. In clinical studies in adults, 39% (15/38) of responding patients lost HBeAg 1 to 6 months following the end of INTRON A therapy. Of responding patients who lost HBsAg, 58% (7/12) did so 1 to 6 months post-treatment.

A transient increase in ALT greater than or equal to 2 times baseline value (flare) can occur during INTRON A therapy for chronic hepatitis B. In clinical trials in adults and pediatrics, this flare generally occurred 8 to 12 weeks after initiation of therapy and was more frequent in responders (adults 63%, 24/38; pediatrics 59%, 10/17) than in nonresponders (adults 27%, 13/48; pediatrics 35%, 19/55). However, in adults and pediatrics, elevations in bilirubin greater than or equal to 3 mg/dL (greater than or equal to 2 times ULN) occurred infrequently (adults 2%, 2/86; pediatrics 3%, 2/72) during therapy. When ALT flare occurs, in general, INTRON A therapy should be continued unless signs and symptoms of liver failure are observed. During ALT flare, clinical symptomatology and liver function tests including ALT, prothrombin time, alkaline phosphatase, albumin, and bilirubin, should be monitored at approximately 2-week intervals (see WARNINGS).

Dosage Administration

General

IMPORTANT: INTRON® A is supplied as 1) Powder for Injection/Reconstitution; 2) Solution for Injection in Vials. Not all dosage forms and strengths are appropriate for some indications. It is important that you carefully read the instructions below for the indication you are treating to ensure you are using an appropriate dosage form and strength.

To enhance the tolerability of INTRON A, injections should be administered in the evening when possible.

To reduce the incidence of certain adverse reactions, acetaminophen may be administered at the time of injection.

The solution should be allowed to come to room temperature before using.

Hairy Cell Leukemia

(see DOSAGE AND ADMINISTRATION, General)

Dose: The recommended dose for the treatment of hairy cell leukemia is 2 million IU/m² administered intramuscularly or subcutaneously 3 times a week for up to 6 months. Patients with platelet counts of less than 50,000/mm³ should not be administered INTRON A intramuscularly, but instead by subcutaneous administration. Patients who are responding to therapy may benefit from continued treatment.

Dosage Forms for This Indication

Dosage Form Concentration Route Fixed Doses
Powder 10 MIU (single dose) 10 MIU/mL IM, SC N/A
Solution 18 MIU multidose 6 MIU/mL IM, SC N/A
Solution 25 MIU multidose 10 MIU/mL IM, SC N/A

NOTE: INTRON A Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.

Dose Adjustment

If severe adverse reactions develop, the dosage should be modified (50% reduction) or therapy should be temporarily withheld until the adverse reactions abate and then resume at 50% (1 MIU/m² TIW).

  • If severe adverse reactions persist or recur following dosage adjustment, INTRON A should be permanently discontinued.
  • INTRON A should be discontinued for progressive disease or failure to respond after six months of treatment.
  • Malignant Melanoma (see DOSAGE AND ADMINISTRATION, General)

INTRON A adjuvant treatment of malignant melanoma is given in two phases, induction and maintenance.

Induction Recommended Dose

The recommended daily dose of INTRON A in induction is 20 million IU/m² as an intravenous infusion, over 20 minutes, 5 consecutive days per week, for 4 weeks (see Dose Adjustment below).

Dosage Forms for This Indication

Dosage Form Concentration Route
Powder 10 MIU 10 MIU/mL IV
Powder 18 MIU 18 MIU/mL IV
Powder 50 MIU 50 MIU/mL IV

NOTE: INTRON A Solution for Injection in vials is NOT recommended for intravenous administration and should not be used for the induction phase of malignant melanoma.

NOTE: INTRON A Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.

Dose Adjustment

NOTE: Regular laboratory testing should be performed to monitor laboratory abnormalities for the purpose of dose modifications (see PRECAUTIONS, Laboratory Tests).

  • INTRON A should be withheld for severe adverse reactions, including granulocyte counts greater than 250/mm³ but less than 500/mm³ or SGPT/SGOT greater than 5- 10x upper limit of normal, until adverse reactions abate. INTRON A treatment should be restarted at 50% of the previous dose.
  • INTRON A should be permanently discontinued for:
    • Toxicity that does not abate after withholding INTRON A
    • Severe adverse reactions which recur in patients receiving reduced doses of INTRON A
    • Granulocyte count less than 250/mm³ or SGPT/SGOT of greater than 10x upper limit of normal
Maintenance Recommended Dose

The recommended dose of INTRON A for maintenance is 10 million IU/m² as a subcutaneous injection three times per week for 48 weeks (see Dose Adjustment below).

Dosage Forms for This Indication

Dosage Form Concentration Route Fixed Doses
Powder 10 MIU (single dose)* 10 MIU/mL SC N/A
Powder 18 MIU (single dose)** 18 MIU/mL SC N/A
Solution 18 MIU multidose 6 MIU/mL SC N/A
Solution 25 MIU multidose 10 MIU/mL SC N/A
*Patients receiving 50% dose reduction only
**Patients receiving full dose only

NOTE: INTRON A Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.

Dose Adjustment

NOTE: Regular laboratory testing should be performed to monitor laboratory abnormalities for the purpose of dose modifications (see PRECAUTIONS, Laboratory Tests).

  • INTRON A should be withheld for severe adverse reactions, including granulocyte counts greater than 250/mm³ but less than 500/mm³ or SGPT/SGOT greater than 5- 10x upper limit of normal, until adverse reactions abate. INTRON A treatment should be restarted at 50% of the previous dose.
  • INTRON A should be permanently discontinued for:
    • Toxicity that does not abate after withholding INTRON A
    • Severe adverse reactions which recur in patients receiving reduced doses of INTRON A
    • Granulocyte count less than 250/mm³ or SGPT/SGOT of greater than 10x upper limit of normal
Follicular Lymphoma

(see DOSAGE AND ADMINISTRATION, General)

Dose: The recommended dose of INTRON A for the treatment of follicular lymphoma is 5 million IU subcutaneously three times per week for up to 18 months in conjunction with anthracycline-containing chemotherapy regimen and following completion of the chemotherapy regimen.

Dosage Forms for This Indication

Dosage Form Concentration Route Fixed Doses
Powder 10 MIU (single dose) 10 MIU/mL SC N/A
Solution 18 MIU multidose 6 MIU/mL SC N/A
Solution 25 MIU multidose 10 MIU/mL SC N/A

NOTE: INTRON A Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.

Dose Adjustment
  • Doses of myelosuppressive drugs were reduced by 25% from a full-dose CHOP regimen, and cycle length increased by 33% (e.g., from 21 to 28 days) when alpha interferon was added to the regimen.
  • Delay chemotherapy cycle if neutrophil count was less than 1500/mm³ or platelet count was less than 75,000/mm³.
  • INTRON A should be permanently discontinued if SGOT exceeds greater than 5x the upper limit of normal or serum creatinine greater than 2.0 mg/dL (see WARNINGS).
  • Administration of INTRON A therapy should be withheld for a neutrophil count less than 1000/mm³, or a platelet count less than 50,000/mm³.
  • INTRON A dose should be reduced by 50% (2.5 MIU TIW) for a neutrophil count greater than 1000/mm³, but less than 1500/mm³. The INTRON A dose may be reescalated to the starting dose (5 million IU TIW) after resolution of hematologic toxicity (ANC greater than 1500/mm³).
Condylomata Acuminata

(see DOSAGE AND ADMINISTRATION, General)

Dose: The recommended dose is 1.0 million IU per lesion in a maximum of 5 lesions in a single course. The lesions should be injected three times weekly on alternate days for 3 weeks. An additional course may be administered at 12 to 16 weeks.

Dosage Forms for This Indication

Dosage Form Concentration
Powder 10 MIU (single dose) 10 MIU/mL
Solution 25 MIU multidose 10 MIU/mL

NOTE: INTRON A Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.

NOTE: Do not use the following formulations for this indication:

  • the 18 million or 50 million IU Powder for Injection
  • the 18 million IU multidose INTRON A Solution for Injection

Dose Adjustment: None

Technique for Injection: The injection should be administered intralesionally using a Tuberculin or similar syringe and a 25- to 30-gauge needle. The needle should be directed at the center of the base of the wart and at an angle almost parallel to the plane of the skin (approximately that in the commonly used PPD test). This will deliver the interferon to the dermal core of the lesion, infiltrating the lesion and causing a small wheal. Care should be taken not to go beneath the lesion too deeply; subcutaneous injection should be avoided, since this area is below the base of the lesion. Do not inject too superficially since this will result in possible leakage, infiltrating only the keratinized layer and not the dermal core.

AIDS-Related Kaposi's Sarcoma

(see DOSAGE AND ADMINISTRATION, General)

Dose: The recommended dose of INTRON A for Kaposi's Sarcoma is 30 million IU/m²/dose administered subcutaneously or intramuscularly three times a week until disease progression or maximal response has been achieved after 16 weeks of treatment. Dose reduction is frequently required (see Dose Adjustment below).

Dosage Forms for This Indication

Dosage Form Concentration Route
Powder 50 MIU 50 MIU/mL IM, SC

NOTE: INTRON A Solution for Injection in vials should NOT be used for AIDSRelated Kaposi's Sarcoma.

NOTE: INTRON A Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.

Dose Adjustment

  • INTRON A dose should be reduced by 50% or withheld for severe adverse reactions.
  • INTRON A may be resumed at a reduced dose if severe adverse reactions abate with interruption of dosing.
  • INTRON A should be permanently discontinued if severe adverse reactions persist or if they recur in patients receiving a reduced dose.
Chronic Hepatitis C

(see DOSAGE AND ADMINISTRATION, General)

Dose: The recommended dose of INTRON A for the treatment of chronic hepatitis C is 3 million IU three times a week (TIW) administered subcutaneously or intramuscularly. In patients tolerating therapy with normalization of ALT at 16 weeks of treatment, INTRON A therapy should be extended to 18 to 24 months (72 to 96 weeks) at 3 million IU TIW to improve the sustained response rate (see CLINICAL PHARMACOLOGY, Chronic Hepatitis C). Patients who do not normalize their ALTs or have persistently high levels of HCV RNA after 16 weeks of therapy rarely achieve a sustained response with extension of treatment. Consideration should be given to discontinuing these patients from therapy.

When INTRON A is administered in combination with REBETOL®, patients with impaired renal function and/or those over the age of 50 should be carefully monitored with respect to the development of anemia. See REBETOL prescribing information for dosing when used in combination with REBETOL for adults and pediatric patients.

Dosage Forms for This Indication

Dosage Form Concentration Route Fixed Doses
Solution 18 MIU multidose 6 MIU/mL IM, SC N/A

Dose Adjustment: If severe adverse reactions develop during INTRON A treatment, the dose should be modified (50% reduction) or therapy should be temporarily discontinued until the adverse reactions abate. If intolerance persists after dose adjustment, INTRON A therapy should be discontinued.

Chronic Hepatitis B

Adults

(see DOSAGE AND ADMINISTRATION, General)

Dose: The recommended dose of INTRON A for the treatment of chronic hepatitis B is 30 to 35 million IU per week, administered subcutaneously or intramuscularly, either as 5 million IU daily (QD) or as 10 million IU three times a week (TIW) for 16 weeks.

Dosage Forms for This Indication

Dosage Form Concentration Route Fixed Doses
Powder 10 MIU (single dose) 10 MIU/mL IM, SC N/A
Solution 25 MIU multidose 10 MIU/mL IM, SC N/A

NOTE: INTRON A Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.

Chronic Hepatitis B

Pediatrics

(see DOSAGE AND ADMINISTRATION, General)

Dose: The recommended dose of INTRON A for the treatment of chronic hepatitis B is 3 million IU/m² three times a week (TIW) for the first week of therapy followed by dose escalation to 6 million IU/m² TIW (maximum of 10 million IU TIW) administered subcutaneously for a total duration of 16 to 24 weeks.

Dosage Forms for This Indication

Dosage Form Concentration Route Fixed Doses
Powder 10 MIU (single dose) 10 MIU/mL SC N/A
Solution 25 MIU multidose 10 MIU/mL SC N/A

NOTE: INTRON A Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.

Dose Adjustment: If severe adverse reactions or laboratory abnormalities develop during INTRON A therapy, the dose should be modified (50% reduction) or discontinued if appropriate, until the adverse reactions abate. If intolerance persists after dose adjustment, INTRON A therapy should be discontinued.

For patients with decreases in white blood cell, granulocyte or platelet counts, the following guidelines for dose modification should be followed:

 

INTRON A Dose White Blood Cell Count Granulocyte Count Platelet Count
Reduce 50% < 1.5 x 109/L < 0.75 x 109/L < 50 x 109/L
Permanently Discontinue < 1.0 x 109/L < 0.5 x 109/L < 25 x 109/L

INTRON A therapy was resumed at up to 100% of the initial dose when white blood cell, granulocyte, and/or platelet counts returned to normal or baseline values.

PREPARATION AND ADMINISTRATION Reconstitution of INTRON® A Powder for Injection The reconstituted solution is clear and colorless to light yellow. The INTRON A powder reconstituted with Sterile Water for Injection USP is a single-use vial and does not contain a preservative. DO NOT RE-ENTER VIAL AFTER WITHDRAWING THE DOSE. DISCARD UNUSED PORTION (see DOSAGE AND ADMINISTRATION). Once the dose from the single-dose vial has been withdrawn, the sterility of any remaining product can no longer be guaranteed. Pooling of unused portions of some medications has been linked to bacterial contamination and morbidity.

  • Intramuscular, Subcutaneous, or Intralesional Administration

Inject 1 mL Diluent (Sterile Water for Injection USP) for INTRON A into the INTRON A vial. Swirl gently to hasten complete dissolution of the powder. The appropriate INTRON A dose should then be withdrawn and injected intramuscularly, subcutaneously, or intralesionally (see Medication Guide for detailed instructions).

