Abacavir

Class: HIV Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
- Reverse Transcriptase Inhibitors
VA Class: AM800
Chemical Name: (1S-cis)-4-[2-Amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol sulfate (salt) (2:1)
Molecular Formula: C₁₄H₁₈N₆O)₂ • H₂SO₄
CAS Number: 188062-50-2
Brands: Triumeq (combination), Ziagen

Abacavir Sulfate is also contained as an ingredient in the following combinations:
Abacavir Sulfate and Lamivudine
Abacavir Sulfate, Lamivudine, and Zidovudine

Medically reviewed by Drugs.com. Last updated on April 21, 2020.

• Overview
• Side Effects
• Dosage
• Professional
• Interactions
• More

Introduction

Antiretroviral; HIV nucleoside reverse transcriptase inhibitor (NRTI).^{1 2 3 46 200}

Uses for Abacavir

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

Abacavir Dosage and Administration

General

Screen all patients for HLA-B*5701 allele before initiating or reinitiating abacavir or fixed combination containing abacavir.^{1 200 201 228 229 240} Abacavir and abacavir-containing preparations contraindicated in HLA-B*5701-positive individuals.^{1 200 201 228 229 240} (See Hypersensitivity Reactions under Cautions.)

Administration

Oral Administration

Abacavir (Ziagen): Administer orally once or twice daily without regard to meals.¹ Use oral solution in pediatric patients or when solid oral dosage form is inappropriate.¹ Use scored 300-mg tablets in adults, adolescents, and children weighing ≥14 kg who can reliably swallow tablets.¹ Use in conjunction with other antiretrovirals for treatment of HIV-1.¹

Abacavir/lamivudine (Epzicom): Administer orally once daily without regard to meals.²²⁸ Use in conjunction with other antiretrovirals for treatment of HIV-1.²²⁸

Abacavir/dolutegravir/lamivudine (Triumeq): Administer orally once daily without regard to meals.²⁴⁰ Use alone as a complete treatment regimen or in conjunction with other antiretrovirals for treatment of HIV-1.²⁴⁰

Abacavir/lamivudine/zidovudine (Trizivir): Administer orally twice daily without regard to meals.²²⁹ Use alone as a complete treatment regimen or in conjunction with other antiretrovirals for treatment of HIV-1.²²⁹

Do not use abacavir, abacavir/lamivudine, abacavir/dolutegravir/lamivudine, abacavir/lamivudine/zidovudine concomitantly with any other abacavir-containing preparation.^{1 228 229 240}

Because antiretrovirals in the fixed combinations also are available in single-entity or other fixed-combination preparations, take care to ensure that therapy is not duplicated when a fixed combination is used in conjunction with other antiretrovirals.^{228 229 240} (See Precautions Related to Use of Fixed Combinations under Cautions.)

Dosage

Available as abacavir sulfate;¹ dosage expressed in terms of abacavir.¹

Pediatric Patients

Treatment of HIV Infection

Oral

Abacavir (Ziagen 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. ^{1 201} When oral solution used for initial therapy, experts recommend twice-daily regimen initially;²⁰¹ then, based on response, consider switching to once-daily regimen after approximately 24 weeks of therapy.²⁰¹

Abacavir (Ziagen tablets) in children weighing ≥14 kg able to swallow tablets: See Table 1 and Table 2.¹ Although once- or twice-daily regimen can be used, experts recommend once-daily regimen.²⁰¹

Abacavir/lamivudine (Epzicom) in children and adolescents weighing ≥25 kg: 1 tablet (abacavir 600 mg and lamivudine 300 mg) once daily.²²⁸

Abacavir/lamivudine/zidovudine (Trizivir) in pediatric patients weighing ≥40 kg: 1 tablet (abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg) twice daily.^{200 229}

Adults

Treatment of HIV Infection

Oral

Abacavir (Ziagen): 300 mg twice daily or 600 mg once daily.¹

Abacavir/lamivudine (Epzicom): 1 tablet (abacavir 600 mg and lamivudine 300 mg) once daily.²²⁸

