Drugs Details

Drugs Info of Innohep
Drugs Details
  • Drugs Type  : FDA
  • Date : 17th Feb 2015 01:28 am
  • Brand Name : Innohep
  • Generic Name :  tinzaparin (Pronunciation: tin ZA pa rin)
Descriptions

INNOHEP® is a sterile solution, containing tinzaparin sodium, a low molecular weight heparin. It is available in a multiple dose 2 mL vial.

Each 2 mL vial contains 20,000 anti-Factor Xa IU (anti-Xa) of tinzaparin sodium per mL, for a total of 40,000 IU, and 3.1 mg/mL sodium metabisulfite as a stabilizer. The vial contains 10 mg/mL benzyl alcohol as a preservative. Sodium hydroxide may be added to achieve a pH range of 5.0 to 7.5.

Table 1 Composition of 20,000 anti-Xa IU/mL INNOHEP® (tinzaparin sodium injection)

Component Quantity per mL
Tinzaparin sodium 20,000 anti-Xa IU
Benzyl alcohol, USP 10 mg
Sodium metabisulfite, USP 3.106 mg1
Sodium hydroxide, USP as necessary
Water for Injection, USP q.s. to 1 mL
1 Corresponding to 3.4 mg/mL sodium bisulfite

Tinzaparin sodium is the sodium salt of a low molecular weight heparin obtained by controlled enzymatic depolymerization of heparin from porcine intestinal mucosa using heparinase from Flavobacterium heparinum. The majority of the components have a 2-O-sulpho-4-enepyranosuronic acid structure at the non-reducing end and a 2-N,6-O-disulpho-D-glucosamine structure at the reducing end of the chain.

Potency is determined by means of a biological assay and interpreted by the first International Low Molecular Weight Heparin Standard as units of anti-factor Xa (anti-Xa) activity per milligram. The mean tinzaparin sodium anti-factor Xa activity is approximately 100 IU per milligram. The average molecular weight ranges between 5,500 and 7,500 daltons. The molecular weight distribution is:

< 2,000 Daltons < 10%
2,000 to 8,000 Daltons 60% to 72%
> 8,000 Daltons 22% to 36%

Structural Formula:

 

Innohep®
(tinzaparin sodium)  Structural Formula Illustration

What are the possible side effects of tinzaparin (Innohep)?

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 tinzaparin and call your doctor at once if you have a serious side effect such as:

  • unusual bleeding (nose, mouth, vagina, or rectum), bleeding from wounds or needle injections, any bleeding that will not stop;
  • easy bruising, purple or red pinpoint spots under your skin;
  • pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;
  • black or bloody...

Read All Potential Side Effects and See Pictures of Innohep »

What are the precautions when taking tinzaparin (Innohep)?

See also Warning section.

Before using tinzaparin, tell your doctor or pharmacist if you are allergic to it; or to heparin or pork products; or if you have any other allergies. This product may contain inactive ingredients (such as sulfites, benzyl alcohol), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using tinzaparin, tell your doctor or pharmacist your medical history, especially of: a past blood-clotting problem because of heparin (heparin-induced thrombocytopenia), artificial heart valves, bleeding/blood problems (such as low platelet count, bleeding ulcer), a certain eye problem (diabetic retinopathy), high blood pressure, infections in the heart (bacterial endocarditis), kidney disease, liver disease,...

Read All Potential Precautions of Innohep »


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

Indications

INNOHEP® (tinzaparin) is indicated for the treatment of acute symptomatic deep vein thrombosis with or without pulmonary embolism when administered in conjunction with warfarin sodium. The safety and effectiveness of INNOHEP® (tinzaparin) were established in hospitalized patients.

 

Dosage Administration

All patients should be evaluated for bleeding disorders before administration of INNOHEP® (tinzaparin) . Since coagulation parameters are unsuitable for monitoring INNOHEP® (tinzaparin) activity, routine monitoring of coagulation parameters is not required (see PRECAUTIONS, Laboratory Tests).

Adult Dosage

The recommended dose of INNOHEP® (tinzaparin) for the treatment of DVT with or without PE is 175 anti-Xa IU/kg of body weight, administered SC once daily for at least 6 days and until the patient is adequately anticoagulated with warfarin (INR at least 2.0 for two consecutive days). Warfarin sodium therapy should be initiated when appropriate (usually within 1-3 days of INNOHEP® (tinzaparin) initiation). Pregnancy has little or no influence on the pharmacokinetics of INNOHEP® (tinzaparin) and no dosing adjustment is needed for pregnancy.

As INNOHEP® (tinzaparin) may theoretically affect the PT/INR, patients receiving both INNOHEP® (tinzaparin) and warfarin should have blood for PT/INR determination drawn just prior to the next scheduled dose of INNOHEP® (tinzaparin) .

Table 8 provides INNOHEP® (tinzaparin) doses for the treatment of DVT with or without PE. It is necessary to calculate the appropriate INNOHEP® (tinzaparin) dose for patient weights not displayed in Table 8.

An appropriately calibrated syringe should be used to assure withdrawal of the correct volume of drug from INNOHEP® (tinzaparin) vials.

Table 8 : INNOHEP® (tinzaparin) Weight-based Dosing for Treatment of Deep Vein Thrombosis With or Without Symptomatic Pulmonary Embolism

Patient Body Weight in Pounds DVT Treatment Patient Body Weight in Kilograms
175 IU/kg SC Once Daily 20,000 IU per mL
Dose (IU) Amount (mL)
68-80 6,000 0.3 31-36
81-94 7,000 0.35 37-42
95-107 8,000 0.4 43-48
108-118 9,000 0.45 49-53
119-131 10,000 0.5 54-59
132-144 11,000 0.55 60-65
145-155 12,000 0.6 66-70
156-168 13,000 0.65 71-76
169-182 14,000 0.7 77-82
183-195 15,000 0.75 83-88
196-206 16,000 0.8 89-93
207-219 17,000 0.85 94-99
220-232 18,000 0.9 100-105
233-243 19,000 0.95 106-110
244-256 20,000 1 111-116
257-270 21,000 1.05 117-122
271-283 22,000 1.1 123-128
284-294 23,000 1.15 129-133
295-307 24,000 1.2 134-139
308-320 25,000 1.25 140-145
321-331 26,000 1.3 146-150
332-344 27,000 1.35 151-156
345-358 28,000 1.4 157-162

To calculate the volume (mL) of an INNOHEP® (tinzaparin) 175 anti-Xa IU per kg SC dose for treatment of deep vein thrombosis:

Patient weight (kg) X 0.00875 mL/kg = volume to be administered (mL) subcutaneously

Administration

INNOHEP® (tinzaparin) is a clear, colorless to slightly yellow solution, and as with other parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

INNOHEP® (tinzaparin) is administered by SC injection. It must not be administered by intramuscular or intravenous injection.

Subcutaneous Injection Technique

Patients should be lying down (supine) or sitting and INNOHEP® (tinzaparin) administered by deep SC injection. Administration should be alternated between the left and right anterolateral and left and right posterolateral abdominal wall. The injection site should be varied daily. The whole length of the needle should be introduced into a skin fold held between the thumb and forefinger; the skin fold should be held throughout the injection. To minimize bruising, do not rub the injection site after completion of the injection.

