Drugs Details

Drugs Info of ZIAGEN
Drugs Details
  • Drugs Type  : Multum
  • Date : 24th Dec 2014 02:53 am
  • Brand Name : ZIAGEN
  • Generic Name : (abacavir sulfate) Tablets, for Oral Use
Descriptions

ZIAGEN is the brand name for abacavir sulfate, a synthetic carbocyclic nucleoside analogue with inhibitory activity against HIV-1. The chemical name of abacavir sulfate is (1S,cis)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol sulfate (salt) (2:1). Abacavir sulfate is the enantiomer with 1S, 4R absolute configuration on the cyclopentene ring. It has a molecular formula of (C14H18N6O)2•H2SO4 and a molecular weight of 670.76 daltons. It has the following structural formula:

 

ZIAGEN (abacavir sulfate) Structural Formula Illustration

Abacavir sulfate is a white to off-white solid with a solubility of approximately 77 mg/mL in distilled water at 25°C. It has an octanol/water (pH 7.1 to 7.3) partition coefficient (log P) of approximately 1.20 at 25°C.

ZIAGEN Tablets are for oral administration. Each tablet contains abacavir sulfate equivalent to 300 mg of abacavir as active ingredient and the following inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The tablets are coated with a film that is made of hypromellose, polysorbate 80, synthetic yellow iron oxide, titanium dioxide, and triacetin.

ZIAGEN Oral Solution is for oral administration. Each milliliter (1 mL) of ZIAGEN Oral Solution contains abacavir sulfate equivalent to 20 mg of abacavir (i.e., 20 mg/mL) as active ingredient and the following inactive ingredients: artificial strawberry and banana flavors, citric acid (anhydrous), methylparaben and propylparaben (added as preservatives), propylene glycol, saccharin sodium, sodium citrate (dihydrate), sorbitol solution, and water.

In vivo, abacavir sulfate dissociates to its free base, abacavir. All dosages for ZIAGEN are expressed in terms of abacavir.

What are the possible side effects of abacavir (Ziagen)?

Stop using abacavir and call your doctor at once if you have symptoms of an allergic reaction from two or more of these specific side effect groups:

  • Group 1 - fever;
  • Group 2 - rash;
  • Group 3 - nausea, vomiting, diarrhea, stomach pain;
  • Group 4 - general ill feeling, extreme tiredness, body aches;
  • Group 5 - shortness of breath, cough, sore throat.

Once you have had an allergic reaction to abacavir, you must never use it again. If you stop taking abacavir for any reason, talk to your doctor before you start taking the medication...

Read All Potential Side Effects and See Pictures of Ziagen »

What are the precautions when taking abacavir sulfate (Ziagen)?

See also Warning and How to Use sections.

Before taking abacavir, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver problems (such as hepatitis B or C, or cirrhosis), kidney problems, alcohol use.

Abacavir may increase your risk of a heart attack. Discuss the risks and benefits of treatment with your doctor and ways to lower your risk of heart disease. Tell your doctor if you have heart problems, if you smoke, or if you have other conditions that increase your risk of heart...

Read All Potential Precautions of Ziagen »

Last reviewed on RxList: 9/25/2013
This monograph has been modified to include the generic and brand name in many instances.

Indications

ZIAGEN Tablets and Oral Solution, in combination with other antiretroviral agents, are indicated for the treatment of human immunodeficiency virus (HIV-1) infection.

Additional important information on the use of ZIAGEN for treatment of HIV-1 infection:

ZIAGEN is one of multiple products containing abacavir. Before starting ZIAGEN, review medical history for prior exposure to any abacavir-containing product in order to avoid reintroduction in a patient with a history of hypersensitivity to abacavir [see WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS].

Dosage Administration

  • A Medication Guide and Warning Card that provide information about recognition of hypersensitivity reactions should be dispensed with each new prescription and refill.
  • ZIAGEN may be taken with or without food.

Adult Patients

The recommended oral dose of ZIAGEN for adults is 600 mg daily, administered as either 300 mg twice daily or 600 mg once daily, in combination with other antiretroviral agents.

Pediatric Patients

The recommended oral dose of ZIAGEN Oral Solution in HIV-1-infected pediatric patients aged 3 months and older is 8 mg/kg twice daily (up to a maximum of 300 mg twice daily) in combination with other antiretroviral agents.

ZIAGEN is also available as a scored tablet for HIV-1-infected pediatric patients weighing greater than or equal to 14 kg for whom a solid dosage form is appropriate. Before prescribing ZIAGEN Tablets, children should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow ZIAGEN Tablets, the oral solution formulation should be prescribed. The recommended oral dosage of ZIAGEN Tablets for HIV-1-infected pediatric patients is presented in Table 1.

Table 1: Dosing Recommendations for ZIAGEN Tablets in Pediatric Patients

How Supplied

Dosage Forms And Strengths

ZIAGEN Tablets contain 300 mg of abacavir as abacavir sulfate. The tablets are yellow, biconvex, scored, capsule-shaped, film-coated, and imprinted with “GX 623” on both sides.

ZIAGEN Oral Solution contains 20 mg/mL of abacavir as abacavir sulfate. The solution is a clear to opalescent, yellowish, strawberry-banana-flavored liquid.

Storage And Handling

ZIAGEN Tablets, containing abacavir sulfate equivalent to 300 mg abacavir are yellow, biconvex, scored, capsule-shaped, film-coated, and imprinted with “GX 623” on both sides. They are packaged as follows:

Bottles of 60 tablets (NDC 49702-221-18).

Unit dose blister packs of 60 tablets (NDC 49702-221-44). Each pack contains 6 blister cards of 10 tablets each.

Store at controlled room temperature of 20° to 25°C (68° to 77°F) (see USP).

ZIAGEN Oral Solution is a clear to opalescent, yellowish, strawberry-banana-flavored liquid. Each mL of the solution contains abacavir sulfate equivalent to 20 mg of abacavir. It is packaged in plastic bottles as follows:

Bottles of 240 mL (NDC 49702-222-48) with child-resistant closure. This product does not require reconstitution.

Store at controlled room temperature of 20° to 25°C (68° to 77°F) (see USP). DO NOT FREEZE. May be refrigerated.

Manufactured for: ViiV Healthcare, Research Triangle Park, NC 27709. BY: GlaxoSmithKline Research Triangle Park, NC 27709. Revised: Sep 2013.

Last reviewed on RxList: 9/25/2013
This monograph has been modified to include the generic and brand name in many instances.

Side Effects

The following adverse reactions are discussed in greater detail in other sections of the labeling:

Serious and sometimes fatal hypersensitivity reaction. In one trial, once-daily dosing of abacavir was associated with more severe hypersensitivity reactions [see BOXED WARNING, WARNINGS AND PRECAUTIONS].

  • Lactic acidosis and severe hepatomegaly [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
  • Immune reconstitution syndrome [see WARNINGS AND PRECAUTIONS].
  • Fat redistribution [see WARNINGS AND PRECAUTIONS].
  • Myocardial infarction [see WARNINGS AND PRECAUTIONS].

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adults

Therapy-Naive Adults: Treatment-emergent clinical adverse reactions (rated by the investigator as moderate or severe) with a greater than or equal to 5% frequency during therapy with ZIAGEN 300 mg twice daily, lamivudine 150 mg twice daily, and efavirenz 600 mg daily compared with zidovudine 300 mg twice daily, lamivudine 150 mg twice daily, and efavirenz 600 mg daily from CNA30024 are listed in Table 2.

Table 2: Treatment-Emergent (All Causality) Adverse Reactions of at Least Moderate Intensity (Grades 2-4, ≥ 5% Frequency) in Therapy-Naive Adults (CNA30024a) Through 48 Weeks of Treatment

Adverse Reaction ZIAGEN plus Lamivudine plus Efavirenz
(n = 324)
Zidovudine plus Lamivudine plus Efavirenz
(n = 325)
Dreams/sleep disorders 10% 10%
Drug hypersensitivity 9% < 1%b
Headaches/migraine 7% 11%
Nausea 7% 11%
Fatigue/malaise 7% 10%
Diarrhea 7% 6%
Rashes 6% 12%
Abdominal pain/gastritis/ gastrointestinal signs and symptoms 6% 8%
Depressive disorders 6% 6%
Dizziness 6% 6%
Musculoskeletal pain 6% 5%
Bronchitis 4% 5%
Vomiting 2% 9%
aThis trial used double-blind ascertainment of suspected hypersensitivity reactions. During the blinded portion of the trial, suspected hypersensitivity to abacavir was reported by investigators in 9% of 324 subjects in the abacavir group and 3% of 325 subjects in the zidovudine group.
bTen (3%) cases of suspected drug hypersensitivity were reclassified as not being due to abacavir following unblinding.

Treatment-emergent clinical adverse reactions (rated by the investigator as moderate or severe) with a greater than or equal to 5% frequency during therapy with ZIAGEN 300 mg twice daily, lamivudine 150 mg twice daily, and zidovudine 300 mg twice daily compared with indinavir 800 mg 3 times daily, lamivudine 150 mg twice daily, and zidovudine 300 mg twice daily from CNA3005 are listed in Table 3.