Abacavir/dolutegravir/lamivudine (Triumeq): 1 tablet (600 mg of abacavir, 50 mg of dolutegravir, and 300 mg of lamivudine) once daily.²⁴⁰

Abacavir/lamivudine/zidovudine (Trizivir): 1 tablet (abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg) twice daily.²²⁹

Postexposure Prophylaxis of HIV following Occupational Exposure (PEP)†

Oral

Abacavir (Ziagen): 600 mg once daily.¹⁹⁹ Use in conjunction with other antiretrovirals (see Postexposure Prophylaxis following Occupational Exposure to HIV under Uses).¹⁹⁹

Initiate PEP as soon as possible following occupational exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.¹⁹⁹

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection

Oral

Abacavir (Ziagen) in children ≥3 months of age: Maximum 300 mg twice daily or 600 mg once daily.¹

Special Populations

Hepatic Impairment

Treatment of HIV Infection

Oral

Abacavir (Ziagen) in adults with mild hepatic impairment (Child-Pugh score 5–6): 200 mg twice daily (i.e., 10 mL of oral solution twice daily).¹ Contraindicated in those with moderate or severe hepatic impairment.¹

Abacavir/lamivudine, abacavir/dolutegravir/lamivudine, abacavir/lamivudine/zidovudine: Not recommended in patients with mild hepatic impairment.^{228 229 240} Contraindicated in those with moderate or severe hepatic impairment.^{228 229 240}

Renal Impairment

Treatment of HIV Infection

Abacavir (Ziagen): Dosage recommendations not available for patients with impaired renal function.^{1 45 46} Some experts state dosage adjustments not needed.²⁰⁰

Abacavir/lamivudine, abacavir/dolutegravir/lamivudine, abacavir/lamivudine/zidovudine: Not recommended in patients with Cl_cr <50 mL/minute.^{228 229 240}

Geriatric Patients

Abacavir (Ziagen): Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹

Abacavir/lamivudine, abacavir/dolutegravir/lamivudine, abacavir/lamivudine/zidovudine: Use with caution.^{228 229 240} (See Geriatric Use under Cautions.)

Cautions for Abacavir

Contraindications

• Abacavir, abacavir/lamivudine, abacavir/dolutegravir/lamivudine, abacavir/lamivudine/zidovudine: HLA-B*5701-positive patients.^{1 228 229 240} (See Hypersensitivity Reactions under Cautions.)

• Abacavir, abacavir/lamivudine, abacavir/dolutegravir/lamivudine, abacavir/lamivudine/zidovudine: Previous hypersensitivity reaction to abacavir or any ingredient in the formulation.^{1 228 229 240} (See Hypersensitivity Reactions under Cautions.)

• Abacavir, abacavir/lamivudine, abacavir/dolutegravir/lamivudine, abacavir/lamivudine/zidovudine: Moderate or severe hepatic impairment.^{1 228 229 240}

• Abacavir/dolutegravir/lamivudine: Concomitant use with dofetilide.²⁴⁰

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).^{1 228 229 240}

Hypersensitivity manifestations usually involve ≥2 of the following groups: fever, rash, GI (e.g., nausea, vomiting, diarrhea, abdominal pain), constitutional (e.g., generalized malaise, fatigue, achiness), and respiratory (e.g., pharyngitis, dyspnea, cough).^{1 47 228 229 240} 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.^{1 47 228 229 240}

Usually apparent within first 6 weeks of abacavir therapy (median time to onset is 9 days), but may occur at any time during therapy.^{1 50 228 229 240} Incidence may be greater in those receiving once-daily abacavir than in those receiving twice-daily abacavir.^{1 80 81}

Patients carrying the HLA-B*5701 allele are at higher risk for abacavir hypersensitivity,^{1 71 85 86 87 89 228 229 240} although hypersensitivity reactions also reported in those who do not carry the HLA-B*5701 allele.^{1 228 229 240} Negative result on HLA-B*5701 testing does not absolutely rule out possibility of some form of hypersensitivity reaction.^{71 86 87 90 98}