Please refer to the Medication Guide for detailed, step-by-step instructions on how to inject the INTRON A dose. After preparation and administration of the INTRON A injection, it is essential to follow the procedure for proper disposal of syringes and needles (see Medication Guide for detailed instructions).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

  • Intravenous Infusion

The infusion solution should be prepared immediately prior to use. Based on the desired dose, the appropriate vial strength(s) of INTRON A should be reconstituted with the diluent provided. Inject 1 mL Diluent (Sterile Water for Injection USP) for INTRON A into the INTRON A vial. Swirl gently to hasten complete dissolution of the powder. The appropriate INTRON A dose should then be withdrawn and injected into a 100-mL bag of 0.9% Sodium Chloride Injection USP. The final concentration of INTRON A should not be less than 10 million IU/100 mL.

Please refer to the Medication Guide for detailed, step-by-step instructions on how to inject the INTRON A dose. After preparation and administration of INTRON A, it is essential to follow the procedure for proper disposal of syringes and needles.

INTRON A Solution for Injection in Vials INTRON A Solution for Injection is supplied in two multidose vials. The solutions for injection do not require reconstitution prior to administration; the solution is clear and colorless.

The appropriate dose should be withdrawn from the vial and injected intramuscularly, subcutaneously, or intralesionally.

INTRON A Solution for Injection is not recommended for intravenous administration.

Please refer to the Medication Guide for detailed, step-by-step instructions on how to inject the INTRON A dose. After preparation and administration of INTRON A, it is essential to follow the procedure for proper disposal of syringes and needles.

How Supplied

INTRON® A Powder for Injection

INTRON A Powder for Injection, 10 million IU per vial and Diluent for INTRON A (Sterile Water for Injection USP) 1 mL per vial; boxes containing 1 INTRON A vial and 1 vial of INTRON A Diluent (NDC 0085-0571-02).

INTRON A Powder for Injection, 18 million IU per vial and Diluent for INTRON A (Sterile Water for Injection USP) 1 mL per vial; boxes containing 1 vial of INTRON A and 1 vial of INTRON A Diluent (NDC 0085-1110-01).

INTRON A Powder for Injection, 50 million IU per vial and Diluent for INTRON A (Sterile Water for Injection USP) 1 mL per vial; boxes containing 1 INTRON A vial and 1 vial of INTRON A Diluent (NDC 0085-0539-01).

INTRON A Solution for Injection in Vials

INTRON A Solution for Injection, 18 million IU multidose vial (22.8 million IU per 3.8 mL per vial); boxes containing 1 vial of INTRON A Solution for Injection (NDC 00851168- 01).

INTRON A Solution for Injection, 25 million IU multidose vial (32 million IU per 3.2 mL per vial); boxes containing 1 vial of INTRON A Solution for Injection (NDC 00851133- 01).

Storage

  • INTRON A Powder for Injection/Reconstitution
    INTRON A Powder for Injection should be stored in the refrigerator at 2° to 8°C (36°- 46°F). After reconstitution, the solution should be used immediately, but may be stored up to 24 hours at 2° to 8°C (36°-46°F). Throw away any medicine left in the vial after you withdraw 1 dose.
  • INTRON A Solution for Injection in Vials
    INTRON A Solution for Injection in vials should be stored in the refrigerator at 2° to 8°C (36°-46°F).
    INTRON A Solution for Injection should not be frozen and should be kept away from heat. Throw away any unused INTRON A Solution for Injection remaining in the vial after one month.

REFERENCES

4. Schiller J, et al. J Biol Response Mod. 1989;8:252-261.

11. Kauppila A, et al. Int J Cancer. 1982;29:291 -294.

Manufactured by: Schering Corporation, a subsidiary of Merck & Co., Inc. Whitehouse Station, NJ 08889 US. Rev. 04/2014


This monograph has been modified to include the generic and brand name in many instances.

Side Effects

General

The adverse experiences listed below were reported to be possibly or probably related to INTRON® A therapy during clinical trials. Most of these adverse reactions were mild to moderate in severity and were manageable. Some were transient and most diminished with continued therapy.

The most frequently reported adverse reactions were “flu-like” symptoms, particularly fever, headache, chills, myalgia, and fatigue. More severe toxicities are observed generally at higher doses and may be difficult for patients to tolerate.

TREATMENT-RELATED ADVERSE EXPERIENCES BY INDICATION

View Enlarged Table

Hairy Cell Leukemia

The adverse reactions most frequently reported during clinical trials in 145 patients with hairy cell leukemia were the “flu-like” symptoms of fever (68%), fatigue (61%), and chills (46%).

Malignant Melanoma

The INTRON A dose was modified because of adverse events in 65% (n=93) of the patients. INTRON A therapy was discontinued because of adverse events in 8% of the patients during induction and 18% of the patients during maintenance. The most frequently reported adverse reaction was fatigue, which was observed in 96% of patients. Other adverse reactions that were recorded in greater than 20% of INTRON A-treated patients included neutropenia (92%), fever (81%), myalgia (75%), anorexia (69%), vomiting/nausea (66%), increased SGOT (63%), headache (62%), chills (54%), depression (40%), diarrhea (35%), alopecia (29%), altered taste sensation (24%), dizziness/vertigo (23%), and anemia (22%).

Adverse reactions classified as severe or life threatening (ECOG Toxicity Criteria grade 3 or 4) were recorded in 66% and 14% of INTRON A-treated patients, respectively. Severe adverse reactions recorded in greater than 10% of INTRON A-treated patients included neutropenia/leukopenia (26%), fatigue (23%), fever (18%), myalgia (17%), headache (17%), chills (16%), and increased SGOT (14%). Grade 4 fatigue was recorded in 4% and grade 4 depression was recorded in 2% of INTRON A-treated patients. No other grade 4 AE was reported in more than 2 INTRON A-treated patients. Lethal hepatotoxicity occurred in 2 INTRON A-treated patients early in the clinical trial. No subsequent lethal hepatotoxicities were observed with adequate monitoring of liver function tests (see PRECAUTIONS, Laboratory Tests).

Follicular Lymphoma

Ninety-six percent of patients treated with CHVP plus INTRON A therapy and 91% of patients treated with CHVP alone reported an adverse event of any severity. Asthenia, fever, neutropenia, increased hepatic enzymes, alopecia, headache, anorexia, “flu-like” symptoms, myalgia, dyspnea, thrombocytopenia, paresthesia, and polyuria occurred more frequently in the CHVP plus INTRON A-treated patients than in patients treated with CHVP alone. Adverse reactions classified as severe or life threatening (World Health Organization grade 3 or 4) recorded in greater than 5% of CHVP plus INTRON A-treated patients included neutropenia (34%), asthenia (10%), and vomiting (10%). The incidence of neutropenic infection was 6% in CHVP plus INTRON A versus 2% in CHVP alone. One patient in each treatment group required hospitalization.

Twenty-eight percent of CHVP plus INTRON A-treated patients had a temporary modification/interruption of their INTRON A therapy, but only 13 patients (10%) permanently stopped INTRON A therapy because of toxicity. There were four deaths on study; two patients committed suicide in the CHVP plus INTRON A arm and two patients in the CHVP arm had unwitnessed sudden death. Three patients with hepatitis B (one of whom also had alcoholic cirrhosis) developed hepatotoxicity leading to discontinuation of INTRON A. Other reasons for discontinuation included intolerable asthenia (5/135), severe flu symptoms (2/135), and one patient each with exacerbation of ankylosing spondylitis, psychosis, and decreased ejection fraction.

Condylomata Acuminata

Eighty-eight percent (311/352) of patients treated with INTRON A for condylomata acuminata who were evaluable for safety reported an adverse reaction during treatment. The incidence of the adverse reactions reported increased when the number of treated lesions increased from one to five. All 40 patients who had five warts treated reported some type of adverse reaction during treatment.

Adverse reactions and abnormal laboratory test values reported by patients who were re-treated were qualitatively and quantitatively similar to those reported during the initial INTRON A treatment period.

AIDS-Related Kaposi's Sarcoma

In patients with AIDS-Related Kaposi's Sarcoma, some type of adverse reaction occurred in 100% of the 74 patients treated with 30 million IU/m² three times a week and in 97% of the 29 patients treated with 35 million IU per day.

Of these adverse reactions, those classified as severe (World Health Organization grade 3 or 4) were reported in 27% to 55% of patients. Severe adverse reactions in the 30 million IU/m² TIW study included: fatigue (20%), influenza-like symptoms (15%), anorexia (12%), dry mouth (4%), headache (4%), confusion (3%), fever (3%), myalgia (3%), and nausea and vomiting (1% each). Severe adverse reactions for patients who received the 35 million IU QD included: fever (24%), fatigue (17%), influenza-like symptoms (14%), dyspnea (14%), headache (10%), pharyngitis (7%), and ataxia, confusion, dysphagia, GI hemorrhage, abnormal hepatic function, increased SGOT, myalgia, cardiomyopathy, face edema, depression, emotional lability, suicide attempt, chest pain, and coughing (1 patient each). Overall, the incidence of severe toxicity was higher among patients who received the 35 million IU per day dose.

Chronic Hepatitis C

Adults

Two studies of extended treatment (18-24 months) with INTRON A show that approximately 95% of all patients treated experience some type of adverse event and that patients treated for extended duration continue to experience adverse events throughout treatment. Most adverse events reported are mild to moderate in severity. However, 29/152 (19%) of patients treated for 18 to 24 months experienced a serious adverse event compared to 11/163 (7%) of those treated for 6 months. Adverse events which occur or persist during extended treatment are similar in type and severity to those occurring during short-course therapy.

Of the patients achieving a complete response after 6 months of therapy, 12/79 (15%) subsequently discontinued INTRON A treatment during extended therapy because of adverse events, and 23/79 (29%) experienced severe adverse events (WHO grade 3 or 4) during extended therapy.

In patients using combination treatment with INTRON A and REBETOL, the primary toxicity observed was hemolytic anemia. Reductions in hemoglobin levels occurred within the first 1 to 2 weeks of therapy. Cardiac and pulmonary events associated with anemia occurred in approximately 10% of patients treated with INTRON A/REBETOL therapy. See REBETOL prescribing information for additional information.

Chronic Hepatitis C

Pediatrics

In pediatric patients with chronic hepatitis C treated with INTRON A 3 MIU/m² three times weekly and REBETOL 15 mg/kg per day, all subjects (n=118) had at least one adverse event during 24-48 weeks of treatment, of which 80% were considered to be mild or moderate in severity. Six percent discontinued therapy due to adverse reactions and dose modifications were required in 30% of subjects, most commonly for anemia and neutropenia. Adverse events occurring in more than 50% of subjects included headache, fever, fatigue and anorexia. Adverse events occurring in 20-50% of subjects included influenza-like symptoms, abdominal pain, vomiting, nausea, myalgia, pharyngitis, diarrhea, viral infection, rigors, weight decrease, musculoskeletal pain, alopecia and dizziness. The most common laboratory test abnormalities were neutropenia (34%) and anemia (27%). Depression was reported in 13% (n=15) of children. Three of these subjects had suicidal ideation, and one attempted suicide. Weight loss and slowed growth are common in pediatric patients during combination therapy with INTRON A and REBETOL. Following treatment, rebound growth and weight gain occurred in most subjects. Long-term follow-up data in pediatric subjects, however, indicates that INTRON A in combination with REBETOL may induce a growth inhibition that results in reduced adult height in some patients (see PRECAUTIONS, Pediatric Use).

Chronic Hepatitis B

Adults

In patients with chronic hepatitis B, some type of adverse reaction occurred in 98% of the 101 patients treated at 5 million IU QD and 90% of the 78 patients treated at 10 million IU TIW. Most of these adverse reactions were mild to moderate in severity, were manageable, and were reversible following the end of therapy.

Adverse reactions classified as severe (causing a significant interference with normal daily activities or clinical state) were reported in 21% to 44% of patients. The severe adverse reactions reported most frequently were the “flu-like” symptoms of fever (28%), fatigue (15%), headache (5%), myalgia (4%), rigors (4%), and other severe “flulike” symptoms, which occurred in 1% to 3% of patients. Other severe adverse reactions occurring in more than one patient were alopecia (8%), anorexia (6%), depression (3%), nausea (3%), and vomiting (2%).

To manage side effects, the dose was reduced, or INTRON A therapy was interrupted in 25% to 38% of patients. Five percent of patients discontinued treatment due to adverse experiences.

Chronic Hepatitis B

Pediatrics

In pediatric patients with chronic hepatitis B (n=72) during 16-24 weeks of treatment, the most frequently reported adverse events were those commonly associated with interferon treatment: flu-like symptoms (100%), gastrointestinal system disorders (46%), and nausea and vomiting (40%). Neutropenia (13%) and thrombocytopenia (3%) were also reported. None of the adverse events was life threatening and most were moderate to severe and resolved upon dose reduction or drug discontinuation.

ABNORMAL LABORATORY TEST VALUES BY INDICATION

View Enlarged Table

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of INTRON A alone or in combination with REBETOL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and Lymphatic System Disorders

pancytopenia (concurrent anemia, leukopenia, thrombocytopenia), aplastic anemia, pure red cell aplasia, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura

Ear and Labyrinth Disorders

hearing loss

Endocrine Disorders

hypopituitarism

Eye Disorders

Vogt-Koyanagi-Harada syndrome, serous retinal detachment

Gastrointestinal Disorders

pancreatitis

General Disorders and Administration Site Conditions

asthenic conditions (including asthenia, malaise, fatigue)

Immune System Disorders

cases of acute hypersensitivity reactions, including anaphylaxis and angioedema, systemic lupus erythematosus, sarcoidosis or exacerbation of sarcoidosis

Musculoskeletal and Connective Tissue Disorders

myositis

Nervous System Disorders

peripheral neuropathy

Psychiatric Disorders

homicidal ideation, psychosis including hallucinations

Renal and Urinary Disorders

renal failure, renal insufficiency, nephrotic syndrome

Respiratory, Thoracic, and Mediastinal Disorders

pulmonary hypertension

Skin and Subcutaneous Tissue Disorders

injection site necrosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, urticaria

Read the Intron A (interferon alfa-2b, recombinant for injection) Side Effects Center for a complete guide to possible side effects

Interactions

Interactions between INTRON A and other drugs have not been fully evaluated. Caution should be exercised when administering INTRON A therapy in combination with other potentially myelosuppressive agents such as zidovudine. Concomitant use of alpha interferon and theophylline decreases theophylline clearance, resulting in a 100% increase in serum theophylline levels.

