Abacavir Sulfate

Name: Abacavir Sulfate

Uses for Abacavir Sulfate

Treatment of HIV Infection

Treatment of HIV-1 infection in adults, adolescents, and pediatric patients ≥3 months of age;1 used in conjunction with other antiretrovirals.1 200 201

Single-entity abacavir used with another NRTI (dual NRTIs) in conjunction with an HIV integrase strand transfer inhibitor (INSTI), HIV nonnucleoside reverse transcriptase inhibitor (NNRTI), or HIV protease inhibitor (PI) in INSTI-, NNRTI-, or PI-based regimens.200 201 Also commercially available in fixed combinations containing abacavir and lamivudine with or without a third antiretroviral;228 229 240 these fixed combinations used in certain patient groups to decrease pill burden and improve compliance.200

For initial treatment in HIV-infected adults and adolescents, experts state that the dual NRTI option of abacavir and lamivudine is a recommended dual NRTI option for use in most INSTI-, NNRTI-, and PI-based regimens, but should be used only in patients who are HLA-B*5701 negative.200

For initial treatment in antiretroviral-naive pediatric patients, experts state that abacavir and lamivudine (or emtricitabine) is a preferred dual NRTI option and abacavir and zidovudine is an alternative dual NRTI option for use in PI-, NNRTI-, or INSTI-based regimens in children ≥3 months of age who are HLA-B*5701 negative.201

Abacavir/lamivudine fixed combination (Epzicom) can be used in adults and pediatric patients weighing ≥25 kg when dual NRTI option of abacavir and lamivudine is indicated;228 used in conjunction with antiretrovirals from another class (not another NRTI).228

Abacavir/dolutegravir/lamivudine fixed combination (Triumeq) can be used in adults;200 240 used alone as a complete treatment regimen or in conjunction with other antiretrovirals.200 240

Abacavir/lamivudine/zidovudine fixed combination (Trizivir) can be used in adults and adolescents weighing ≥ 40 kg;200 229 used alone as a complete treatment regimen or in conjunction with other antiretrovirals.200 229 Intended only for regimens that require all 3 drugs; data limited regarding use in patients with baseline viral loads >100,000 copies/mL.229

Triple NRTI regimen of abacavir, lamivudine, and zidovudine not recommended for initial treatment in antiretroviral-naive patients because of inferior antiretroviral activity.200 201

Triple NRTI regimen of abacavir, tenofovir disoproxil fumarate (tenofovir DF), and either lamivudine or emtricitabine not recommended at any time because of high rate of virologic failure.110 200 201

Do not use abacavir or fixed combinations containing abacavir in HLA-B*5701-positive individuals.1 200 201 228 229 240 (See Hypersensitivity Reactions under Cautions.)200

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)

Postexposure prophylaxis of HIV infection following occupational exposure† (PEP) in health-care personnel and others exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV.199

USPHS recommends 3-drug regimen of raltegravir in conjunction with emtricitabine and tenofovir DF as the preferred regimen for PEP following occupational exposures to HIV.199 Abacavir is one of several alternative agents that may be used in PEP regimens, but use only with expert consultation since HLA-B*5701 testing required and such testing may not be available or practical prior to initiating PEP.199

Management of occupational exposures to HIV is complex and evolving; consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) whenever possible.199 Do not delay initiation of PEP while waiting for expert consultation.199

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)

Antiretrovirals are used for postexposure prophylaxis of HIV infection following nonoccupational exposure† (nPEP) in individuals exposed to blood, genital secretions, or other potentially infectious body fluids that might contain HIV when the exposure represents a substantial risk for HIV transmission.198

When nPEP indicated in adults and adolescents ≥13 years of age with normal renal function, CDC states preferred regimen is either raltegravir or dolutegravir used in conjunction with emtricitabine and tenofovir DF (given as emtricitabine/tenofovir DF; Truvada);198 recommended alternative in these patients is ritonavir-boosted darunavir used in conjunction with emtricitabine/tenofovir DF.198

CDC states do not use abacavir in any nPEP regimens;198 need for prompt initiation of nPEP does not allow time for HLA-B*5701 screening.198

Consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or the National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) if nPEP indicated in certain exposed individuals (e.g., pregnant women, children, those with medical conditions such as renal impairment) or if considering a regimen not included in CDC guidelines, source virus is known or likely to be resistant to antiretrovirals, or healthcare provider is inexperienced in prescribing antiretrovirals.198 Do not delay initiation of nPEP while waiting for expert consultation.198

