MICKL

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

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

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

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.