Table 3: Treatment-Emergent (All Causality) Adverse Reactions of at Least Moderate Intensity (Grades 2-4, ≥ 5% Frequency) in Therapy-Naive Adults (CNA3005) Through 48 Weeks of Treatment

Adverse Reaction ZIAGEN plus Lamivudine/Zidovudine
(n = 262)
Indinavir plus Lamivudine/Zidovudine
(n = 264)
Nausea 19% 17%
Headache 13% 9%
Malaise and fatigue 12% 12%
Nausea and vomiting 10% 10%
Hypersensitivity reaction 8% 2%
Diarrhea 7% 5%
Fever and/or chills 6% 3%
Depressive disorders 6% 4%
Musculoskeletal pain 5% 7%
Skin rashes 5% 4%
Ear/nose/throat infections 5% 4%
Viral respiratory infections 5% 5%
Anxiety 5% 3%
Renal signs/symptoms < 1% 5%
Pain (non-site-specific) < 1% 5%

Five subjects receiving ZIAGEN in CNA3005 experienced worsening of pre-existing depression compared with none in the indinavir arm. The background rates of pre-existing depression were similar in the 2 treatment arms.

ZIAGEN Once Daily Versus ZIAGEN Twice Daily (CNA30021): Treatment-emergent clinical adverse reactions (rated by the investigator as at least moderate) with a greater than or equal to 5% frequency during therapy with ZIAGEN 600 mg once daily or ZIAGEN 300 mg twice daily, both in combination with lamivudine 300 mg once daily and efavirenz 600 mg once daily from CNA30021, were similar. For hypersensitivity reactions, subjects receiving ZIAGEN once daily showed a rate of 9% in comparison with a rate of 7% for subjects receiving ZIAGEN twice daily. However, subjects receiving ZIAGEN 600 mg once daily, experienced a significantly higher incidence of severe drug hypersensitivity reactions and severe diarrhea compared with subjects who received ZIAGEN 300 mg twice daily. Five percent (5%) of subjects receiving ZIAGEN 600 mg once daily had severe drug hypersensitivity reactions compared with 2% of subjects receiving ZIAGEN 300 mg twice daily. Two percent (2%) of subjects receiving ZIAGEN 600 mg once daily had severe diarrhea while none of the subjects receiving ZIAGEN 300 mg twice daily had this event.

Laboratory Abnormalities: Laboratory abnormalities (Grades 3-4) in therapy-naive adults during therapy with ZIAGEN 300 mg twice daily, lamivudine 150 mg twice daily, and efavirenz 600 mg daily compared with zidovudine 300 mg twice daily, lamivudine 150 mg twice daily, and efavirenz 600 mg daily from CNA30024 are listed in Table 4.

Table 4: Laboratory Abnormalities (Grades 3-4) in Therapy-Naive Adults (CNA30024) Through 48 Weeks of Treatment

Grade 3/4 Laboratory Abnormalities ZIAGEN plus Lamivudine plus Efavirenz
(n = 324)
Zidovudine plus Lamivudine plus Efavirenz
(n = 325)
Elevated CPK ( > 4 X ULN) 8% 8%
Elevated ALT ( > 5 X ULN) 6% 6%
Elevated AST ( > 5 X ULN) 6% 5%
Hypertriglyceridemia ( > 750 mg/dL) 6% 5%
Hyperamylasemia ( > 2 X ULN) 4% 5%
Neutropenia (ANC < 750/mm³) 2% 4%
Anemia (Hgb ≤ 6.9 gm/dL) < 1% 2%
Thrombocytopenia (Platelets < 50,000/mm³) 1% < 1%
Leukopenia (WBC ≤ 1,500/mm³) < 1% 2%
ULN = Upper limit of normal.
n = Number of subjects assessed.

Laboratory abnormalities in CNA3005 are listed in Table 5.

Table 5: Treatment-Emergent Laboratory Abnormalities (Grades 3-4) in CNA3005

Grade 3/4 Laboratory Abnormalities Number of Subjects by Treatment Group
ZIAGEN plus Lamivudine/Zidovudine
(n = 262)
Indinavir plus Lamivudine/Zidovudine
(n = 264)
Elevated CPK ( > 4 x ULN) 18 (7%) 18 (7%)
ALT ( > 5.0 x ULN) 16 (6%) 16 (6%)
Neutropenia ( < 750/mm³) 13 (5%) 13 (5%)
Hypertriglyceridemia ( > 750 mg/dL) 5 (2%) 3 (1%)
Hyperamylasemia ( > 2.0 x ULN) 5 (2%) 1 ( < 1%)
Hyperglycemia ( > 13.9 mmol/L) 2 ( < 1%) 2 ( < 1%)
Anemia (Hgb ≤ 6.9 g/dL) 0 (0%) 3 (1%)
ULN = Upper limit of normal.
n = Number of subjects assessed.

The frequencies of treatment-emergent laboratory abnormalities were comparable between treatment groups in CNA30021.

Pediatric Trials

Therapy-Experienced Pediatric Subjects: Treatment-emergent clinical adverse reactions (rated by the investigator as moderate or severe) with a greater than or equal to 5% frequency during therapy with ZIAGEN 8 mg/kg twice daily, lamivudine 4 mg/kg twice daily, and zidovudine 180 mg/m² twice daily compared with lamivudine 4 mg/kg twice daily and zidovudine 180 mg/m² twice daily from CNA3006 are listed in Table 6.

Table 6: Treatment-Emergent (All Causality) Adverse Reactions of at Least Moderate Intensity (Grades 2-4, ≥ 5% Frequency) in Therapy-Experienced Pediatric Subjects (CNA3006) Through 16 Weeks of Treatment

Adverse Reaction ZIAGEN plus Lamivudine plus Zidovudine
(n = 102)
Lamivudine plus Zidovudine
(n = 103)
Fever and/or chills 9% 7%
Nausea and vomiting 9% 2%
Skin rashes 7% 1%
Ear/nose/throat infections 5% 1%
Pneumonia 4% 5%
Headache 1% 5%

Laboratory Abnormalities: In CNA3006, laboratory abnormalities (anemia, neutropenia, liver function test abnormalities, and CPK elevations) were observed with similar frequencies as in a trial of therapy-naive adults (CNA30024). Mild elevations of blood glucose were more frequent in pediatric subjects receiving ZIAGEN (CNA3006) as compared with adult subjects (CNA30024).

Other Adverse Events: In addition to adverse reactions and laboratory abnormalities reported in Tables 2, 3, 4, 5, and 6, other adverse reactions observed in the expanded access program were pancreatitis and increased GGT.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following reactions have been identified during postmarketing use of ZIAGEN. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to ZIAGEN.

Body as a Whole: Redistribution/accumulation of body fat.

Cardiovascular: Myocardial infarction.

Hepatic: Lactic acidosis and hepatic steatosis.

Skin: Suspected Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving abacavir primarily in combination with medications known to be associated with SJS and TEN, respectively. Because of the overlap of clinical signs and symptoms between hypersensitivity to abacavir and SJS and TEN, and the possibility of multiple drug sensitivities in some patients, abacavir should be discontinued and not restarted in such cases.

There have also been reports of erythema multiforme with abacavir use.

Read the Ziagen (abacavir sulfate) Side Effects Center for a complete guide to possible side effects

Interactions

Ethanol

Abacavir has no effect on the pharmacokinetic properties of ethanol. Ethanol decreases the elimination of abacavir causing an increase in overall exposure [see CLINICAL PHARMACOLOGY].

Methadone

The addition of methadone has no clinically significant effect on the pharmacokinetic properties of abacavir. In a trial of 11 HIV-1-infected subjects receiving methadone-maintenance therapy with 600 mg of ZIAGEN twice daily (twice the currently recommended dose), oral methadone clearance increased [see CLINICAL PHARMACOLOGY]. This alteration will not result in a methadone dose modification in the majority of patients; however, an increased methadone dose may be required in a small number of patients.

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

Learn More »

Last reviewed on RxList: 9/25/2013
This monograph has been modified to include the generic and brand name in many instances.

Warnings

No Information Available!

Precautions

Hypersensitivity Reaction

Serious and sometimes fatal hypersensitivity reactions have been associated with ZIAGEN and other abacavir-containing products. Patients who carry the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction to abacavir. Prior to initiating therapy with abacavir, screening for the HLA-B*5701 allele is recommended; this approach has been found to decrease the risk of a hypersensitivity reaction. Screening is also recommended prior to reinitiation of abacavir in patients of unknown HLA-B*5701 status who have previously tolerated abacavir. For HLA-B*5701-positive patients, treatment with an abacavir-containing regimen is not recommended and should be considered only with close medical supervision and under exceptional circumstances when the potential benefit outweighs the risk.

HLA-B*5701-negative patients may develop a hypersensitivity reaction to abacavir; however, this occurs significantly less frequently than in HLA-B*5701-positive patients. Regardless of HLA-B*5701 status, permanently discontinue ZIAGEN if hypersensitivity cannot be ruled out, even when other diagnoses are possible.

Important information on signs and symptoms of hypersensitivity, as well as clinical management, is presented below.