Read the Intron A Drug Interactions Center for a complete guide to possible interactions

Learn More »


This monograph has been modified to include the generic and brand name in many instances.

Warnings

General

Moderate to severe adverse experiences may require modification of the patient's dosage regimen, or in some cases termination of INTRON® A therapy. Because of the fever and other “flu-like” symptoms associated with INTRON A administration, it should be used cautiously in patients with debilitating medical conditions, such as those with a history of pulmonary disease (e.g., chronic obstructive pulmonary disease) or diabetes mellitus prone to ketoacidosis. Caution should also be observed in patients with coagulation disorders (e.g., thrombophlebitis, pulmonary embolism) or severe myelosuppression.

Cardiovascular Disorders

INTRON A therapy should be used cautiously in patients with a history of cardiovascular disease. Those patients with a history of myocardial infarction and/or previous or current arrhythmic disorder who require INTRON A therapy should be closely monitored (see PRECAUTIONS, Laboratory Tests). Cardiovascular adverse experiences, which include hypotension, arrhythmia, or tachycardia of 150 beats per minute or greater, and rarely, cardiomyopathy and myocardial infarction have been observed in some INTRON A-treated patients. Some patients with these adverse events had no history of cardiovascular disease. Transient cardiomyopathy was reported in approximately 2% of the AIDS-Related Kaposi's Sarcoma patients treated with INTRON A. Hypotension may occur during INTRON A administration, or up to 2 days post-therapy, and may require supportive therapy including fluid replacement to maintain intravascular volume.

Supraventricular arrhythmias occurred rarely and appeared to be correlated with preexisting conditions and prior therapy with cardiotoxic agents. These adverse experiences were controlled by modifying the dose or discontinuing treatment, but may require specific additional therapy.

Cerebrovascular Disorders

Ischemic and hemorrhagic cerebrovascular events have been observed in patients treated with interferon alpha-based therapies, including INTRON A. Events occurred in patients with few or no reported risk factors for stroke, including patients less than 45 years of age. Because these are spontaneous reports, estimates of frequency cannot be made and a causal relationship between interferon alpha-based therapies and these events is difficult to establish.

Neuropsychiatric Disorders

DEPRESSION AND SUICIDAL BEHAVIOR INCLUDING SUICIDAL IDEATION, SUICIDAL ATTEMPTS, AND COMPLETED SUICIDES, HOMICIDAL IDEATION, AND AGGRESSIVE BEHAVIOR SOMETIMES DIRECTED TOWARDS OTHERS, HAVE BEEN REPORTED IN ASSOCIATION WITH TREATMENT WITH ALPHA INTERFERONS, INCLUDING INTRON A THERAPY. If patients develop psychiatric problems, including clinical depression, it is recommended that the patients be carefully monitored during treatment and in the 6-month follow-up period.

INTRON A should be used with caution in patients with a history of psychiatric disorders. INTRON A therapy should be discontinued for any patient developing severe psychiatric disorder during treatment. Obtundation and coma have also been observed in some patients, usually elderly, treated at higher doses. While these effects are usually rapidly reversible upon discontinuation of therapy, full resolution of symptoms has taken up to 3 weeks in a few severe episodes. If psychiatric symptoms persist or worsen, or suicidal ideation or aggressive behavior towards others is identified, it is recommended that treatment with INTRON A be discontinued and the patient followed, with psychiatric intervention as appropriate. Narcotics, hypnotics, or sedatives may be used concurrently with caution and patients should be closely monitored until the adverse effects have resolved. Suicidal ideation or attempts occurred more frequently among pediatric patients, primarily adolescents, compared to adult patients (2.4% versus 1%) during treatment and off-therapy follow-up. Cases of encephalopathy have also been observed in some patients, usually elderly, treated with higher doses of INTRON A.

Treatment with interferons may be associated with exacerbated symptoms of psychiatric disorders in patients with co-occurring psychiatric and substance use disorders. If treatment with interferons is initiated in patients with prior history or existence of psychiatric condition or with a history of substance use disorders, treatment considerations should include the need for drug screening and periodic health evaluation, including psychiatric symptom monitoring. Early intervention for reemergence or development of neuropsychiatric symptoms and substance use is recommended.

Bone Marrow Toxicity

INTRON A therapy suppresses bone marrow function and may result in severe cytopenias including aplastic anemia. It is advised that complete blood counts (CBC) be obtained pretreatment and monitored routinely during therapy (see PRECAUTIONS, Laboratory Tests). INTRON A therapy should be discontinued in patients who develop severe decreases in neutrophil (less than 0.5 x 109/L) or platelet counts (less than 25 x 109/L) (see DOSAGE AND ADMINISTRATION, Guidelines for Dose Modification).

Ophthalmologic Disorders

Decrease or loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots; optic neuritis, papilledema, and serous retinal detachment may be induced or aggravated by treatment with interferon alfa-2b or other alpha interferons. All patients should receive an eye examination at baseline. Patients with preexisting ophthalmologic disorders (e.g., diabetic or hypertensive retinopathy) should receive periodic ophthalmologic exams during interferon alpha treatment. Any patient who develops ocular symptoms should receive a prompt and complete eye examination. Interferon alfa-2b treatment should be discontinued in patients who develop new or worsening ophthalmologic disorders.

Endocrine Disorders

Infrequently, patients receiving INTRON A therapy developed thyroid abnormalities, either hypothyroid or hyperthyroid. The mechanism by which INTRON A may alter thyroid status is unknown. Patients with preexisting thyroid abnormalities whose thyroid function cannot be maintained in the normal range by medication should not be treated with INTRON A. Prior to initiation of INTRON A therapy, serum TSH should be evaluated. Patients developing symptoms consistent with possible thyroid dysfunction during the course of INTRON A therapy should have their thyroid function evaluated and appropriate treatment instituted. Therapy should be discontinued for patients developing thyroid abnormalities during treatment whose thyroid function cannot be normalized by medication. Discontinuation of INTRON A therapy has not always reversed thyroid dysfunction occurring during treatment. Diabetes mellitus has been observed in patients treated with alpha interferons. Patients with these conditions who cannot be effectively treated by medication should not begin INTRON A therapy. Patients who develop these conditions during treatment and cannot be controlled with medication should not continue INTRON A therapy.

Gastrointestinal Disorders

Hepatotoxicity, including fatality, has been observed in interferon alpha-treated patients, including those treated with INTRON A. Any patient developing liver function abnormalities during treatment should be monitored closely and if appropriate, treatment should be discontinued.

Pulmonary Disorders

Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis, some resulting in respiratory failure and/or patient deaths, may be induced or aggravated by INTRON A or other alpha interferons. Recurrence of respiratory failure has been observed with interferon rechallenge. The etiologic explanation for these pulmonary findings has yet to be established. Any patient developing fever, cough, dyspnea, or other respiratory symptoms should have a chest X-ray taken. If the chest X-ray shows pulmonary infiltrates or there is evidence of pulmonary function impairment, the patient should be closely monitored, and, if appropriate, interferon alpha treatment should be discontinued. While this has been reported more often in patients with chronic hepatitis C treated with interferon alpha, it has also been reported in patients with oncologic diseases treated with interferon alpha.

Autoimmune Disorders

Rare cases of autoimmune diseases including thrombocytopenia, vasculitis, Raynaud's phenomenon, rheumatoid arthritis, lupus erythematosus, and rhabdomyolysis have been observed in patients treated with alpha interferons, including patients treated with INTRON A. In very rare cases the event resulted in fatality. The mechanism by which these events developed and their relationship to interferon alpha therapy is not clear. Any patient developing an autoimmune disorder during treatment should be closely monitored and, if appropriate, treatment should be discontinued.

Human Albumin

The powder formulations of this product contain albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.

AIDS-Related Kaposi's Sarcoma

INTRON A therapy should not be used for patients with rapidly progressive visceral disease (see CLINICAL PHARMACOLOGY). Also of note, there may be synergistic adverse effects between INTRON A and zidovudine. Patients receiving concomitant zidovudine have had a higher incidence of neutropenia than that expected with zidovudine alone. Careful monitoring of the WBC count is indicated in all patients who are myelosuppressed and in all patients receiving other myelosuppressive medications. The effects of INTRON A when combined with other drugs used in the treatment of AIDS-related disease are unknown.

Chronic Hepatitis C And Chronic Hepatitis B

Patients with decompensated liver disease, autoimmune hepatitis or a history of autoimmune disease, and patients who are immunosuppressed transplant recipients should not be treated with INTRON A. There are reports of worsening liver disease, including jaundice, hepatic encephalopathy, hepatic failure, and death following INTRON A therapy in such patients. Therapy should be discontinued for any patient developing signs and symptoms of liver failure.

Chronic hepatitis B patients with evidence of decreasing hepatic synthetic functions, such as decreasing albumin levels or prolongation of prothrombin time, who nevertheless meet the entry criteria to start therapy, may be at increased risk of clinical decompensation if a flare of aminotransferases occurs during INTRON A treatment. In such patients, if increases in ALT occur during INTRON A therapy for chronic hepatitis B, they should be followed carefully, including close monitoring of clinical symptomatology and liver function tests including ALT, prothrombin time, alkaline phosphatase, albumin, and bilirubin. In considering these patients for INTRON A therapy, the potential risks must be evaluated against the potential benefits of treatment.

Peripheral Neuropathy

Peripheral neuropathy has been reported when alpha interferons were given in combination with telbivudine. In one clinical trial, an increased risk and severity of peripheral neuropathy was observed with the combination use of telbivudine and pegylated interferon alfa-2a as compared to telbivudine alone. The safety and efficacy of telbivudine in combination with interferons for the treatment of chronic hepatitis B has not been demonstrated.

Use With Ribavirin (see also REBETOL® prescribing information)

REBETOL may cause birth defects and/or death of the unborn child. REBETOL therapy should not be started until a report of a negative pregnancy test has been obtained immediately prior to planned initiation of therapy. Patients should use at least two forms of contraception and have monthly pregnancy tests (see CONTRAINDICATIONS and PATIENT INFORMATION).

Combination treatment with INTRON A and REBETOL was associated with hemolytic anemia. Hemoglobin less than 10 g/dL was observed in approximately 10% of adult and pediatric patients in clinical trials. Anemia occurred within 1 to 2 weeks of initiation of ribavirin therapy. Combination treatment with INTRON A and REBETOL should not be used in patients with creatinine clearance less than 50 mL/min. See REBETOL prescribing information for additional information.

Precautions

General

Acute serious hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) have been observed rarely in INTRON® A-treated patients; if such an acute reaction develops, the drug should be discontinued immediately and appropriate medical therapy instituted. Transient rashes have occurred in some patients following injection, but have not necessitated treatment interruption.

While fever may be related to the flu-like syndrome reported commonly in patients treated with interferon, other causes of persistent fever should be ruled out.

There have been reports of interferon, including INTRON A, exacerbating preexisting psoriasis and sarcoidosis as well as development of new sarcoidosis. Therefore, INTRON A therapy should be used in these patients only if the potential benefit justifies the potential risk.

Variations in dosage, routes of administration, and adverse reactions exist among different brands of interferon. Therefore, do not use different brands of interferon in any single treatment regimen.

Triglycerides

Elevated triglyceride levels have been observed in patients treated with interferons, including INTRON A therapy. Elevated triglyceride levels should be managed as clinically appropriate. Hypertriglyceridemia may result in pancreatitis. Discontinuation of INTRON A therapy should be considered for patients with persistently elevated triglycerides (e.g., triglycerides greater than 1000 mg/dL) associated with symptoms of potential pancreatitis, such as abdominal pain, nausea, or vomiting.

Information for Patients

Patients receiving INTRON A alone or in combination with REBETOL® should be informed of the risks and benefits associated with treatment and should be instructed on proper use of the product. To supplement your discussion with a patient, you may wish to provide patients with a copy of the MEDICATION GUIDE.

Patients should be informed of, and advised to seek medical attention for, symptoms indicative of serious adverse reactions associated with this product. Such adverse reactions may include depression (suicidal ideation), cardiovascular (chest pain), ophthalmologic toxicity (decrease in/or loss of vision), pancreatitis or colitis (severe abdominal pain), and cytopenias (high persistent fevers, bruising, dyspnea). Patients should be advised that some side effects such as fatigue and decreased concentration might interfere with the ability to perform certain tasks. Patients who are taking INTRON A in combination with REBETOL must be thoroughly informed of the risks to a fetus. Female patients and female partners of male patients must be told to use two forms of birth control during treatment and for six months after therapy is discontinued (see Medication Guide).

Patients should be advised to remain well hydrated during the initial stages of treatment and that use of an antipyretic may ameliorate some of the flu-like symptoms.

If a decision is made to allow a patient to self-administer INTRON A, they should be instructed, based on their treatment, if they should inject a dose of INTRON® A subcutaneously or intramuscularly. If it is too difficult for them to inject themselves, they should be instructed to ask someone who has been trained to give the injection to them. Patients should be instructed on the importance of site selection for self-administering the injection, as well as the importance on rotating the injection sites. A puncture resistant container for the disposal of needles and syringes should be supplied. Patients self-administering INTRON A should be instructed on the proper disposal of needles and syringes and cautioned against reuse.