Screen all patients for HLA-B*5701 allele prior to initiating or reinitiating abacavir or fixed combination containing abacavir.^{1 200 201 228 229 240}

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.^{1 200 201 228 229 240}

Immediately discontinue abacavir or abacavir-containing preparation as soon as a hypersensitivity reaction is first suspected.^{1 228 229 240} Monitor clinical status, including liver function tests, and initiate appropriate therapy.^{1 228 229 240} Never reinitiate abacavir or abacavir-containing preparation following a hypersensitivity reaction, regardless of HLA-B*5701 allele status and even when other diagnoses are possible (e.g., acute-onset respiratory disease, gastroenteritis, reactions to other drugs).^{1 228 229 240} If hypersensitivity is ruled out, manufacturer states abacavir or other abacavir-containing preparation may be reinitiated, but only if medical care is readily accessible.^{1 228 229 240} 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.^{1 65 69 228 229 240}

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.^{1 228 229 240} In such cases, discontinue abacavir and do not reinitiate the drug because patient may have multiple drug sensitivities.^{1 228 229 240} Manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis are similar to those of abacavir hypersensitivity.^{1 228 229 240} Erythema multiforme also reported with abacavir.^{1 228 229 240}

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving HIV NRTIs (including abacavir) alone or in conjunction with other antiretrovirals.^{1 228 229 240} Reported most frequently in women; obesity and long-term NRTI therapy also may be risk factors.¹ Has been reported in patients with no known risk factors.¹

Use particular caution in patients with known risk factors for liver disease.¹

Discontinue abacavir or abacavir-containing preparation 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).^{1 228 229 240}

Other Warnings and Precautions

Cardiovascular Effects

MI reported in some patients receiving abacavir.¹

In response to conflicting data regarding a possible association between abacavir and MI,^{1 102 106 108 228 229 240} FDA conducted a meta-analysis of 26 randomized clinical trials that evaluated use of abacavir in adults.^{107 109} This meta-analysis did not identify an increased risk of MI in patients receiving abacavir.^{1 107 109 228 229 240} FDA recommends that clinicians continue to prescribe abacavir according to approved labeling^{1 107} and that patients not discontinue abacavir without consulting their clinician.¹⁰⁷

As a precaution in patients receiving antiretroviral therapy (including abacavir), consider patient’s underlying risk of CHD and minimize any modifiable risk factors (e.g., hypertension, hyperlipidemia, diabetes mellitus, smoking).^{1 228 229 240}

Precautions Related to Use of Fixed Combinations

Abacavir/lamivudine, abacavir/dolutegravir/lamivudine, abacavir/lamivudine/zidovudine: Consider cautions, precautions, contraindications, and drug interactions associated with each drug in the fixed combination.^{228 229 240} Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) for each drug.^{228 229 240}

Because the antiretrovirals contained in abacavir/lamivudine, abacavir/dolutegravir/lamivudine, and abacavir/lamivudine/zidovudine also are available in single-entity or other fixed-combination preparations, take care to ensure that therapy not duplicated when a fixed combination is used in conjunction with other antiretrovirals.^{228 229 240}

Do not use multiple abacavir-containing preparations concomitantly.^{1 228 229 240}

Do not use abacavir/lamivudine concomitantly with any preparation containing abacavir or lamivudine.²²⁸ In addition, do not use concomitantly with any preparation containing emtricitabine.²²⁸

Do not use abacavir/dolutegravir/lamivudine concomitantly with any preparation containing abacavir or lamivudine.²⁴⁰ In addition, do not use concomitantly with any preparation containing emtricitabine.²⁴⁰

Do not use abacavir/lamivudine/zidovudine concomitantly with any preparation containing abacavir, lamivudine, or zidovudine.²²⁹ In addition, do not use concomitantly with any preparation containing emtricitabine.²²⁹

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance.^{1 228 229 240}

Mechanisms and long-term consequences of adipogenic effects unknown;^{1 228 229 240} causal relationship not established.^{1 228 229 240}