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Abacavir Sulfate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

20 mg (of abacavir) per mL*

Abacavir Sulfate Oral Solution

Ziagen

ViiV

Tablets, film-coated, scored

300 mg (of abacavir)*

Abacavir Sulfate Tablets

Ziagen

ViiV

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Abacavir Sulfate Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

300 mg (of abacavir) with Lamivudine 150 mg and Zidovudine 300 mg*

Abacavir Sulfate, Lamivudine, and Zidovudine Tablets

Trizivir

ViiV

600 mg (of abacavir) with Lamivudine 300 mg*

Abacavir Sulfate and Lamivudine Tablets

Epzicom

ViiV

600 mg (of abacavir) with Dolutegravir 50 mg and Lamivudine 300 mg

Triumeq

ViiV

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 per 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 Healthecare, Research Triangle Park, NC 27709. by: Research Triangle Park, NC 27709. Revised: Mar 2017

Side effects

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

  • Serious and sometimes fatal hypersensitivity reactions [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
  • Lactic acidosis and severe hepatomegaly with steatosis [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 In Adult Subjects

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 clinical practice.

Serious And Fatal Abacavir-Associated Hypersensitivity Reactions

In clinical trials, serious and sometimes fatal hypersensitivity reactions have occurred with abacavir [see BOXED WARNING, WARNINGS AND PRECAUTIONS]. These reactions have been characterized by 2 or more of the following signs or symptoms: (1) fever; (2) rash; (3) gastrointestinal symptoms (including nausea, vomiting, diarrhea, or abdominal pain); (4) constitutional symptoms (including generalized malaise, fatigue, or achiness); (5) respiratory symptoms (including dyspnea, cough, or pharyngitis). Almost all abacavir hypersensitivity reactions include fever and/or rash as part of the syndrome.

Other signs and symptoms have included lethargy, headache, myalgia, edema, arthralgia, and paresthesia. Anaphylaxis, liver failure, renal failure, hypotension, adult respiratory distress syndrome, respiratory failure, myolysis, and death have occurred in association with these hypersensitivity reactions. Physical findings have included lymphadenopathy, mucous membrane lesions (conjunctivitis and mouth ulcerations), and maculopapular or urticarial rash (although some patients had other types of rashes and others did not have a rash). There were reports of erythema multiforme. Laboratory abnormalities included elevated liver chemistries, elevated creatine phosphokinase, elevated creatinine, and lymphopenia, and abnormal chest x-ray findings (predominantly infiltrates, which were localized).

Additional Adverse Reactions With Use Of ZIAGEN

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, Greater than or Equal to 5% Frequency) in Therapy-Naive Adults (CNA30024a) through 48 Weeks of Treatment

Adverse Reaction ZIAGEN plus Lamivudine plus Efavirenz
(n = 324)
Zidovudine plusLamivudine 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%
a This 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.
b Ten (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, Greater than or Equal to 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 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/mm ) 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.

Clinical Trials Experience In Pediatric Subjects

Therapy-Experienced Pediatric Subjects (Twice-Daily Dosing)

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 per kg twice daily, lamivudine 4 mg per kg twice daily, and zidovudine 180 mg per m² twice daily compared with lamivudine 4 mg per kg twice daily and zidovudine 180 mg per 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, Greater than or Equal to 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.

Pediatric Subjects Once-Daily versus Twice-Daily Dosing (COL105677): The safety of once-daily compared with twice-daily dosing of ZIAGEN was assessed in the ARROW trial. Primary safety assessment in the ARROW trial was based on Grade 3 and Grade 4 adverse events. The frequency of Grade 3 and 4 adverse events was similar among subjects randomized to once-daily dosing compared with subjects randomized to twice-daily dosing. One event of Grade 4 hepatitis in the once-daily cohort was considered as uncertain causality by the investigator and all other Grade 3 or 4 adverse events were considered not related by the investigator.

Postmarketing Experience

The following adverse reactions have been identified during postmarketing use of ZIAGEN. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposures.

Body as a Whole

Redistribution/accumulation of body fat.

Cardiovascular

Myocardial infarction.

Hepatic

Lactic acidosis and hepatic steatosis [see WARNINGS AND PRECAUTIONS].

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 [see ADVERSE REACTIONS].

Clinical pharmacology

Mechanism Of Action

Abacavir is an antiretroviral agent [see Microbiology].