Signs and Symptoms of Hypersensitivity

Hypersensitivity to abacavir is a multi-organ clinical syndrome usually characterized by a sign or symptom in 2 or more of the following groups.

Group 1: Fever
Group 2: Rash
Group 3: Gastrointestinal (including nausea, vomiting, diarrhea, or abdominal pain)
Group 4: Constitutional (including generalized malaise, fatigue, or achiness)
Group 5: Respiratory (including dyspnea, cough, or pharyngitis).

Hypersensitivity to abacavir following the presentation of a single sign or symptom has been reported infrequently.

Hypersensitivity to abacavir was reported in approximately 8% of 2,670 subjects (n = 206) in 9 clinical trials (range: 2% to 9%) with enrollment from November 1999 to February 2002. Data on time to onset and symptoms of suspected hypersensitivity were collected on a detailed data collection module. The frequencies of symptoms are shown in Figure 1. Symptoms usually appeared within the first 6 weeks of treatment with abacavir, although the reaction may occur at any time during therapy. Median time to onset was 9 days; 89% appeared within the first 6 weeks; 95% of subjects reported symptoms from 2 or more of the 5 groups listed above.

Figure 1: Hypersensitivity-Related Symptoms Reported With ≥ 10% Frequency in Clinical Trials (n = 206 Subjects)

View Enlarged Table

Other less common signs and symptoms of hypersensitivity include lethargy, myolysis, edema, abnormal chest x-ray findings (predominantly infiltrates, which can be localized), and paresthesia. Anaphylaxis, liver failure, renal failure, hypotension, adult respiratory distress syndrome, respiratory failure, and death have occurred in association with hypersensitivity reactions. In one trial, 4 subjects (11%) receiving ZIAGEN 600 mg once daily experienced hypotension with a hypersensitivity reaction compared with 0 subjects receiving ZIAGEN 300 mg twice daily.

Physical findings associated with hypersensitivity to abacavir in some patients include lymphadenopathy, mucous membrane lesions (conjunctivitis and mouth ulcerations), and rash. The rash usually appears maculopapular or urticarial, but may be variable in appearance. There have been reports of erythema multiforme. Hypersensitivity reactions have occurred without rash.

Laboratory abnormalities associated with hypersensitivity to abacavir in some patients include elevated liver function tests, elevated creatine phosphokinase, elevated creatinine, and lymphopenia.

Clinical Management of Hypersensitivity

Discontinue ZIAGEN as soon as a hypersensitivity reaction is suspected. To minimize the risk of a life-threatening hypersensitivity reaction, permanently discontinue ZIAGEN if hypersensitivity cannot be ruled out, even when other diagnoses are possible (e.g., acute onset respiratory diseases such as pneumonia, bronchitis, pharyngitis, or influenza; gastroenteritis; or reactions to other medications).

Following a hypersensitivity reaction to abacavir, NEVER restart ZIAGEN or any other abacavir-containing product because more severe symptoms can occur within hours and may include life-threatening hypotension and death.

When therapy with ZIAGEN has been discontinued for reasons other than symptoms of a hypersensitivity reaction, and if reinitiation of ZIAGEN or any other abacavir-containing product is under consideration, carefully evaluate the reason for discontinuation of ZIAGEN to ensure that the patient did not have symptoms of a hypersensitivity reaction. If the patient is of unknown HLA-B*5701 status, screening for the allele is recommended prior to reinitiation of ZIAGEN.

If hypersensitivity cannot be ruled out, DO NOT reintroduce ZIAGEN or any other abacavir-containing product. Even in the absence of the HLA-B*5701 allele, it is important to permanently discontinue abacavir and not rechallenge with abacavir if a hypersensitivity reaction cannot be ruled out on clinical grounds, due to the potential for a severe or even fatal reaction.

If symptoms consistent with hypersensitivity are not identified, reintroduction can be undertaken with continued monitoring for symptoms of a hypersensitivity reaction. Make patients aware that a hypersensitivity reaction can occur with reintroduction of ZIAGEN or any other abacavir-containing product and that reintroduction of ZIAGEN or any other abacavir-containing product needs to be undertaken only if medical care can be readily accessed by the patient or others.

Risk Factor

HLA-B*5701 Allele: Trials have shown that carriage of the HLA-B*5701 allele is associated with a significantly increased risk of a hypersensitivity reaction to abacavir.

CNA106030 (PREDICT-1), a randomized, double-blind trial, evaluated the clinical utility of prospective HLA-B*5701 screening on the incidence of abacavir hypersensitivity reaction in abacavir-naive HIV-1-infected adults (n = 1,650). In this trial, use of pre-therapy screening for the HLA-B*5701 allele and exclusion of subjects with this allele reduced the incidence of clinically suspected abacavir hypersensitivity reactions from 7.8% (66/847) to 3.4% (27/803). Based on this trial, it is estimated that 61% of patients with the HLA-B*5701 allele will develop a clinically suspected hypersensitivity reaction during the course of abacavir treatment compared with 4% of patients who do not have the HLA-B*5701 allele.

Screening for carriage of the HLA-B*5701 allele is recommended prior to initiating treatment with abacavir. Screening is also recommended prior to reinitiation of abacavir in patients of unknown HLA-B*5701 status who have previously tolerated abacavir. For HLA-B*5701-positive patients, initiating or reinitiating treatment with an abacavir-containing regimen is not recommended and should be considered only with close medical supervision and under exceptional circumstances where potential benefit outweighs the risk.

Skin patch testing is used as a research tool and should not be used to aid in the clinical diagnosis of abacavir hypersensitivity.

In any patient treated with abacavir, the clinical diagnosis of hypersensitivity reaction must remain the basis of clinical decision-making. Even in the absence of the HLA-B*5701 allele, it is important to permanently discontinue abacavir and not rechallenge with abacavir if a hypersensitivity reaction cannot be ruled out on clinical grounds, due to the potential for a severe or even fatal reaction.

Lactic Acidosis/Severe Hepatomegaly With Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including abacavir and other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Particular caution should be exercised when administering ZIAGEN to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with ZIAGEN should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).

Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including ZIAGEN. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.

Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable and can occur many months after initiation of treatment.

Fat Redistribution

Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.

Myocardial Infarction

In a published prospective, observational, epidemiological trial designed to investigate the rate of myocardial infarction in patients on combination antiretroviral therapy, the use of abacavir within the previous 6 months was correlated with an increased risk of myocardial infarction (MI).1 In a sponsor-conducted pooled analysis of clinical trials, no excess risk of myocardial infarction was observed in abacavir-treated subjects as compared with control subjects. In totality, the available data from the observational cohort and from clinical trials are inconclusive.

As a precaution, the underlying risk of coronary heart disease should be considered when prescribing antiretroviral therapies, including abacavir, and action taken to minimize all modifiable risk factors (e.g., hypertension, hyperlipidemia, diabetes mellitus, smoking).

REFERENCES

1. Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study Group. Lancet. 2008;371 (9622):1417-1426.

Patient Counseling Information

See FDA-approved patient labeling (Medication Guide)

Information About Therapy With ZIAGEN

Hypersensitivity Reaction: Inform patients:

  • that a Medication Guide and Warning Card summarizing the symptoms of the abacavir hypersensitivity reaction and other product information will be dispensed by the pharmacist with each new prescription and refill of ZIAGEN, and encourage the patient to read the Medication Guide and Warning Card every time to obtain any new information that may be present about ZIAGEN. (The complete text of the Medication Guide is reprinted at the end of this document.)
  • to carry the Warning Card with them.
  • how to identify a hypersensitivity reaction [see Medication Guide].
  • that if they develop symptoms consistent with a hypersensitivity reaction they should call their doctor right away to determine if they should stop taking ZIAGEN.
  • that a hypersensitivity reaction can worsen and lead to hospitalization or death if ZIAGEN is not immediately discontinued.
  • that in one trial, more severe hypersensitivity reactions were seen when ZIAGEN was dosed 600 mg once daily.
  • to not restart ZIAGEN or any other abacavir-containing product following a hypersensitivity reaction because more severe symptoms can occur within hours and may include life-threatening hypotension and death.
  • that a hypersensitivity reaction is usually reversible if it is detected promptly and ZIAGEN is stopped right away.
  • that if they have interrupted ZIAGEN for reasons other than symptoms of hypersensitivity (for example, those who have an interruption in drug supply), a serious or fatal hypersensitivity reaction may occur with reintroduction of abacavir.
  • to not restart ZIAGEN or any other abacavir-containing product without medical consultation and that restarting abacavir needs to be undertaken only if medical care can be readily accessed by the patient or others.
  • ZIAGEN should not be coadministered with EPZICOM® (abacavir sulfate and lamivudine) Tablets or TRIZIVIR® (abacavir sulfate, lamivudine, and zidovudine) Tablets.

Lactic Acidosis/Hepatomegaly: Inform patients that some HIV medicines, including ZIAGEN, can cause a rare, but serious condition called lactic acidosis with liver enlargement (hepatomegaly) [see BOXED WARNING, WARNINGS AND PRECAUTIONS].

Redistribution/Accumulation of Body Fat: Inform patients that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time [see WARNINGS AND PRECAUTIONS].