Patients should be instructed that the Sterile Water for Injection vial supplied with Intron A Powder for Injection contains an excess amount of diluent (5 mL) and only 1 mL should be withdrawn to reconstitute Intron A Powder for Injection. The vial of Sterile Water for Injection is intended for single use only. Discard the unused portion of sterile water. Do not save or reuse.

Dental and Periodontal Disorders

Dental and periodontal disorders have been reported in patients receiving ribavirin and interferon combination therapy. In addition, dry mouth could have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the combination of REBETOL and interferon alfa-2b. Patients should brush their teeth thoroughly twice daily and have regular dental examinations. In addition, some patients may experience vomiting. If this reaction occurs, they should be advised to rinse out their mouth thoroughly afterwards.

Laboratory Tests

In addition to those tests normally required for monitoring patients, the following laboratory tests are recommended for all patients on INTRON A therapy, prior to beginning treatment and then periodically thereafter.

  • Standard hematologic tests — including hemoglobin, complete and differential white blood cell counts, and platelet count.
  • Blood chemistries — electrolytes, liver function tests, and TSH.

Those patients who have preexisting cardiac abnormalities and/or are in advanced stages of cancer should have electrocardiograms taken prior to and during the course of treatment.

Mild-to-moderate leukopenia and elevated serum liver enzyme (SGOT) levels have been reported with intralesional administration of INTRON A (see ADVERSE REACTIONS); therefore, the monitoring of these laboratory parameters should be considered.

Baseline chest X-rays are suggested and should be repeated if clinically indicated.

For malignant melanoma patients, differential WBC count and liver function tests should be monitored weekly during the induction phase of therapy and monthly during the maintenance phase of therapy.

For specific recommendations in chronic hepatitis C and chronic hepatitis B, see INDICATIONS AND USAGE.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Studies with INTRON A have not been performed to determine carcinogenicity.

Interferon may impair fertility. In studies of interferon administration in nonhuman primates, menstrual cycle abnormalities have been observed. Decreases in serum estradiol and progesterone concentrations have been reported in women treated with human leukocyte interferon.12 Therefore, fertile women should not receive INTRON A therapy unless they are using effective contraception during the therapy period. INTRON A therapy should be used with caution in fertile men.

Mutagenicity studies have demonstrated that INTRON A is not mutagenic.

Studies in mice (0.1, 1.0 million IU/day), rats (4, 20, 100 million IU/kg/day), and cynomolgus monkeys (1.1 million IU/kg/day; 0.25, 0.75, 2.5 million IU/kg/day) injected with INTRON A for up to 9 days, 3 months, and 1 month, respectively, have revealed no evidence of toxicity. However, in cynomolgus monkeys (4, 20, 100 million IU/kg/day) injected daily for 3 months with INTRON A, toxicity was observed at the mid and high doses and mortality was observed at the high dose.

However, due to the known species-specificity of interferon, the effects in animals are unlikely to be predictive of those in man.

INTRON A in combination with REBETOL should be used with caution in fertile men. See the REBETOL prescribing information for additional information.

Pregnancy Category C INTRON A has been shown to have abortifacient effects in Macaca mulatta (rhesus monkeys) at 15 and 30 million IU/kg (estimated human equivalent of 5 and 10 million IU/kg, based on body surface area adjustment for a 60-kg adult). There are no adequate and well-controlled studies in pregnant women. INTRON A therapy should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Pregnancy Category X applies to combination treatment with INTRON A and REBETOL (see CONTRAINDICATIONS). See REBETOL prescribing information for additional information. Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin. REBETOL therapy is contraindicated in women who are pregnant and in the male partners of women who are pregnant. See CONTRAINDICATIONS and the REBETOL prescribing information.

Ribavirin Pregnancy Registry: A Ribavirin Pregnancy Registry has been established to monitor maternal-fetal outcomes of pregnancies in female patients and female partners of male patients exposed to ribavirin during treatment and for 6 months following cessation of treatment. Physicians and patients are encouraged to report such cases by calling 1-800-593-2214.

Nursing Mothers

It is not known whether this drug is excreted in human milk. However, studies in mice have shown that mouse interferons are excreted into the milk. Because of the potential for serious adverse reactions from the drug in nursing infants, a decision should be made whether to discontinue nursing or to discontinue INTRON A therapy, taking into account the importance of the drug to the mother.

Pediatric Use

General

Safety and effectiveness in pediatric patients have not been established for indications other than chronic hepatitis B and chronic hepatitis C. Chronic Hepatitis B Safety and effectiveness in pediatric patients ranging in age from 1 to 17 years have been established based upon one controlled clinical trial (see CLINICAL PHARMACOLOGY, INDICATIONS AND USAGE, and DOSAGE AND ADMINISTRATION, Chronic Hepatitis B Pediatrics).

Chronic Hepatitis C Safety and effectiveness in pediatric patients ranging in age from 3 to 16 years have been established based upon clinical studies in 118 patients. See REBETOL prescribing information for additional information. Suicidal ideation or attempts occurred more frequently among pediatric patients compared to adult patients (2.4% versus 1%) during treatment and off-therapy follow-up (see WARNINGS, Neuropsychiatric Disorders). During a 48-week course of therapy there was a decrease in the rate of linear growth (mean percentile assignment decrease of 7%) and a decrease in the rate of weight gain (mean percentile assignment decrease of 9%). A general reversal of these trends was noted during the 24-week post-treatment period.

Long-term data in a limited number of patients suggests that combination therapy may induce a growth inhibition that results in reduced final adult height in some patients (see ADVERSE REACTIONS, Chronic Hepatitis C Pediatrics).

Geriatric Use

In all clinical studies of INTRON A, including studies as monotherapy and in combination with REBETOL (ribavirin USP) Capsules, only a small percentage of the subjects were aged 65 and over. These numbers were too few to determine if they respond differently from younger subjects except for the clinical trials of INTRON A in combination with REBETOL, where elderly subjects had a higher frequency of anemia (67%) than did younger patients (28%).

In a database consisting of clinical study and postmarketing reports for various indications, cardiovascular adverse events and confusion were reported more frequently in elderly patients receiving INTRON A therapy compared to younger patients.

In general, INTRON A therapy should be administered to elderly patients cautiously, reflecting the greater frequency of decreased hepatic, renal, bone marrow, and/or cardiac function and concomitant disease or other drug therapy. INTRON A is known to be substantially excreted by the kidney, and the risk of adverse reactions to INTRON A may be greater in patients with impaired renal function. Because elderly patients often have decreased renal function, patients should be carefully monitored during treatment, and dose adjustments made based on symptoms and/or laboratory abnormalities (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).


This monograph has been modified to include the generic and brand name in many instances.

OverDose

There is limited experience with overdosage. Postmarketing surveillance includes reports of patients receiving a single dose as great as 10 times the recommended dose. In general, the primary effects of an overdose are consistent with the effects seen with therapeutic doses of interferon alfa-2b. Hepatic enzyme abnormalities, renal failure, hemorrhage, and myocardial infarction have been reported with single administration overdoses and/or with longer durations of treatment than prescribed (see ADVERSE REACTIONS). Toxic effects after ingestion of interferon alfa-2b are not expected because interferons are poorly absorbed orally. Consultation with a poison center is recommended.

Treatment There is no specific antidote for interferon alfa-2b. Hemodialysis and peritoneal dialysis are not considered effective for treatment of overdose.

ContrainDications

INTRON® A is contraindicated in patients with:

  • Hypersensitivity to interferon alpha or any component of the product
  • Autoimmune hepatitis
  • Decompensated liver disease

INTRON A and REBETOL® combination therapy is additionally contraindicated in:

  • Patients with hypersensitivity to ribavirin or any other component of the product
  • Women who are pregnant
  • Men whose female partners are pregnant
  • Patients with hemoglobinopathies (e.g., thalassemia major, sickle cell anemia)
  • Patients with creatinine clearance less than 50 mL/min. See REBETOL prescribing information for additional information.


This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

General

The interferons are a family of naturally occurring small proteins and glycoproteins with molecular weights of approximately 15,000 to 27,600 daltons produced and secreted by cells in response to viral infections and to synthetic or biological inducers.

Preclinical Pharmacology

Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. Once bound to the cell membrane, interferons initiate a complex sequence of intracellular events. In vitro studies demonstrated that these include the induction of certain enzymes, suppression of cell proliferation, immunomodulating activities such as enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of lymphocytes for target cells, and inhibition of virus replication in virus-infected cells.

In a study using human hepatoblastoma cell line HB 611, the in vitro antiviral activity of alpha interferon was demonstrated by its inhibition of hepatitis B virus (HBV) replication.

The correlation between these in vitro data and the clinical results is unknown. Any of these activities might contribute to interferon's therapeutic effects.

Pharmacokinetics

The pharmacokinetics of INTRON® A were studied in 12 healthy male volunteers following single doses of 5 million IU/m² administered intramuscularly, subcutaneously, and as a 30-minute intravenous infusion in a crossover design.

The mean serum INTRON A concentrations following intramuscular and subcutaneous injections were comparable. The maximum serum concentrations obtained via these routes were approximately 18 to 116 IU/mL and occurred 3 to 12 hours after administration. The elimination half-life of INTRON A following both intramuscular and subcutaneous injections was approximately 2 to 3 hours. Serum concentrations were undetectable by 16 hours after the injections.

After intravenous administration, serum INTRON A concentrations peaked (135273 IU/mL) by the end of the 30-minute infusion, then declined at a slightly more rapid rate than after intramuscular or subcutaneous drug administration, becoming undetectable 4 hours after the infusion. The elimination half-life was approximately 2 hours.

Urine INTRON A concentrations following a single dose (5 million IU/m²) were not detectable after any of the parenteral routes of administration. This result was expected since preliminary studies with isolated and perfused rabbit kidneys have shown that the kidney may be the main site of interferon catabolism.

There are no pharmacokinetic data available for the intralesional route of administration.

Serum Neutralizing Antibodies

In INTRON A-treated patients tested for antibody activity in clinical trials, serum anti-interferon neutralizing antibodies were detected in 0% (0/90) of patients with hairy cell leukemia, 0.8% (2/260) of patients treated intralesionally for condylomata acuminata, and 4% (1/24) of patients with AIDS-Related Kaposi's Sarcoma. Serum neutralizing antibodies have been detected in less than 3% of patients treated with higher INTRON A doses in malignancies other than hairy cell leukemia or AIDS-Related Kaposi's Sarcoma. The clinical significance of the appearance of serum anti-interferon neutralizing activity in these indications is not known.

Serum anti-interferon neutralizing antibodies were detected in 7% (12/168) of patients either during treatment or after completing 12 to 48 weeks of treatment with 3 million IU TIW of INTRON A therapy for chronic hepatitis C and in 13% (6/48) of patients who received INTRON A therapy for chronic hepatitis B at 5 million IU QD for 4 months, and in 3% (1/33) of patients treated at 10 million IU TIW. Serum anti-interferon neutralizing antibodies were detected in 9% (5/53) of pediatric patients who received INTRON A therapy for chronic hepatitis B at 6 million IU/m² TIW. Among all chronic hepatitis B or C patients, pediatrics and adults with detectable serum neutralizing antibodies, the titers detected were low (22/24 with titers less than or equal to 1:40 and 2/24 with titers less than or equal to 1:160). The appearance of serum anti-interferon neutralizing activity did not appear to affect safety or efficacy.

Hairy Cell Leukemia

In clinical trials in patients with hairy cell leukemia, there was depression of hematopoiesis during the first 1 to 2 months of INTRON A treatment, resulting in reduced numbers of circulating red and white blood cells, and platelets. Subsequently, both splenectomized and nonsplenectomized patients achieved substantial and sustained improvements in granulocytes, platelets, and hemoglobin levels in 75% of treated patients and at least some improvement (minor responses) occurred in 90%. INTRON A treatment resulted in a decrease in bone marrow hypercellularity and hairy cell infiltrates. The hairy cell index (HCI), which represents the percent of bone marrow cellularity times the percent of hairy cell infiltrate, was greater than or equal to 50% at the beginning of the study in 87% of patients. The percentage of patients with such an HCI decreased to 25% after 6 months and to 14% after 1 year. These results indicate that even though hematologic improvement had occurred earlier, prolonged INTRON A treatment may be required to obtain maximal reduction in tumor cell infiltrates in the bone marrow.

The percentage of patients with hairy cell leukemia who required red blood cell or platelet transfusions decreased significantly during treatment and the percentage of patients with confirmed and serious infections declined as granulocyte counts improved. Reversal of splenomegaly and of clinically significant hypersplenism was demonstrated in some patients.

A study was conducted to assess the effects of extended INTRON A treatment on duration of response for patients who responded to initial therapy. In this study, 126 responding patients were randomized to receive additional INTRON A treatment for 6 months or observation for a comparable period, after 12 months of initial INTRON A therapy. During this 6-month period, 3% (2/66) of INTRON A-treated patients relapsed compared with 18% (11/60) who were not treated. This represents a significant difference in time to relapse in favor of continued INTRON A treatment (P=0.006/0.01, Log Rank/Wilcoxon). Since a small proportion of the total population had relapsed, median time to relapse could not be estimated in either group. A similar pattern in relapses was seen when all randomized treatment, including that beyond 6 months, and available follow-up data were assessed. The 15% (10/66) relapses among INTRON A patients occurred over a significantly longer period of time than the 40% (24/60) with observation (P=0.0002/0.0001, Log Rank/Wilcoxon). Median time to relapse was estimated, using the Kaplan-Meier method, to be 6.8 months in the observation group but could not be estimated in the INTRON A group.

