No

Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside); Reverse Transcriptase Inhibitor

Treatment of HIV infections in combination with other antiretroviral agents

Unknown

Clinical effects on the fetus: Administer during pregnancy only if benefits to mother outweigh risks to the fetus

Breast-feeding/lactation: HIV-infected mothers are discouraged from breast-feeding to decrease potential transmission of HIV

Health professionals are encouraged to contact the antiretroviral pregnancy registry to monitor outcomes of pregnant women exposed to abacavir (1-800-258-4263)

Prior hypersensitivity to abacavir (or carbovir) or any component of the formulation; do not rechallenge patients who have experienced hypersensitivity to abacavir

Should always be used as a component of a multidrug regimen. Fatal hypersensitivity reactions have occurred. Patients exhibiting symptoms of fever, skin rash, fatigue, and GI symptoms (eg, abdominal pain, nausea, vomiting) should discontinue therapy immediately and call for medical attention. Ziagen® SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. To report these events on abacavir hypersensitivity, a registry has been established (1-800-270-0425). Use with caution in patients with hepatic dysfunction; prior liver disease, prolonged use, and obesity may be risk factors for development of lactic acidosis and severe hepatomegaly with steatosis.

Note: Hypersensitivity reactions, which may be fatal, occur in ~5% of patients (see Warnings/Precautions). Symptoms may include anaphylaxis, fever, rash, fatigue, diarrhea, abdominal pain, nausea and vomiting. Less common symptoms may include edema, lethargy, malaise, myalgia, shortness of breath, mouth ulcerations, conjunctivitis, lymphadenopathy, hepatic failure and renal failure.

Adults:

Central nervous system: Insomnia (7%)

Gastrointestinal: Nausea (47%), vomiting (16%), diarrhea (12%), anorexia (11%), pancreatitis

Neuromuscular & skeletal: Weakness

Endocrine & metabolic: Hyperglycemia, hypertriglyceridemia (25%)

Miscellaneous: Elevated transaminases

Children:

Central nervous system: Fever (19%), headache (16%)

Dermatologic: Rash (11%)

Gastrointestinal: Nausea (38%), vomiting (38%), diarrhea (16%), anorexia (9%)

Ethanol may increase the risk of toxicity

Abacavir increases the AUC of amprenavir

Store at room temperature; do not freeze oral solution. Oral solution may be refrigerated.

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.

Distribution: V_d: 0.86 L/kg

Protein binding 27% to 33%

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

Bioavailability: 83%

Half-life: 1.5 hours

Time to maximum peak: 0.7-1.7 hours

Elimination: Primarily in urine, as metabolites, (1.2% unchanged); fecal elimination accounted for only 16% of the total dose

Oral:

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

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

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

No information available to require special precautions

No effects or complications reported

This is not a cure for AIDS or AIDS complex, nor will it reduce the risk of transmission to others. Long-term effects are not known. You will need frequent blood tests to adjust dosage for maximum therapeutic effect. Take as directed, for full course of therapy; do not discontinue (even if feeling better). You may experience headache or muscle pain or weakness. Report skin rash, acute headache, severe nausea or vomiting, or difficulty breathing. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Solution, oral (strawberry-banana flavored): 20 mg/mL (240 mL)

Tablet: 300 mg

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):S165-74.

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; http://www.pediatrics.org/cgi/content/full/103/4/e47.

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," April 15, 1999, http://www.hivatis.org.