Information About HIV-1 Infection: ZIAGEN is not a cure for HIV-1 infection and patients may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. Patients should remain under the care of a physician when using ZIAGEN. Patients should be advised to avoid doing things that can spread HIV-1 infection to others.

  • Do not share needles or other injection equipment.
  • Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades.
  • Do not have any kind of sex without protection. Always practice safe sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood.
  • Do not breastfeed. We do not know if ZIAGEN can be passed to your baby in your breast milk and whether it could harm your baby. Also, mothers with HIV-1 should not breastfeed because HIV-1 can be passed to the baby in the breast milk.

Patients should be informed to take all HIV medications exactly as prescribed.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity

Abacavir was administered orally at 3 dosage levels to separate groups of mice and rats in 2-year carcinogenicity studies. Results showed an increase in the incidence of malignant and non-malignant tumors. Malignant tumors occurred in the preputial gland of males and the clitoral gland of females of both species, and in the liver of female rats. In addition, non-malignant tumors also occurred in the liver and thyroid gland of female rats. These observations were made at systemic exposures in the range of 6 to 32 times the human exposure at the recommended dose. It is not known how predictive the results of rodent carcinogenicity studies may be for humans.

Mutagenicity

Abacavir induced chromosomal aberrations both in the presence and absence of metabolic activation in an in vitro cytogenetic study in human lymphocytes. Abacavir was mutagenic in the absence of metabolic activation, although it was not mutagenic in the presence of metabolic activation in an L5178Y mouse lymphoma assay. Abacavir was clastogenic in males and not clastogenic in females in an in vivo mouse bone marrow micronucleus assay.

Abacavir was not mutagenic in bacterial mutagenicity assays in the presence and absence of metabolic activation.

Impairment of Fertility

Abacavir had no adverse effects on the mating performance or fertility of male and female rats at a dose approximately 8 times the human exposure at the recommended dose based on body surface area comparisons.

Use In Specific Populations

Pregnancy

Pregnancy Category C

Studies in pregnant rats showed that abacavir is transferred to the fetus through the placenta. Fetal malformations (increased incidences of fetal anasarca and skeletal malformations) and developmental toxicity (depressed fetal body weight and reduced crown-rump length) were observed in rats at a dose which produced 35 times the human exposure based on AUC. Embryonic and fetal toxicities (increased resorptions, decreased fetal body weights) and toxicities to the offspring (increased incidence of stillbirth and lower body weights) occurred at half of the above-mentioned dose in separate fertility studies conducted in rats. In the rabbit, no developmental toxicity and no increases in fetal malformations occurred at doses that produced 8.5 times the human exposure at the recommended dose based on AUC.

There are no adequate and well-controlled studies in pregnant women. ZIAGEN should be used during pregnancy only if the potential benefits outweigh the risk.

Antiretroviral Pregnancy Registry

To monitor maternal-fetal outcomes of pregnant women exposed to ZIAGEN, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.

Nursing Mothers

The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection.

Although it is not known if abacavir is excreted in human milk, abacavir is secreted into the milk of lactating rats. Because of both the potential for HIV-1 transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving ZIAGEN.

Pediatric Use

The safety and effectiveness of ZIAGEN have been established in pediatric patients 3 months to 13 years of age. Use of ZIAGEN in these age-groups is supported by pharmacokinetic trials and evidence from adequate and well-controlled trials of ZIAGEN in adults and pediatric patients [see DOSAGE AND ADMINISTRATION, CLINICAL PHARMACOLOGY, Clinical Studies].

Geriatric Use

Clinical studies of ZIAGEN did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Last reviewed on RxList: 9/25/2013
This monograph has been modified to include the generic and brand name in many instances.

OverDose

There is no known antidote for ZIAGEN. It is not known whether abacavir can be removed by peritoneal dialysis or hemodialysis.

ContrainDications

ZIAGEN is contraindicated in patients with:

  • previously demonstrated hypersensitivity to abacavir or any other component of the products. NEVER restart ZIAGEN or any other abacavir-containing product following a hypersensitivity reaction to abacavir, regardless of HLA-B*5701 status [see WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS].
  • moderate or severe hepatic impairment [see DOSAGE AND ADMINISTRATION].

Last reviewed on RxList: 9/25/2013
This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

Mechanism of Action

Abacavir is an antiviral agent [See Microbiology].

Pharmacokinetics

Pharmacokinetics in Adults

The pharmacokinetic properties of abacavir have been studied in asymptomatic, HIV-1-infected adult subjects after administration of a single intravenous (IV) dose of 150 mg and after single and multiple oral doses. The pharmacokinetic properties of abacavir were independent of dose over the range of 300 to 1,200 mg/day.

Absorption and Bioavailability

Abacavir was rapidly and extensively absorbed after oral administration. The geometric mean absolute bioavailability of the tablet was 83%. After oral administration of 300 mg twice daily in 20 subjects, the steady-state peak serum abacavir concentration (Cmax) was 3.0 ± 0.89 mcg/mL (mean ± SD) and AUC(0-12 hr) was 6.02 ± 1.73 mcg•hr/mL. After oral administration of a single dose of 600 mg of abacavir in 20 subjects, Cmax was 4.26 ± 1.19 mcg/mL (mean ± SD) and AUC∞ was 11.95 ± 2.51 mcg•hr/mL.

Distribution

The apparent volume of distribution after IV administration of abacavir was 0.86 ± 0.15 L/kg, suggesting that abacavir distributes into extravascular space. In 3 subjects, the CSF AUC(0-6 hr) to plasma abacavir AUC(0-6 hr) ratio ranged from 27% to 33%.

Binding of abacavir to human plasma proteins is approximately 50%. Binding of abacavir to plasma proteins was independent of concentration. Total blood and plasma drug-related radioactivity concentrations are identical, demonstrating that abacavir readily distributes into erythrocytes.

Metabolism

In humans, abacavir is not significantly metabolized by cytochrome P450 enzymes. The primary routes of elimination of abacavir are metabolism by alcohol dehydrogenase (to form the 5'-carboxylic acid) and glucuronyl transferase (to form the 5'-glucuronide). The metabolites do not have antiviral activity. In vitro experiments reveal that abacavir does not inhibit human CYP3A4, CYP2D6, or CYP2C9 activity at clinically relevant concentrations.

Elimination

Elimination of abacavir was quantified in a mass balance trial following administration of a 600-mg dose of 14C-abacavir: 99% of the radioactivity was recovered, 1.2% was excreted in the urine as abacavir, 30% as the 5'-carboxylic acid metabolite, 36% as the 5'-glucuronide metabolite, and 15% as unidentified minor metabolites in the urine. Fecal elimination accounted for 16% of the dose.

In single-dose trials, the observed elimination half-life (t½) was 1.54 ± 0.63 hours. After intravenous administration, total clearance was 0.80 ± 0.24 L/hr/kg (mean ± SD).

Effects of Food on Oral Absorption: Bioavailability of abacavir tablets was assessed in the fasting and fed states. There was no significant difference in systemic exposure (AUC∞) in the fed and fasting states; therefore, ZIAGEN Tablets may be administered with or without food. Systemic exposure to abacavir was comparable after administration of ZIAGEN Oral Solution and ZIAGEN Tablets. Therefore, these products may be used interchangeably.

Special Populations

Renal Impairment: The pharmacokinetic properties of ZIAGEN have not been determined in patients with impaired renal function. Renal excretion of unchanged abacavir is a minor route of elimination in humans.

Hepatic Impairment: The pharmacokinetics of abacavir have been studied in subjects with mild hepatic impairment (Child-Pugh score 5 to 6). Results showed that there was a mean increase of 89% in the abacavir AUC and an increase of 58% in the half-life of abacavir after a single dose of 600 mg of abacavir. The AUCs of the metabolites were not modified by mild liver disease; however, the rates of formation and elimination of the metabolites were decreased. A dose of 200 mg (provided by 10 mL of ZIAGEN Oral Solution) administered twice daily is recommended for patients with mild liver disease. The safety, efficacy, and pharmacokinetics of abacavir have not been studied in patients with moderate or severe hepatic impairment; therefore, ZIAGEN is contraindicated in these patients.

Pediatric Patients: The pharmacokinetics of abacavir have been studied after either single or repeat doses of ZIAGEN in 68 pediatric subjects. Following multiple-dose administration of ZIAGEN 8 mg/kg twice daily, steady-state AUC(0-12 hr) and Cmax were 9.8 ± 4.56 mcg•hr/mL and 3.71 ± 1.36 mcg/mL (mean ± SD), respectively [see Use in Specific Populations]. In addition, to support dosing of ZIAGEN scored tablet (300 mg) for pediatric patients 14 kg to greater than 30 kg, analysis of actual and simulated pharmacokinetic data indicated comparable exposures are expected following administration of 300 mg scored tablet and the 8 mg/kg dosing regimen using oral solution.

Geriatric Patients: The pharmacokinetics of ZIAGEN have not been studied in patients over 65 years of age.

Gender: A population pharmacokinetic analysis in HIV-1-infected male (n = 304) and female (n = 67) subjects showed no gender differences in abacavir AUC normalized for lean body weight.