How Supplied

INNOHEP® (tinzaparin) is available in a multiple dose 2 mL vial in the following packages:

Box of 1 - 2 mL vial (20,000 anti-Xa IU per mL) NDC 50222-342-08

Box of 10 - 2 mL vials (20,000 anti-Xa IU per mL) NDC 50222-342-53

Store at 25° C (77° F); excursions permitted to 15°-30° C (59°-86° F) [See USP Controlled Room Temperature].

Keep out of the reach of children.

Manufactured by: LEO Pharmaceutical Products, DK-2750 Ballerup, Denmark. Distributed by: LEO Pharma Inc., 1 Sylvan Way, Parsippany, NJ 07054. 1-877-494-4536. Revised: May 2010.


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

Side Effects

Bleeding: Bleeding is the most common adverse event associated with INNOHEP® (tinzaparin sodium injection); however, the incidence of major bleeding is low. In clinical trials, the definition of major bleeding included bleeding accompanied by ≥ 2 gram/dL decrease in hemoglobin, requiring transfusion of 2 or more units of blood products, or bleeding which was intracranial, retroperitoneal, or into a major prosthetic joint. The data are provided in Table 4.

Table 4 : Major Bleeding Events1 in Treatment of Acute Deep Vein Thrombosis With or Without Pulmonary Embolism

Indication Treatment Group1
Treatment of Acute DVT With or Without PE INNOHEP® (tinzaparin)
N=519
%
Heparin
N=524
%
Major Bleeding Events2 0.83 2.73
1 INNOHEP® (tinzaparin) 175 IU/kg once daily SC. Unfractionated heparin initial IV bolus of 5,000 IU followed by continuous IV infusion adjusted to an aPTT of 1.5 to 2.5 or initial IV bolus of 50 IU/kg followed by continuous IV infusion adjusted to an aPTT of 2.0 to 3.0. In all groups treatment continued for approximately 6 to 8 days, and all patients received oral anticoagulant treatment commencing in the first 2 to 3 days.
2 Bleeding accompanied by ≥ 2 gram/dL decline in hemoglobin, requiring transfusion of or more units of blood products, or bleeding which was intracranial, retroperitoneal, or into a major prosthetic joint.
3 The 95% CI on the difference in major bleeding event rates (1.9%) was 0.33%, 3.47%.

Fatal or nonfatal hemorrhage from any tissue or organ can occur. The signs, symptoms, and severity will vary according to the location and degree or extent of the bleeding. Hemorrhagic complications may present as, but are not limited to, paralysis; paresthesia; headache, chest, abdomen, joint, muscle or other pain; dizziness; shortness of breath, difficult breathing or swallowing; swelling; weakness; hypotension, shock, or coma. Therefore, the possibility of hemorrhage should be considered in evaluating the condition of any anticoagulated patient with complaints which do not indicate an obvious diagnosis (see WARNINGS, Hemorrhage).

Thrombocytopenia

In clinical studies thrombocytopenia was identified in 1% of patients treated with INNOHEP® (tinzaparin) . Severe thrombocytopenia (platelet count < 50,000/mm³) occurred in 0.13% (see WARNINGS, Thrombocytopenia).

Elevations of Serum Aminotransferases

Asymptomatic increases in aspartate (AST [SGOT]) and/or alanine (ALT [SGPT]) aminotransferase levels greater than 3 times the upper limit of normal of the laboratory reference range have been reported in up to 8.8% and 13% for AST and ALT, respectively, of patients receiving tinzaparin sodium for the treatment of DVT. Similar increases in aminotransferase levels have also been observed in patients and healthy volunteers treated with heparin and other low molecular weight heparins. Such elevations are reversible and are rarely associated with increases in bilirubin (see PRECAUTIONS, Laboratory Tests).

Local Reactions

Mild local irritation, pain, hematoma, and ecchymosis may follow SC injection of INNOHEP® (tinzaparin) . Injection site hematoma has been reported in approximately 16% of patients treated with INNOHEP® (tinzaparin) .

Hypersensitivity

Anaphylactic/anaphylactoid reactions may occur in association with INNOHEP® use (see CONTRAINDICATIONS and WARNINGS).

Adverse Events

Adverse events with INNOHEP® (tinzaparin) or heparin reported at a frequency of ≥ 1% in clinical trials with patients undergoing treatment for proximal DVT with or without PE, are provided in Table 5.

Table 5 : Adverse Events Occurring in ≥ 1% in Treatment of Acute Deep Vein Thrombosis With or Without Pulmonary Embolism Studies

Adverse Events Treatment Group1
INNOHEP® (tinzaparin)
N=519
n (%)
Heparin
N=524
n (%)
Urinary Tract Infection 19 (3.7%) 18 (3.4%)
Pulmonary Embolism 12 (2.3%) 12 (2.3%)
Chest Pain 12 (2.3%) 8 (1.5%)
Epistaxis 10 (1.9%) 7 (1.3%)
Headache 9 (1.7%) 9 (1.7%)
Nausea 9 (1.7%) 10 (1.9%)
Hemorrhage NOS 8 (1.5%) 23 (4.4%)
Back Pain 8 (1.5%) 2 (0.4%)
Fever 8 (1.5%) 11 (2.1%)
Pain 8 (1.5%) 7 (1.3%)
Constipation 7 (1.3%) 9 (1.7%)
Rash 6 (1.2%) 8 (1.5%)
Dyspnea 6 (1.2%) 9 (1.7%)
Vomiting 5 (1.0%) 8 (1.5%)
Hematuria 5 (1.0%) 6 (1.1%)
Abdominal Pain 4 (0.8%) 6 (1.1%)
Diarrhea 3 (0.6%) 7 (1.3%)
Anemia 0 7 (1.3%)
NOS = not otherwise specified
1 INNOHEP® (tinzaparin) 175 IU/kg once daily SC. Unfractionated heparin initial IV bolus of 5,000 IU followed by continuous IV infusion adjusted to an aPTT of 1.5 to 2.5 or initial IV bolus of 50 IU/kg followed by continuous IV infusion adjusted to an aPTT of 2.0 to 3.0. In all groups treatment continued for approximately 6 to 8 days, and all patients received oral anticoagulant treatment commencing in the first 2 to 3 days.

Other Adverse Events in Completed or Ongoing Trials

Other adverse events reported at a frequency of ≥ 1% in 4,000 patients who received INNOHEP® (tinzaparin) in completed or ongoing clinical trials are listed by body system:

Body as a Whole: injection site hematoma, reaction unclassified.

Cardiovascular Disorders, General: hypotension, hypertension.

Central and Peripheral Nervous System Disorders: dizziness.

Gastrointestinal System Disorders: flatulence, gastrointestinal disorder (not otherwise specified), dyspepsia.

Heart Rate and Rhythm Disorders: tachycardia.

Myo-, Endo-, Pericardial and Valve Disorders: angina pectoris.

Platelet, Bleeding and Clotting Disorders: hematoma, thrombocytopenia.

Psychiatric Disorders: insomnia, confusion.

Red Blood Cell Disorders: anemia.

Resistance Mechanism Disorders: healing impaired, infection.

Respiratory System Disorders: pneumonia, respiratory disorder.

Skin and Appendages Disorders: rash erythematous, pruritus, bullous eruption, skin disorder.

Urinary System Disorders: urinary retention, dysuria.

