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.
Warning
- Hypersensitivity Reactions
-
Serious and sometimes fatal hypersensitivity reactions, with multiorgan failure involvement, reported with abacavir.1 228 229 240 Individuals with the human leukocyte antigen (HLA)-B*5701 allele are at higher risk for abacavir hypersensitivity reactions, although such reactions have occurred in those without the HLA-B*5701 allele.1 228 229 240 Contraindicated in patients who are HLA-B*5701 positive and in those with prior hypersensitivity reaction to abacavir.1 228 229 240 (See Hypersensitivity Reactions under Cautions.)
-
Screen all patients for HLA-B*5701 allele prior to initiation or reinitiation of abacavir or fixed combinations containing abacavir, unless patient has previously documented HLA-B*5701 allele assessment.1 228 229 240 (See Hypersensitivity Reactions under Cautions.)
-
Immediately discontinue abacavir or abacavir-containing preparation if hypersensitivity reaction suspected, regardless of patient’s HLA-B*5701 status and even when other diagnoses are possible.1 228 229 240
-
Following a hypersensitivity reaction, never reinitiate abacavir or any abacavir-containing preparation because more severe symptoms, including death, can occur within hours.1 228 229 240 Similar severe reactions also reported rarely following reintroduction of abacavir-containing preparation in patients with no history of abacavir hypersensitivity.1 228 229 240
- Lactic Acidosis and Severe Hepatomegaly
-
Lactic acidosis and severe hepatomegaly with steatosis (including some fatalities) reported in patients receiving HIV nucleoside reverse transcriptase inhibitors (NRTIs) alone or in conjunction with other antiretrovirals.1 228 229 Discontinue if clinical or laboratory findings suggest lactic acidosis or pronounced hepatotoxicity.1 228 229 240 (See Lactic Acidosis and Severe Hepatomegaly with Steatosis under Cautions.)
- Fixed Combinations
-
If using abacavir/lamivudine (Epzicom), abacavir/dolutegravir/lamivudine (Triumeq), or abacavir/lamivudine/zidovudine (Trizivir), consider that severe, acute exacerbations of HBV reported following discontinuance of lamivudine in patients coinfected with HBV and HIV-1.228 229 240 Monitor hepatic function with both clinical and laboratory follow-up for at least several months after discontinuance of lamivudine-containing preparations in coinfected patients.228 229 240 If appropriate, initiation of HBV treatment may be warranted.228 229 240
-
If using abacavir/lamivudine/zidovudine (Trizivir), consider that zidovudine has been associated with hematologic toxicity (including neutropenia and severe anemia), particularly in those with advanced HIV-1 disease,229 and that prolonged zidovudine use has been associated with symptomatic myopathy.229
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
Weight (kg) |
AM dose |
PM dose |
14 to <20 |
150 mg (half tablet) |
150 mg (half tablet) |
20 to <25 |
150 mg (half tablet) |
300 mg |
≥25 |
300 mg |
300 mg |
Weight (kg) |
Once-daily dose |
14 to <20 |
300 mg |
20 to <25 |
450 mg (one and one-half tablets) |
≥25 |
600 mg (2 tablets) |
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 Clcr <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 labeling1 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 Clcr <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
Drug |
Interaction |
Comments |
---|---|---|
Alcohol |
Increased abacavir AUC and half-life; no effect on alcohol concentrations1 |
Although common metabolic pathways are involved, clinically important interaction not expected1 |
Atazanavir |
No in vitro evidence of antagonistic antiretroviral effects203 |
|
Darunavir |
Pharmacokinetic interactions not expected204 No in vitro evidence of antagonistic antiretroviral effects203 |
|
Delavirdine |
||
Didanosine |
No in vitro evidence of antagonistic antiretroviral effects1 |
|
Dolutegravir |
No in vitro evidence of antagonistic antiretroviral effects236 |
|
Efavirenz |
Pharmacokinetic interactions unlikely45 46 In vitro evidence of additive antiretroviral effects 213 |
|
Elbasvir and grazoprevir |
Fixed combination of elbasvir and grazoprevir (elbasvir/grazoprevir): Clinically important interactions with abacavir not expected177 |
|
Elvitegravir |
Elvitegravir, ritonavir-boosted elvitegravir, or cobicistat-boosted elvitegravir: No clinically important interactions with abacavir242 No in vitro evidence of antagonistic antiretroviral effects242 |
|
Emtricitabine |
No in vitro evidence of antagonistic antiretroviral effects 1 |
|
Etravirine |
No in vitro evidence of antagonistic antiretroviral effects214 |
|
Fosamprenavir |
Pharmacokinetic interaction unlikely205 In vitro evidence of synergistic antiretroviral effects205 |
|
Lamivudine |
No clinically important pharmacokinetic interactions1 63 229 No in vitro evidence of antagonistic antiretroviral effects1 |
|
Ledipasvir and sofosbuvir |
Fixed combination of ledipasvir and sofosbuvir (ledipasvir/sofosbuvir): Clinically important interactions with abacavir not expected181 |
|
Lopinavir and ritonavir |
Fixed combination of lopinavir and ritonavir (lopinavir/ritonavir): Possible decreased abacavir concentrations207 |
Clinical importance unknown207 |
Maraviroc |
No in vitro evidence of antagonistic antiretroviral effects224 |
|
Methadone |
Increased clearance of methadone;1 no effect on abacavir pharmacokinetics1 |
Experts state dosage adjustments not necessary;200 manufacturer of abacavir states an increase in methadone dosage may be required in a small number of patients1 |
Nelfinavir |
In vitro evidence of synergistic antiretroviral effects208 |
|
Nevirapine |
Pharmacokinetic interactions unlikely45 46 No in vitro evidence of antagonistic antiretroviral effects1 |
|
Raltegravir |
In vitro evidence of additive or synergistic antiretroviral effects225 |
|
Ribavirin |
No in vitro effect on antiretroviral activity of abacavir against HIV-11 |
|
Rilpivirine |
Pharmacokinetic interaction not expected226 No in vitro evidence of antagonistic antiretroviral effects226 |
|
Simeprevir |
Clinically important interaction with abacavir not expected187 |
|
Stavudine |
No in vitro evidence of antagonistic antiretroviral effects1 |
|
Tenofovir |
Pharmacokinetic interactions unlikely221 No in vitro evidence of antagonistic antiretroviral effects1 |
|
Tipranavir |
Ritonavir-boosted tipranavir: Decreased abacavir AUC200 211 In vitro evidence of additive antiretroviral effects211 |
Appropriate dosages for concomitant use with respect to safety and efficacy not established200 211 |
Zidovudine |
No clinically important pharmacokinetic interactions1 63 229 No in vitro evidence of antagonistic antiretroviral effects1 |
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
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
-
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 vitro1 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
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
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 |
AHFS DI Essentials™. © Copyright 2021, Selected Revisions May 1, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
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104. Trizivir (abacavir sulfate, lamivudine, and zidovudine) tablets risk evaluation and mitigation strategy (REMS). From FDA website. http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM144268.pdf
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