Brand name: Ziagen
Drug class: HIV Nucleoside and Nucleotide Reverse Transcriptase Inhibitors

Medically reviewed by Drugs.com on Mar 10, 2024. Written by ASHP.

Introduction

Antiretroviral; HIV nucleoside reverse transcriptase inhibitor (NRTI).

Uses for Abacavir

Treatment of HIV Infection

Used in conjunction with other antiretroviral agents for treatment of HIV-1 infection in adults, adolescents, and pediatric patients ≥3 months of age.

Also used in conjunction with other antiretroviral agents for treatment of HIV infection in full-term infants from birth^{† [off-label]}.

Commercially available as a single entity preparation and in various fixed-combination preparations containing additional antiretroviral agents.

Commonly used as part of a dual-NRTI “backbone” of a fully suppressive antiretroviral regimen; consult guidelines for the most current information on recommended regimens. Selection of an initial antiretroviral regimen should be individualized based on factors such as virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug interaction potential, resistance test results, comorbid conditions, access, and cost.

Do notuse abacavir or fixed combinations containing abacavir in HLA-B*5701-positive individuals.

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)

Postexposure prophylaxis of HIV infection following occupational exposure^{† [off-label]} (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.

Recommended as an alternative agent for PEP only in consultation with an HIV expert in patients who are negative for HLA-B*5701. Not recommended for use as PEP following nonoccupational exposure to HIV due to time required for HLA-B*5701 testing.

Abacavir Dosage and Administration

General

Pretreatment Screening

• Screen all patients for HLA-B*5701 allele before abacavir or a fixed-combination preparation containing abacavir is initiated or reinitiated, unless there is documentation of previous HLA-B*5701 allele assessment. Contraindicated in HLA-B*5701-positive individuals.

Administration

Oral Administration

Administer orally once or twice daily without regard to meals.

If a dose is missed, administer the dose as soon as possible. Do not double the next dose or take more than the prescribed dose.

Use oral solution in pediatric patients or when solid oral dosage form is inappropriate. Use scored 300-mg tablets in adults, adolescents, and children weighing ≥14 kg who can reliably swallow tablets.

Commercially available as a single entity preparation and in the following fixed-combination tablets for oral use: abacavir and lamivudine (Epzicom); abacavir, lamivudine, and zidovudine (Trizivir); and abacavir, dolutegravir, and lamivudine (Triumeq and Triumeq PD). Exercise care to ensure that therapy is not duplicated if a fixed combination is used in conjunction with other antiretrovirals.

Dosage

Available as abacavir sulfate; dosage expressed in terms of abacavir.

Pediatric Patients

Treatment of HIV Infection

Oral

Abacavir oral solution in children and adolescents ≥3 months of age: 8 mg/kg (up to 300 mg) twice daily or 16 mg/kg (up to 600 mg) once daily.

Abacavir tablets in children weighing ≥14 kg able to swallow tablets: See Table 1 and Table 2.

Adults

Treatment of HIV Infection

Oral

300 mg twice daily or 600 mg once daily.

Postexposure Prophylaxis of HIV following Occupational Exposure (PEP)† [off-label]

Oral

600 mg once daily. Use in conjunction with other antiretrovirals.

Initiate PEP as soon as possible following occupational exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.

Special Populations

Hepatic Impairment

In adults with mild hepatic impairment (Child-Pugh class A): 200 mg twice daily (i.e., 10 mL of oral solution twice daily). Contraindicated in those with moderate or severe hepatic impairment.

Renal Impairment

No specific dosage recommendations for patients with impaired renal function.

Geriatric Patients

No specific dosage recommendations for geriatric patients. Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Cautions for Abacavir

Contraindications

• Presence of the human leukocyte antigen (HLA)-B*5701 allele.

• Moderate or severe hepatic impairment.

• History of hypersensitivity reaction to abacavir.

Warnings/Precautions

Warnings

Hypersensitivity Reactions

Serious, sometimes fatal, hypersensitivity reactions reported with abacavir or fixed combinations containing abacavir (abacavir/lamivudine, abacavir/dolutegravir/lamivudine, abacavir/lamivudine/zidovudine). (See Boxed Warning.) Patients carrying the HLA-B*5701 allele are at higher risk for abacavir hypersensitivity, although hypersensitivity reactions also reported in those who do not carry the allele. Abacavir and abacavir-containing preparations contraindicated in patients positive for HLA-B*5701 allele and in those with history of prior hypersensitivity reactions to abacavir.

Hypersensitivity manifestations usually involve signs or symptoms from ≥2 of the following: fever, rash, GI (e.g., nausea, vomiting, diarrhea, abdominal pain), constitutional (e.g., generalized malaise, fatigue, achiness), and respiratory (e.g., pharyngitis, dyspnea, cough). Lethargy, myalgia, chills, myolysis, headache, arthralgia, edema, tachycardia, abnormal chest radiographs (predominantly infiltrates, which may be localized), paresthesia, lymphadenopathy, and mucous membrane lesions (e.g., conjunctivitis, mouth ulceration) also may occur. Usually apparent within first 6 weeks of abacavir therapy (median time to onset is 9 days), but may occur at any time.