Vascular (Extracardiac) Disorders: thrombophlebitis deep, thrombophlebitis leg deep.

Serious adverse events reported in clinical trials or from post-marketing experience are included in Tables 6 and 7, respectively:

Table 6 : Serious Adverse Events Associated With INNOHEP® (tinzaparin) in Clinical Trials

Category Serious Adverse Event
Bleeding-related Anorectal bleeding
Cerebral/intracranial bleeding
Epistaxis
Gastrointestinal hemorrhage
Hemarthrosis
Hematemesis
Hematuria
Hemopericardium
Hemorrhage NOS
Injection site bleeding
Melena
Purpura
Retroperitoneal/intra-abdominal bleeding
Vaginal hemorrhage
Wound hematoma
Organ dysfunction Angina pectoris
Cardiac arrhythmia
Dependent edema
Myocardial infarction/coronary thrombosis
Thromboembolism
Fetal/neonatal Congenital anomaly
Fetal death
Fetal distress
Cutaneous Bullous eruption
Erythematous rash
Maculopapular rash
Skin necrosis
Hematologic Granulocytopenia
Thrombocytopenia
Allergic reactions Allergic reaction
Injection site reaction Cellulitis
Neoplastic Neoplasm

Table 7 : Other Serious Adverse Events Associated With INNOHEP® (tinzaparin) from Post-Marketing Surveillance

Category Serious Adverse Event
Organ dysfunction Cholestatic hepatitis
Increase in hepatic enzymes
Peripheral ischemia
Priapism
Bleeding-related Hematoma
Hemoptysis
Ocular hemorrhage
Rectal bleeding
Cutaneous reactions Epidermal necrolysis
Ischemic necrosis
Stevens-Johnson syndrome
Urticaria
Hematologic Agranulocytosis
Pancytopenia
Thrombocythemia
Injection site reactions Abscess
Necrosis
Allergic reactions Allergic purpura
Angioedema
Fetal/neonatal Cutis aplasia of the scalp
Neonatal hypotonia
General Acute febrile reaction

Ongoing Safety Surveillance

When neuraxial anesthesia (epidural/spinal anesthesia) or spinal puncture is employed, patients anticoagulated or scheduled to be anticoagulated with low molecular weight heparins or heparinoids for prevention of thromboembolic complications are at risk of developing an epidural or spinal hematoma which can result in long-term or permanent paralysis (see BOXED WARNING).

Spinal epidural hematoma in association with neuraxial anesthesia or spinal puncture with INNOHEP (tinzaparin) ® has been reported.

Spinal epidural hematoma with INNOHEP® (tinzaparin) administered at a therapeutic dose has been reported in at least one patient who had not received neuraxial anesthesia or spinal puncture.

Read the Innohep (tinzaparin) Side Effects Center for a complete guide to possible side effects

Interactions

Because of increased risk of bleeding, INNOHEP® (tinzaparin) should be used with caution in patients receiving oral anticoagulants, platelet inhibitors (e.g., salicylates, dipyridamole, sulfinpyrazone, dextran, NSAIDs including ketorolac tromethamine, ticlopidine, and clopidogrel), and thrombolytics. If coadministration is essential, close clinical and laboratory monitoring of these patients is advised (see PRECAUTIONS, Laboratory Tests).

Laboratory Test Interactions

Elevation of Serum Transaminases

Asymptomatic reversible increases in aspartate (AST [SGOT]) and alanine (ALT [SGPT]) aminotransferase levels have occurred in patients during treatment with INNOHEP® (tinzaparin) (see ADVERSE REACTIONS, Elevations of Serum Aminotransferases). Similar increases in transaminase levels have also been observed in patients and volunteers treated with heparin and other low molecular weight heparins.

Since aminotransferase determinations are important in the differential diagnosis of myocardial infarction, liver disease, and pulmonary emboli, elevations that might be caused by drugs like INNOHEP® (tinzaparin) should be interpreted with caution.

Read the Innohep 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

INNOHEP® (tinzaparin) is not intended for intramuscular or intravenous administration.

INNOHEP® (tinzaparin) cannot be used interchangeably (unit for unit) with heparin or other low molecular weight heparins as they differ in manufacturing process, molecular weight distribution, anti-Xa and anti-IIa activities, units, and dosage. Each of these medications has its own instructions for use.

INNOHEP® (tinzaparin) should not be used in patients with a history of heparin-induced thrombocytopenia (see CONTRAINDICATIONS).

Increased Risk for Death in Elderly Patients with Renal Insufficiency

INNOHEP (tinzaparin) ® may increase the risk for death, compared to UFH, when administered to elderly patients with renal insufficiency.

A clinical study compared INNOHEP (tinzaparin) ® (175 IU/kg once daily; N = 269) and UFH (N = 268) in the initial treatment of deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in elderly patients with renal insufficiency (i.e., patients aged 70 years or older with estimated creatinine clearance of ≤ 30 mL/min or patients aged 75 years or older with estimated creatinine clearance of ≤ 60 mL/min). Oral anticoagulants were co-administered beginning on Days 1-3 and study treatment was continued for at least five days until the international normalized ratio (INR) was between 2-3 on two successive days; oral anticoagulants were then continued alone and patients were followed until 90 days after the start of treatment. Overall mortality rates were 6.3% in patients treated with UFH and 11.5% in patients treated with INNOHEP (tinzaparin) ®. Consider the use of alternatives to INNOHEP (tinzaparin) ® in elderly patients with renal insufficiency.

Hemorrhage

INNOHEP® (tinzaparin) , like other anticoagulants, should be used with extreme caution in conditions with increased risk of hemorrhage, such as bacterial endocarditis; severe uncontrolled hypertension; congenital or acquired bleeding disorders including hepatic failure and amyloidosis; active ulcerative and angiodysplastic gastrointestinal disease; hemorrhagic stroke; shortly after brain, spinal or ophthalmological surgery, or in patients treated concomitantly with platelet inhibitors. Bleeding can occur in any tissue or organ of the body during therapy with INNOHEP® (tinzaparin) . Hemorrhage in some cases has been reported to result in death or permanent disability. A hemorrhagic event should be seriously considered in the presence of an unexplained fall in hematocrit, hemoglobin, or blood pressure. If severe hemorrhage occurs, INNOHEP® (tinzaparin) should be discontinued.

Spinal or epidural hematomas can occur with the associated use of low molecular weight heparins or heparinoids and spinal/epidural anesthesia or spinal puncture which can result in long-term or permanent paralysis. The risk of these events is higher with the use of post-operative indwelling epidural catheters or with the concomitant use of additional drugs affecting hemostasis such as NSAIDs (see BOXED WARNING and PRECAUTIONS: DRUG INTERACTIONS).

Thrombocytopenia

Thrombocytopenia can occur with the administration of INNOHEP® (tinzaparin) .

In clinical studies, thrombocytopenia (platelet count < 100,000/mm³ if baseline value ≥ 150,000/mm³, ≥ 50% decline if baseline < 150,000/mm³) was identified in 1% of patients given INNOHEP® (tinzaparin) ; severe thrombocytopenia (platelet count less than 50,000/mm³) occurred in 0.13%.