Race: There are no significant differences between blacks and Caucasians in abacavir pharmacokinetics.

Drug Interactions

In human liver microsomes, abacavir did not inhibit cytochrome P450 isoforms (2C9, 2D6, 3A4). Based on these data, it is unlikely that clinically significant drug interactions will occur between abacavir and drugs metabolized through these pathways.

Lamivudine and/or Zidovudine: Due to the common metabolic pathways of abacavir and zidovudine via glucuronyl transferase, 15 HIV-1-infected subjects were enrolled in a crossover trial evaluating single doses of abacavir (600 mg), lamivudine (150 mg), and zidovudine (300 mg) alone or in combination. Analysis showed no clinically relevant changes in the pharmacokinetics of abacavir with the addition of lamivudine or zidovudine or the combination of lamivudine and zidovudine. Lamivudine exposure (AUC decreased 15%) and zidovudine exposure (AUC increased 10%) did not show clinically relevant changes with concurrent abacavir.

Ethanol: Due to the common metabolic pathways of abacavir and ethanol via alcohol dehydrogenase, the pharmacokinetic interaction between abacavir and ethanol was studied in 24 HIV-1-infected male subjects. Each subject received the following treatments on separate occasions: a single 600-mg dose of abacavir, 0.7 g/kg ethanol (equivalent to 5 alcoholic drinks), and abacavir 600 mg plus 0.7 g/kg ethanol. Coadministration of ethanol and abacavir resulted in a 41% increase in abacavir AUC∞ and a 26% increase in abacavir t½. In males, abacavir had no effect on the pharmacokinetic properties of ethanol, so no clinically significant interaction is expected in men. This interaction has not been studied in females.

Methadone: In a trial of 11 HIV-1-infected subjects receiving methadone-maintenance therapy (40 mg and 90 mg daily), with 600 mg of ZIAGEN twice daily (twice the currently recommended dose), oral methadone clearance increased 22% (90% CI: 6% to 42%). This alteration will not result in a methadone dose modification in the majority of patients; however, an increased methadone dose may be required in a small number of patients. The addition of methadone had no clinically significant effect on the pharmacokinetic properties of abacavir.

Microbiology

Abacavir is a carbocyclic synthetic nucleoside analogue. Abacavir is converted by cellular enzymes to the active metabolite, carbovir triphosphate (CBV-TP), an analogue of deoxyguanosine-5'-triphosphate (dGTP). CBV-TP inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. The lack of a 3'-OH group in the incorporated nucleotide analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated. CBV-TP is a weak inhibitor of cellular DNA polymerases α, β, and γ.

Antiviral Activity

The antiviral activity of abacavir against HIV-1 was evaluated against a T-cell tropic laboratory strain HIV-1IIIB in lymphoblastic cell lines, a monocyte/macrophage tropic laboratory strain HIV-1BaL in primary monocytes/macrophages, and clinical isolates in peripheral blood mononuclear cells. The concentration of drug necessary to effect viral replication by 50 percent (EC50) ranged from 3.7 to 5.8 μM (1 μM = 0.28 mcg/mL) and 0.07 to 1.0 μM against HIV-1IIIB and HIV-1BaL, respectively, and was 0.26 ± 0.18 μM against 8 clinical isolates. The EC50 values of abacavir against different HIV-1 clades (A-G) ranged from 0.0015 to 1.05 μM, and against HIV-2 isolates, from 0.024 to 0.49 μM. The antiviral activity of abacavir in cell culture was not antagonized when combined with the nucleoside reverse transcriptase inhibitors (NRTIs) didanosine, emtricitabine, lamivudine, stavudine, tenofovir, zalcitabine or zidovudine, the non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine, or the protease inhibitor (PI) amprenavir. Ribavirin (50 μM) had no effect on the anti–HIV-1 activity of abacavir in cell culture.

Resistance

HIV-1 isolates with reduced susceptibility to abacavir have been selected in cell culture and were also obtained from subjects treated with abacavir. Genotypic analysis of isolates selected in cell culture and recovered from abacavir-treated subjects demonstrated that amino acid substitutions K65R, L74V, Y115F, and M184V/I in RT contributed to abacavir resistance. In a trial of therapy-naive adults receiving ZIAGEN 600 mg once daily (n = 384) or 300 mg twice daily (n = 386), in a background regimen of lamivudine 300 mg once daily and efavirenz 600 mg once daily (CNA30021), the incidence of virologic failure at 48 weeks was similar between the 2 groups (11% in both arms). Genotypic (n = 38) and phenotypic analyses (n = 35) of virologic failure isolates from this trial showed that the RT substitutions that emerged during abacavir once-daily and twice-daily therapy were K65R, L74V, Y115F, and M184V/I. The substitution M184V/I was the most commonly observed substitution in virologic failure isolates from subjects receiving abacavir once daily (56%, 10/18) and twice daily (40%, 8/20).

Thirty-nine percent (7/18) of the isolates from subjects who experienced virologic failure in the abacavir once-daily arm had a greater than 2.5-fold decrease in abacavir susceptibility with a median-fold decrease of 1.3 (range: 0.5 to 11) compared with 29% (5/17) of the failure isolates in the twice-daily arm with a median-fold decrease of 0.92 (range: 0.7 to 13).

Cross-Resistance

Cross-resistance has been observed among NRTIs. Isolates containing abacavir resistance-associated substitutions, namely, K65R, L74V, Y115F, and M184V, exhibited cross-resistance to didanosine, emtricitabine, lamivudine, tenofovir, and zalcitabine in cell culture and in subjects. The K65R substitution can confer resistance to abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zalcitabine; the L74V substitution can confer resistance to abacavir, didanosine, and zalcitabine; and the M184V substitution can confer resistance to abacavir, didanosine, emtricitabine, lamivudine, and zalcitabine. An increasing number of thymidine analogue mutations (TAMs: M41L, D67N, K70R, L210W, T215Y/F, K219E/R/H/Q/N) is associated with a progressive reduction in abacavir susceptibility.

Animal Toxicology and/or Pharmacology

Myocardial degeneration was found in mice and rats following administration of abacavir for 2 years. The systemic exposures were equivalent to 7 to 24 times the expected systemic exposure in humans. The clinical relevance of this finding has not been determined.

Clinical Studies

Adults

Therapy-Naive Adults

CNA30024 was a multicenter, double-blind, controlled trial in which 649 HIV-1-infected, therapy-naive adults were randomized and received either ZIAGEN (300 mg twice daily), lamivudine (150 mg twice daily), and efavirenz (600 mg once daily); or zidovudine (300 mg twice daily), lamivudine (150 mg twice daily), and efavirenz (600 mg once daily). The duration of double-blind treatment was at least 48 weeks. Trial participants were male (81%), Caucasian (51%), black (21%), and Hispanic (26%). The median age was 35 years; the median pretreatment CD4+ cell count was 264 cells/mm³, and median plasma HIV-1 RNA was 4.79 log10 copies/mL. The outcomes of randomized treatment are provided in Table 7.

Table 7: Outcomes of Randomized Treatment Through Week 48 (CNA30024)

Outcome ZIAGEN plus Lamivudine plus Efavirenz
(n = 324)
Zidovudine plus Lamivudine plus Efavirenz
(n = 325)
Respondera 69% (73%) 69% (71%)
Virologic failuresb 6% 4%
Discontinued due to adverse reactions 14% 16%
Discontinued due to other reasonsc 10% 11%
aSubjects achieved and maintained confirmed HIV-1 RNA ≤ 50 copies/mL ( < 400 copies/mL) through Week 48 (Roche AMPLICOR Ultrasensitive HIV-1 MONITOR® standard test 1.0 PCR).
bIncludes viral rebound, insufficient viral response according to the investigator, and failure to achieve confirmed ≤ 50 copies/mL by Week 48.
cIncludes consent withdrawn, lost to follow up, protocol violations, those with missing data, clinical progression, and other.

After 48 weeks of therapy, the median CD4+ cell count increases from baseline were 209 cells/mm³ in the group receiving ZIAGEN and 155 cells/mm³ in the zidovudine group. Through Week 48, 8 subjects (2%) in the group receiving ZIAGEN (5 CDC classification C events and 3 deaths) and 5 subjects (2%) on the zidovudine arm (3 CDC classification C events and 2 deaths) experienced clinical disease progression.

CNA3005 was a multicenter, double-blind, controlled trial in which 562 HIV-1-infected, therapy-naive adults were randomized to receive either ZIAGEN (300 mg twice daily) plus COMBIVIR® (lamivudine 150 mg/zidovudine 300 mg twice daily), or indinavir (800 mg 3 times a day) plus COMBIVIR twice daily. The trial was stratified at randomization by pre-entry plasma HIV-1 RNA 10,000 to 100,000 copies/mL and plasma HIV-1 RNA greater than 100,000 copies/mL. Trial participants were male (87%), Caucasian (73%), black (15%), and Hispanic (9%). At baseline the median age was 36 years; the median baseline CD4+ cell count was 360 cells/mm³, and median baseline plasma HIV-1 RNA was 4.8 log10 copies/mL. Proportions of subjects with plasma HIV-1 RNA less than 400 copies/mL (using Roche AMPLICOR HIV-1 MONITOR Test) through 48 weeks of treatment are summarized in Table 8.

