Serious and sometimes fatal hypersensitivity reactions, with multiple organ involvement, have occurred with abacavir.
Patients who carry the HLA-B*5701 allele are at a higher risk of a hypersensitivity reaction to abacavir; although, hypersensitivity reactions have occurred in patients who do not carry HLA-B*5701 allele.
Abacavir is contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA-B*5701–positive patients. All patients should be screened for the HLA-B*5701 allele prior to initiating therapy with abacavir or reinitiation of therapy with abacavir, unless patients have a previously documented HLA-B*5701 allele assessment. Discontinue abacavir immediately if a hypersensitivity reaction is suspected, regardless of HLA-B*5701 status and even when other diagnoses are possible.
Following a hypersensitivity reaction to abacavir, never restart abacavir or any abacavir-containing product because more severe symptoms including death, can occur within hours. Similar severe reactions have also occurred rarely following the reintroduction of abacavir-containing products in patients who have no history of abacavir hypersensitivity.
HIV-1 infection, treatment: Oral: 300 mg twice daily or 600 mg once daily in combination with other antiretroviral agents. Note: Abacavir, in combination with lamivudine and either efavirenz, raltegravir, boosted atazanavir, or boosted darunavir, should not be used in patients with pretreatment HIV RNA ≥100,000 copies/mL (HHS [adult] 2019).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Mild impairment (Child-Pugh class A): 200 mg twice daily (oral solution is recommended).
Moderate to severe impairment (Child-Pugh class B or C): Use is contraindicated (has not been studied).
(For additional information see "Abacavir: Pediatric drug information")
HIV-1 infection, treatment: Note: Use in combination with other antiretroviral (ARV) agents. Gene mutation and ARV resistance patterns should be evaluated (refer to https://www.iasusa.org/ for more information) when necessary.
Infants ≥3 months, Children, and Adolescents: Oral:
Twice-daily dosing:
Weight-directed dosing: Oral solution: 8 mg/kg/dose twice daily; maximum dose: 300 mg/dose. Note: Weight-band dosing may be used in certain patients weighing at least 14 kg; especially rapid growing younger children (HHS [pediatric] 2019).
Weight-band dosing for patients ≥14 kg: Tablets (scored 300 mg tablets), oral solution:
14 to <20 kg: 150 mg twice daily.
20 to <25 kg: 150 mg in the morning and 300 mg in the evening.
≥25 kg: 300 mg twice daily.
Once-daily dosing: Note: For infants and young children beginning therapy with liquid formulations of abacavir, initiation with once-daily abacavir is not generally recommended. In clinically stable patients with undetectable viral load/percentage for more than 6 months (24 weeks) on the liquid formulation of abacavir twice daily, the daily dose can be changed from twice daily to once daily with liquid or tablet formulations. Initiation with once-daily dosing is recommended for children who can be treated with tablet formulation (HHS [pediatric] 2019).
Weight-directed dosing: Oral solution: 16 mg/kg/dose once daily; maximum dose: 600 mg/dose. Note: Weight-band dosing may be used in certain patients weighing ≥14 kg; especially rapid growing younger children (HHS [pediatric] 2019).
Weight-band dosing for patients ≥14 kg: Tablets (scored 300 mg tablets), oral solution:
14 to <20 kg: 300 mg once daily.
20 to <25 kg: 450 mg once daily.
≥25 kg: 600 mg once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, renal is a minor route of elimination.
All patients:
Mild impairment: Dosing adjustment is required; however, pediatric-specific recommendations are not available (HHS [pediatric] 2019).
Moderate to severe hepatic impairment (Child-Pugh class B or C): Use is contraindicated.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Oral:
Ziagen: 20 mg/mL (240 mL) [contains methylparaben, propylene glycol, propylparaben, saccharin sodium; strawberry-banana flavor]
Generic: 20 mg/mL (15 mL [DSC], 240 mL)
Tablet, Oral:
Ziagen: 300 mg [DSC]
Ziagen: 300 mg [scored]
Generic: 300 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Oral:
Ziagen: 20 mg/mL (240 mL)
Tablet, Oral:
Ziagen: 300 mg
Generic: 300 mg
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020977s035,020978s038lbl.pdf#page=27, must be dispensed with this medication. A Warning Card (summarizing symptoms of hypersensitivity), which is available with the product information, must also be dispensed with this medication for each new outpatient prescription and refill.