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.^{1 228 229 240}

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.^{1 228 229 240}

Specific Populations

Pregnancy

Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].^{1 202 228 229 240}

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.^{1 202 228}

Experts state that abacavir and lamivudine is a preferred dual NRTI option for initial antiretroviral regimens in antiretroviral-naive pregnant women, but use only in those negative for HLA-B*5701.²⁰²

A triple NRTI regimen of abacavir, lamivudine, and zidovudine not recommended for initial treatment in antiretroviral-naive pregnant women because of inferior virologic efficacy.²⁰²

Lactation

Abacavir distributed into human milk and has been detected in plasma of at least 1 breast-feeding child.²⁰² (See Distribution under Pharmacokinetics.)

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.^{1 202}

Pediatric Use

Abacavir (Ziagen): Safety and efficacy not established in neonates and infants <3 months of age.¹ Adverse effects reported in children similar to those reported in adults (e.g., hypersensitivity reactions, GI effects).^{1 6 23 34}

Abacavir/lamivudine (Epzicom): Do not use in pediatric patients weighing <25 kg.²²⁸

Abacavir/lamivudine/zidovudine (Trizivir): Do not use in pediatric patients or in adolescents weighing <40 kg.²²⁹

Abacavir/dolutegravir/lamivudine (Triumeq): Safety and efficacy not established in pediatric patients <18 years of age.²⁴⁰

Geriatric Use

Abacavir (Ziagen): Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.¹ Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.^{1 228 229 240}

Abacavir/lamivudine, abacavir/dolutegravir/lamivudine, abacavir/lamivudine/zidovudine: Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.^{228 229 240} Use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.^{228 229 240}

Hepatic Impairment

Abacavir (Ziagen): Use with caution in those with known risk factors for liver disease.¹ Dosage adjustment necessary in adults with mild hepatic impairment.¹ (See Hepatic Impairment under Dosage and Administration.) Contraindicated in those with moderate or severe hepatic impairment.¹

Abacavir/lamivudine, abacavir/dolutegravir/lamivudine, abacavir/lamivudine/zidovudine: Not recommended in patients with mild hepatic impairment.^{228 229 240} Contraindicated in patients with moderate or severe hepatic impairment.^{228 229 240}

Renal Impairment

Abacavir (Ziagen): Pharmacokinetics not fully determined in patients with impaired renal function;¹ renal excretion of unchanged abacavir only a minor route of elimination.¹

Abacavir/lamivudine, abacavir/dolutegravir/lamivudine, abacavir/lamivudine/zidovudine: Do not use in patients with Cl_cr <50 mL/minute.^{228 229 240}

Common Adverse Effects

Hypersensitivity reactions, GI effects (nausea, vomiting, diarrhea, anorexia), insomnia, fever and/or chills, headache, malaise, fatigue.¹

Interactions for Abacavir

Abacavir not metabolized by CYP isoenzymes¹ and does not inhibit CYP3A4, 2C9, or 2D6.¹ Interactions with drugs metabolized by these CYP isoenzymes unlikely.¹

The following drug interactions are based on studies using abacavir.¹ Drug interaction studies not performed using abacavir/lamivudine, abacavir/dolutegravir/lamivudine, or abacavir/lamivudine/zidovudine.^{228 229 240} When fixed combinations used, consider interactions associated with each drug in the fixed combination.^{228 229 240}

Specific Drugs

Abacavir Pharmacokinetics

Absorption

Bioavailability

Mean absolute oral bioavailability of abacavir is 83%.^{1 46} Rapidly absorbed following oral administration.^{1 2 6 19 23 43}

Commercially available abacavir tablets and oral solution are bioequivalent.⁴⁶

Fixed-combination tablet containing abacavir 600 mg and lamivudine 300 mg (abacavir/lamivudine; Epzicom) is bioequivalent to two 300-mg tablets of abacavir and two 150-mg tablets of lamivudine given simultaneously.²²⁸