Table 8: Outcomes of Randomized Treatment Through Week 48 (CNA3005)

Outcome ZIAGEN plus Lamivudine/Zidovudine
(n = 262)
Indinavir plus Lamivudine/Zidovudine
(n = 265)
Respondera 49% 50%
Virologic failureb 31% 28%
Discontinued due to adverse reactions 10% 12%
Discontinued due to other reasonsc 11% 10%
aSubjects achieved and maintained confirmed HIV-1 RNA < 400 copies/mL.
bIncludes viral rebound and failure to achieve confirmed < 400 copies/mL by Week 48.
cIncludes consent withdrawn, lost to follow up, protocol violations, those with missing data, clinical progression, and other.

Treatment response by plasma HIV-1 RNA strata is shown in Table 9.

Table 9: Proportions of Responders Through Week 48 By Screening Plasma HIV-1 RNA Levels (CNA3005)

Screening HIV-1 RNA (copies/mL) ZIAGEN plus Lamivudine/ Zidovudine
(n = 262)
Indinavir plus Lamivudine/ Zidovudine
(n = 265)
< 400 copies/mL n < 400 copies/mL n
≥ 10,000 - ≤ 100,000 50% 166 48% 165
> 100,000 48% 96 52% 100

In subjects with baseline viral load greater than 100,000 copies/mL, percentages of subjects with HIV-1 RNA levels less than 50 copies/mL were 31% in the group receiving abacavir versus 45% in the group receiving indinavir.

Through Week 48, an overall mean increase in CD4+ cell count of about 150 cells/mm³ was observed in both treatment arms. Through Week 48, 9 subjects (3.4%) in the group receiving abacavir sulfate (6 CDC classification C events and 3 deaths) and 3 subjects (1.5%) in the group receiving indinavir (2 CDC classification C events and 1 death) experienced clinical disease progression.

CNA30021 was an international, multicenter, double-blind, controlled trial in which 770 HIV-1-infected, therapy-naive adults were randomized and received either abacavir 600 mg once daily or abacavir 300 mg twice daily, both in combination with lamivudine 300 mg once daily and efavirenz 600 mg once daily. The double-blind treatment duration was at least 48 weeks. Trial participants had a mean age of 37 years; were male (81%), Caucasian (54%), black (27%), and American Hispanic (15%). The median baseline CD4+ cell count was 262 cells/mm³ (range 21 to 918 cells/mm³) and the median baseline plasma HIV-1 RNA was 4.89 log10 copies/mL (range: 2.60 to 6.99 log10 copies/mL). The outcomes of randomized treatment are provided in Table 10.

Table 10: Outcomes of Randomized Treatment Through Week 48 (CNA30021)

Outcome ZIAGEN 600 mg q.d. plus EPIVIR plus Efavirenz
(n = 384)
ZIAGEN 300 mg b.i.d. plus EPIVIR plus Efavirenz
(n = 386)
Respondera 64% (71%) 65% (72%)
Virologic failureb 11% (5%) 11% (5%)
Discontinued due to adverse reactions 13% 11%
Discontinued due to other reasonsc 11% 13%
aSubjects achieved and maintained confirmed HIV-1 RNA < 50 copies/mL ( < 400 copies/mL) through Week 48 (Roche AMPLICOR Ultrasensitive HIV-1 MONITOR standard test version 1.0).
bIncludes viral rebound, failure to achieve confirmed < 50 copies/mL ( < 400 copies/mL) by Week 48, and insufficient viral load response.
cIncludes consent withdrawn, lost to follow up, protocol violations, clinical progression, and other.

After 48 weeks of therapy, the median CD4+ cell count increases from baseline were 188 cells/mm³ in the group receiving abacavir 600 mg once daily and 200 cells/mm³ in the group receiving abacavir 300 mg twice daily. Through Week 48, 6 subjects (2%) in the group receiving ZIAGEN 600 mg once daily (4 CDC classification C events and 2 deaths) and 10 subjects (3%) in the group receiving ZIAGEN 300 mg twice daily (7 CDC classification C events and 3 deaths) experienced clinical disease progression. None of the deaths were attributed to trial medications.

Pediatric Trials

Therapy-Experienced Pediatric Subjects

CNA3006 was a randomized, double-blind trial comparing ZIAGEN 8 mg/kg twice daily plus lamivudine 4 mg/kg twice daily plus zidovudine 180 mg/m² twice daily versus lamivudine 4 mg/kg twice daily plus zidovudine 180 mg/m² twice daily. Two hundred and five therapy-experienced pediatric subjects were enrolled: female (56%), Caucasian (17%), black (50%), Hispanic (30%), median age of 5.4 years, baseline CD4+ cell percent greater than 15% (median = 27%), and median baseline plasma HIV-1 RNA of 4.6 log10 copies/mL. Eighty percent and 55% of subjects had prior therapy with zidovudine and lamivudine, respectively, most often in combination. The median duration of prior nucleoside analogue therapy was 2 years. At 16 weeks the proportion of subjects responding based on plasma HIV-1 RNA less than or equal to 400 copies/mL was significantly higher in subjects receiving ZIAGEN plus lamivudine plus zidovudine compared with subjects receiving lamivudine plus zidovudine, 13% versus 2%, respectively. Median plasma HIV-1 RNA changes from baseline were -0.53 log10 copies/mL in the group receiving ZIAGEN plus lamivudine plus zidovudine compared with -0.21 log10 copies/mL in the group receiving lamivudine plus zidovudine. Median CD4+ cell count increases from baseline were 69 cells/mm³ in the group receiving ZIAGEN plus lamivudine plus zidovudine and 9 cells/mm³ in the group receiving lamivudine plus zidovudine.

Last reviewed on RxList: 9/25/2013
This monograph has been modified to include the generic and brand name in many instances.

Patient Information

ZIAGEN®
(ZY-uh-jen)
(abacavir sulfate) Tablets and Oral Solution

Read this Medication Guide before you start taking ZIAGEN and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment. Be sure to carry your ZIAGEN Warning Card with you at all times.

What is the most important information I should know about ZIAGEN?

1. Serious allergic reaction (hypersensitivity reaction). ZIAGEN contains abacavir (also contained in EPZICOM® and TRIZIVIR®). Patients taking ZIAGEN may have a serious allergic reaction (hypersensitivity reaction) that can cause death. Your risk of this allergic reaction is much higher if you have a gene variation called HLA-B*5701. Your healthcare provider can determine with a blood test if you have this gene variation.

If you get a symptom from 2 or more of the following groups while taking ZIAGEN, call your healthcare provider right away to find out if you should stop taking ZIAGEN.

 

Symptom(s)  
Group 1 Fever
Group 2 Rash
Group 3 Nausea, vomiting, diarrhea, abdominal (stomach area) pain
Group 4 Generally ill feeling, extreme tiredness, or achiness
Group 5 Shortness of breath, cough, sore throat

A list of these symptoms is on the Warning Card your pharmacist gives you. Carry this Warning Card with you at all times.

If you stop ZIAGEN because of an allergic reaction, never take ZIAGEN (abacavir sulfate) or any other abacavir-containing medicine (EPZICOM and TRIZIVIR) again. If you take ZIAGEN or any other abacavir-containing medicine again after you have had an allergic reaction, within hours you may get life-threatening symptoms that may include very low blood pressure or death. If you stop ZIAGEN for any other reason, even for a few days, and you are not allergic to ZIAGEN, talk with your healthcare provider before taking it again. Taking ZIAGEN again can cause a serious allergic or life-threatening reaction, even if you never had an allergic reaction to it before.

If your healthcare provider tells you that you can take ZIAGEN again, start taking it when you are around medical help or people who can call a healthcare provider if you need one.

2. Lactic Acidosis (buildup of acid in the blood). Some human immunodeficiency virus (HIV) medicines, including ZIAGEN, can cause a rare but serious condition called lactic acidosis. Lactic acidosis is a serious medical emergency that can cause death and must be treated in the hospital.

Call your healthcare provider right away if you get any of the following signs or symptoms of lactic acidosis:

  • you feel very weak or tired
  • you have unusual (not normal) muscle pain
  • you have trouble breathing
  • you have stomach pain with nausea and vomiting
  • you feel cold, especially in your arms and legs
  • you feel dizzy or light-headed
  • you have a fast or irregular heartbeat

3. Serious liver problems. Some people who have taken medicines like ZIAGEN have developed serious liver problems called hepatotoxicity, with liver enlargement (hepatomegaly) and fat in the liver (steatosis). Hepatomegaly with steatosis is a serious medical emergency that can cause death.

Call your healthcare provider right away if you get any of the following signs or symptoms of liver problems:

  • your skin or the white part of your eyes turns yellow (jaundice)
  • your urine turns dark
  • your bowel movements (stools) turn light in color
  • you don't feel like eating food for several days or longer
  • you feel sick to your stomach (nausea)
  • you have lower stomach area (abdominal) pain

You may be more likely to get lactic acidosis or serious liver problems if you are female, very overweight, or have been taking nucleoside analogue medicines for a long time.