May be administered with or without food.
Oral: May be administered without regard to food
Hazardous agent (NIOSH 2016 [group 2]).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.
NIOSH recommends single gloving for administration of intact tablets or capsules. NIOSH recommends double gloving, a protective gown, and (if there is a potential for vomit or spit up) eye/face protection for administration of an oral liquid (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).
HIV-1 infection: Treatment of HIV-1 infection in combination with other antiretroviral agents
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Rates of adverse reactions were defined during combination therapy with other antiretrovirals.
>10%:
Central nervous system: Headache (adults: ≤13%; infants, children, & adolescents: 1%), fatigue (≤12%), malaise (≤12%)
Gastrointestinal: Nausea (7% to 19%)
1% to 10%:
Central nervous system: Abnormal dreams (≤10%), sleep disorder (≤10%), chills (≤9%), migraine (≤7%), depression (6%), dizziness (6%), anxiety (5%)
Dermatologic: Skin rash (5% to 7%)
Endocrine & metabolic: Hypertriglyceridemia (grades 3/4: 2% to 6%)
Gastrointestinal: Nausea and vomiting (9% to 10%), diarrhea (7%), abdominal pain (≤6%), gastritis (≤6%), gastrointestinal signs and symptoms (≤6%), increased serum amylase (grades 3/4: 2% to 4%), vomiting (2%)
Hematologic & oncologic: Neutropenia (grades 3/4: 2% to 5%), thrombocytopenia (grades 3/4: 1%)
Hepatic: Increased serum alanine aminotransferase (grades 3/4: 6%), increased serum aspartate aminotransferase (grades 3/4: 6%)
Hypersensitivity: Drug-induced hypersensitivity (9%), hypersensitivity reaction (including anaphylaxis and multiorgan failure; 8%; excluding subjects carrying the HLA-B*5701 allele: 1%)
Neuromuscular & skeletal: Increased creatine phosphokinase (grades 3/4: 7% to 8%), musculoskeletal pain (5% to 6%)
Respiratory: ENT infection (5%), viral respiratory tract infection (5%), bronchitis (4%), pneumonia (infants, children, & adolescents: 4%)
Miscellaneous: Fever (≤9%)
Frequency not defined:
Endocrine & metabolic: Increased gamma-glutamyl transferase
Gastrointestinal: Pancreatitis
<1%, postmarketing, and/or case reports: Anemia, autoimmune disease, erythema multiforme, Graves disease, Guillain-Barre syndrome, hepatomegaly, hyperglycemia, immune reconstitution syndrome, lactic acidosis, leukopenia, lipotrophy, liver steatosis, myocardial infarction, pain, polymyositis, redistribution of body fat, renal function abnormality, Stevens-Johnson syndrome, toxic epidermal necrolysis
Hypersensitivity to abacavir or any component of the formulation; patients who are positive for the HLA-B*5701 allele; moderate to severe hepatic impairment
Concerns related to adverse effects:
• Hypersensitivity reactions: [US Boxed Warning]: Serious and sometimes fatal hypersensitivity reactions have occurred. Patients who carry the HLA-B*5701 allele are at a higher risk for a hypersensitivity reaction to abacavir, although hypersensitivity reactions have occurred in patients who do not carry the HLA-B*5701 allele. All patients should be screened for the HLA-B*5701 allele prior to initiating or reinitiation of therapy unless patients have had a previously documented HLA-B*5701 allele assessment. Discontinue abacavir if a hypersensitivity reaction is suspected. Abacavir is contraindicated in patients who have the HLA-B*5701 allele or in patients with a prior hypersensitivity reaction to abacavir. Reintroduction of any abacavir-containing product can result in life-threatening or fatal hypersensitivity reactions, even in patients who have no history of hypersensitivity to abacavir therapy. Such reactions can occur within hours. An allergy to abacavir should be documented in the medical record of allele-positive patients. Reactions usually occur within 9 days of starting abacavir; ~90% occur within 6 weeks, although these reactions may occur at any time during therapy (HHS [adult] 2019). These reactions usually include signs or symptoms from two or more of the following: Fever, skin rash, constitutional symptoms (malaise, fatigue, aches), respiratory symptoms (eg, pharyngitis, dyspnea, cough), and GI symptoms (eg, abdominal pain, diarrhea, nausea, vomiting). Other signs and symptoms include lethargy, headache, myalgia, edema, abnormal chest x-ray findings, arthralgia and paresthesia. Anaphylaxis, liver failure, renal failure, hypotension, adult respiratory distress syndrome, respiratory failure, myolysis, and death have occurred in association with hypersensitivity reactions. Physical findings (lymphadenopathy, mucous membrane lesions, and rash [maculopapular, urticarial or variable]) may occur. Erythema multiforme has also been reported. Laboratory abnormalities (eg, elevated liver function tests, elevated creatine phosphokinase, elevated creatinine, and lymphopenia) may occur. Abacavir should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status. Abacavir SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. If abacavir is restarted following an interruption in therapy not associated with symptoms of a hypersensitivity reaction, carefully evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or cannot be ruled out regardless of HLA-B*5701 status. If abacavir is restarted, continually monitor for symptoms of a hypersensitivity reaction. Make the patient aware that reintroduction should only take place if medical care is readily accessible.