Thrombocytopenia of any degree should be monitored closely. If the platelet count falls below 100,000/mm³, INNOHEP® (tinzaparin) should be discontinued. Cases of thrombocytopenia with disseminated thrombosis also have been observed in clinical practice with heparins, and low molecular weight heparins, including tinzaparin sodium. Some of these cases were complicated by organ infarction with secondary organ dysfunction or limb ischemia, and have resulted in death.

Hypersensitivity

INNOHEP® (tinzaparin) contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown, but is probably low. Sulfite sensitivity is more frequent in asthmatic people than in non-asthmatic people.

Priapism

Priapism has been reported from post-marketing surveillance as a rare occurrence. In some cases surgical intervention was required.

Miscellaneous

INNOHEP® (tinzaparin) multiple dose vial contains benzyl alcohol as a preservative. The administration of medications containing benzyl alcohol as a preservative to premature neonates has been associated with a fatal “Gasping Syndrome.” Because benzyl alcohol may cross the placenta, INNOHEP® (tinzaparin) preserved with benzyl alcohol should be used with caution in pregnant women only if clearly needed (see PRECAUTIONS, Pregnancy).

 

Precautions

General

INNOHEP® (tinzaparin) should not be mixed with other injections or infusions.

INNOHEP® (tinzaparin) should be used with care in patients with a bleeding diathesis, uncontrolled arterial hypertension, or a history of recent gastrointestinal ulceration, diabetic retinopathy, and hemorrhage.

Consistent with expected age-related changes in renal function, elderly patients and patients with renal insufficiency may show reduced elimination of tinzaparin sodium. INNOHEP® (tinzaparin) should be used with care in these patients (see WARNINGS and CLINICAL PHARMACOLOGY, Special Populations).

Laboratory Tests

Periodic complete blood counts including platelet count and hematocrit or hemoglobin, and stool tests for occult blood are recommended during treatment with INNOHEP® (tinzaparin) . When administered at the recommended doses, routine anticoagulation tests such as prothrombin time (PT) and activated partial thromboplastin time (aPTT) are relatively insensitive measures of INNOHEP® (tinzaparin) activity and, therefore, are unsuitable for monitoring.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term studies in animals have been performed to evaluate the carcinogenic potential of tinzaparin sodium.

Tinzaparin sodium displayed no genotoxic potential in an in vitro bacterial cell mutation assay (AMES test), in vitro Chinese hamster ovary cell forward gene mutation test, in vitro human lymphocyte chromosomal aberration assay, and in vivo mouse micronucleus assay. Tinzaparin sodium at SC doses up to 1800 IU/kg/day in rats (about 2 times the maximum recommended human dose based on body surface area) was found to have no effect on fertility and reproductive performance.

Pregnancy

Pregnancy - Category B

All pregnancies have a background risk of birth defects, loss, or other adverse outcome regardless of drug exposure. The fetal risk summary below describes the potential of INNOHEP® (tinzaparin) to increase the risk of developmental abnormalities above background risk.

Fetal Risk Summary

INNOHEP® (tinzaparin) is not predicted to increase the risk of developmental abnormalities.

INNOHEP® (tinzaparin) does not cross the placenta, based on human and animal studies, and shows no evidence of teratogenic effects or fetotoxicity.

Clinical Considerations

Pregnancy alone confers an increased risk for thromboembolism that is even higher for women with preexisting thromboembolic disease, certain high risk pregnancy conditions, and a history of complications during a previous pregnancy.

All patients receiving anticoagulants such as tinzaparin, including pregnant women, are at risk for bleeding. Pregnant women receiving tinzaparin should be carefully monitored for evidence of bleeding or excessive anticoagulation. Hemorrhage can occur at any site and may lead to death of mother and/or fetus. Pregnant women should be apprised of the potential hazard to the fetus and the mother if tinzaparin is administered during pregnancy. Consideration for use of a shorter acting agent should be specifically addressed as delivery approaches.

Data

Human Data -Fifty-four women pregnant or planning to become pregnant with conditions requiring anticoagulation received INNOHEP® (tinzaparin) in an open-label, prospective, pregnancy dose finding study. (See CLINICAL PHARMACOLOGY, Special Populations, Pregnancy.) Patients received 50 to 175 IU/kg/day, with dosing starting as early as prior to conception or as late as 32 weeks gestation. Duration of exposure ranged from 3 to 463 days (median 159 days). From 55 pregnancies, there were 50 live births, 3 first trimester miscarriages, and 2 intrauterine deaths at 17 and 30 weeks. Approximately 6% of pregnancies were complicated by fetal distress.

Approximately 10% of pregnant women receiving INNOHEP® (tinzaparin) experienced significant vaginal bleeding. A cause and effect relationship for the above observations has not been established.

Animal Data -Teratogenicity studies have been performed in rats at SC doses up to 1800 IU/kg/day (about 2 times the maximum recommended human dose based on body surface area) and in rabbits at SC doses up to 1900 IU/kg/day (about 4 times the maximum recommended human dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to tinzaparin sodium. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. INNOHEP® (tinzaparin) does not cross the placenta.

Cases of “Gasping Syndrome” have occurred in premature infants when large amounts of benzyl alcohol have been administered (99 – 404 mg/kg/day). The 2 mL vial of INNOHEP® (tinzaparin) contains 20 mg of benzyl alcohol (10 mg of benzyl alcohol per mL) (see WARNINGS, Miscellaneous). If INNOHEP® (tinzaparin) is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of potential hazards to the fetus.

Nursing Mothers

In studies where tinzaparin sodium was administered subcutaneously to lactating rats, very low levels of tinzaparin sodium were found in breast milk. It is not known whether tinzaparin sodium is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when INNOHEP® (tinzaparin) is administered to nursing women.

Pediatric Use

Safety and effectiveness of tinzaparin sodium in pediatric patients have not been established.

Geriatric Use

INNOHEP (tinzaparin) ® may increase the risk for death, compared to UFH, when administered to elderly patients with renal insufficiency (see WARNINGS and PRECAUTIONS).

In the clinical studies for the treatment of DVT described in the Clinical Studies section, 58% of patients were 65 or older and 29% were 75 and over. In these studies, no significant overall differences in safety or effectiveness were observed between these subjects and younger subjects.


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

OverDose

Symptoms/Treatment

Accidental overdosage of INNOHEP® (tinzaparin sodium injection) may lead to bleeding complications (see WARNINGS, Hemorrhage). Nosebleeds, blood in urine or tarry stools may be noted as the first signs of bleeding. Easy bruising or petechial hemorrhages may precede frank bleeding. In case of minor bleeding, the patient should be monitored for signs of more severe bleeding.

Of patients known to have received an overdose of tinzaparin sodium in clinical trials, defined as one or more doses > 200 IU/kg for the treatment of DVT or > 100 IU/kg for the prevention of DVT, approximately 16% experienced a bleeding complication.

Of spontaneous reports of probable overdosing with tinzaparin sodium, approximately 81% were accompanied by bleeding, usually hematoma. Most patients who have bleeding complications while receiving INNOHEP® (tinzaparin) can be controlled by discontinuing INNOHEP® (tinzaparin) , applying pressure to the site, if possible, and replacing volume and hemostatic blood elements (e.g., red blood cells, fresh frozen plasma, platelets) as required. In the event that this is ineffective, protamine sulfate can be administered.