What is ZIAGEN?

ZIAGEN is a prescription medicine used to treat HIV infection. ZIAGEN is a medicine called a nucleoside analogue reverse transcriptase inhibitor (NRTI). ZIAGEN is always used with other anti-HIV medicines. When used in combination with these other medicines, ZIAGEN helps lower the amount of HIV in your blood.

  • ZIAGEN does not cure HIV infection or AIDS.
  • It is not known if ZIAGEN will help you live longer or have fewer of the medical problems that people get with HIV or AIDS.
  • It is very important that you see your doctor regularly while you are taking ZIAGEN.

Who should not take ZIAGEN?

Do not take ZIAGEN if you:

  • are allergic to abacavir or any of the ingredients in ZIAGEN. See the end of this Medication Guide for a complete list of ingredients in ZIAGEN.
  • have certain liver problems.

What should I tell my healthcare provider before taking ZIAGEN?

Before you take ZIAGEN, tell your healthcare provider if you:

  • have been tested and know whether or not you have a particular gene variation called HLA-B*5701.
  • have hepatitis B virus infection or have other liver problems.
  • have heart problems, smoke, or have diseases that increase your risk of heart disease such as high blood pressure, high cholesterol, or diabetes.
  • are pregnant or plan to become pregnant. It is not known if ZIAGEN will harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant.
    Pregnancy Registry. If you take ZIAGEN while you are pregnant, talk to your healthcare provider about how you can take part in the Pregnancy Registry for ZIAGEN. The purpose of the pregnancy registry is to collect information about the health of you and your baby.
  • are breastfeeding or plan to breastfeed. Do not breastfeed. We do not know if ZIAGEN can be passed to your baby in your breast milk and whether it could harm your baby. Also, mothers with HIV-1 should not breastfeed because HIV-1 can be passed to the baby in the breast milk.

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take:

  • alcohol
  • methadone
  • TRIZIVIR (abacavir sulfate, lamivudine, and zidovudine)
  • EPZICOM (abacavir sulfate and lamivudine)

Ask your healthcare provider if you are not sure if you take one of the medicines listed above.

ZIAGEN may affect the way other medicines work, and other medicines may affect how ZIAGEN works.

Know the medicines you take. Keep a list of your medicines with you to show to your healthcare provider and pharmacist when you get a new medicine.

How should I take ZIAGEN?

  • Take ZIAGEN exactly as your healthcare provider tells you to take it.
  • ZIAGEN is taken by mouth as a tablet or a strawberry-and banana-flavored liquid.
  • ZIAGEN may be taken with or without food.
  • Do not skip doses.
  • Children aged 3 months and older can also take ZIAGEN. The child's healthcare provider will decide the right dose and whether the child should take the tablet or liquid, based on the child's weight. The dose should not be more than the recommended adult dose.
  • Do not let your ZIAGEN run out.
    If you stop your anti-HIV medicines, even for a short time, the amount of virus in your blood may increase and the virus may become harder to treat. If you take too much ZIAGEN, call your healthcare provider or poison control center or go to the nearest hospital emergency room right away.

What are the possible side effects of ZIAGEN?

  • ZIAGEN can cause serious side effects including allergic reactions, lactic acidosis, and liver problems. See “What is the most important information I should know about ZIAGEN?”
  • Changes in immune system (Immune Reconstitution Syndrome). Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider if you start having new or worse symptoms of infection after you start taking ZIAGEN.
  • Changes in body fat (fat redistribution). Changes in body fat (lipoatrophy or lipodystrophy) can happen in some people taking antiretroviral medicines including ZIAGEN. These changes may include:
    • more fat in or around your trunk, upper back and neck (buffalo hump), breast, or chest
    • loss of fat in your legs, arms, or face
  • Heart attack (myocardial infarction). Some HIV medicines including ZIAGEN may increase your risk of heart attack.

The most common side effects of ZIAGEN in adults include:

  • bad dreams or sleep problems
  • nausea
  • headache
  • tiredness
  • vomiting

The most common side effects of ZIAGEN in children include:

  • fever and chills
  • nausea
  • vomiting
  • rash
  • ear, nose, or throat infections

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of ZIAGEN. For more information, ask your healthcare provider or pharmacist.

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

How should I store ZIAGEN?

  • Store ZIAGEN at room temperature, between 68°F to 77°F (20°C to 25°C).
  • Do not freeze ZIAGEN.
  • Keep ZIAGEN and all medicines out of the reach of children.

General information for safe and effective use of ZIAGEN

Avoid doing things that can spread HIV infection to others.

  • Do not share needles or other injection equipment.
  • Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades.
  • Do not have any kind of sex without protection. Always practice safe sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ZIAGEN for a condition for which it was not prescribed. Do not give ZIAGEN to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about ZIAGEN. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for the information that is written for healthcare professionals.

For more information go to www.ZIAGEN.com or call 1-877-844-8872.

What are the ingredients in ZIAGEN?

Tablets

Active ingredient: abacavir sulfate

Inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate, and a film-coating made of hypromellose, polysorbate 80, synthetic yellow iron oxide, titanium dioxide, and triacetin.

Oral Solution

Active ingredient: abacavir sulfate

Inactive ingredients: artificial strawberry and banana flavors, citric acid (anhydrous), methylparaben and propylparaben (added as preservatives), propylene glycol, saccharin sodium, sodium citrate (dihydrate), sorbitol solution, and water.

This Medication Guide has been approved by the US Food and Drug Administration.

Last reviewed on RxList: 9/25/2013
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.

 

ABACAVIR - ORAL

 

(a-BAK-a-vir)

 

COMMON BRAND NAME(S): Ziagen

 

WARNING: In some patients, abacavir has caused a serious (sometimes fatal) allergic reaction. Your doctor may order a blood test to measure your risk before you start this medication or take it again. If the blood test shows you are at greater risk, your doctor should discuss the risks and benefits of abacavir and other treatment choices with you. Symptoms of an allergic reaction may include any of the following: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing, fever, extreme tiredness, nausea, vomiting, diarrhea, stomach pain, muscle aches, sore throat, or cough. Get medical help right away if you experience any of these symptoms. If you have stopped taking abacavir because of an allergic reaction, you must never take any form of abacavir again. Notify all of your doctors and pharmacists if you have stopped taking abacavir due to an allergic reaction. Read the warning card provided with this medication for more details.

Rarely, abacavir has caused severe (sometimes fatal) liver problems and a certain metabolic problem (lactic acidosis). Get medical help right away if you develop any of the following symptoms: nausea, vomiting, stomach/abdominal pain, unusual tiredness, dark urine, yellowing eyes/skin, deep/rapid breathing, or drowsiness. These serious side effects may occur more often in women and obese patients.

 

USES: This drug is used with other HIV medications to help control HIV infection. It helps to decrease the amount of HIV in your body so your immune system can work better. This lowers your chance of getting HIV complications (such as new infections, cancer) and improves your quality of life. Abacavir belongs to a class of drugs known as nucleoside reverse transcriptase inhibitors-NRTI.

Abacavir is not a cure for HIV infection. To decrease your risk of spreading HIV disease to others, do all of the following: (1) continue to take all HIV medications exactly as prescribed by your doctor, (2) always use an effective barrier method (latex or polyurethane condoms/dental dams) during all sexual activity, and (3) do not share personal items (such as needles/syringes, toothbrushes, and razors) that may have contacted blood or other body fluids. Consult your doctor or pharmacist for more details.

 

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This medication may also be used in combination with other HIV medications to reduce the risk of getting HIV infection after contact with the virus. Consult your doctor for more details.

 

HOW TO USE: Read the Medication Guide and Warning Card provided by your pharmacist before you start taking abacavir and each time you get a refill. Carry the Warning Card with you at all times. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth, usually 1-2 times daily with or without food or as directed by your doctor. If you are using the liquid form of this medication, carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose.

Dosage is based on your medical condition and response to treatment.

If you stop using abacavir even for a short time and then restart the drug, you have an increased chance of developing a very serious (possibly fatal) allergic reaction. Refill your medication before you run out. Do not stop treatment unless directed by your doctor. Before restarting abacavir, consult your doctor or pharmacist, and be sure you have easy access to medical care.

It is very important to continue taking this medication (and other HIV medications) exactly as prescribed by your doctor. Do not skip any doses. Do not increase your dose, take this drug more often than prescribed, or stop taking it (or other HIV medicines) even for a short time unless directed to do so by your doctor. Skipping or changing your dose without approval from your doctor may cause the amount of virus to increase, make the infection more difficult to treat (resistant), or worsen side effects.

This medication works best when the amount of drug in your body is kept at a constant level. Therefore, take this drug at evenly spaced intervals. To help you remember, take it at the same time(s) each day.

Consumer Overview Side Effect

SIDE EFFECTS: See also Warning and How to Use sections.

Trouble sleeping or loss of appetite may occur. If any of these effects persist or worsen, notify 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.