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.
• Lactic acidosis/hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender or obesity) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
Disease-related concerns:
• Coronary heart disease: Use has been associated with an increased risk of MI in some cohort studies (Elion 2018; HHS [adult] 2019). Consider using with caution in patients with risks for coronary heart disease and minimizing modifiable risk factors (eg, hypertension, hyperlipidemia, diabetes mellitus, smoking) prior to use.
• Hepatic impairment: Use with caution and adjust dosage in patients with mild hepatic impairment (contraindicated in moderate to severe impairment).
Dosage form specific issues:
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
• Sorbitol: Oral solution contains sorbitol. Use oral solution with caution in patients who are fructose intolerant; may experience abdominal discomfort and/or diarrhea with administration of the oral solution.
May cause mild hyperglycemia; more common in pediatric patients. Oral solution contains sorbitol, which has been shown to decrease exposure of concurrently administered lamivudine solution in adults. Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Substrate of BCRP/ABCG2; Inhibits MRP2
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Betibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination
Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Risk C: Monitor therapy
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
Elivaldogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Elivaldogene Autotemcel. Management: Avoid use of antiretroviral medications for at least one month, or for the amount of time required for elimination of the retroviral medication, prior to stem cell mobilization and until the all apheresis cycles are finished Risk X: Avoid combination
Levomethadone: May diminish the therapeutic effect of Abacavir. Abacavir may decrease the serum concentration of Levomethadone. Risk C: Monitor therapy
Methadone: May diminish the therapeutic effect of Abacavir. Abacavir may decrease the serum concentration of Methadone. Risk C: Monitor therapy
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy
Riociguat: Abacavir may increase the serum concentration of Riociguat. Risk C: Monitor therapy
The Health and Human Services (HHS) perinatal HIV guidelines consider abacavir a preferred nucleoside reverse transcriptase inhibitor for patients with HIV infection who are not yet pregnant but are trying to conceive.
Viral suppression sustained below the limits of detection with antiretroviral therapy (ART) and modification of therapy (if needed) is recommended in all patients with HIV infection who are planning a pregnancy. Optimization of the health of the person who will become pregnant and a discussion of the potential risks and benefits of ART during pregnancy is also recommended prior to conception. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth.
Health care providers caring for couples planning a pregnancy when one or both partners are diagnosed with HIV infection may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2021).
Abacavir has a high level of transfer across the human placenta.
No increased risk of overall teratogenic effects has been observed following first trimester exposure according to data collected by the antiretroviral pregnancy registry. Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes including preterm delivery, stillbirth, low birth weight, and small for gestational age infants. Actual risks may be influenced by maternal factors, such as disease severity, gestational age at initiation of therapy, and specific ART regimen, therefore close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children not diagnosed with HIV infection but who were exposed to ART in utero or as a neonate and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential metabolic dysfunction.
HLA-B*5701 allele status should be evaluated and documented as negative prior to use; abacavir is contraindicated in all patients who are positive for the HLA-B*5701 allele, including patients who are pregnant.
The Health and Human Services (HHS) perinatal HIV guidelines consider abacavir a preferred nucleoside reverse transcriptase inhibitor (NRTI) for pregnant patients with HIV infection who are antiretroviral naive, who have had ART therapy in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). In addition, patients who become pregnant while taking abacavir may continue if viral suppression is effective and the regimen is well tolerated.