In cases of serious bleeding or large overdose, protamine sulfate (1% solution) can be given by slow IV infusion at a dose of 1 mg protamine for every 100 anti-Xa IU of INNOHEP® (tinzaparin) given. A second infusion of 0.5 mg protamine sulfate per 100 anti-Xa IU of INNOHEP® (tinzaparin) may be administered if the aPTT measured 2 to 4 hours after the first infusion remains prolonged. Even with the additional dose of protamine, the aPTT may remain more prolonged than would usually be found following administration of protamine to reverse unfractionated heparin. Protamine does not completely neutralize tinzaparin sodium anti-Xa activity (maximum about 60%).

Particular care should be taken to avoid overdosage with protamine sulfate. Administration of protamine sulfate can cause severe hypotensive and anaphylactoid reactions. Because fatal reactions have been reported with protamine sulfate, it should be given only when resuscitation facilities are readily available. For additional information consult the labeling of Protamine Sulfate Injection, USP, products.

Single SC doses of tinzaparin sodium at 22,000 and 7,700 IU/kg (about 10 and 7 times the maximum recommended human dose, respectively, based upon body surface area) were lethal to mice and rats, respectively. Symptoms of acute toxicity included hematoma formation and bleeding at the injection site, anemia, decreased motor activity, unsteady gait, piloerection, and ptosis.

ContrainDications

INNOHEP® (tinzaparin) is contraindicated in patients with active major bleeding, in patients with (or history of) heparin-induced thrombocytopenia, or in patients with hypersensitivity to tinzaparin sodium.

Patients with known hypersensitivity to heparin, sulfites, benzyl alcohol, or pork products should not be treated with INNOHEP® (tinzaparin) .


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

Clinical Pharamacology

Tinzaparin sodium is a low molecular weight heparin with antithrombotic properties. Tinzaparin sodium inhibits reactions that lead to the clotting of blood including the formation of fibrin clots, both in vitro and in vivo. It acts as a potent co-inhibitor of several activated coagulation factors, especially Factors Xa and IIa (thrombin). The primary inhibitory activity is mediated through the plasma protease inhibitor, antithrombin.

Bleeding time is usually unaffected by tinzaparin sodium. Activated partial thromboplastin time (aPTT) is prolonged by therapeutic doses of tinzaparin sodium used in the treatment of deep vein thrombosis (DVT). Prothrombin time (PT) may be slightly prolonged with tinzaparin sodium treatment but usually remains within the normal range. Neither aPTT nor PT can be used for therapeutic monitoring of tinzaparin sodium.

Neither unfractionated heparin nor tinzaparin sodium have intrinsic fibrinolytic activity; therefore, they do not lyse existing clots. Tinzaparin sodium induces release of tissue factor pathway inhibitor, which may contribute to the antithrombotic effect. Heparin is also known to have a variety of actions that are independent of its anticoagulant effects. These include interactions with endothelial cell growth factors, inhibition of smooth muscle cell proliferation, activation of lipoprotein lipase, suppression of aldosterone secretion, and induction of platelet aggregation.

Pharmacokinetics/Pharmacodynamics

Anti-Xa and anti-IIa activities are the primary biomarkers for assessing tinzaparin sodium exposure because plasma concentrations of low molecular weight heparins cannot be measured directly. Because of analytical assay limitations, anti-Xa activity is the more widely used biomarker. The measurements of anti-Xa and anti-IIa activities in plasma serve as surrogates for the concentrations of molecules which contain the high-affinity binding site for antithrombin (anti-Xa and anti-IIa activities). Monitoring patients based on anti-Xa activity is generally not advised. The data are provided in Figure 1 and Table 2 below.

Studies with tinzaparin sodium in healthy volunteers and patients have been conducted with both fixed-and weight-adjusted dose administration. Recommended therapy with tinzaparin sodium is based on weight-adjusted dosing (see DOSAGE AND ADMINISTRATION).

Figure 1: Mean and Standard Deviation of Anti-Xa Activity Following SC Administration of a Single 4,500 IU* dose and Once Daily Multiple SC Dose of 175 IU/kg Tinzaparin Sodium to Healthy Volunteers

View Enlarged Table

*Dosing based on single dose of 4,500 IU. Mean dose administered was 64.3 IU/kg.

Table 2 : Summary of Pharmacokinetic Parameters (Mean and Standard Deviation) Based on Anti-Xa Activity Following Single and Once Daily Multiple Dose SC Administration of Tinzaparin Sodium to Healthy Volunteers

Parameter (Units) Single Dose (N=23) Multiple Dose (N=14)
4,500 IU* Day 1
175 IU/kg)
  Day 5
175 IU/kg)
Cmax (IU/mL) 0.25 (0.05) 0.87 (0.15) 0.93 (0.15)
Tmax (hr) 3.7 (0.9) 4.4 (0.7) 4.6 (1.0)
AUC0-∞(IU*hr/mL) 2.0 (0.5) 9.0 (1.1) 9.7 (1.4)
Half-life (hr) 3.4 (1.7) 3.3 (0.8) 3.5 (0.6)
*Dosing based on single dose of 4,500 IU. Mean dose administered was 64.3 IU/kg.
Absorption

Plasma levels of anti-Xa activity increase in the first 2 to 3 hours following SC injection of tinzaparin sodium and reach a maximum within 4 to 5 hours. Maximum concentrations (Cmax) of 0.25 and 0.87 IU/mL are achieved following a single SC fixed dose of 4,500 IU (approximately 64.3 IU/kg) and weight-adjusted dose of 175 IU/kg of tinzaparin sodium, respectively. Based on the extent of absorption (AUC0-∞), a comparison of 4,500 IU and 12,250 IU single doses indicates that increases in anti-Xa activity are greater than dose proportional relative to the increase in dose. Following a single SC injection of tinzaparin sodium, the mean anti-Xa to anti-IIa activity ratio, based on the area under the anti-Xa and anti-IIa time profiles, is 2.8 and is higher than that of unfractionated heparin (approximately 1.2). The absolute bioavailability (following 4,500 IU SC and intravenous [IV] administrations) is 86.7% based on anti-Xa activity.

Distribution

The volume of distribution of tinzaparin sodium ranges from 3.1 L to 5.0 L. These values are similar in magnitude to blood volume, suggesting that the distribution of anti-Xa activity is limited to the central compartment.

Metabolism

Low molecular weight heparins are partially metabolized by desulphation and depolymerization.

Elimination

In healthy volunteers, the elimination half-life following SC administration of 4,500 IU or 175 IU/kg tinzaparin sodium is approximately 3-4 hours based on anti-Xa activity. Clearance following IV administration of 4,500 IU tinzaparin sodium is approximately 1.7 L/hr. The primary route of elimination is renal. Anti-Xa activity did not accumulate with once daily dosing of 175 IU/kg for five days in healthy volunteers. (See Figure 1 and Table 2.)

Special Populations

Population Pharmacokinetics

Anti-Xa concentrations from approximately 180 patients receiving SC tinzaparin sodium once daily (175 IU/kg body weight) as the treatment of proximal DVT and approximately 240 patients undergoing elective hip replacement surgery receiving SC tinzaparin sodium once daily (~65 IU/kg body weight) were analyzed by population pharmacokinetic methods. The results indicate that neither age nor gender significantly alter tinzaparin sodium clearance based on anti-Xa activity (see PRECAUTIONS, General). However, a reduction in tinzaparin sodium clearance was observed in patients with impaired renal function (reduced calculated creatinine clearance) (see Special Populations, Renal Impairment). Weight is also an important factor for the prediction of tinzaparin sodium clearance, consistent with the recommendation that INNOHEP® (tinzaparin) therapy be based on weight-adjusted dosing (see DOSAGE AND ADMINISTRATION).