Fixed-combination tablet containing abacavir 600 mg, dolutegravir 50 mg, and lamivudine 300 mg (abacavir/dolutegravir/lamivudine; Triumeq) is bioequivalent to a 50-mg tablet of dolutegravir administered simultaneously with a fixed-combination tablet containing 600 mg of abacavir and 300 mg of lamivudine.²⁴⁰

Fixed-combination tablet containing abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg (abacavir/lamivudine/zidovudine; Trizivir) is bioequivalent to a 300-mg abacavir tablet, 150-mg lamivudine tablet, and 300-mg zidovudine tablet given simultaneously.^{229 68}

Food

Food does not have a clinically important effect on abacavir bioavailability.^{1 46 68}

Abacavir/lamivudine, abacavir/lamivudine/zidovudine: Food does not affect AUC of abacavir, lamivudine, or zidovudine when the drugs are given as fixed combinations.^{68 228 229}

Abacavir/dolutegravir/lamivudine: Administration with high-fat meal increases dolutegravir peak plasma concentrations and AUC by 37 and 48%, respectively, compared with administration in fasting state;²⁴⁰ abacavir peak plasma concentrations decreased by 23%;²⁴⁰ lamivudine exposures not affected.²⁴⁰

Special Populations

Pediatric patients: Plasma concentrations attained with abacavir oral solution are similar to those observed in adults;¹ plasma concentrations attained with abacavir oral tablets are higher than those observed in pediatric patients receiving the oral solution.¹

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.¹ Mean peak plasma concentrations 1.6- to 2.3-fold higher when abacavir is administered once daily compared with administration twice daily.¹

Mild hepatic impairment (Child-Pugh score 5–6): AUC of abacavir is 89% higher than in those with normal hepatic function.¹

Pregnant women: Pharmacokinetics similar to that in nonpregnant women;²⁰² AUC in pregnant women similar to that reported in women 6–12 weeks postpartum and in nonpregnant individuals.²⁰²

Distribution

Extent

Abacavir is extensively distributed following oral administration.¹

Abacavir is distributed into CSF following oral administration.^{1 6 20 46 62 84}

Abacavir crosses human placenta.^{82 83} Concentrations in cord blood at time of delivery generally similar to maternal serum concentrations.⁸²

Abacavir is distributed into human milk.²⁰² In a study in 15 women receiving abacavir at 1 month postpartum, milk-to-plasma ratio was 0.85 and the drug was detected in the plasma of at least 1 breast-feeding child.²⁰²

Plasma Protein Binding

Abacavir is 50% bound to plasma proteins; binding independent of drug concentrations.¹

Elimination

Metabolism

Abacavir is metabolized in the liver by alcohol dehydrogenase and glucuronyltransferase to inactive metabolites.¹

Intracellularly, abacavir is phosphorylated and then converted to the active carbovir triphosphate by cellular kinases.^{1 3 6} Intracellular (host cell) conversion to carbovir triphosphate is necessary for the antiviral activity of the drug.^{1 2 3 4 6 7 8 9}

Elimination Route

82.2% of abacavir oral dose excreted in urine; 16% excreted in feces.^{1 46}

Half-life

About 1.5 hours.^{1 6 7 46}

Special Populations

Half-life of abacavir increased 58% in patients with mild hepatic impairment (Child-Pugh score 5–6).¹

Half-life was 1.33 hours in 1 patient with renal failure (GFR <10 mL/minute) undergoing peritoneal dialysis.¹⁸

Stability

Storage

Oral

Solution

Abacavir (Ziagen): 20–25°C.¹ May be refrigerated;¹ do not freeze.¹

Tablets

Abacavir (Ziagen): 20–25°C.¹

Abacavir/lamivudine (Epzicom): 25°C (may be exposed to 15–30°C).²²⁸

Abacavir/dolutegravir/lamivudine (Triumeq): 25°C (may be exposed to 15–30°C).²⁴⁰ Store and dispense in original package;²⁴⁰ do not remove desiccant;²⁴⁰ protect from moisture.²⁴⁰