Subsequent follow-up with a median time of approximately 40 months demonstrated an overall survival of 87.8%. In a comparable historical control group followed for 24 months, overall median survival was approximately 40%.

Malignant Melanoma

The safety and efficacy of INTRON A was evaluated as adjuvant to surgical treatment in patients with melanoma who were free of disease (post surgery) but at high risk for systemic recurrence. These included patients with lesions of Breslow thickness greater than 4 mm, or patients with lesions of any Breslow thickness with primary or recurrent nodal involvement. In a randomized, controlled trial in 280 patients, 143 patients received INTRON A therapy at 20 million IU/m² intravenously five times per week for 4 weeks (induction phase) followed by 10 million IU/m² subcutaneously three times per week for 48 weeks (maintenance phase). In the clinical trial, the median daily INTRON A dose administered to patients was 19.1 million IU/m² during the induction phase and 9.1 million IU/m² during the maintenance phase. INTRON A therapy was begun less than or equal to 56 days after surgical resection. The remaining 137 patients were observed.

INTRON A therapy produced a significant increase in relapse-free and overall survival. Median time to relapse for the INTRON A-treated patients versus observation patients was 1.72 years versus 0.98 years (P < 0.01, stratified Log Rank). The estimated 5-year relapse-free survival rate, using the Kaplan-Meier method, was 37% for INTRON A-treated patients versus 26% for observation patients. Median overall survival time for INTRON A-treated patients versus observation patients was 3.82 years versus 2.78 years (P=0.047, stratified Log Rank). The estimated 5-year overall survival rate, using the Kaplan-Meier method, was 46% for INTRON A-treated patients versus 37% for observation patients.

In a second study of 642 resected high-risk melanoma patients, subjects were randomized equally to one of three groups: high-dose INTRON A therapy for 1 year (same schedule as above), low-dose INTRON A therapy for 2 years (3 MU/d TIW SC), and observation. Consistent with the earlier trial, high-dose INTRON A therapy demonstrated an improvement in relapse-free survival (3-year estimated RFS 48% versus 41%; median RFS 2.4 versus 1.6 years, P=not significant). Relapse-free survival in the low-dose INTRON A arm was similar to that seen in the observation arm. Neither high-dose nor low-dose INTRON A therapy showed a benefit in overall survival as compared to observation in this study.

Follicular Lymphoma

The safety and efficacy of INTRON A in conjunction with CHVP, a combination chemotherapy regimen, was evaluated as initial treatment in patients with clinically aggressive, large tumor burden, Stage III/IV follicular Non-Hodgkin's Lymphoma. Large tumor burden was defined by the presence of any one of the following: a nodal or extranodal tumor mass with a diameter of greater than 7 cm; involvement of at least three nodal sites (each with a diameter of greater than 3 cm); systemic symptoms; splenomegaly; serous effusion, orbital or epidural involvement; ureteral compression; or leukemia.

In a randomized, controlled trial, 130 patients received CHVP therapy and 135 patients received CHVP therapy plus INTRON A therapy at 5 million IU subcutaneously three times weekly for the duration of 18 months. CHVP chemotherapy consisted of cyclophosphamide 600 mg/m², doxorubicin 25 mg/m², and teniposide (VM26) 60 mg/m², administered intravenously on Day 1 and prednisone at a daily dose of 40 mg/m² given orally on Days 1 to 5. Treatment consisted of six CHVP cycles administered monthly, followed by an additional six cycles administered every 2 months for 1 year. Patients in both treatment groups received a total of 12 CHVP cycles over 18 months.

The group receiving the combination of INTRON A therapy plus CHVP had a significantly longer progression-free survival (2.9 years versus 1.5 years, P=0.0001, Log Rank test). After a median follow-up of 6.1 years, the median survival for patients treated with CHVP alone was 5.5 years while median survival for patients treated with CHVP plus INTRON A therapy had not been reached (P=0.004, Log Rank test). In three additional published, randomized, controlled studies of the addition of interferon alpha to anthracycline-containing combination chemotherapy regimens,1-3 the addition of interferon alpha was associated with significantly prolonged progression-free survival. Differences in overall survival were not consistently observed.

Condylomata Acuminata

Condylomata acuminata (venereal or genital warts) are associated with infections of the human papilloma virus (HPV). The safety and efficacy of INTRON A in the treatment of condylomata acuminata were evaluated in three controlled double-blind clinical trials. In these studies, INTRON A doses of 1 million IU per lesion were administered intralesionally three times a week (TIW), in less than or equal to 5 lesions per patient for 3 weeks. The patients were observed for up to 16 weeks after completion of the full treatment course.

INTRON A treatment of condylomata was significantly more effective than placebo, as measured by disappearance of lesions, decreases in lesion size, and by an overall change in disease status. Of 192 INTRON A-treated patients and 206 placebo-treated patients who were evaluable for efficacy at the time of best response during the course of the study, 42% of INTRON A patients versus 17% of placebo patients experienced clearing of all treated lesions. Likewise, 24% of INTRON A patients versus 8% of placebo patients experienced marked (75% to less than 100%) reduction in lesion size, 18% versus 9% experienced moderate (50% to 75%) reduction in lesion size, 10% versus 42% had a slight (less than 50%) reduction in lesion size, 5% versus 24% had no change in lesion size, and 0% versus 1% experienced exacerbation (P < 0.001).

In one of these studies, 43% (54/125) of patients in whom multiple (less than or equal to 3) lesions were treated experienced complete clearing of all treated lesions during the course of the study. Of these patients, 81% remained cleared 16 weeks after treatment was initiated.

Patients who did not achieve total clearing of all their treated lesions had these same lesions treated with a second course of therapy. During this second course of treatment, 38% to 67% of patients had clearing of all treated lesions. The overall percentage of patients who had cleared all their treated lesions after two courses of treatment ranged from 57% to 85%.

INTRON A-treated lesions showed improvement within 2 to 4 weeks after the start of treatment in the above study; maximal response to INTRON A therapy was noted 4 to 8 weeks after initiation of treatment.

The response to INTRON A therapy was better in patients who had condylomata for shorter durations than in patients with lesions for a longer duration.

Another study involved 97 patients in whom three lesions were treated with either an intralesional injection of 1.5 million IU of INTRON A per lesion followed by a topical application of 25% podophyllin, or a topical application of 25% podophyllin alone. Treatment was given once a week for 3 weeks. The combined treatment of INTRON A and podophyllin was shown to be significantly more effective than podophyllin alone, as determined by the number of patients whose lesions cleared. This significant difference in response was evident after the second treatment (Week 3) and continued through 8 weeks post-treatment. At the time of the patient's best response, 67% (33/49) of the INTRON A-and podophyllin-treated patients had all three treated lesions clear while 42% (20/48) of the podophyllin-treated patients had all three clear (P=0.003).

AIDS-Related Kaposi's Sarcoma

The safety and efficacy of INTRON A in the treatment of Kaposi's Sarcoma (KS), a common manifestation of the Acquired Immune Deficiency Syndrome (AIDS), were evaluated in clinical trials in 144 patients.

In one study, INTRON A doses of 30 million IU/m² were administered subcutaneously three times per week (TIW) to patients with AIDS-Related KS. Doses were adjusted for patient tolerance. The average weekly dose delivered in the first 4 weeks was 150 million IU; at the end of 12 weeks this averaged 110 million IU/week; and by 24 weeks averaged 75 million IU/week.

Forty-four percent of asymptomatic patients responded versus 7% of symptomatic patients. The median time to response was approximately 2 months and 1 month, respectively, for asymptomatic and symptomatic patients. The median duration of response was approximately 3 months and 1 month, respectively, for the asymptomatic and symptomatic patients. Baseline T4/T8 ratios were 0.46 for responders versus 0.33 for nonresponders.

In another study, INTRON A doses of 35 million IU were administered subcutaneously, daily (QD), for 12 weeks. Maintenance treatment, with every other day dosing (QOD), was continued for up to 1 year in patients achieving antitumor and antiviral responses. The median time to response was 2 months and the median duration of response was 5 months in the asymptomatic patients.

In all studies, the likelihood of response was greatest in patients with relatively intact immune systems as assessed by baseline CD4 counts (interchangeable with T4 counts). Results at doses of 30 million IU/m² TIW and 35 million IU/QD were subcutaneously similar and are provided together in TABLE 1. This table demonstrates the relationship of response to baseline CD4 count in both asymptomatic and symptomatic patients in the 30 million IU/m² TIW and the 35 million IU/QD treatment groups.

In the 30 million IU study group, 7% (5/72) of patients were complete responders and 22% (16/72) of the patients were partial responders. The 35 million IU study had 13% (3/23 patients) complete responders and 17% (4/23) partial responders.

For patients who received 30 million IU TIW, the median survival time was longer in patients with CD4 greater than 200 (30.7 months) than in patients with CD4 less than or equal to 200 (8.9 months). Among responders, the median survival time was 22.6 months versus 9.7 months in nonresponders.

Chronic Hepatitis C

The safety and efficacy of INTRON A in the treatment of chronic hepatitis C was evaluated in 5 randomized clinical studies in which an INTRON A dose of 3 million IU three times a week (TIW) was assessed. The initial three studies were placebo-controlled trials that evaluated a 6-month (24-week) course of therapy. In each of the three studies, INTRON A therapy resulted in a reduction in serum alanine aminotransferase (ALT) in a greater proportion of patients versus control patients at the end of 6 months of dosing. During the 6 months of follow-up, approximately 50% of the patients who responded maintained their ALT response. A combined analysis comparing pretreatment and post-treatment liver biopsies revealed histological improvement in a statistically significantly greater proportion of INTRON A-treated patients compared to controls.

Two additional studies have investigated longer treatment durations (up to 24 months).5,6 Patients in the two studies to evaluate longer duration of treatment had hepatitis with or without cirrhosis in the absence of decompensated liver disease. Complete response to treatment was defined as normalization of the final two serum ALT levels during the treatment period. A sustained response was defined as a complete response at the end of the treatment period, with sustained normal ALT values lasting at least 6 months following discontinuation of therapy.

In Study 1, all patients were initially treated with INTRON A 3 million IU TIW subcutaneously for 24 weeks (run-in-period). Patients who completed the initial 24-week treatment period were then randomly assigned to receive no further treatment, or to receive 3 million IU TIW for an additional 48 weeks. In Study 2, patients who met the entry criteria were randomly assigned to receive INTRON A 3 million IU TIW subcutaneously for 24 weeks or to receive INTRON A 3 million IU TIW subcutaneously for 96 weeks. In both studies, patient follow-up was variable and some data collection was retrospective.

Results show that longer durations of INTRON A therapy improved the sustained response rate (see TABLE 2). In patients with complete responses (CR) to INTRON A therapy after 6 months of treatment (149/352 [42%]), responses were less often sustained if drug was discontinued (21/70 [30%]) than if it was continued for 18 to 24 months (44/79 [56%]). Of all patients randomized, the sustained response rate in the patients receiving 18 or 24 months of therapy was 22% and 26%, respectively, in the two trials. In patients who did not have a CR by 6 months, additional therapy did not result in significantly more responses, since almost all patients who responded to therapy did so within the first 16 weeks of treatment.

A subset (less than 50%) of patients from the combined extended dosing studies had liver biopsies performed both before and after INTRON A treatment. Improvement in necroinflammatory activity as assessed retrospectively by the Knodell (Study 1) and Scheuer (Study 2) Histology Activity Indices was observed in both studies. A higher number of patients (58%, 45/78) improved with extended therapy than with shorter (6 months) therapy (38%, 34/89) in this subset.

Combination treatment with INTRON A and REBETOL® (ribavirin USP) provided a significant reduction in virologic load and improved histologic response in adult patients with compensated liver disease who were treatment-naïve or had relapsed following therapy with alpha interferon alone; pediatric patients previously untreated with alpha interferon experienced a sustained virologic response. See REBETOL prescribing information for additional information.

Chronic Hepatitis B

Adults

The safety and efficacy of INTRON A in the treatment of chronic hepatitis B were evaluated in three clinical trials in which INTRON A doses of 30 to 35 million IU per week were administered subcutaneously (SC), as either 5 million IU daily (QD), or 10 million IU three times a week (TIW) for 16 weeks versus no treatment. All patients were 18 years of age or older with compensated liver disease, and had chronic hepatitis B virus (HBV) infection (serum HBsAg positive for at least 6 months) and HBV replication (serum HBeAg positive). Patients were also serum HBV-DNA positive, an additional indicator of HBV replication, as measured by a research assay.7,8 All patients had elevated serum alanine aminotransferase (ALT) and liver biopsy findings compatible with the diagnosis of chronic hepatitis. Patients with the presence of antibody to human immunodeficiency virus (anti-HIV) or antibody to hepatitis delta virus (anti-HDV) in the serum were excluded from the studies.

Virologic response to treatment was defined in these studies as a loss of serum markers of HBV replication (HBeAg and HBV DNA). Secondary parameters of response included loss of serum HBsAg, decreases in serum ALT, and improvement in liver histology.

In each of two randomized controlled studies, a significantly greater proportion of INTRON A-treated patients exhibited a virologic response compared with untreated control patients (see TABLE 3). In a third study without a concurrent control group, a similar response rate to INTRON A therapy was observed. Pretreatment with prednisone, evaluated in two of the studies, did not improve the response rate and provided no additional benefit.

The response to INTRON A therapy was durable. No patient responding to INTRON A therapy at a dose of 5 million IU QD or 10 million IU TIW relapsed during the follow-up period, which ranged from 2 to 6 months after treatment ended. The loss of serum HBeAg and HBV DNA was maintained in 100% of 19 responding patients followed for 3.5 to 36 months after the end of therapy.

In a proportion of responding patients, loss of HBeAg was followed by the loss of HBsAg. HBsAg was lost in 27% (4/15) of patients who responded to INTRON A therapy at a dose of 5 million IU QD, and 35% (8/23) of patients who responded to 10 million IU TIW. No untreated control patient lost HBsAg in these studies.