Renal Impairment
Population Pharmacokinetics

In patients being treated with tinzaparin sodium (175 IU/kg) for DVT, a population pharmacokinetic (PK) analysis determined that tinzaparin sodium clearance based on anti-Xa activity was related to creatinine clearance calculated by the Cockcroft Gault equation. In this PK analysis, a reduction in tinzaparin sodium clearance in moderate (30-50 mL/min) and severe ( < 30 mL/min) renal impairment was observed. Patients with severe renal impairment exhibited a 24% reduction in tinzaparin sodium clearance relative to patients with normal renal function ( > 80 mL/min).

Hemodialysis Studies

In a study of 12 chronic renal failure patients undergoing hemodialysis, anti-Xa clearance was reduced 28%, consistent with estimates from the population PK analyses. In another study of 6 patients undergoing hemodialysis, the half-life of anti-Xa activity following a single IV dose of 75 IU/kg of tinzaparin sodium on an off-dialysis day was prolonged relative to that for healthy volunteers (5.2 versus 1.6 hours).

INNOHEP (tinzaparin) ® may increase the risk for death, compared to unfractionated heparin (UFH), when administered to elderly patients with renal insufficiency (see WARNINGS and PRECAUTIONS).

Hepatic Impairment

No prospective studies have assessed tinzaparin sodium pharmacokinetics or pharmacodynamics in hepatically-impaired patients. However, the hepatic route is not a major route of elimination of low molecular weight heparins (see WARNINGS, Hemorrhage).

Elderly

In a controlled clinical study of elderly patients with renal insufficiency, more patients died after INNOHEP (tinzaparin) ® therapy, compared to patients who received therapy with UFH (see WARNINGS and PRECAUTIONS).

Since renal function declines with age, elimination of tinzaparin sodium may be reduced in elderly patients. In a prospective study of 30 elderly patients [6 men, 24 women; aged 87.0±5.9 years; mean body weight 62.7±14.6 kg; creatinine clearance 40.6±15.3 mL/min (range 20-72)] treated with tinzaparin sodium 175 IU/kg once daily for ten days for acute venous thromboembolism, there was no accumulation of anti-Xa activity based on peak anti-Xa activity levels.

Obesity

Based on the results of a prospective clinical study and the population PK analyses, weight-based dosing is appropriate for heavy/obese patients. Tinzaparin sodium PK parameters based on anti-Xa activity are independent of body weight and body mass index (BMI) when tinzaparin sodium is dosed on a weight basis at 175 IU/kg or 75 IU/kg. In a prospective study of heavy/obese subjects (101 to 165 kg; BMI 26-61 kg/m²), anti-Xa activity time profiles were similar to those in normal-weight volunteer studies. Data at the 175 IU/kg dose are shown in Figure 2. Clinical trial experience is limited in patients with a BMI > 40 kg/m².

Figure 2 : Mean and Standard Deviation of Anti-Xa Activity Following a Single SC Administration of 175 IU/kg Tinzaparin Sodium to Obese Subjects and Normal-Weight Volunteers

View Enlarged Table
Pregnancy

The disposition of INNOHEP® (tinzaparin) was studied in 54 pregnant patients in any trimester. In this open-label, prospective, dose finding study, those treated with an INNOHEP® (tinzaparin) dose of 175 IU/kg had similar 24-hour anti-Xa curves at 28 (n=17) and 36 (n=20) weeks gestation. The 175 IU/kg dose resulted in a mean anti-Xa level of 0.3 to 1.0 IU/mL 4 hours after administration. Mean anti-Xa levels 4 hours post dose suggest that as pregnancy advances there is no clinically significant decrease in anti-Xa levels. Pregnancy has little or no influence on the pharmacokinetics of INNOHEP® (tinzaparin) and no dosing adjustment is needed for pregnancy. (See DOSAGE AND ADMINISTRATION.)

Clinical Studies

Treatment of Acute Deep Vein Thrombosis (DVT) With or Without Pulmonary Embolism (PE)

In a randomized, multicenter, double-blind trial INNOHEP® (tinzaparin sodium injection) was compared to unfractionated heparin in 435 hospitalized patients with symptomatic, proximal DVT. Six percent of the enrolled patients had symptomatic pulmonary embolism confirmed by segmental or greater lung scan defect. The study patients ranged in age from 19 to 92 years (mean 61±17 years), 55% were male, 88% were white and 8% black. Patients received either INNOHEP® (tinzaparin) SC once daily according to body weight (175 IU/kg) and a placebo IV bolus followed by continuous placebo IV infusion, or unfractionated heparin as an initial IV bolus dose (5,000 IU) followed by continuous IV infusion of unfractionated heparin with the rate adjusted according to the aPTT (1.5 to 2.5 times control value) and a once daily SC placebo injection. Treatment continued for approximately 6 days, and both treatment groups also received oral warfarin sodium starting on Day 2 which continued to Day 90 with doses titrated to a target INR of 2.0 to 3.0.

The 90-day cumulative thromboembolic (TE) rate [recurrent DVT or PE] with INNOHEP® (tinzaparin) was not significantly different than the rate with unfractionated heparin. The data are provided in Table 3.

Table 3 : Efficacy of Once Daily INNOHEP® (tinzaparin) in the Treatment of Acute Deep Vein Thrombosis

Indication Dosing Regimen
Treatment of Acute DVT INNOHEP (tinzaparin) 1® 175 IU/kg
Once Daily
SC
n (%)
Heparin1 5,000 IU Bolus then aPTT Adjusted Continuous Infusion
IVn
(%)
Intent to Treat Population2 216 (100%) 219 (100%)
Patient Outcome at 90 Days  
  Total TE3 Events 6 (2.8%)4 15 (6.8%)4
     DVTs 3 (1.4%) 9 (4.1%)
     PEs 3 (1.4%) 6 (2.7%)
1 Patients were also treated with warfarin sodium commencing within 24-48 hours of tinzaparin sodium or standard heparin therapy.
2 All randomized patients who received at least one dose of active study drug.
3 TE = thromboembolic events (DVT and/or PE).
4 The 95% Confidence Interval (CI) for the total TE event rate difference (4.0%) was 0.07%, 8.07%.

Mortality with INNOHEP® (tinzaparin) was 4.6% (10 patients) and with heparin 9.6% (21 patients). The 95% confidence interval (CI) for the mortality difference was 0.16%, 9.76%.

In a multicenter, open-label, randomized clinical trial INNOHEP® (tinzaparin) was compared to unfractionated heparin as initial treatment for hospitalized patients with symptomatic PE not requiring thrombolytic therapy, embolectomy, or vena cava interruption. Patients were excluded if they carried an unusually high risk for thromboembolic and/or bleeding events or other complications. Of the 608 patients treated, 422 had documented DVT. Prior to determination of study eligibility and randomization, patients were allowed to receive unfractionated heparin; 78% of the patients received unfractionated heparin at therapeutic doses for up to 24 hours, and an additional 4% received heparin at therapeutic doses for greater than 24 hours. After randomization, INNOHEP® (tinzaparin) was administered SC once daily, 175 IU/kg body weight; heparin as an initial IV bolus (50 IU/kg) followed by continuous IV infusion with the rate adjusted according to the aPTT (2 to 3 times control value). For both groups, treatment continued for approximately 8 days. All patients also received oral anticoagulant treatment starting in the first 3 days which continued to Day 90.