Screen all patients for HLA-B*5701 allele prior to initiating or reinitiating abacavir or fixed combinations containing abacavir.

Immediately discontinue abacavir or abacavir-containing preparations as soon as a hypersensitivity reaction is first suspected. Monitor clinical status, including liver function tests, and initiate appropriate therapy. Never reinitiate abacavir or abacavir-containing preparations following a hypersensitivity reaction, regardless of HLA-B*5701 allele status and even when other diagnoses are possible. Severe or fatal hypersensitivity reactions can occur within hours after reintroduction of the drug in patients with no identified history of abacavir hypersensitivity or with unrecognized manifestations of hypersensitivity to the drug.

Stevens-Johnson syndrome and toxic epidermal necrolysis reported during postmarketing experience in patients receiving abacavir concomitantly with other drugs known to be associated with these severe adverse effects. In such cases, discontinue abacavir and do not reinitiate the drug because the patient may have multiple drug sensitivities. Manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis are similar to those of abacavir hypersensitivity. Erythema multiforme also reported with abacavir.

Other Warnings and Precautions

Hepatic Effects and Lactic Acidosis

Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving HIV NRTIs (including abacavir) alone or in conjunction with other antiretrovirals. Female sex and obesity may be risk factors for development of lactic acidosis and severe hepatomegaly with steatosis.

Suspend treatment if there are clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (e.g., hepatomegaly and steatosis even in the absence of markedly increased serum aminotransferase concentrations).

Myocardial Infarction

MI reported in some patients receiving abacavir.

Based on totality of data, evidence to support a causal relationship to abacavir inconclusive. To date, there is no established biological mechanism to explain a potential increase in risk of MI.

Consider patient’s underlying risk of CHD and minimize any modifiable risk factors (e.g., hypertension, hyperlipidemia, diabetes mellitus, smoking).

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii]); this may necessitate further evaluation and treatment.

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) also reported in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy.

Specific Populations

Pregnancy

Antiretroviral Pregnancy Registry at 800-258-4263.

Data from the Antiretroviral Pregnancy Registry show no difference in the risk of overall major birth defects for abacavir compared with background rate for major birth defects.

Abacavir crosses placenta and is distributed into cord blood. Concentrations in neonatal plasma at birth essentially equal to those in maternal plasma at delivery. In animal reproductive studies, developmental toxicities and fetal malformations reported at exposures 35 times usual human exposure. No developmental effects observed at exposures 3.5 times usual human exposure.

Lactation

Distributed into human milk. Effects on the breastfed infant or on milk production not known.

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.

Females and Males of Reproductive Potential

No evidence of adverse effects on fertility in animal studies.

Pediatric Use

Safety and efficacy not established in neonates and infants <3 months of age. Adverse effects in children similar to those reported in adults (e.g., hypersensitivity reactions, GI effects).

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults. Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Hepatic Impairment

Dosage adjustment necessary in adults with mild hepatic impairment. Contraindicated in those with moderate or severe hepatic impairment.

Renal Impairment

Pharmacokinetics not fully determined in patients with impaired renal function; renal excretion of unchanged abacavir only a minor route of elimination.

Common Adverse Effects

Adverse effects of at least moderate intensity (≥10%) in adults: nausea, headache, fatigue and malaise, nausea and vomiting, dreams/sleep disorders.

Adverse effects of at least moderate intensity (≥5%) in pediatric patients: fever and/or chills, nausea and vomiting, skin rash, ear, nose, and throat infections.

Drug Interactions

Potential to inhibit CYP1A1 and CYP3A4. Does not induce nor inhibit CYP2C9 or CYP2D6. Not expected to affect substrates of organic anion transporter polypeptide (OATP)1B1 or OATP1B3, breast cancer resistance protein (BCRP), P-glycoprotein (P-gp), organic cation transporter (OCT)1, OCT2, or multidrug and toxic extrusion protein (MATE)1 and MATE2-K.

Substrate of BCRP and P-gp; however, concomitant use of modulators of these transporters not expected to have clinically relevant effects. In vitro, not a substrate of OATP1B1, OAP1B3, OCT1, OCT2, OAT1, MATE1, MATE2-K, or multidrug resistance-associated protein (MRP)2, or MRP4; therefore, concomitant use of agents that modulate these transporters not expected to affect abacavir concentrations.

The following drug interactions are based on studies using abacavir. Additional drug interactions may exist for fixed-dose combinations containing abacavir and lamivudine (Epzicom); abacavir, lamivudine, and zidovudine (Trizivir); and abacavir, dolutegravir, and lamivudine (Triumeq and Triumeq PD). See full prescribing information for these combination products.

Specific Drugs

Abacavir Pharmacokinetics

Absorption

Bioavailability

Mean absolute oral bioavailability of abacavir is 83%. Rapidly absorbed following oral administration.