Pharmacokinetics

Pharmacokinetics In Adults

The pharmacokinetic properties of abacavir were independent of dose over the range of 300 to 1,200 mg per day.

Absorption and Bioavailability: Following oral administration, abacavir is rapidly absorbed and extensively distributed. The geometric mean absolute bioavailability of the tablet was 83%. Plasma abacavir AUC was similar following administration of the oral solution or tablets. 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 per mL (mean ± SD) and AUC(0-12 h) was 6.02 ± 1.73 mcg•hour per mL. After oral administration of a single dose of 600 mg of abacavir in 20 subjects, Cmax was 4.26 ± 1.19 mcg per mL (mean ± SD) and AUC∞ was 11.95 ± 2.51 mcg•hour per mL.

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

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

Metabolism and Elimination: 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 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 per hour per kg (mean ± SD).

Effects Of Food On Oral Absorption

Bioavailability of abacavir tablets was assessed in the fasting and fed states with no significant difference in systemic exposure (AUC∞); 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.

Specific 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 Class A). 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 [see CONTRAINDICATIONS, Use in Specific Populations].

Pregnancy: Abacavir: Abacavir pharmacokinetics were studied in 25 pregnant women during the last trimester of pregnancy receiving abacavir 300 mg twice daily. Abacavir exposure (AUC) during pregnancy was similar to those in postpartum and in HIV-infected non-pregnant historical controls. Consistent with passive diffusion of abacavir across the placenta, abacavir concentrations in neonatal plasma cord samples at birth were essentially equal to those in maternal plasma at delivery.

Pediatric Patients: The pharmacokinetics of abacavir have been studied after either single or repeat doses of ZIAGEN in 169 pediatric subjects. Subjects receiving abacavir oral solution according to the recommended dosage regimen achieved plasma concentrations of abacavir similar to adults. Subjects receiving abacavir oral tablets achieved higher plasma concentrations of abacavir than subjects receiving oral solution.

The pharmacokinetics of abacavir dosed once daily in HIV-1-infected pediatric subjects aged 3 months through 12 years was evaluated in 3 trials (PENTA 13 [n = 14], PENTA 15 [n = 18], and ARROW [n = 36]). All 3 trials were 2-period, crossover, open-label pharmacokinetic trials of twice- versus once-daily dosing of abacavir and lamivudine. For the oral solution as well as the tablet formulation, these 3 trials demonstrated that once-daily dosing provides comparable AUC0-24 to twice-daily dosing of abacavir at the same total daily dose. The mean Cmax was approximately 1.6- to 2.3-fold higher with abacavir once-daily dosing compared with twice-daily dosing.

Geriatric Patients: The pharmacokinetics of ZIAGEN have not been studied in subjects older than 65 years.

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 or clinically relevant racial differences between blacks and whites 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: Fifteen HIV-1-infected subjects were enrolled in a crossover-designed drug interaction 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: Abacavir has no effect on the pharmacokinetic properties of ethanol. Ethanol decreases the elimination of abacavir causing an increase in overall exposure. 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 per kg ethanol (equivalent to 5 alcoholic drinks), and abacavir 600 mg plus 0.7 g per kg ethanol. Coadministration of ethanol and abacavir resulted in a 41% increase in abacavir AUC∞ and a 26% increase in abacavir t½. 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 [see DRUG INTERACTIONS]. 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.

Antiviral Activity

The antiviral activity of abacavir against HIV-1 was assessed in a number of cell lines including primary monocytes/macrophages and peripheral blood mononuclear cells (PBMCs). EC50 values ranged from 3.7 to 5.8 microM (1 microM = 0.28 mcg per mL) and 0.07 to 1.0 microM against HIV-1IIIB and HIV-1BaL, respectively, and the mean EC50 value was 0.26 ± 0.18 microM against 8 clinical isolates. The median EC50 values of abacavir were 344 nM (range: 14.8 to 676 nM), 16.9 nM (range: 5.9 to 27.9 nM), 8.1 nM (range: 1.5 to 16.7 nM), 356 nM (range: 35.7 to 396 nM), 105 nM (range: 28.1 to 168 nM), 47.6 nM (range: 5.2 to 200 nM), 51.4 nM (range: 7.1 to 177 nM), and 282 nM (range: 22.4 to 598 nM) against HIV-1 clades A-G and group O viruses (n = 3 except n = 2 for clade B), respectively. The EC50 values against HIV-2 isolates (n = 4), ranged from 0.024 to 0.49 microM. 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 microM) used in the treatment of chronic HCV infection 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. 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 emerged in HIV-1 RT. M184V or I substitutions resulted in an approximately 2-fold decrease in susceptibility to abacavir. Substitutions K65R, L74M, or Y115F with M184V or I conferred a 7-to 8-fold reduction in abacavir susceptibility, and combinations of three substitutions were required to confer more than an 8-fold reduction in susceptibility.