The HHS perinatal HIV guidelines consider abacavir in combination with lamivudine to be a preferred NRTI backbone for initial therapy in antiretroviral-naive pregnant patients. This backbone is not recommended with atazanavir/ritonavir or efavirenz if pretreatment HIV RNA is >100,000 copies/mL. In addition, the HHS perinatal HIV guidelines consider abacavir in combination with lamivudine and dolutegravir to be a preferred integrase strand transfer inhibitor regimen for initial therapy in antiretroviral-naive patients who are pregnant.
Abacavir is not a preferred option for empiric treatment when acute HIV infection is diagnosed during pregnancy and is not recommended unless the patient is known to be negative for the HLA-B*5701 allele.
The pharmacokinetics of abacavir are not significantly changed by pregnancy, and dose adjustment is not needed for patients who are pregnant.
ART is recommended for all pregnant people with HIV infection to maximize their health, maintain the viral load below the limit of detection, and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Patients on fully suppressive regimens prior to pregnancy generally may continue the same regimen considering known pregnancy outcomes and pharmacokinetic data. Monitoring of patients who are pregnant is more frequent than in patients who are not pregnant. ART initiated during pregnancy can be modified after delivery. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth.
Data collection to monitor pregnancy and infant outcomes following exposure to ART is ongoing. Health care providers are encouraged to enroll patients exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or http://www.APRegistry.com).
Health care providers caring for pregnant patients with HIV infection and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2021).
Abacavir is present in breast milk.
Abacavir was detected in the serum of an infant following exposure via breast milk.
Maternal or infant antiretroviral therapy does not completely eliminate the risk of postnatal HIV transmission. In addition, multiclass-resistant virus has been detected in breastfeeding infants despite maternal therapy. In the United States, where formula is usually accessible, affordable, safe, and sustainable, and the risk of infant mortality due to diarrhea and respiratory infections is low, the Health and Human Services (HHS) perinatal HIV guidelines do not recommend breastfeeding for patients with HIV infection when safer infant feeding options are available.
Information is available for counseling and managing patients with HIV infection who are considering breastfeeding (1-888-448-8765). In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth (HHS [perinatal] 2021).
CBC with differential, CD4 count, HIV RNA plasma levels, serum transaminases, fasting lipid panel; serum creatine kinase, serum amylase (as clinically indicated); HLA-B*5701 genotype status prior to initiation of therapy and prior to reinitiation of therapy in patients of unknown HLA-B*5701 status; signs and symptoms of hypersensitivity.
Nucleoside reverse transcriptase inhibitor. Abacavir is a guanosine analogue which is phosphorylated to carbovir triphosphate which interferes with HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
Absorption: Rapid and extensive absorption
Distribution: Vd: 0.86 ± 0.15 L/kg
CSF to plasma AUC ratio: 27% to 33%
Protein binding: 50%
Metabolism: Hepatic via alcohol dehydrogenase and glucuronyl transferase to inactive carboxylate and glucuronide metabolites; not significantly metabolized by cytochrome P450 enzymes; intracellulary metabolized to carbovir triphosphate.
Bioavailability: Tablet: 83%; Solution and tablet provide comparable AUCs
Half-life elimination (serum):
Pediatric patients ≥3 months to ≤13 years: 1 to 1.5 hours (Hughes 1999; Kline 1999)
Adults: 1.54 ± 0.63 hours
Hepatic impairment (mild): Increases half-life by 58%
Half-life, intracellular: 12 to 26 hours
Time to peak:
Pediatric patients ≥3 months to ≤13 years: Within 1.5 hours (Hughes 1999)
Adults: 0.7 to 1.7 hours
Excretion: Urine: ~83% (1.2% as unchanged drug, 30% as 5'-carboxylic acid metabolite, 36% as the glucuronide, and 15% as other metabolites); feces (16% total dose)
Clearance (apparent): Single dose 8 mg/kg (Hughes 1999):
Pediatric patients ≥3 months to ≤13 years: 17.84 mL/minute/kg
Adults: 10.14 mL/minute/kg
Hepatic function impairment: In mild hepatic impairment (Child-Pugh score 5 to 6), AUC increased 89%.
Solution (Abacavir Sulfate Oral)
20 mg/mL (per mL): $0.65
Solution (Ziagen Oral)
20 mg/mL (per mL): $0.73
Tablets (Abacavir Sulfate Oral)
300 mg (per each): $2.98 - $10.05
Tablets (Ziagen Oral)
300 mg (per each): $11.17
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