Commercially available abacavir tablets and oral solution are interchangeable.

Food

Food does not have a clinically important effect on abacavir bioavailability.

Special Populations

Pediatric patients: Plasma concentrations attained with abacavir oral solution are similar to those observed in adults; plasma concentrations attained with abacavir oral tablets are higher than those observed in pediatric patients receiving the oral solution.

HIV-1-infected pediatric patients 3 months to 12 years of age: AUC of abacavir reported with once-daily regimen of oral solution or tablets is comparable to AUC of abacavir reported with twice-daily regimen of oral solution or tablets. Mean peak plasma concentrations 1.6- to 2.3-fold higher when abacavir is administered once daily compared with administration twice daily.

Mild hepatic impairment (Child-Pugh class A): AUC of abacavir is 89% higher than in those with normal hepatic function.

Distribution

Extent

Abacavir is extensively distributed following oral administration.

Distributed into CSF.

Crosses human placenta. Concentrations in cord blood at time of delivery generally similar to maternal serum concentrations.

Distributed into human milk.

Plasma Protein Binding

50% bound to plasma proteins; binding independent of drug concentrations.

Elimination

Metabolism

Abacavir is metabolized in the liver by alcohol dehydrogenase and glucuronyltransferase to inactive metabolites.

Intracellularly, abacavir is phosphorylated and then converted to the active carbovir triphosphate by cellular kinases. Intracellular (host cell) conversion to carbovir triphosphate is necessary for the antiviral activity of the drug.

Elimination Route

82.2% of abacavir oral dose excreted in urine; 16% excreted in feces.

Half-life

About 1.5 hours.

Special Populations

Half-life of abacavir increased 58% in patients with mild hepatic impairment (Child-Pugh class A).

Stability

Storage

Oral

Solution

20–25°C. May be refrigerated; do not freeze.

Tablets

20–25°C.

Actions and Spectrum

• Abacavir is a carbocyclic NRTI.

• Pharmacologically related to, but structurally different from, other NRTIs (e.g., didanosine, emtricitabine, lamivudine, zidovudine); also differs pharmacologically and structurally from other currently available antiretrovirals.

• A prodrug that is inactive until converted intracellularly to carbovir triphosphate.

• Active in vitro against HIV-1 and HIV-2. Has some in vitro activity against HBV and cytomegalovirus (CMV), but is inactive against other human viruses tested, including herpes simplex virus (HSV) types 1 and 2, varicella-zoster virus, and influenza virus type A.

• Inhibits replication of HIV by interfering with viral RNA-directed DNA polymerase (reverse transcriptase).

• HIV-1 with reduced susceptibility to abacavir have been produced in vitro and has emerged during therapy with the drug.

• Abacavir-resistant HIV may be cross-resistant to some other NRTIs (e.g., didanosine, emtricitabine, lamivudine, tenofovir). HIV isolates highly resistant to multiple NRTIs also have reduced susceptibility to abacavir.

Advice to Patients

• A medication guide and warning card must be provided to the patient each time abacavir or fixed combination containing abacavir is dispensed. The medication guide and warning card include information on symptoms of abacavir hypersensitivity reactions.

• Advise patients to read the medication guide and warning card prior to initiating therapy and each time a prescription is refilled; advise patients to carry the warning card on their person.

• Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician. Importance of taking abacavir as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.

• Advise patients that if they miss a dose of abacavir to take the dose as soon as they remember, and to not double their next dose.

• Possibility of potentially fatal hypersensitivity reactions to abacavir. Discontinue the drug and consult clinician immediately if signs or symptoms of hypersensitivity, including fever, rash, GI symptoms (nausea, vomiting, diarrhea, abdominal pain), constitutional symptoms (generalized fatigue, malaise, achiness), or respiratory symptoms (sore throat, shortness of breath, cough) occur while receiving abacavir or abacavir-containing preparations.

• Do not restart abacavir or abacavir-containing preparations after a hypersensitivity reaction since more severe symptoms may recur within hours, which may include life-threatening hypotension and death.

• Advise patients that if abacavir therapy is interrupted for reasons other than hypersensitivity (e.g., interruption in drug supply), it should not be reinitiated without consulting a clinician since a severe or fatal hypersensitivity reaction can occur when the drug is reintroduced. Reinitiate the drug under such circumstances only if medical care is readily available.

• Advise patients to dispose of unused abacavir after a hypersensitivity reaction occurs to avoid accidentally restarting the medication.

• Advise patients that lactic acidosis and severe hepatomegaly have been reported. Advise patients to stop taking abacavir if symptoms of lactic acidosis or significant hepatotoxicity occur (e.g., yellowing of skin or eyes, nausea, dark urine, light-colored stool).

• Advise patients to report signs and symptoms of infection as inflammation from a previous infection may occur after starting combination antiretroviral therapy including abacavir.

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, and any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise HIV-infected women not to breast-feed.

• Advise patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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

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