Abacavir/lamivudine/zidovudine (Trizivir): 25°C (may be exposed to 15–30°C).²²⁹

Actions and Spectrum

• Abacavir is a carbocyclic NRTI.^{1 2 3 4 46}

• Pharmacologically related to, but structurally different from, other NRTIs (e.g., didanosine, emtricitabine, lamivudine, stavudine, zidovudine); also differs pharmacologically and structurally from other currently available antiretrovirals.^{1 200}

• A prodrug that is inactive until converted intracellularly to carbovir triphosphate.^{1 2 3 4}

• Active in vitro against HIV-1 and HIV-2.^{1 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.²

• Inhibits replication of HIV by interfering with viral RNA-directed DNA polymerase (reverse transcriptase).¹

• HIV-1 with reduced susceptibility to abacavir have been produced in vitro^{1 2 4 6} and have emerged during therapy with the drug.^{1 2 6 16 60 61}

• Abacavir-resistant HIV may be cross-resistant to some other NRTIs (e.g., didanosine, emtricitabine, lamivudine, stavudine, tenofovir).^{1 4 6 16 49} HIV isolates highly resistant to multiple NRTIs also have reduced susceptibility to abacavir.^{6 16}

Advice to Patients

• Medication guide and warning card must be provided to the patient each time abacavir or fixed combination containing abacavir is dispensed.^{1 228 229 240} Medication guide and warning card include information on symptoms of abacavir hypersensitivity reactions.^{1 228 229 240}

• Importance of patient reading the medication guide and warning card prior to initiating therapy and each time prescription is refilled;^{1 228 229 240} importance of carrying the warning card.^{1 228 229 240}

• Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician.^{1 228 229 240} Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.^{1 228 229 240}

• Importance of using abacavir in conjunction with other antiretrovirals—not for monotherapy.^{1 228 229 240} Abacavir/lamivudine used in conjunction with other antiretrovirals;²²⁸ abacavir/dolutegravir/lamivudine used alone as a complete treatment regimen or in conjunction with other antiretrovirals;²⁴⁰ abacavir/lamivudine/zidovudine used alone as a complete treatment regimen or in conjunction with other antiretrovirals.²²⁹

• Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.^{1 228 229 240}

• Advise patients that sustained decreases in plasma HIV RNA have been associated with reduced risk of progression to AIDS and death.²²⁶

• Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others.²⁰⁰ Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids), never sharing personal items that can have blood or body fluids on them (e.g., toothbrushes, razor blades), and never reusing or sharing needles.^{1 200}

• Possibility of potentially fatal hypersensitivity reactions to abacavir.^{1 228 229 240} Discontinue the drug and consult clinicians 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 preparation.^{1 228 229 240}

• Do not restart abacavir or abacavir-containing preparation after a hypersensitivity reaction since more severe symptoms may recur within hours and may include life-threatening hypotension and death.^{1 228 229 240}

• 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 clinicians since a severe or fatal hypersensitivity reaction can occur when the drug is reintroduced.^{1 228 229 240} Reinitiate the drug under such circumstances only if medical care is readily available.^{1 228 229 240}

• If taking abacavir (Ziagen), importance of not taking another abacavir-containing preparation.¹ If taking abacavir/lamivudine (Epzicom), importance of not taking another abacavir- or lamivudine-containing preparation.²²⁸ If taking abacavir/dolutegravir/lamivudine (Triumeq), importance of not taking another abacavir- or lamivudine- containing preparation.²⁴⁰ If taking abacavir/lamivudine/zidovudine (Trizivir), importance of not taking another abacavir-, lamivudine-, or zidovudine-containing preparation.²²⁹

• Advise patients that lactic acidosis and severe hepatomegaly have been reported.^{1 228 229 240}

• Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.^{1 228 229 240}

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, and any concomitant illnesses.^{1 228 229 240}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 228 229 240} Advise HIV-infected women not to breast-feed.¹

• Importance of advising patients of other important precautionary information.^{1 228 229 240} (See Cautions.)

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

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

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