Thromboembolic events were infrequent for both treatment groups. No difference was observed between the two treatment groups for incidence of recurrence of thromboembolic events.
This monograph has been modified to include the generic and brand name in many instances.

Patient Information

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.


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.

 

TINZAPARIN - INJECTION

 

(TIN-za-PAR-in)

 

WARNING: Tell your doctor if you use/have used tinzaparin before having any procedures involving puncture of the spine or needles left in the spine to give pain-blocking medication (including lumbar punctures, indwelling spinal/epidural catheters). Also, before starting tinzaparin, tell your doctor if you have had any of these procedures. Using this medication before/after these procedures has rarely caused severe bruising/bleeding in the spine (epidural/spinal hematoma). This effect may cause paralysis that may be permanent. Your doctor may try to decrease the risk of these side effects by having you stop the medication for a certain amount of time before and after the procedure. Follow your doctor's instructions carefully. Discuss the risks and benefits of treatment with your doctor. Get medical help right away if you have any of these serious side effects: back pain, tingling, weakness, numbness, or loss of control over your bladder or bowels. (See also Precautions section.)

This risk is increased the longer the needles are left in the spine or the more often these spinal puncture procedures are done. Using other "blood-thinning" or anti-platelet medications such as aspirin, clopidogrel, or warfarin, or nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen, also increases the risk. Tell your doctor if you are taking any of these medications. Do not stop taking any prescribed medication without first consulting your doctor. Your doctor will monitor you closely while you are using this medication.

 

USES: Tinzaparin is used to treat serious blood clots, usually in the legs. Tinzaparin may also be used to treat blood clots in the lungs. It is usually used with another "blood thinner" medication (warfarin). If untreated, blood clots can travel to the lungs, heart, or brain, causing serious (possibly fatal) breathing problems, heart attack, or stroke.

This drug may also be used to prevent blood clots after certain surgeries with an increased risk of blood clots (such as knee or hip replacement). It may also be used to prevent clotting in certain catheters used by patients on hemodialysis.

Tinzaparin is known as a "blood thinner" (anticoagulant). It is a type of heparin called low-molecular-weight heparin. It works by blocking certain natural substances in the blood that cause clotting.

 

HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start using tinzaparin and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

You should be lying down or sitting when you inject yourself. Inject this medication under the skin of the stomach/abdomen, as directed by your doctor, usually once daily. Do not inject into a muscle. The dosage and length of treatment are based on your medical condition, weight, and response to treatment. Use this medication regularly to get the most benefit from it. To help you remember, use it at the same time each day.

If you are using this medication at home, learn all preparation and usage instructions from your health care professional and the product package. Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Do not mix any other medication in the same injection. Before injecting each dose, clean the injection site with rubbing alcohol. Change the injection site each time to lessen injury under the skin. To minimize bruising, do not rub the injection site after a shot. Learn how to store and discard medical supplies safely.

When treating a blood clot, another "blood thinner" (warfarin) is usually started 1 to 3 days after you start using tinzaparin. Your doctor will direct you to use both of these medications until the warfarin is working well. Do not stop either of these medications until your doctor directs you to stop.

To prevent blood clots due to surgery, your doctor may direct you to start using this medication before or after surgery and continue for several days. Follow your doctor's directions closely.

This medication may also be given by injection into a vein (to prevent clotting of certain hemodialysis catheters) by a health care professional as directed by your doctor.

Consumer Overview Side Effect

SIDE EFFECTS: Pain, bruising, redness, and swelling at the injection site may occur. Headache, nosebleed, and fever may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

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: easy bleeding/bruising, dark urine, persistent nausea/vomiting/loss of appetite, yellowing eyes/skin.

This medication may rarely cause serious bleeding. (See also Warning section.) Tell your doctor right away if you have any signs of serious bleeding, including: shortness of breath, coughing up blood, chest pain, cold/blue fingers or toes, unusual dizziness, fast/irregular heartbeat, joint/muscle pain, mental/mood changes (such as confusion), difficulty moving, numbness/tingling, severe stomach/abdominal pain, bloody/black/tarry stools, red/pinkish urine, vomit that looks like coffee grounds.

Get medical help right away if you have any very serious side effects, including: seizures, fainting, severe/persistent headache, slurred speech, vision problems, weakness on one side of the body.

Rarely, males may have a painful or prolonged erection lasting 4 or more hours. If this occurs, stop using this drug and get medical help right away, or permanent problems could occur.

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 Innohep (tinzaparin) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: See also Warning section.

Before using tinzaparin, tell your doctor or pharmacist if you are allergic to it; or to heparin or pork products; or if you have any other allergies. This product may contain inactive ingredients (such as sulfites, benzyl alcohol), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using tinzaparin, tell your doctor or pharmacist your medical history, especially of: a past blood-clotting problem because of heparin (heparin-induced thrombocytopenia), artificial heart valves, bleeding/blood problems (such as low platelet count, bleeding ulcer), a certain eye problem (diabetic retinopathy), high blood pressure, infections in the heart (bacterial endocarditis), kidney disease, liver disease, stomach/intestinal problems (such as recent ulcers, colitis), stroke, recent spinal procedures or puncture, spine problems (such as spinal deformity), recent surgery (especially on the eye, brain, or spine).

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

Limit alcohol while taking this drug because it may increase the risk of stomach bleeding.

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

Older adults may be more sensitive to the side effects of this drug, especially bleeding. If you are elderly and have kidney problems, your doctor may stop tinzaparin and prescribe a different medication for your condition. Consult your doctor for more details.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor. If you become pregnant or think you may be pregnant, tell your doctor immediately. Since the benzyl alcohol in tinzaparin can affect the unborn baby, a preservative-free product should be used by pregnant women if possible.

It is unknown if this drug passes into breast milk. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: See also Warning section.

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: mifepristone, other drugs that can cause bleeding/bruising (including antiplatelet drugs such as clopidogrel, NSAIDs such as ketorolac, "blood thinners" such as dabigatran).

Check all prescription and nonprescription medicine labels carefully since many medications contain pain relievers/fever reducers (NSAIDs such as ibuprofen, naproxen, aspirin) which can increase the risk of bleeding when used with tinzaparin. However, if your doctor has directed you to take low-dose aspirin for heart attack or stroke prevention (usually at dosages of 81-325 milligrams a day), you should continue taking it unless your doctor instructs you otherwise. Ask your doctor or pharmacist for more details.

 

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: uncontrolled bleeding.

 

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (such as complete blood count including platelets, kidney/liver function, tests to check for blood in the stool) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

 

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

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.

 

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

 

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

Patient Detailed Side Effect

Brand Names: Innohep

Generic Name: tinzaparin (Pronunciation: tin ZA pa rin)

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

What is tinzaparin (Innohep)?

Tinzaparin is an anticoagulant that helps prevent the formation of blood clots.

Tinzaparin is used together with warfarin (Coumadin) to treat a type of blood clot called deep vein thrombosis (DVT), which can lead to blood clots in the lungs (pulmonary embolism).