Some people may experience worsening of a previous medical condition (such as an old infection) as their immune systems improve, or develop new conditions because their immune systems have become overactive. This reaction may occur at any time (soon after starting HIV treatment or many months later). Tell your doctor right away if you have any serious side effects, including: unexplained weight loss, persistent muscle aches/weakness, joint pain, numbness/tingling of the hands/feet/arms/legs, severe tiredness, vision changes, severe/persistent headaches, signs of infection (such as fever, chills, trouble breathing, cough, non-healing skin sores), signs of an overactive thyroid (such as irritability, nervousness, heat intolerance, fast/pounding/irregular heartbeat, bulging eyes, unusual growth in the neck/thyroid known as a goiter), signs of a certain nerve problem known as Guillain-Barre Syndrome (such as difficulty breathing/swallowing/moving your eyes, drooping face, paralysis, slurred speech).

Tell your doctor right away if you have any serious side effects, including: mental/mood changes (depression, anxiety).

Changes in body fat (such as increased fat in the upper back and stomach areas, decreased fat in the arms and legs) may occur while you are taking HIV medication. The cause and long-term effects of these changes are unknown. Discuss the risks and benefits of therapy with your doctor, as well as the possible role of exercise to reduce this side effect.

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 Ziagen (abacavir sulfate) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: See also Warning and How to Use sections.

Before taking abacavir, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver problems (such as hepatitis B or C, or cirrhosis), kidney problems, alcohol use.

Abacavir may increase your risk of a heart attack. Discuss the risks and benefits of treatment with your doctor and ways to lower your risk of heart disease. Tell your doctor if you have heart problems, if you smoke, or if you have other conditions that increase your risk of heart disease such as high blood pressure, diabetes, or high cholesterol levels.

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

During pregnancy, this medication should be used only when clearly needed. However, HIV medicines are now usually given to pregnant women with HIV. Treatment has been shown to decrease the risk of HIV transmission to the baby. Abacavir may be part of that treatment. Discuss the risks and benefits with your doctor.

It is not known if this medication passes into breast milk. Because breast milk can transmit HIV, do not breast-feed.

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: alcohol, methadone.

This medication must not be taken with other medications that contain abacavir. Check the labels on all your other prescription medications to make sure they do not contain abacavir. If you have any questions, consult your doctor or pharmacist.

 

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.

 

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (such as liver tests, viral load, T-cell counts) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

Keep all medical and laboratory appointments.

 

MISSED DOSE: If you miss a dose, take 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 abacavir solution or tablets at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. Abacavir solution may also be stored in the refrigerator. Do not freeze. Do not store in the bathroom. Keep all medicines 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 for more details about how to safely discard your product.

 

Information last revised January 2014. Copyright(c) 2014 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Ziagen

Generic Name: abacavir (Pronunciation: a BAK a veer)

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

What is abacavir (Ziagen)?

Abacavir is an antiviral medication that prevents human immunodeficiency virus (HIV) cells from multiplying in your body.

Abacavir is used to treat HIV, which causes the acquired immunodeficiency syndrome (AIDS). Abacavir is not a cure for HIV or AIDS.

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

Ziagen 250 mg

oblong, yellow, imprinted with GX623

What are the possible side effects of abacavir (Ziagen)?

Stop using abacavir and call your doctor at once if you have symptoms of an allergic reaction from two or more of these specific side effect groups:

  • Group 1 - fever;
  • Group 2 - rash;
  • Group 3 - nausea, vomiting, diarrhea, stomach pain;
  • Group 4 - general ill feeling, extreme tiredness, body aches;
  • Group 5 - shortness of breath, cough, sore throat.

Once you have had an allergic reaction to abacavir, you must never use it again. If you stop taking abacavir for any reason, talk to your doctor before you start taking the medication again.

Abacavir may cause lactic acidosis (a build-up of lactic acid in the body, which can be fatal). Lactic acidosis can start slowly and get worse over time. Get emergency medical help if you have even mild symptoms of lactic acidosis, such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired.

Abacavir can cause other serious side effects that may not be signs of an allergic reaction. Call your doctor at once if you have:

  • the first sign of any skin rash, no matter how mild;
  • signs of a new infection such as flu symptoms, chills, easy bruising or unusual bleeding, loss of appetite, mouth sores;
  • severe pain in your upper stomach spreading to your back;
  • itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
  • increased sweating, tremors in your hands, anxiety, feeling irritable, sleep problems (insomnia);
  • diarrhea, unexplained weight loss, menstrual changes, impotence, loss of interest in sex;
  • swelling in your neck or throat (enlarged thyroid);
  • weakness or prickly feeling in your fingers or toes;
  • problems with walking, breathing, speech, swallowing, or eye movement; or
  • severe lower back pain, loss of bladder or bowel control.

Less serious side effects may include:

  • strange dreams;
  • headache, ear pain;
  • cold symptoms such as stuffy nose, sneezing, sinus pain; or
  • changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and trunk).

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 Ziagen (abacavir sulfate) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about abacavir (Ziagen)?

Stop using abacavir and call your doctor at once if you have any of these signs of an allergic reaction: fever; rash; nausea, vomiting, diarrhea, stomach pain; general ill feeling, extreme tiredness, body aches; shortness of breath, cough, sore throat.

Once you have had an allergic reaction to abacavir, you must never use it again.

Read the Warning Card that comes with this medication, and carry it with you at all times so you will know the symptoms of allergic reaction to watch for.

Some people develop lactic acidosis while taking abacavir. Early symptoms may get worse over time and this condition can be fatal. Get emergency medical help if you have even mild symptoms such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired.

Abacavir can also cause severe or life-threatening effects on your liver. Call your doctor at once if you have any of these symptoms while taking abacavir: pain in your upper stomach, itching, loss of appetite, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes).

Do not allow this medicine to run out completely before you get your prescription refilled. It is important that you not stop taking abacavir once you have started. If you miss several doses in a row, you may have a dangerous or even fatal allergic reaction once you start taking abacavir again. If you stop taking abacavir for any reason, talk to your doctor before you start taking the medication again.

Side Effects Centers
  • Ziagen

Patient Detailed How Take

What should I discuss with my healthcare provider before taking abacavir (Ziagen)?

Do not take this medication if you have ever had an allergic reaction to any medicine that contains abacavir, including Ziagen, Epzicom, or Trizivir. Once you have had an allergic reaction to abacavir, you must never use it again.

Some people develop a life-threatening condition called lactic acidosis while taking abacavir. You may be more likely to develop lactic acidosis if you are overweight or have liver disease, if you are a woman, or if you have taken HIV or AIDS medications for a long time. Talk with your doctor about your individual risk.

Abacavir can also cause severe or life-threatening effects on your liver. You should not take abacavir if you have moderate or severe liver disease.

Do not take abacavir with any other medication that contains abacavir, such as Epzicom or Trizivir.

To make sure you can safely take abacavir, tell your doctor if you have any of these other conditions:

  • heart disease, high blood pressure;
  • liver disease;
  • a risk factor for heart disease such as smoking, diabetes, or high cholesterol; or
  • if you have used an HIV medication in the past, such as didanosine (Videx), emtricitabine (Atripla, Complera, Emtriva, Truvada), lamivudine (Combivir, Epivir, Epzicom, Trizivir), stavudine (Zerit), tenofovir (Viread), zalcitabine (Hivid), or zidovudine (Retrovir).

You may need a blood test before you start taking abacavir for the first time, or if you are restarting the medication after stopping for reasons not related to an allergic reaction.

FDA pregnancy category C. It is not known whether abacavir will harm an unborn baby. HIV can be passed to your baby if you are not properly treated during pregnancy. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Take all of your HIV medicines as directed to control your infection.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of abacavir on the baby.

Women with HIV or AIDS should not breast feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk.

How should I take abacavir (Ziagen)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Abacavir can be taken with or without food.

Measure liquid medicine with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Abacavir comes with a Medication Guide and a Warning Card that lists the symptoms of an allergic reaction. Read this information carefully and carry the Warning Card with you at all times so you will know what symptoms to watch for.

Use abacavir regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

HIV/AIDS is usually treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice. Every person with HIV or AIDS should remain under the care of a doctor.

To be sure this medicine is helping your condition and is not causing harmful effects, your blood will need to be tested often. Your liver function may also need to be tested. Visit your doctor regularly.

Store at room temperature away from moisture and heat.

You may store the oral solution (liquid) in the refrigerator but do not let it freeze.

Patient Detailed Avoid Taking

What happens if I miss a dose (Ziagen)?

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

Do not allow your medicine to run out completely before you get your prescription refilled. It is important that you not stop taking abacavir once you have started. If you miss several doses, you may have a dangerous or even fatal allergic reaction once you start taking this medication again.

What happens if I overdose (Ziagen)?

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

What should I avoid while taking abacavir (Ziagen)?

Avoid drinking alcohol. It may increase your risk of liver damage.

Taking this medication will not prevent you from passing HIV to other people. Avoid having unprotected sex or sharing razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

What other drugs will affect abacavir (Ziagen)?

Tell your doctor about all other medicines you use, especially methadone (Diskets, Dolophine, Methadose).

There may be other drugs that can interact with abacavir. 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 pharmacist can provide more information about abacavir.


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: 10.02. Revision date: 11/13/2012.

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