Thirty-nine percent (7 of 18) of the isolates from subjects who experienced virologic failure in the abacavir once-daily arm had a greater than 2.5-fold mean decrease in abacavir susceptibility with a median-fold decrease of 1.3 (range: 0.5 to 11) compared with 29% (5 of 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, and tenofovir in cell culture and in subjects. An increasing number of thymidine analogue mutation substitutions (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 at a dose of 600 mg. The clinical relevance of this finding has not been determined.

Clinical Studies

Adult Trials

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%), white (51%), black (21%), and Hispanic (26%). The median age was 35 years; the median pretreatment CD4+ cell count was 264 cells per mm³, and median plasma HIV-1 RNA was 4.79 log10 copies per 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%
a Subjects achieved and maintained confirmed HIV-1 RNA less than or equal to 50 copies per mL (less than 400 copies per mL) through Week 48 (Roche AMPLICOR Ultrasensitive HIV-1 MONITOR® standard test 1.0 PCR).
b Includes viral rebound, insufficient viral response according to the investigator, and failure to achieve confirmed less than or equal to 50 copies per mL by Week 48.
c Includes 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 per mm³ in the group receiving ZIAGEN and 155 cells per 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 per mL and plasma HIV-1 RNA greater than 100,000 copies per mL. Trial participants were male (87%), white (73%), black (15%), and Hispanic (9%). At baseline the median age was 36 years; the median baseline CD4+ cell count was 360 cells per mm³, and median baseline plasma HIV-1 RNA was 4.8 log10 copies per mL. Proportions of subjects with plasma HIV-1 RNA less than 400 copies per 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%
a Subjects achieved and maintained confirmed HIV-1 RNA less than 400 copies per mL.
b Includes viral rebound and failure to achieve confirmed less than 400 copies per mL by Week 48.
c Includes 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 per mL, percentages of subjects with HIV-1 RNA levels less than 50 copies per 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 per mm³ was observed in both treatment arms. Through Week 48, 9 subjects (3.4%) in the group receiving abacavir (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%), white (54%), black (27%), and American Hispanic (15%). The median baseline CD4+ cell count was 262 cells per mm³ (range: 21 to 918 cells per mm³) and the median baseline plasma HIV-1 RNA was 4.89 log10 copies per mL (range: 2.60 to 6.99 log10 copies per 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%
a Subjects achieved and maintained confirmed HIV-1 RNA less than 50 copies per mL (less than 400 copies per mL) through Week 48 (Roche AMPLICOR Ultrasensitive HIV-1 MONITOR standard test version 1.0).
b Includes viral rebound, failure to achieve confirmed less than 50 copies per mL (less than 400 copies per mL) by Week 48, and insufficient viral load response.
c Includes 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 per mm³ in the group receiving abacavir 600 mg once daily and 200 cells per 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 per kg twice daily plus lamivudine 4 mg per kg twice daily plus zidovudine 180 mg per m² twice daily versus lamivudine 4 mg per kg twice daily plus zidovudine 180 mg per m² twice daily. Two hundred and five therapy-experienced pediatric subjects were enrolled: female (56%), white (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 per 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 per 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 per mL in the group receiving ZIAGEN plus lamivudine plus zidovudine compared with -0.21 log10 copies per mL in the group receiving lamivudine plus zidovudine. Median CD4+ cell count increases from baseline were 69 cells per mm³ in the group receiving ZIAGEN plus lamivudine plus zidovudine and 9 cells per mm³ in the group receiving lamivudine plus zidovudine.

Once-Daily Dosing

ARROW (COL105677) was a 5-year randomized, multicenter trial which evaluated multiple aspects of clinical management of HIV-1 infection in pediatric subjects. HIV-1-infected, treatment-naive subjects aged 3 months to 17 years were enrolled and treated with a first-line regimen containing ZIAGEN and lamivudine, dosed twice daily according to World Health Organization recommendations. After a minimum of 36 weeks of treatment, subjects were given the option to participate in Randomization 3 of the ARROW trial, comparing the safety and efficacy of once-daily dosing with twice-daily dosing of ZIAGEN and lamivudine, in combination with a third antiretroviral drug, for an additional 96 weeks. Of the 1,206 original ARROW subjects, 669 participated in Randomization 3. Virologic suppression was not a requirement for participation at baseline for Randomization 3 (following a minimum of 36 weeks of twice-daily treatment), 75% of subjects in the twice-daily cohort were virologically suppressed compared with 71% of subjects in the once-daily cohort.

