Abacavir

Pronunciation

(a BAK a veer)

U.S. Brand Names

Ziagen

Synonyms

Abacavir Sulfate; ABC

Generic Available

No

Canadian Brand Names

Ziagen

Use

Treatment of HIV infections in combination with other antiretroviral agents

Pregnancy Risk Factor

C

Pregnancy Implications

It is not known if abacavir crosses the human placenta. Cases of lactic acidosis/hepatic steatosis syndrome have been reported in pregnant women receiving nucleoside analogues. It is not known if pregnancy itself potentiates this known side effect; however, pregnant women may be at increased risk of lactic acidosis and liver damage. Hepatic enzymes and electrolytes should be monitored frequently during the 3rd trimester of pregnancy in women receiving nucleoside analogues. The pharmacokinetics of abacavir during pregnancy are currently under study. The Perinatal HIV Guidelines Working Group considers abacavir to be an alternative NRTI in dual nucleoside combination regimens. Health professionals are encouraged to contact the antiretroviral pregnancy registry to monitor outcomes of pregnant women exposed to antiretroviral medications (1-800-258-4263 or www.APRegistry.com).

Lactation

Excretion in breast milk unknown/contraindicated

Contraindications

Hypersensitivity to abacavir (or carbovir) or any component of the formulation (do not rechallenge patients who have experienced hypersensitivity to abacavir); moderate-to-severe hepatic impairment

Warnings/Precautions

Should always be used as a component of a multidrug regimen. Serious and sometimes fatal hypersensitivity reactions have occurred. Patients exhibiting 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) should discontinue therapy immediately and call for medical attention. Abacavir should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible. Abacavir SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted (interruption in drug supply, temporary discontinuation while treating other conditions). Reactions occurred within hours. In some cases, signs of hypersensitivity may have been previously present, but attributed to other medical conditions (acute onset respiratory diseases, gastroenteritis, reactions to other medications). If abacavir is restarted following an interruption in therapy, evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or if hypersensitivity cannot be ruled out. To report these events on abacavir hypersensitivity, a registry has been established (1-800-270-0425). Use with caution in patients with mild hepatic dysfunction (contraindicated in moderate-to-severe dysfunction). Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) have occurred with antiretroviral nucleoside analogues; female gender, obesity, and prolonged treatment may increase the risk of hepatotoxicity.

Adverse Reactions

Hypersensitivity reactions (which may be fatal) occur in ~5% of patients (see Warnings/Precautions). Symptoms may include anaphylaxis, fever, rash (including erythema multiforme), fatigue, diarrhea, abdominal pain; respiratory symptoms (eg, pharyngitis, dyspnea, cough, adult respiratory distress syndrome, or respiratory failure); headache, malaise, lethargy, myalgia, myolysis, arthralgia, edema, paresthesia, nausea and vomiting, mouth ulcerations, conjunctivitis, lymphadenopathy, hepatic failure, and renal failure.

Note: Rates of adverse reactions were defined during combination therapy with other antiretrovirals (lamivudine and efavirenz or lamivudine and zidovudine). Only reactions which occurred at a higher frequency than in the comparator group are noted. Adverse reaction rates attributable to abacavir alone are not available.

>10%:

Central nervous system: Headache (7% to 13%), fatigue and malaise (7% to 12%)

Gastrointestinal: Nausea (7% to 19%, children 9%)

1% to 10%:

Central nervous system: Depression (6%), dizziness (6%), fever (6%, children 9%), anxiety (5%), abnormal dreams (10%)

Dermatologic; Rash (5% to 6%, children 7%)

Gastrointestinal: Diarrhea (7%), vomiting (2% to 10%, children 9%), abdominal pain (6%)

Hematologic: Thrombocytopenia (1%)

Hepatic: AST increased (6%)

Neuromuscular and skeletal: Musculoskeletal pain (5% to 6%)

Respiratory: Bronchitis (4%), respiratory viral infection (5%)

Miscellaneous: Hypersensitivity reactions (9%; may include reactions to other components of antiretroviral regimen), infection (EENT 5%)

<1% (Limited to important or life-threatening): Erythema multiforme, hepatotoxicity, lactic acidosis, pancreatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis

Drug Interactions

Amprenavir: Abacavir increases the AUC of amprenavir

Methadone: Abacavir may decrease the serum concentration of methadone (clearance increased 22%); in a minority of patients, methadone dosage increase may be required.

Ribavirin: Concomitant use of ribavirin and nucleoside analogues may increase the risk of developing lactic acidosis (includes adefovir, didanosine, lamivudine, stavudine, zalcitabine, zidovudine).

Ethanol/Nutrition/Herb Interactions

Ethanol: Ethanol may increase the risk of toxicity.

Stability

Store oral solution and tablets at controlled room temperature of 20C to 25C (68F to 77F). Oral solution may be refrigerated; do not freeze.

Mechanism of Action

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.