In an ongoing study to assess the long-term durability of virologic response, 64 patients responding to INTRON A therapy have been followed for 1.1 to 6.6 years after treatment; 95% (61/64) remain serum HBeAg negative, and 49% (30/61) lost serum HBsAg.

INTRON A therapy resulted in normalization of serum ALT in a significantly greater proportion of treated patients compared to untreated patients in each of two controlled studies (see TABLE 4). In a third study without a concurrent control group, normalization of serum ALT was observed in 50% (12/24) of patients receiving INTRON A therapy.

Virologic response was associated with a reduction in serum ALT to normal or near normal (less than or equal to 1.5 x the upper limit of normal) in 87% (13/15) of patients responding to INTRON A therapy at 5 million IU QD, and 100% (23/23) of patients responding to 10 million IU TIW.

Improvement in liver histology was evaluated in Studies 1 and 3 by comparison of pretreatment and 6-month post-treatment liver biopsies using the semiquantitative Knodell Histology Activity Index.9 No statistically significant difference in liver histology was observed in treated patients compared to control patients in Study 1. Although statistically significant histological improvement from baseline was observed in treated patients in Study 3 (P ≤ 0.01), there was no control group for comparison. Of those patients exhibiting a virologic response following treatment with 5 million IU QD or 10 million IU TIW, histological improvement was observed in 85% (17/20) compared to 36% (9/25) of patients who were not virologic responders. The histological improvement was due primarily to decreases in severity of necrosis, degeneration, and inflammation in the periportal, lobular, and portal regions of the liver (Knodell Categories I + II + III). Continued histological improvement was observed in four responding patients who lost serum HBsAg and were followed 2 to 4 years after the end of INTRON A therapy.10

Pediatrics

The safety and efficacy of INTRON A in the treatment of chronic hepatitis B was evaluated in one randomized controlled trial of 149 patients ranging from 1 year to 17 years of age. Seventy-two patients were treated with 3 million IU/m² of INTRON A therapy administered subcutaneously three times a week (TIW) for 1 week; the dose was then escalated to 6 million IU/m² TIW for a minimum of 16 weeks up to 24 weeks. The maximum weekly dosage was 10 million IU TIW. Seventy-seven patients were untreated controls. Study entry and response criteria were identical to those described in the adult patient population.

Patients treated with INTRON A therapy had a better response (loss of HBV DNA and HBeAg at 24 weeks of follow-up) compared to the untreated controls (24% [17/72] versus 10% [8/77] P=0.05). Sixteen of the 17 responders treated with INTRON A therapy remained HBV DNA and HBeAg negative and had a normal serum ALT 12 to 24 months after completion of treatment. Serum HBsAg became negative in 7 out of 17 patients who responded to INTRON A therapy. None of the control patients who had an HBV DNA and HBeAg response became HBsAg negative. At 24 weeks of follow-up, normalization of serum ALT was similar in patients treated with INTRON A therapy (17%, 12/72) and in untreated control patients (16%, 12/77). Patients with a baseline HBV DNA less than 100 pg/mL were more likely to respond to INTRON A therapy than were patients with a baseline HBV DNA greater than 100 pg/mL (35% versus 9%, respectively). Patients who contracted hepatitis B through maternal vertical transmission had lower response rates than those who contracted the disease by other means (5% versus 31%, respectively). There was no evidence that the effects on HBV DNA and HBeAg were limited to specific subpopulations based on age, gender, or race.

TABLE 1 : RESPONSE BY BASELINE CD4 COUNT* IN AIDS-RELATED KS PATIENTS

  30 million IU/m2 TIW, SC and 35 million IU QD, SC
Asymptomatic Symptomatic
CD4 < 200 4/14 (29%) 0/19 (0%)
200 ≤ CD4 ≤ 400 6/12 (50%) 0/5 (0%)
  } 58%  
CD4 > 400 5/7 (71%) 0/0 (0%)
* Data for CD4, and asymptomatic and symptomatic classification were not available for all patients.

TABLE 2 : SUSTAINED ALT RESPONSE RATE VERSUS DURATION OF THERAPY IN CHRONIC HEPATITIS C PATIENTS

Study Number INTRON A 3 Million IU TIW
Treatment Group* -Number of Patients (%)
INTRON A 3 million IU 24 weeks of treatment INTRON A 3 million IU 72 or 96 weeks of treatment Difference (Extended — 24 weeks) (95% CI)‡
ALT responseat the end of follow-up
1 12/101 (12%) 23/104 (22%) 10% (-3, 24)
2 9/67 (13%) 21/80 (26%) 13% (-4, 30)
Combined Studies 21/168 (12.5%) 44/184 (24%) 11.4% (2, 21)
ALT response at the end of treatment
1 40/101 (40%) 51/104 (49%) -
2 32/67 (48%) 35/80 (44%) --
* Intent-to-treat groups.
† Study 1: 72 weeks of treatment; Study 2: 96 weeks of treatment.
‡ Confidence intervals adjusted for multiple comparisons due to 3 treatment arms in the study.

TABLE 3 : VIROLOGIC RESPONSE* IN CHRONIC HEPATITIS B PATIENTS

Study Number Treatment Group† -Number of Patients (%)
INTRON A 5 million IU QD INTRON A 10 million IU TIW Untreated Controls P‡ Value
17 15/38 (39%) - 3/42 (7%) 0.0009
2 -- 10/24 (42%) 1/22 (5%) 0.005
38 -- 13/24§ (54%) 2/27 (7%)§ NA§
All Studies 15/38 (39%) 23/48 (48%) 6/91 (7%) --
* Loss of HBeAg and HBV DNA by 6 months post-therapy.
† Patients pretreated with prednisone not shown.
‡ INTRON A treatment group versus untreated control.
§ Untreated control patients evaluated after 24-week observation period. A subgroup subsequently received INTRON A therapy. A direct comparison is not applicable (NA).

TABLE 4 : ALT RESPONSES* IN CHRONIC HEPATITIS B PATIENTS

Study Number INTRON A 5 million IU QD INTRON A 10 million IU TIW Untreated Controls P†Value
1 16/38 (42%) -- 8/42 (19%) 0.03
2 -- 10/24 (42%) 1/22 (5%) 0.0034
3 -- 12/24* (50%) 2/27 (7%)‡ NA‡
All Studies 16/38 (42%) 22/48 (46%) 11/91 (12%) --
* Reduction in serum ALT to normal by 6 months post-therapy.
† INTRON A treatment group versus untreated control.
‡ Untreated control patients evaluated after 24-week observation period. A subgroup subsequently received INTRON A therapy. A direct comparison is not applicable (NA).

REFERENCES

1. Smalley R, et al. N Engl J Med. 1992;327:1336-1341.

2. Aviles A, et al. Leukemia and Lymphoma. 1996;20:495-499.

3. Unterhalt M, et al. Blood. 1996;88(10 Suppl 1):1744A.

5. Poynard T, et al. N Engl J Med. 1995;332(22)1457-1462.

6. Lin R, et al. J Hepatol. 1995;23:487-496.

7. Perrillo R, et al. N Engl J Med. 1990;323:295-301.

8. Perez V, et al. J Hepatol. 1990;11:S113-S117.

9. Knodell R, et al. Hepatology. 1981;1:431-435.

10. Perrillo R, et al. Ann Intern Med. 1991;115:113-115.


This monograph has been modified to include the generic and brand name in many instances.

 

Patient Information

Instructions for Use

INTRON® A
(In-tron-aye)
(Interferon alfa-2b, recombinant) Powder for Solution

Be sure that you read, understand, and follow these instructions before injecting INTRON A. Your healthcare provider should show you how to prepare, measure, and inject INTRON A properly before you use it for the first time. Ask your healthcare provider if you have any questions.

Before starting, collect all of the supplies that you will need to use for preparing and injecting INTRON A. For each injection you will need the following supplies:

  • 1 vial of INTRON A powder for solution
  • 1 vial of sterile water for injection (diluent). The vial contains an excess amount of sterile water (5 mL). You will only need to withdraw 1 mL to prepare your single dose.
  • 1 single-use disposable syringe and needle
  • 1 cotton ball or gauze
  • 2 alcohol swabs
  • 1 sharps disposal container for throwing away (dispose of) your used syringes, needles, and vials. See “How should I dispose of used syringes, needles, and vials?” at the end of this Instructions for Use.

Important:

  • Never re-use disposable syringes and needles.
  • The vial of mixed INTRON A should be used right away. Do not mix more than 1 vial of INTRON A at a time. If you do not use the vial of prepared solution right away, store it in a refrigerator and use within 24 hours. See the end of this Instructions for Use for information about “How should I store INTRON A?”
  • After mixing, throw away (discard) the vial of INTRON A after you withdraw one dose of medicine.
  • Make sure you have the right syringe and needle to use with INTRON A. Your healthcare provider should tell you what syringes and needles to use to inject INTRON A.

How should I prepare a dose of INTRON A?

Before you inject INTRON A, the powder must be mixed with 1 mL (cc) of the sterile water for injection (diluent) from the INTRON A vial package.

1. Find a clean, well-lit, flat work surface.

2. Get one of your INTRON A vial packages. Check the date printed on the carton. Make sure that the expiration date has not passed.

3. Wash your hands well with soap and water. Keep your work area, your hands, and injection site clean to decrease the risk of infection (See Figure A).

Figure A

Wash your hands well - Illustration

4. Gently warm the vial of diluent by slowly rolling the vial in the palms of your hands for one minute (See Figure B).

Figure B

Gently warm the vial - Illustration

5. Remove the protective plastic cap from the tops of both vials (INTRON A powder and the diluent). Clean the rubber stopper on the top of both vials with an alcohol swab (See Figure C).

Figure C

Remove the protective plastic cap - Illustration

6. Open the package for the syringe (See Figure D) you are using and if it does not have a needle attached, then attach a new needle to the syringe.

Figure D

Open the package for the syringe - Illustration

7. Remove the needle cover from the syringe. Fill the syringe with air by pulling the plunger back to 1 mL (See Figure E).

Figure E

Fill the syringe with air by pulling the plunger back to 1 mL - Illustration

8. Hold the diluent vial on your flat work surface. Do not touch the cleaned rubber stopper (See Figure F).

Figure F

Hold the diluent vial on your flat work surface - Illustration

9. Push the needle straight down through the middle of the rubber stopper of the diluent vial and slowly inject all the air from the syringe into the air space above the diluent (See Figure G).

Figure G

Push the needle straight down through the middle of the rubber stopper - Illustration

10. Keep the needle in the vial. Turn the vial upside down and make sure the tip of the needle is in the diluent.

  • Important: The sterile water for injection vial contains an excess amount of sterile water (5 mL). You will only need to withdraw 1 mL to prepare your single dose.
  • Slowly pull the plunger back to fill the syringe with diluent to the 1 mL mark on the side of the syringe (See Figure H).

Figure H

Slowly pull the plunger back to fill the syringe with diluent to the 1 mL mark - Illustration

11. With the needle still inserted in the vial, check the syringe for air bubbles (See Figure I).

  • If there are any air bubbles, gently tap the syringe with your finger until the air bubbles rise to the top of the syringe.
  • Slowly push the plunger up to remove the air bubbles.

If you push diluent back into the vial, slowly pull back on the plunger to again draw 1 mL of diluent back into the syringe.

Figure I

Gently tap the syringe - Illustration

12. Remove the needle from the vial. Do not let the syringe touch anything.

13. Throw away the diluent that is left over in the vial. Do not save any leftover diluent or use it again. See “How should I dispose of used syringes, needles, and vials” at the end of this Instructions for Use.

14. Insert the needle through the center of the rubber stopper of the INTRON A powder vial. Do not touch the cleaned rubber stopper.

  • Place the needle tip, at an angle, against the side of the INTRON A powder vial (See Figure J).

Figure J

Place the needle tip, at an angle, against the side of the INTRON A powder vial - Illustration
  • Slowly push the plunger down to inject the diluent into the vial. The stream of liquid should run down the sides of the glass vial.
  • To prevent bubbles from forming, do not aim the stream of diluent directly on the medicine in the bottom of the vial.
  • Do not remove the needle from the vial.

15. Gently swirl the INTRON A vial in a circular motion until the powder is completely dissolved (See Figure K).

Figure K

Gently swirl the INTRON A vial - Illustration
  • Do not shake the vial. If any powder remains undissolved in the vial, gently turn the vial upside down until all of the powder is dissolved.
  • The solution may look cloudy or bubbly for a few minutes. If air bubbles do form, wait until the solution settles and all bubbles rise to the top. Then withdraw your dose from the vial.

16. After the INTRON A completely dissolves, the solution should be clear and colorless to light yellow, without particles. Do not use the mixed solution if you see particles in it, or it is not clear and colorless to light yellow.

17. With the needle in the vial, turn the vial upside down (See Figure L).

Figure L

Turn the vial upside down - Illustration
  • Hold the vial with one hand. Be sure the tip of the needle is in the INTRON A solution. Slowly pull the plunger back to fill the syringe with the exact amount of INTRON A into the syringe that your healthcare provider told you to use.

18. With the needle still inserted in the vial, check the syringe for air bubbles. If you see any air bubbles, gently tap the syringe with your finger until the air bubbles rise to the top of the syringe (See Figure M).

Figure M

gently tap the syringe - Illustration

19. Slowly push the plunger up to remove the air bubbles. If you push solution back into the vial, slowly pull back on the plunger again to draw the correct amount of INTRON A solution back into the syringe.

20. Do not remove the needle from the vial. Lay the vial and syringe on its side on your flat work surface until you are ready to inject the INTRON A solution.

How should I choose a site for injection?