The proportions of subjects with HIV-1 RNA less than 80 copies per mL through 96 weeks are shown in Table 11. The differences between virologic responses in the two treatment arms were comparable across baseline characteristics for gender and age.

Table 11: Virologic Outcome of Randomized Treatment at Week 96a (ARROW Randomization 3)

Outcome ZIAGEN plus Lamivudine Twice-Daily Dosing
(n = 333)
ZIAGEN plus Lamivudine Once-Daily Dosing
(n = 336)
HIV-1 RNA < 80 copies/mLb 70% 67%
HIV-1 RNA ≥ 80 copies/mLc 28% 31%
No virologic data
  Discontinued due to adverse event or death 1% < 1%
  Discontinued study for other reasonsd 0% < 1%
  Missing data during window but on study 1% 1%
a Analyses were based on the last observed viral load data within the Week 96 window.
b Predicted difference (95% CI) of response rate is -4.5% (-11% to 2%) at Week 96.
c Includes subjects who discontinued due to lack or loss of efficacy or for reasons other than an adverse event or death, and had a viral load value of greater than or equal to 80 copies per mL, or subjects who had a switch in background regimen that was not permitted by the protocol.
d Other includes reasons such as withdrew consent, loss to follow-up, etc. and the last available HIV-1 RNA less than 80 copies per mL (or missing).

Patient information

ZIAGEN®
(ZY-uh-jen)
(abacavir) Tablets

ZIAGEN®
(abacavir) Oral Solution

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

ZIAGEN can cause serious side effects, including:

  • Serious allergic reactions (hypersensitivity reaction) that can cause death have happened with ZIAGEN and other abacavir-containing products. 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) or any other abacavir-containing medicine (EPZICOM®, TRIUMEQ®, or TRIZIVIR®) again.

  • If you have an allergic reaction, dispose of any unused ZIAGEN. Ask your pharmacist how to properly dispose of medicines.
  • 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.

  • Build-up of acid in your blood (lactic acidosis). Lactic acidosis can happen in some people who take ZIAGEN. Lactic acidosis is a serious medical emergency that can cause death. Call your healthcare provider right away if you get any of the following symptoms that could be signs of lactic acidosis:
    • feel very weak or tired
    • unusual (not normal) muscle pain
    • trouble breathing
    • stomach pain with nausea and vomiting
    • feel cold, especially in your arms and legs
    • feel dizzy or light-headed
    • have a fast or irregular heartbeat
  • Serious liver problems can happen in people who take ZIAGEN. In some cases, these serious liver problems can lead to death. Your liver may become large (hepatomegaly) and you may develop fat in your liver (steatosis) when you take ZIAGEN. Call your healthcare provider right away if you have any of the following signs of liver problems:
    • your skin or the white part of your eyes turns yellow (jaundice)
    • dark or “tea-colored” urine
    • light-colored stools (bowel movements)
    • loss of appetite for several days or longer
    • nausea
    • pain, aching, or tenderness on the right side of your stomach area

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

What is ZIAGEN?

ZIAGEN is a prescription HIV-1 (Human Immunodeficiency Virus type 1) medicine used with other antiretroviral medicines to treat HIV-1 infection. HIV-1 is the virus that causes Acquired Immune Deficiency Syndrome (AIDS).

The safety and effectiveness of ZIAGEN has not been established in children under 3 months of age.

When used with other antiretroviral medicines to treat HIV-1 infection, ZIAGEN may help:

  • reduce the amount of HIV-1 in your blood. This is called “viral load”.
  • increase the number of CD4+ (T) cells in your blood, that help fight off other infections.

Reducing the amount of HIV-1 and increasing the CD4+ (T) cells in your blood may help improve your immune system. This may reduce your risk of death or getting infections that can happen when your immune system is weak (opportunistic infections).

ZIAGEN does not cure HIV-1 infection or AIDS. You must keep taking HIV-1 medicines to control HIV1 infection and decrease HIV-related illnesses.

Who should not take ZIAGEN?