Pharmacodynamics/Kinetics

Absorption: Rapid and extensive absorption

Distribution: Vd: 0.86 L/kg

Protein binding: 50%

Metabolism: Hepatic via alcohol dehydrogenase and glucuronyl transferase to inactive carboxylate and glucuronide metabolites

Bioavailability: 83%

Half-life elimination: 1.5 hours

Time to peak: 0.7-1.7 hours

Excretion: Primarily urine (as metabolites, 1.2% as unchanged drug); feces (16% total dose)

Dosage

Oral:

Children: 3 months to 16 years: 8 mg/kg body weight twice daily (maximum 300 mg twice daily) in combination with other antiretroviral agents

Adults: 300 mg twice daily or 600 mg once daily in combination with other antiretroviral agents

Dosage adjustment in hepatic impairment:

Mild dysfunction (Child-Pugh score 5-6): 200 mg twice daily (oral solution is recommended)

Moderate-to-severe dysfunction: Use is contraindicated by the manufacturer

Administration

May be administered with or without food.

Dietary Considerations

May be taken with or without food.

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medications during treatment without consulting prescriber. This drug will not cure HIV; use appropriate precautions to prevent spread to other persons. Take as directed, for full course of therapy; do not discontinue if feeling better. Maintain adequate hydration (2-3 L/day of fluids) unless advised by prescriber to restrict fluids. Avoid alcohol to decrease risk of hypersensitivity reaction. You may be susceptible to infection (avoid crowds and exposure to known infections and do not have any vaccinations without consulting prescriber). May cause dizziness or weakness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); or nausea or vomiting (small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report immediately symptoms of hypersensitivity (eg, fever, skin rash, fatigue, persistent nausea, vomiting, diarrhea, or abdominal pain); respiratory symptoms (eg, pharyngitis, dyspnea, or cough); headache; malaise or lethargy; loss of sensation, pain, tingling, or numbness in toes, feet, muscles or joints; edema, mouth sores, conjunctivitis, swollen glands, alterations in urinary pattern; swelling of extremities or weight gain. If you are instructed to stop the medication, do not take this medication in the future. Do not restart without specific instruction by your prescriber. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Do not breast-feed.

Additional Information

A medication guide is available and should be dispensed with each prescription or refill for abacavir. A warning card is also available and patients should be instructed to carry this card with them.

A high rate of early virologic nonresponse was observed when abacavir, lamivudine, and tenofovir were used as the initial regimen in treatment-naive patients. Use of this combination is not recommended; patients currently on this regimen should be closely monitored for modification of therapy.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May cause fatigue, lethargy, malaise, insomnia, and headache

Mental Health: Effects on Psychiatric Treatment

Side effects mimic depressive symptoms; caution with benzodiazepines or other CNS depressants and antidepressants

Dosage Forms

Solution, oral: 20 mg/mL (240 mL) [strawberry-banana flavor]

Tablet: 300 mg

References

Foster RH and Faulds D, "Abacavir,"Drugs, 1998, 55(5):729-36.

Havlir DV and Lange JM, "New Antiretrovirals and New Combinations,"AIDS, 1998, 12(Suppl A):165-74.

"Guidelines for the Use of Antiretroviral Agents in HIV-infected Adults and Adolescents. Panel on Clinical Practices for Treatment of HIV Infection," March 23, 2004. Available at: http://www.aidsinfo.nih.gov. Accessed June 1, 2004.

Kline MW, Blanchard S, Fletcher CV, et al, "A Phase I Study of Abacavir (1592U89) Alone and in Combination With Other Antiretroviral Agents in Infants and Children With Human Immunodeficiency Virus Infection,"Pediatrics, 1999, 103(4):e47. Available at: http://www.pediatrics.org/cgi/content/full/103/4/e47.

Mallal S, Nolan D, Witt C, et al, "Association Between Presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and Hypersensitivity to HIV-1 Reverse-Transcriptase Inhibitor Abacavir,"Lancet, 2002, 359:727-32.

"Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV-1 Transmission in the United States," June 23, 2004. Available at: http://www.aidsinfo.nih.gov. Accessed July 1, 2004.

Schmit JC and Weber B, "Recent Advances in Antiretroviral Therapy and HIV Infection Monitoring,"Intervirology, 1997, 40(5-6)304-21.

"Three New Drugs for HIV Infection,"Med Lett Drugs Ther, 1998, 40(1041):114-6.

Weverling GJ, Lange JM, Jurriaans S, et al, "Alternative Multidrug Regimen Provides Improved Suppression of HIV-1 Replication Over Triple Therapy,"AIDS, 1998, 12(11):F117-22.

Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, "Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection," January 20, 2004. Available at: http://www.aidsinfo.nih.gov.

International Brand Names

Abacavir Elea (AR); Bezalip (VE); Filabac (AR); Ziagen (AT, AU, BE, CA, CH, CR, DE, DK, DO, EC, ES, FI, FR, GB, GT, HN, IE, IL, IT, NO, NZ, PA, PL, PT, RO, RU, SE, SG, SI, SV, TR, YU); Ziagenavir (AR, BR, TH)

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