Abacavir

BRAND NAMES

• Ziagen: Ziagen is a prescription medication approved by the U.S. Food and Drug Administration (FDA) for treating HIV in adults, children, and infants. Abacavir, the active ingredient in Ziagen, is always taken in combination with other HIV medications.

MECHANISM OF ACTION:

Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) that works by targeting the HIV reverse transcriptase enzyme. Once inside the body, abacavir is converted into its active form, carbovir triphosphate, which mimics the natural nucleotides used by the virus to synthesize DNA. When incorporated into the viral DNA chain during replication, carbovir triphosphate causes premature termination of the DNA strand, preventing the virus from multiplying and reducing the overall viral load in the body.

PHARMACOKINETICS:

Absorption: 

Abacavir is an antiretroviral drug that is quickly and efficiently absorbed after oral intake, exhibiting a high bioavailability of around 83%. Because of this efficient absorption, it can be taken with or without food. The medication typically reaches its peak concentration in the bloodstream within 1 to 1.7 hours.

Distribution

Abacavir's volume of distribution is 0.86 ± 0.15 L/kg following IV administration. Plasma protein binding is about 50% and has an independent relationship with the plasma concentration of the drug. Excretion is 82.2% (1.2% unchanged) in urine and 16% in the feces. The drug's half-life is 1.54 ± 0.63 hours.

Metabolism

Abacavir, a nucleoside reverse transcriptase inhibitor (NRTI), is mainly metabolized in the liver via two separate enzymatic pathways. Only a small portion, less than 2%, of the drug is excreted unchanged.

Elimination

Abacavir is mainly eliminated through liver metabolism, where it is converted into inactive metabolites that are subsequently excreted through the kidneys and feces. The kidneys have a minimal role in clearing the unchanged drug.

PHARMACODYNAMICS

Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) effective against Human Immunodeficiency Virus Type 1 (HIV-1). It is phosphorylated into active metabolites that compete with natural nucleotides for incorporation into viral DNA, inhibiting the HIV reverse transcriptase enzyme competitively and causing premature termination of DNA synthesis. The drug’s concentration required to inhibit viral replication by 50% (EC50) ranges from 3.7 to 5.8 μM (1 μM = 0.28 mcg/mL) for HIV-1IIIB, 0.07 to 1.0 μM for HIV-1BaL, and averages 0.26 ± 0.18 μM against eight clinical isolates. In cell culture, abacavir shows synergistic effects when combined with the NRTI zidovudine, the non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine, and the protease inhibitor (PI) amprenavir. It also exhibits additive effects when used alongside other NRTIs such as didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zalcitabine.

ADMINISTRATION

Abacavir is administered orally, usually in the form of tablets or oral solution. It is prescribed as part of a combination antiretroviral therapy regimen and should always be taken with other HIV medications to ensure effective viral suppression. Abacavir can be taken with or without food, providing flexibility in dosing. The dosage and frequency depend on the patient’s age, weight, and clinical condition. It is important to follow the prescribed schedule consistently to maintain optimal drug levels and reduce the risk of resistance. Before starting treatment, patients should be screened for the HLA-B*5701 allele to minimize the risk of hypersensitivity reactions.

DOSAGE AND STRENGTH

For occupational HIV exposure, the U.S. Public Health Service recommends abacavir at 300 mg twice daily or 600 mg once daily for 28 days, if tolerated. It should be started as soon as possible—ideally within hours of exposure—and used only as part of an alternative regimen under expert guidance. For pediatric HIV treatment (age 3 months and older), the oral solution is dosed at 8 mg/kg twice daily or 16 mg/kg once daily, with a maximum of 600 mg per day. Tablet dosing varies by weight:

• 14 to <20 kg: 150 mg twice daily or 300 mg once daily

• 20 to <25 kg: 150 mg in the morning and 300 mg in the evening, or 450 mg once daily

• 25 kg or more: 300 mg twice daily or 600 mg once daily.

DRUG INTERACTIONS

Abacavir can have significant drug interactions that necessitate close monitoring. Because of the risk of a serious hypersensitivity reaction, individuals who have previously experienced such a reaction to abacavir must never be re-exposed to any product containing the drug.

FOOD INTERACTIONS

Abacavir does not have any known interactions with food and can be taken with or without meals. Taking it with food may help minimize stomach discomfort. However, it does have a significant interaction with alcohol.

CONTRAINDICATIONS

The contraindications of abacavir include having the HLA-B*5701 allele, a history of hypersensitivity to abacavir, or moderate-to-severe hepatic (liver) impairment.

SIDE EFFECTS

• Fatigue or feeling unusually tired

• Sleep disturbances or unusual dreams

• Headache, fever, chills, or a general feeling of being unwell

• Nausea or vomiting

• Skin rash

• In children: nasal congestion, sneezing, sore throat, or ear pain

TOXICITY

Abacavir's most serious toxicity is a potentially fatal hypersensitivity reaction, which is strongly linked to the HLA-B*5701 gene variant. In addition, abacavir can cause lactic acidosis, liver toxicity, and cardiovascular side effects.