Do not take ZIAGEN if you:

  • have a certain type of gene variation called the HLA-B*5701 allele. Your healthcare provider will test you for this before prescribing treatment with ZIAGEN.
  • 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 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 or have had liver problems, including hepatitis B or C virus infection.
  • have heart problems, smoke, or have diseases that increase your risk of heart disease such as high blood pressure, high cholesterol, or diabetes.
  • drink alcohol or take medicines that contain alcohol.
  • are pregnant or plan to become pregnant. Talk to your healthcare provider if you are pregnant or plan to become pregnant.
    Pregnancy Registry. There is a pregnancy registry for women who take antiretroviral medicines during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry.
  • are breastfeeding or plan to breastfeed. Do not breastfeed if you take ZIAGEN.
    • You should not breastfeed if you have HIV-1 because of the risk of passing HIV-1 to your baby.

Tell your healthcare provider about all the medicines you take, including prescription and over-thecounter medicines, vitamins, and herbal supplements.

Some medicines interact with ZIAGEN. Keep a list of your medicines to show your healthcare provider and pharmacist. You can ask your healthcare provider or pharmacist for a list of medicines that interact with ZIAGEN. Do not start taking a new medicine without telling your healthcare provider. Your healthcare provider can tell you if it is safe to take ZIAGEN with other medicines.

Tell your healthcare provider if you take:

  • any other medicine to treat HIV-1
  • methadone

How should I take ZIAGEN?

  • Take ZIAGEN exactly as your healthcare provider tells you.
  • Do not change your dose or stop taking ZIAGEN without talking with your healthcare provider. If you miss a dose of ZIAGEN, take it as soon as you remember. Do not take 2 doses at the same time. If you are not sure about your dosing, call your healthcare provider.
  • Stay under the care of a healthcare provider while taking ZIAGEN.
  • ZIAGEN may be taken with or without food.
  • For children aged 3 months and older, your healthcare provider will prescribe a dose of ZIAGEN based on your child's body weight.
  • Tell your healthcare provider if you or your child has trouble swallowing tablets. ZIAGEN comes as a tablet or as a liquid (oral solution).
  • Do not run out of ZIAGEN. The virus in your blood may increase and the virus may become harder to treat. When your supply starts to run out, get more from your healthcare provider or pharmacy.
  • If you take too much ZIAGEN, call your healthcare provider 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:
  • See “What is the most important information I should know about ZIAGEN?”
  • Changes in your immune system (Immune Reconstitution Syndrome) can happen when your start taking HIV-1 medicines. 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 right away if you start having new symptoms after you start taking ZIAGEN.
  • Changes in body fat can happen in people who take HIV-1 medicines. These changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the middle of your body (trunk). Loss of fat from the legs, arms, and face may also happen. The exact cause and long-term health effects of these conditions are not known.
  • Heart attack (myocardial infarction). Some HIV-1 medicines including ZIAGEN may increase your risk of heart attack.

The most common side effects of ZIAGEN in adults include:

  • nausea
  • headache
  • generally not feeling well
  • tiredness
  • vomiting
  • bad dreams or sleep problems

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 oral solution. You may store ZIAGEN oral solution in a refrigerator.

Keep ZIAGEN and all medicines out of the reach of children.

General information for safe and effective use of ZIAGEN

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.

If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for the information about ZIAGEN that is written for health professionals.

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

What are the ingredients in ZIAGEN?

Active ingredient: abacavir

Inactive ingredients:

Tablets:

Colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate

Tablet film-coating contains: hypromellose, polysorbate 80, synthetic yellow iron oxide, titanium dioxide, and triacetin.

Oral Solution:

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.

WARNING CARD

ZIAGEN®
(abacavir) Tablets and Oral Solution

Patients taking ZIAGEN may have a serious allergic reaction (hypersensitivity reaction) that can cause death. 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 this medicine.

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

Always carry this Warning Card with you to help recognize symptoms of this allergic reaction.

(Back of Card)

WARNING CARD

ZIAGEN® (abacavir) tablets and oral solution

If you must stop treatment with ZIAGEN because you have had an allergic reaction to abacavir, NEVER take ZIAGEN or another abacavir-containing medicine (EPZICOM®, TRIUMEQ®, or TRIZIVIR®) again. If you have an allergic reaction, dispose of any unused ZIAGEN. Ask your pharmacist how to properly dispose of medicines. If you take ZIAGEN or another 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.

Please read the Medication Guide for additional information on ZIAGEN.

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.

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.

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