Tinzaparin may also be used for purposes not listed in this medication guide.

What are the possible side effects of tinzaparin (Innohep)?

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 tinzaparin and call your doctor at once if you have a serious side effect such as:

  • unusual bleeding (nose, mouth, vagina, or rectum), bleeding from wounds or needle injections, any bleeding that will not stop;
  • easy bruising, purple or red pinpoint spots under your skin;
  • pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;
  • black or bloody stools, coughing up blood or vomit that looks like coffee grounds;
  • numbness, tingling, or muscle weakness (especially in your legs and feet);
  • loss of movement in any part of your body;
  • sudden weakness, severe headache, confusion, or problems with speech, vision, or balance;
  • chest pain; or
  • pain or burning when you urinate.

Less serious side effects may include:

  • mild headache, dizziness;
  • back pain;
  • fever;
  • pain, irritation, swelling, or bruising of the skin where the medicine was injected;
  • nausea, vomiting, stomach pain, gas;
  • diarrhea, constipation;
  • mild skin rash; or
  • sleep problems (insomnia).

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 Innohep (tinzaparin) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about tinzaparin (Innohep)?

You should not use this medication if you are allergic to tinzaparin, heparin, sulfites, benzyl alcohol, or pork products, or if you have active bleeding or a history of low platelet counts after receiving heparin.

Tell any doctor who treats you that you are using tinzaparin. If you need anesthesia for a medical procedure or surgery, you may need to stop using the medicine for a short time.

Tinzaparin may cause you to bleed more easily, especially if you have: a bleeding disorder, hemorrhagic stroke, an infection in the lining of your heart, uncontrolled high blood pressure, stomach or intestinal bleeding or ulcer, kidney disease, liver failure, amyloidosis (a build-up of certain proteins in tissues and organs of the body), or if you have had recent brain, spine, or eye surgery.

Tinzaparin can cause a very serious blood clot around your brain or spinal cord if you undergo a spinal tap or receive spinal anesthesia (epidural), especially if you have a genetic spinal defect, a history of spinal surgery or repeated spinal taps, or if you are using other medications to treat or prevent blood clots. Symptoms of this type of blood clot include numbness, tingling, muscle weakness, or loss of movement.

Blood clots around the brain or spinal cord may occur during a spinal tap or epidural if you are using tinzaparin with other drugs that can affect blood clotting, including aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) such as Advil or Motrin, and any other medications to treat or prevent blood clots.

Many other drugs (including some over-the-counter medicines) can increase your risk of bleeding or life-threatening blood clots, and it is very important to tell your doctor about all medicines you have recently used.

Tell your caregivers at once if you have signs of bleeding such as black or bloody stools, coughing up blood, confusion, feeling like you might pass out, or any bleeding that will not stop.

Side Effects Centers
  • Innohep

Patient Detailed How Take

What should I discuss with my healthcare provider before using tinzaparin (Innohep)?

You should not use this medication if you are allergic to tinzaparin, heparin, sulfites, benzyl alcohol, or pork products, or if you have:

  • active or uncontrolled bleeding; or
  • if you have ever had low platelet counts after receiving heparin.

Tinzaparin may cause you to bleed more easily, especially if you have:

  • a bleeding disorder that is inherited or caused by disease;
  • hemorrhagic stroke;
  • an infection of the lining of your heart (also called bacterial endocarditis);
  • uncontrolled high blood pressure;
  • stomach or intestinal bleeding or ulcer;
  • liver failure;
  • kidney disease (especially if you are an older adult);
  • recent brain, spine, or eye surgery; or
  • amyloidosis (a build-up of certain proteins in tissues and organs of the body).

Tinzaparin can cause a very serious blood clot around your brain or spinal cord if you undergo a spinal tap or receive spinal anesthesia (epidural). This type of blood clot could cause long-term paralysis, and may be more likely to occur if you have:

  • a genetic spinal defect;
  • a history of spinal surgery or repeated spinal taps; or
  • if you are using other medications to treat or prevent blood clots.

To make sure you can safely use tinzaparin, tell your doctor if you have other medical conditions, especially:

  • recent stomach ulcer; or
  • eye problems caused by diabetes.

FDA pregnancy category B. Tinzaparin is not expected to harm an unborn baby. However, some forms of this medication contain a preservative that may be harmful to a newborn. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether tinzaparin 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.

How should I use tinzaparin (Innohep)?

Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Tinzaparin is usually given every day until your bleeding condition improves. Follow the directions on your prescription label.

Tinzaparin must not be used as a substitute for heparin. These two drugs are manufactured differently and have different dosages.

Tinzaparin is injected under the skin. You may be shown how to use injections 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.

You should be sitting or lying down during the injection. Do not inject tinzaparin into a muscle or a vein.

Use a different place on your stomach each time you give the injection. Your care provider will show you the best places on your body to inject the medication. Do not inject into the same place two times in a row.

Prepare your dose in a syringe only when you are ready to give yourself an injection. Do not use the medication if it has changed colors or has particles in it. Call your doctor for a new prescription.

Use a disposable needle only once. 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.

Tell any doctor who treats you that you are using tinzaparin. If you need surgery or dental work, tell the surgeon or dentist ahead of time that you are using this medication.

To be sure this medication is not causing harmful effects, your blood and your stool (bowel movement) may need to be tested often. Your nerve and muscle function may also need to be tested. Visit your doctor regularly.

Store at room temperature away from moisture and heat.

Side Effects Centers
  • Innohep

Patient Detailed Avoid Taking

What happens if I miss a dose (Innohep)?

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

What happens if I overdose (Innohep)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose can cause excessive bleeding.

What should I avoid while using tinzaparin (Innohep)?

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

What other drugs will affect tinzaparin (Innohep)?

Many other drugs (including some over-the-counter medicines) can increase your risk of bleeding, or your risk of developing blood clots around the brain or spinal cord during a spinal tap or epidural. It is very important to tell your doctor about all medicines you have recently used, especially:

  • dextran (Gentran, Hyskon);
  • abciximab (ReoPro), eptifibatide (Integrilin), ticagrelor (Brilinta), tirofiban (Aggrastat);
  • alteplase (Activase), reteplase (Retavase), tenecteplase (TNKase), urokinase (Abbokinase);
  • anagrelide (Agrylin), cilostazol (Pletal), clopidogrel (Plavix), dipyridamole (Persantine, Aggrenox), eltrombopag (Promacta), oprelvekin (Neumega), prasugrel (Effient), romiplostim (Nplate), ticagrelor (Brilinta), ticlopidine (Ticlid);
  • argatroban (Acova), bivalirudin (Angiomax), dabigatran (Pradaxa), lepirudin (Refludan);
  • dalteparin (Fragmin), enoxaparin (Lovenox), fondaparinux (Arixtra), heparin, rivaroxaban (Xarelto), warfarin (Coumadin, Jantoven);
  • an NSAID (non-steroidal anti-inflammatory drug) such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others; or
  • salicylates such as aspirin, Nuprin Backache Caplet, Kaopectate, KneeRelief, Pamprin Cramp Formula, Pepto-Bismol, Tricosal, Trilisate, and others.

This list is not complete and other drugs may interact with tinzaparin. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your doctor or pharmacist can provide more information about tinzaparin.


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: 5.04. Revision date: 10/2/2012.

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