Based on your treatment, your healthcare provider will tell you if you should inject a dose of INTRON® A under the skin (subcutaneous injection) or into the muscle (intramuscular injection). If it is too difficult for you to inject, ask someone who has been trained to give injections to help you.

For Subcutaneous Injection

The best sites for injection are areas on your body with a layer of fat between skin and muscle, such as (See Figure N):

  • the front of your middle thighs
  • the outer area of your upper arms
  • the abdomen, except around your belly-button (navel)

Figure N

Sites for injection - Illustration

For Intramuscular Injection

The best sites for injection into your muscle are (See Figure O):

  • the front of your middle thighs
  • your upper arms
  • the upper outer areas of your buttocks

Figure O

Sites for injection - Illustration

You should use a different site each time you inject INTRON® A to avoid soreness at any one site. Do not inject INTRON A into an area where the skin is irritated, red, bruised, infected or has scars, stretch marks, or lumps.

How should I inject a dose of INTRON® A?

21. Clean the injection site with a new alcohol swab. Wait for the skin to dry.

22. Pick up the vial and syringe from your flat work surface. Remove the syringe and needle from the vial.

  • Hold the syringe in the hand that you will use to inject INTRON A.
  • Do not touch the needle or allow it to touch the work surface.

23. With one hand, pinch a fold of the skin at the cleaned injection site.

24. For subcutaneous injection (under the skin):

  • With the other hand, hold the syringe (like a pencil) at a 45-degree angle to the skin. With a quick “dart-like” motion, push the needle into the skin (See Figure P).

Figure P

hold the syringe (like a pencil) at a 45-degree angle to the skin - Illustration

25. For intramuscular injection (into the muscle):

  • Hold the syringe (like a pencil) at a 90-degree angle to the skin.
  • With a quick “dart-like” motion, push the needle into the muscle (See Figure Q).

Figure Q

Hold the syringe (like a pencil) at a 90-degree angle - Illustration

26. After the needle is inserted, remove the hand used to pinch the skin and use it to hold the syringe barrel.

  • Pull the plunger back slightly.
  • If no blood is present in the syringe, inject the medicine by gently pushing the plunger all the way down the syringe barrel, until the syringe is empty.
  • If blood comes into the syringe, the needle has entered a blood vessel. Do not inject INTRON® A.
    • Withdraw the needle and dispose of the syringe and needle in the sharps disposal container. See section “How should I dispose of used syringes, needles, and vials?” at the end of this Instructions for Use.
    • If there is bleeding, cover the injection site with a bandage.
    • Then, repeat steps 1 through 25 with a new dose of INTRON A and inject the medicine at a new injection site.

27. When the syringe is empty, pull the needle out of the skin.

  • Place a cotton ball or gauze over the injection site and press for several seconds. Do not massage the injection site.
  • If there is bleeding, cover the injection site with a bandage.

28. Dispose of used syringes, needles, and vials in the sharps disposal container. (See “How should I dispose of used syringes, needles, and vials?” below.)

How should I dispose of used syringes, needles, and vials?

  • Put your used needles, syringes and vials in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles, syringes and vials in your household trash.
  • If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
    • made of a heavy-duty plastic,
    • closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
    • upright and stable during use,
    • leak-resistant, and
    • properly labeled to warn of hazardous waste inside the container.
  • When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used syringes and needles. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
  • Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

Always keep the sharps disposal container out of the reach of children.

How should I store INTRON® A?

  • Before mixing, store in the refrigerator between 36°F to 46°F (2°C to 8°C).
  • After mixing the INTRON A Powder for Injection, use the solution right away or store the solution in the refrigerator for up to 24 hours between 36°F to 46°F (2°C to 8°C). Allow the solution to come to room temperature before using.
  • Do not freeze Intron A.
  • Keep away from heat.
  • Throw away any medicine left in the vial after you withdraw 1 dose.

Keep INTRON A and all medicines out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Instructions for Use

INTRON® A
(In-tron-aye)
(Interferon alfa-2b, recombinant)

Solution for Injection

Be sure that you read, understand and follow these instructions before injecting INTRON A. Your healthcare provider should show you how to prepare, measure and inject INTRON A properly before you use it for the first time. Ask your healthcare provider if you have any questions.

Before starting, collect all of the supplies that you will need to use for preparing and injecting INTRON A. For each injection, you will need the following supplies:

  • 1 vial of INTRON A solution
  • 1 single-use disposable syringe and needle
  • 1 cotton ball or gauze
  • 2 alcohol swabs
  • 1 sharps disposal container for throwing away (dispose of) your used syringes, needles, and vials. See “How should I dispose of used syringes, needles, and vials?” at the end of this Instructions for Use.

Important:

  • Never re-use disposable syringes and needles.
  • Make sure you have the right syringe and needle to use with INTRON A. Your healthcare provider should tell you what syringes and needles to use to inject INTRON A.

How should I prepare a dose of INTRON® A?

1 Find a well lit, clean, flat working surface.

2. Before removing INTRON A from the carton, look at the expiration date printed on the carton. Make sure that the expiration date has not passed. Do not use if the expiration date has passed.

3. Wash your hands well with soap and warm water (See Figure A). Keep your work area, your hands and injection site clean to decrease the risk of infection.

Figure A

Wash your hands well - Illustration

4. Remove 1 vial of INTRON A solution from the carton (See Figure B).

Figure B

Remove 1 vial of INTRON A solution  -  Illustration

5. Look at the vial of INTRON A. The solution should be clear and colorless, without particles. Do not use the vial of INTRON A if the medicine is cloudy, has particles or is not clear and colorless.

6. Remove the protective plastic cap from the top of the INTRON A vial. Clean the rubber stopper on the top of the INTRON A vial with an alcohol swab (See Figure C).

Figure C

Remove the protective plastic cap - Illustration

7. Gently warm the INTRON A solution by slowly rolling the vial in the palms of your hands for about one minute (See Figure D). Do not shake the vial.

Figure D

Gently warm the INTRON A solution - Illustration

8. Open the package of the syringe you are using (See Figure E) and if it does not have a needle attached, then attach a new needle to the syringe.

Figure E

Open the package of the syringe - Illustration

9. Remove the protective cap from the needle of the syringe. Fill the syringe with air by pulling back on the plunger to the mark on the syringe that matches the dose prescribed by your healthcare provider (See Figure F).

Figure F

Fill the syringe with air upto the required dose - Illustration

10. Hold the vial of INTRON A Solution for Injection on your flat working surface (See Figure G). Do not touch the cleaned rubber stopper.

Figure G

Hold the vial of INTRON A Solution for Injection on your flat working surface - Illustration

11. Push the needle straight down through the middle of the rubber stopper of the vial containing the INTRON A solution (See Figure H). Slowly inject all the air from the syringe into the air space above the solution.

Figure H

Push the needle straight down - Illustration

12. Keep the needle in the vial. Turn the vial upside down (See Figure I).

  • Make sure the tip of the needle is in the INTRON A solution.
  • Slowly pull the plunger back to fill the syringe with INTRON A solution to the dose (mL or cc) prescribed by your healthcare provider.

Figure I

Turn the vial upside down - Illustration

13. With the needle still in the vial, check the syringe for air bubbles (See Figure J).

  • If there are any air bubbles, gently tap the syringe with your finger until the air bubbles rise to the top of the syringe.
  • Slowly push the plunger up to remove the air bubbles.
  • If you push solution back into the vial, slowly pull back on the plunger to draw the dose (mL or cc) prescribed by your healthcare provider.

Figure J

Gently tap the syringe - Illustration

14. Do not remove the needle from the vial. Lay the vial and syringe on its side on your flat work surface until you are ready to inject the INTRON A solution.

How should I choose a site for injection?

Based on your treatment, your healthcare provider will tell you if you should inject a dose of INTRON® A under the skin (subcutaneous injection) or into the muscle (intramuscular injection). If it is too difficult for you to inject, ask someone who has been trained to give injections to help you.

For Subcutaneous Injection

The best sites for injection are areas on your body with a layer of fat between skin and muscle such as (See Figure K):

  • the front of your middle thighs
  • the outer area of your upper arms
  • the abdomen, except around your belly button (navel)

Figure K

Sites for injection - Illustration

For Intramuscular Injection

The best sites for injection into your muscle are (See Figure L):

  • the front of your middle thighs
  • your upper arms
  • the upper outer areas of your buttocks

Figure L

best sites for injection into your muscle - Illustration

You should use a different site each time you inject INTRON® A to avoid soreness at any one site. Do not inject INTRON A into an area where the skin is irritated, red, bruised, infected or has scars, stretch marks or lumps.

How should I inject a dose of INTRON® A?

15. Clean the injection site with a new alcohol swab. Wait for the area to dry.

16. Pick up the vial and syringe from your flat work surface. Remove the syringe and needle from the vial.

  • Hold the syringe in the hand that you will use to inject INTRON A.
  • Do not touch the needle or allow it to touch the work surface.

17. With your other hand, pinch a fold of the skin at the cleaned injection site.

For subcutaneous injection (under the skin):

  • Hold the syringe (like a pencil) at a 45-degree angle to the skin. quick “dart-like” motion, push the needle into the skin (See Figure M).

Figure M

Hold the syringe (like a pencil) at a 45-degree angle to the skin - Illustration

For intramuscular injection (into the muscle):

  • Hold the syringe (like a pencil) at a 90-degree angle to the skin. With a quick “dart-like” motion, push the needle into the muscle (See Figure N).

Figure N

Hold the syringe (like a pencil) at a 90-degree angle to the skin -  Illustration

18. After the needle is inserted, remove the hand used to pinch the skin. Use it to hold the syringe barrel.

  • Pull the plunger back slightly.
  • If no blood is present in the syringe, inject the medicine by gently pressing the plunger all the way down the syringe barrel, until the syringe is empty.
  • If blood comes into the syringe, the needle has entered a blood vessel. Do not inject INTRON® A.
    • Withdraw the needle and dispose of the syringe and needle in the sharps disposal container. See “How should I dispose of used syringes, needles and vials?” at the end of this Instructions for Use
    • If there is bleeding, cover the injection site with a bandage.
    • Then, repeat steps 1 through 18 with a new dose of INTRON A and inject the medicine at a new injection site.

19. When the syringe is empty, pull the needle out of the skin.

  • Place a cotton ball or gauze over the injection site and press for several seconds. Do not massage the injection site.
  • If there is bleeding, cover the injection site with a bandage.

20. Dispose of used syringes, needles and vials in the sharps disposal container. See “How should I dispose of used syringes, needles, and vials?” below.

How should I dispose of used syringes, needles, and vials?

  • Put your used needles, syringes and vials in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles, syringes and vials in your household trash.
  • If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
    • made of a heavy-duty plastic,
    • closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
    • upright and stable during use,
    • leak-resistant, and
    • properly labeled to warn of hazardous waste inside the container.
  • When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used syringes and needles. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
  • Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.
  • Always keep the sharps disposal container out of the reach of children.

How should I store INTRON® A?

  • Store in the refrigerator at 36°F to 46°F (2°C to 8°C).
  • Do not freeze Intron A.
  • Allow the INTRON A Solution for Injection to come to room temperature before using. INTRON A Solution in Multidose vials for Injection may be used to give more than 1 injection of medicine.
  • Throw away any unused INTRON A Solution for Injection remaining in the vial after 1 month
  • Keep away from heat.
  • Keep INTRON A and all medicines out of the reach of children.

This monograph has been modified to include the generic and brand name in many instances.

 

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

INTERFERON ALFA(CON) - INJECTION

 

(in-ter-FEER-on AL-fuh)

 

COMMON BRAND NAME(S): Alferon N, Infergen, Intron A, Roferon-A

 

WARNING: This medication can infrequently cause or worsen serious (rarely fatal) medical conditions, including mental/mood conditions (e.g., depression), immune system problems (autoimmune conditions such as lupus or rheumatoid arthritis), circulation problems, or infections. If your medical history includes any of these conditions, tell your doctor promptly. Also, tell your doctor immediately if any serious symptoms or side effects occur (see Side Effects section).

This medication may be combined with ribavirin to treat chronic hepatitis C. Ribavirin may cause harm to an unborn baby or death. Women must avoid pregnancy while they or their male partners are using ribavirin. Ribavirin may cause a blood disorder (hemolytic anemia), which can worsen heart disease. If you are using this medication with ribavirin to treat chronic hepatitis C, also carefully read the drug information for ribavirin.

 

USES: This medication is used to treat various cancers (e.g., leukemia, melanoma, AIDS-related Kaposi's sarcoma). It is also used to treat virus infections (e.g., chronic hepatitis B, chronic hepatitis C, condylomata acuminata). This medication is the same as a protein that your body naturally produces (interferon). In the body, it is thought to work by affecting cell function/growth and the body's natural defenses (immune system) in many ways. Adding more interferon may help your body fight off cancer or virus infections.

 

HOW TO USE: Read the Medication Guide available from your pharmacist before you start using this drug and each time you get a refill. Learn all preparation and usage instructions given by the manufacturer. If you have any questions, consult your doctor or pharmacist.

This medication is given by injection into a muscle or under the skin as directed by your doctor. Rotate the injection site each time you inject this medication to prevent soreness. It may also be given by injection into a vein or directly into a lesion, usually by a health care professional.

If you are giving this medication to yourself at home, learn all preparation and usage instructions from your health care professional. Do not shake the medication container (vial or syringe). Doing so may decrease the effectiveness of the drug. Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Learn how to store and discard medical supplies safely. Never reuse single-use syringes or needles. It is okay to reuse the multidose pen. It is best used in the evening before bedtime to reduce side effects.

Drink plenty of fluids while using this medication unless otherwise directed by your doctor.

Dosage is based on your medical condition and response to therapy. Do not change the dose or how often you use this medication without your doctor's approval. Use this medication regularly to get the most benefit from it. To help you remember, use it at the same time each evening that you have a scheduled dose.

