DrugindexOnline^{2nd edition}

Pronouncation: (ab-ah-KAV-ear)
Class: Antiretroviral, Nucleoside reverse transcriptase inhibitor

Trade Names:
Ziagen
- Tablets 300 mg
- Oral solution 20 mg/mL

Mechanism of Action

Pharmacology

Converted by cellular enzymes to carbovir triphosphate, which inhibits HIV-1 reverse transcriptase and interferes with DNA synthesis.

Pharmacokinetics

Absorption

Rapidly and extensively absorbed. Bioavailability is 83% (tablets). C _max is approximately 3 mcg/mL and AUC _0-12 is approximately 6.02 mcg•h/mL.

Distribution

Vd after IV administration is approximately 0.86 L/kg. Plasma protein binding is approximately 50%.

Metabolism

Metabolized to inactivate metabolites by alcohol dehydrogenase and glucuronyl transferase.

Elimination

Urine is 1.2% as abacavir, 81% as inactive metabolites; feces is 16% of dose. The t _½ is approximately 1.54 h and Cl is approximately 0.8 L/h/kg (after IV administration).

Special Populations

Hepatic Function Impairment

Mild hepatic function impairment (Child-Pugh score 5 to 6) AUC increased 89% and t _½ increased 58%.

Indications and Usage

Treatment of HIV-1 in combination with other antiretroviral agents.

Contraindications

Moderate or severe hepatic function impairment; hypersensitivity to any component of the product.

Dosage and Administration

Adults

PO 300 mg twice daily in combination with other antiretroviral agents.

Adolescents and Children 3 mo to up to 16 yr of age

PO 8 mg/kg twice daily (max, 300 mg twice daily) in combination with other antiretroviral agents.

Hepatic Function Impairment

PO 200 mg twice daily in patients with mild hepatic function impairment (Child-Pugh score 5 to 6).

Storage/Stability

Store tablets and solution at controlled room temperature (68° to 77°F). Solution may be refrigerated but do not freeze.

Drug Interactions

Ethanol

Increases exposure to abacavir by decreasing the elimination and prolonging the t _½ .

Methadone

Plasma levels of methadone may be decreased in some patients, reducing the therapeutic effect.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Insomnia; sleep disorders; headache.

Dermatologic

Skin rashes; Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme (postmarketing).

GI

Nausea; vomiting; diarrhea; loss of appetite; anorexia; pancreatitis.

Metabolic

Elevated blood glucose; elevated triglycerides; redistribution/accumulation of body fat (postmarketing).

Miscellaneous

Hypersensitivity reactions (eg, fever, rash, fatigue, GI symptoms, malaise, lethargy, myalgia, arthralgia, edema, shortness of breath, paresthesia, hypotension, death); fever.

Precautions

Warnings Fatal hypersensitivity reactions Associated with therapy. Drug should not be restarted after suspected reaction. Lactic acidosis and hepatomegaly reported with steatosis (including fatal cases) reported with the use of nucleoside analogues alone or in combination with other antiretrovirals.

Pregnancy

Category C .

Lactation

Undetermined; however, HIV-infected mothers should not breast-feed infants.

Children

Safety and efficacy not established in children under 3 mo.

Elderly

Select dose with caution, reflecting greater frequency of decreased hepatic, renal, or cardiac function and comorbidity.

Fat redistribution

Redistribution/accumulation of body fat have been observed (eg, buffalo hump, peripheral/facial wasting, central obesity).

Patient Information

• Advise patient to review Medication Guide before starting therapy and with each refill of the medication.
• Advise patient to review, and carry with them at all times, the Warning Card summarizing the symptoms of abacavir hypersensitivity reaction.
• Instruct patient to take exactly as prescribed and not to change the dose or discontinue therapy unless advised by health care provider.
• Advise patient to take drug twice daily without regard to meals but to take with food if GI upset occurs.
• Advise patient, family, or caregiver to measure prescribed dose of solution using dosing spoon or dosing syringe.
• Instruct patient that if a dose is missed, to take as soon as remembered, take the next dose at the usual scheduled time.
• Instruct patient to continue to take other HIV medications as prescribed by health care provider.
• Instruct patient to discontinue use and notify health care provider immediately if skin rash or 1 or more symptoms from at least 2 of the following groups are noted: fever; nausea, vomiting, diarrhea, abdominal pain; fatigue, muscle aches, malaise; sore throat, shortness of breath, cough.
• Instruct patient to report the following symptoms immediately to health care provider: profound weakness or tiredness; feeling cold, dizzy, or lightheaded; slow or irregular heartbeat; pain or tingling in the hands or feet; muscle or joint pain.
• Inform patient that drug does not completely eliminate HIV virus and, therefore, does not reduce risk of transmitting HIV. Appropriate precautions must still be followed.
• Advise patient that drug is not a cure for HIV infection. Illnesses associated with HIV infection, including opportunistic infections, may continue to be acquired, and patients should remain under a physician's care.
• Inform patient that redistribution or accumulation of body fat may occur.
• Caution breast-feeding mother to discontinue nursing while receiving medication because of potential for adverse reactions from the medication in breast-feeding infants as well as transmission of HIV virus.