Different brands of interferon alfa can result in different amounts of medication in the blood. This medication comes in different forms (a powder in a vial, a solution in a vial, and a multidose pen). The way you inject this medication depends on the form you are using. Follow your doctor's directions carefully. Do not switch brands without your doctor's permission.

Consumer Overview Side Effect

SIDE EFFECTS: Injection site reactions (pain/swelling/redness), headache, tiredness, diarrhea, upset stomach, loss of appetite, back pain, dizziness, dry mouth, taste changes, nausea, or vomiting may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Flu-like symptoms such as fever, chills, and muscle aches may occur, especially when you first start this medication. These symptoms usually last about 1 day after the injection and improve or go away after a few weeks of continued use. You can reduce these side effects by injecting this medicine at bedtime and using a fever reducer/pain reliever such as acetaminophen before each dose. Consult your doctor or pharmacist for more information.

Tooth and gum problems may sometimes occur during treatment. Having a dry mouth can worsen this side effect. Prevent dry mouth by drinking plenty of water or using a saliva substitute. Brush your teeth well at least twice a day and have regular dental exams. If you experience vomiting during treatment, rinse your mouth afterwards to lessen the chance of tooth and gum problems.

Temporary hair loss may occur. Normal hair growth should return after treatment has ended.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: feeling too hot or cold (more than others around you), fast/irregular heartbeat, increased thirst/urination, menstrual changes (absent/delayed/irregular periods), numbness/tingling of hands/feet, swelling (especially of face/hands/feet), trouble sleeping, trouble walking, vision changes (such as blurred vision, partial loss of vision), easy bleeding/bruising, persistent nausea/vomiting, signs of infection (e.g., fever, persistent sore throat), stomach/abdominal pain, dark urine, black/tarry stools, yellowing eyes/skin.

Get medical help right away if any of these very serious side effects occur: chest pain, seizures, weakness on one side of the body, slurred speech.

This drug may cause you to develop serious mental/mood changes that may get worse during treatment or after your last dose. Tell your doctor right away if you have symptoms such as confusion, depression, suicidal thoughts, unusual irritability, or aggressive behavior. If this occurs, psychiatric therapy and monitoring is recommended during and after treatment with this medication.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Intron A (interferon alfa-2b, recombinant for injection) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: See also Warning section.

Before using interferon alfa, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients (such as albumin), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: severe liver conditions (e.g., autoimmune hepatitis, decompensated liver disease).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: blood cell disorders (e.g., anemia, neutropenia, thrombocytopenia), cancer, diabetes, eye problems, heart disease (e.g., angina, irregular heartbeat), high blood pressure, HIV infection, immune system diseases (e.g., lupus, psoriasis, rheumatoid arthritis), intestinal disease (e.g., colitis), kidney disease, liver disease, lung diseases (e.g., chronic obstructive pulmonary disease-COPD, asthma, pneumonia), mental/mood disorders (e.g., anxiety, depression), high blood triglyceride levels, pancreatitis, seizure disorder, thyroid disease, use/abuse of drugs/alcohol.

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

Do not have immunizations/vaccinations without the consent of your doctor, and avoid contact with people who have recently received oral polio vaccine or flu vaccine inhaled through the nose. Wash your hands well to prevent the spread of infections.

To lower your risk of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Children may be more sensitive to the side effects of this drug, especially mental/mood changes (such as severe depression, thoughts/attempts of suicide). Interferon and ribavirin may also slow down a child's rate of growth. Normal weight gain and rate of growth usually return after treatment is completed but the final adult height may be lower than expected. Monitor your child's height and weight periodically during treatment.

Caution is advised when using this drug in the elderly because they may be more sensitive to the effects of the drug, especially dizziness, mental/mood changes, and effects on the heart.

This medication is not recommended for use during pregnancy due to possible harm to an unborn baby and the risk of serious side effects for the pregnant woman. If you become pregnant or think you may be pregnant, tell your doctor immediately. To avoid pregnancy, both males and females using this drug must use reliable form(s) of birth control (e.g., condoms, birth control pills) during treatment with this drug. Talk with your doctor about effective forms of birth control.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: barbiturates (e.g., phenobarbital), colchicine, drugs that may affect your immune system (e.g., cancer chemotherapy, aldesleukin, cyclosporine), hydroxyurea, stavudine, telbivudine, theophyllines (e.g., aminophylline, theophylline), zidovudine.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: chest pain, persistent nausea/vomiting, stomach/abdominal pain, dark urine.

 

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (such as blood counts, thyroid tests, kidney/liver function, triglyceride levels, eye exams) should be performed before you start treatment, periodically to monitor your progress, or to check for side effects. Depending on your medical history, other tests (such as EKG) may be needed. Consult your doctor for more details.

Do not change brands of interferon without checking with your doctor or pharmacist. Other interferons may not have the same effects on your disease.

 

MISSED DOSE: For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor or pharmacist immediately to establish a new dosing schedule. Do not double the dose to catch up.

 

STORAGE: Store in the refrigerator between 36-46 degrees F (2-8 degrees C) away from light and moisture. Do not freeze. Keep all medications away from children and pets. Consult the product instructions or your pharmacist for more storage details once this medication is mixed.

The multidose pen may be used for up to 4 weeks after the first injection. Do not leave this medication outside of the refrigerator for more than 48 hours. After 4 weeks of use, discard the pen, even if it still contains unused solution.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

 

Information last revised December 2013. Copyright(c) 2013 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Intron A

Generic Name: interferon alfa-2b (Pronunciation: IN ter FEAR on AL fa 2b)

  • What is interferon alfa-2b (Intron A)?
  • What are the possible side effects of interferon alfa-2b (Intron A)?
  • What is the most important information I should know about interferon alfa-2b (Intron A)?
  • What should I discuss with my healthcare provider before using interferon alfa-2b (Intron A)?
  • How should I use interferon alfa-2b (Intron A)?
  • What happens if I miss a dose (Intron A)?
  • What happens if I overdose (Intron A)?
  • What should I avoid while using interferon alfa-2b (Intron A)?
  • What other drugs will affect interferon alfa-2b (Intron A)?
  • Where can I get more information?

What is interferon alfa-2b (Intron A)?

Interferon alfa-2b is made from human proteins. Interferons help the body fight viral infections.

Interferon alfa-2b is used to treat hairy cell leukemia, malignant melanoma, follicular lymphoma, Kaposi's sarcoma caused by AIDS, and certain types of genital warts. Interferon alfa-2b is also used to treat chronic hepatitis B or C.

Interferon alfa-2b is often used in combination with another drug called ribavirin (Rebetol). Some of the information in this medication guide applies to the use of both drugs in this combination.

Interferon alfa-2b may also be used for other purposes not listed in this medication guide.

What are the possible side effects of interferon alfa-2b (Intron A)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using interferon alfa-2b and call your doctor at once if you have a serious side effect such as:

  • severe depression, aggressive behavior, or thoughts of hurting yourself or others;
  • fast, slow, or uneven heart rate, feeling like you might pass out;
  • fever, chills, body aches, flu symptoms, pale skin, easy bruising or bleeding, unusual weakness;
  • vision or hearing problems;
  • urinating less than usual or not at all;
  • severe stomach pain, jaundice (yellowing of the skin or eyes);
  • cough with yellow or green mucus, feeling short of breath;
  • chest pain, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
  • sudden numbness or weakness, headache, confusion, or problems with speech or balance; or
  • a severe blistering, peeling, and red skin rash.

Less serious side effects may include:

  • dizziness, spinning sensation;
  • muscle pain, tired feeling;
  • nausea, vomiting, diarrhea, loss of appetite;
  • dry mouth, dry cough, sore throat, hair loss;
  • mild itching or skin rash; or
  • burning, bleeding, pain, itching, or skin changes where the medicine was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Intron A (interferon alfa-2b, recombinant for injection) Side Effects Center for a complete guide to possible side effects

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What is the most important information I should know about interferon alfa-2b (Intron A)?

Interferon alfa-2b is often used in combination with another drug called ribavirin (Rebetol). Some of the information in this medication guide applies to the use of both drugs in this combination.

Interferon alfa-2b may be harmful to an unborn baby, or may cause a miscarriage. Do not use interferon alfa-2b if you are pregnant, especially if you also take ribavirin (Rebetol). Use 2 forms of effective birth control while you are using this drug combination and for at least 6 months after your treatment ends.

If a man fathers a child while using interferon alfa-2b and ribavirin, the baby may have birth defects. Use a condom to prevent pregnancy during your treatment and for at least 6 months after you stop using this drug combination..

You should not use interferon alfa-2b if you are allergic to interferons, or if you have autoimmune hepatitis, or severe liver problems from causes other than hepatitis B or C.

You should not use the combination of interferon alfa-2b and ribavirin if you have an allergy to either drug, or if you have severe kidney disease, a blood cell disorder, if you are pregnant, or if you are a man and your female sex partner is pregnant.

Side Effects Centers
  • Intron A

Patient Detailed How Take

What should I discuss with my healthcare provider before using interferon alfa-2b (Intron A)?

You should not use this medication if you are allergic to interferons, or if you have autoimmune hepatitis, or severe liver problems from causes other than hepatitis B or C.

You should not use the combination of interferon alfa-2b and ribavirin if you have:

  • severe kidney disease;
  • a blood cell disorder such as thalassemia or sickle cell anemia;
  • if you are allergic to interferons or ribavirin;
  • if you are pregnant; or
  • if you are a man and your female sex partner is pregnant.

If you have any of these other conditions, you may need a dose adjustment or special tests to safely use interferon alfa-2b:

  • diabetes;
  • cancer;
  • bone marrow suppression;
  • a bleeding disorder;
  • a thyroid disorder;
  • breathing problems;
  • a history of depression, mental illness, suicidal thoughts, or drug or alcohol addiction;
  • heart disease, a heart rhythm disorder, or history of a heart attack or blood clots;
  • an autoimmune disorder such as psoriasis, arthritis, or lupus;
  • colitis or other intestinal disorder; or
  • if you have recently received an organ transplant.

This medication may be harmful to an unborn baby, or may cause a miscarriage. Do not use interferon alfa-2b if you are pregnant, especially if you also take ribavirin (Rebetol). The combination of interferon alfa-2b and ribavirin can cause birth defects. Tell your doctor right away if you become pregnant during treatment. Use 2 forms of effective birth control while you are using this drug combination and for at least 6 months after your treatment ends.

If a man fathers a child while using interferon alfa-2b and ribavirin, the baby may have birth defects. Use a condom to prevent pregnancy during your treatment. Continue using condoms for at least 6 months after you stop using this drug combination..

It is not known whether interferon alfa-2b passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

The powder form of interferon alfa-2b contains albumin, but the solution (liquid) form does not. Albumin comes from human plasma (part of the blood) and may contain viruses and other infectious agents that can cause disease. Although donated human plasma is screened, tested, and treated to reduce the risk of it containing anything that could cause disease, there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

How should I use interferon alfa-2b (Intron A)?

Interferon alfa-2b is given as an injection into a muscle, under the skin, or directly into a genital wart. The medicine may also be given through a needle placed into a vein.

Your doctor, nurse, or other healthcare provider will give you this injection. You may be shown how to inject your medicine at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.

Use each disposable needle only one time. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

Do not shake the medication vial (bottle). Vigorous shaking can ruin the medicine. Do not draw your dose into a syringe or IV bag until you are ready to give yourself an injection.

Interferon alfa-2b powder medicine must be mixed with a liquid (diluent) before using it. If you are using the injections at home, be sure you understand how to properly mix and store the medication. Do not use the mixture if it is not clear or light yellow, or if it has any particles in it. Throw it away and mix another dose.

The single-dose vial of interferon alfa-2b is for one use only. Throw the vial away after measuring your dose, even if there is still some medicine in it. Do not save it for later use.

Not all brands, forms, and strengths of interferon alfa-2b are used to treat the same medical conditions. Always check your refills to make sure you have received the correct brand and type of medicine prescribed by your doctor. Ask the pharmacist if you have any questions about the medicine you receive at the pharmacy.

To be sure this medication is not causing harmful effects, your blood will need to be tested on a regular basis. Do not miss any scheduled appointments.

Store interferon alfa-2b in the refrigerator and do not allow it to freeze. After mixing the powder medicine with a diluent, you may store the mixture in the refrigerator but you must use it within 24 hours.

To reduce or prevent certain side effects, your doctor may recommend you take acetaminophen (Tylenol) at the time of your interferon alfa-2b injection. Follow your doctor's instructions about the correct dose.

Side Effects Centers
  • Intron A

Patient Detailed Avoid Taking

What happens if I miss a dose (Intron A)?

Use the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not use extra medicine to make up the missed dose.

What happens if I overdose (Intron A)?

Seek emergency medical attention if you think you have used too much of this medicine. Symptoms of an interferon alfa-2b overdose are not known.

What should I avoid while using interferon alfa-2b (Intron A)?

If you are being treated for hepatitis or genital warts, avoid having unprotected sex or sharing needles, razors, or toothbrushes. Taking this medication will not prevent you from passing hepatitis or genital warts to other people. Talk with your doctor about safe methods of preventing transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

Avoid drinking alcohol if you are also taking acetaminophen (Tylenol) while using interferon alfa-2b.

What other drugs will affect interferon alfa-2b (Intron A)?

Tell your doctor about all other medications you use, especially:

  • zidovudine (Retrovir);
  • theophylline (Elixophyllin, Respbid, Slo-Bid, Theobid, Theo-Dur, Theochron, Theolair, and others); or
  • medicines used to prevent organ transplant rejection, such as sirolimus (Rapamune) or tacrolimus (Prograf).

This list is not complete and there may be other drugs that can interact with interferon alfa-2b. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about interferon alfa-2b.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 8.02. Revision date: 12/15/2010.

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Side Effects Centers
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