Usage
- Abacavir is an antiretroviral medication specifically prescribed for the treatment of Human Immunodeficiency Virus (HIV) infection. It is not a cure for HIV, but it helps manage the infection and slow its progression. It’s always used in combination with other antiretroviral medications as part of antiretroviral therapy (ART).
- Pharmacological Classification: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
- Mechanism of Action: Abacavir inhibits the action of reverse transcriptase, a viral enzyme crucial for HIV replication. By interfering with this enzyme, abacavir prevents the virus from multiplying and spreading within the body.
Alternate Names
- International Nonproprietary Name (INN): Abacavir
- Brand Name: Ziagen
- Combination Products: Abacavir is also available in combination with other antiretroviral drugs in fixed-dose formulations under various brand names (e.g., Epzicom (with lamivudine), Triumeq (with dolutegravir and lamivudine), Trizivir (with lamivudine and zidovudine)).
How It Works
- Pharmacodynamics: Abacavir, after intracellular conversion to its active form, carbovir triphosphate, competes with the natural substrate deoxyguanosine-5’-triphosphate and inhibits the activity of HIV-1 reverse transcriptase. It also acts as a chain terminator of DNA synthesis. These combined actions prevent HIV replication within infected cells.
- Pharmacokinetics:
- Absorption: Abacavir is rapidly and well-absorbed after oral administration, with peak plasma concentrations reached within approximately 1.5 hours. Food does not significantly impact absorption.
- Metabolism: Primarily metabolized in the liver via alcohol dehydrogenase and glucuronyl transferase to inactive metabolites. CYP450 enzyme involvement is minimal.
- Elimination: Primarily eliminated through renal excretion (approximately 83%) with a small portion eliminated in feces. The elimination half-life is about 1.5 hours.
- Mode of Action: Abacavir is an NRTI, a prodrug that requires intracellular phosphorylation to become its active metabolite, carbovir triphosphate. Carbovir triphosphate competes with the natural building blocks of viral DNA and gets incorporated into the extending DNA chain. Since it lacks the 3’-hydroxyl group required for DNA chain elongation, it acts as a chain terminator, stopping the growth of the viral DNA strand and effectively halting viral replication.
- Receptor Binding/Enzyme Inhibition: Abacavir acts by inhibiting the enzyme reverse transcriptase, an enzyme essential for HIV replication. There is no specific receptor binding involved in its action.
Dosage
Standard Dosage
Adults:
- 600 mg once daily OR 300 mg twice daily, in combination with other antiretroviral agents.
Children (≥3 months):
- Oral Solution: 8 mg/kg twice daily OR 16 mg/kg once daily (maximum 600 mg/day)
- Tablets (≥14 kg and able to swallow tablets): Dosing is based on weight and generally ranges from 300 mg to 600 mg daily, administered as a single daily dose or in two divided doses.
- Infants <3 months: Use and dose must be determined by the child’s doctor. Specific weight-based dosing guidelines are available for infants as young as one month.
Special Cases:
- Elderly Patients: Caution is advised due to the increased likelihood of age-related hepatic, renal, or cardiac dysfunction and concomitant diseases or medications. Dosage adjustments may be necessary.
- Patients with Renal Impairment: No dosage adjustment for abacavir is typically needed; however, consider concomitant medications requiring dose adjustment in renal impairment.
- Patients with Hepatic Impairment (Mild-Child Pugh A): Dosage reduction may be needed. Consult specific guidelines and resources. Abacavir is contraindicated in moderate to severe hepatic impairment.
- Patients with Comorbid Conditions: Exercise caution in patients with hypertension, diabetes, and hyperlipidemia, and individualize dosing accordingly.
Clinical Use Cases
Abacavir is indicated for HIV infection and not used in settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations in the same way as other classes of medications might be.
Dosage Adjustments
Dosage modifications should be considered in cases of renal impairment, hepatic impairment, and advanced age. Consider pharmacogenomic factors, such as HLA-B5701 status (abacavir is contraindicated in HLA-B5701 positive patients).
Side Effects
Common Side Effects:
- Headache, fever, fatigue, nausea, vomiting, diarrhea, loss of appetite, cough, rash, insomnia, and abnormal dreams.
Rare but Serious Side Effects:
- Hypersensitivity reaction (fever, rash, gastrointestinal symptoms, respiratory symptoms): Can be life-threatening and requires immediate discontinuation of abacavir.
- Lactic acidosis (buildup of lactic acid in the blood).
- Hepatotoxicity (liver damage).
- Pancreatitis.
Long-Term Effects:
- Potential long-term effects include cardiovascular disease, lipodystrophy (changes in body fat distribution), and insulin resistance.
Adverse Drug Reactions (ADR):
- Hypersensitivity reaction is the most significant ADR, presenting with multiple symptoms like rash, fever, nausea, malaise, and respiratory symptoms. It’s crucial to differentiate hypersensitivity reactions from less severe adverse events to avoid fatal rechallenge.
Contraindications
- Absolute:
- Known hypersensitivity to abacavir.
- Presence of HLA-B*5701 allele.
- Moderate to severe hepatic impairment.
- Relative:
- History of cardiovascular disease.
Drug Interactions
- Abacavir has clinically significant interactions with other drugs, including methadone, orlistat, some antiretrovirals, and medications containing abacavir. Monitor closely for drug interactions and consult drug interaction databases for comprehensive information. Co-administration with alcohol is not contraindicated, but moderation is recommended.
Pregnancy and Breastfeeding
- Pregnancy: Abacavir can be used during pregnancy if the potential benefit outweighs the potential risk to the fetus. No dose adjustment is needed during pregnancy. A pregnancy exposure registry is available.
- Breastfeeding: Breastfeeding is not recommended while taking abacavir due to the potential for transmission of HIV to the infant through breast milk.
Drug Profile Summary
- Mechanism of Action: Nucleoside reverse transcriptase inhibitor (NRTI)
- Side Effects: Common: Headache, fever, fatigue, nausea, vomiting, diarrhea. Serious: Hypersensitivity reaction, lactic acidosis, hepatotoxicity.
- Contraindications: Hypersensitivity to abacavir, presence of HLA-B*5701 allele, moderate to severe hepatic impairment.
- Drug Interactions: Consult drug interaction databases for a comprehensive list.
- Pregnancy & Breastfeeding: Can be used in pregnancy if benefits outweigh risks; breastfeeding is not recommended.
- Dosage: Adults: 600 mg once daily OR 300 mg twice daily. Children (≥3 months): Weight-based dosing.
- Monitoring Parameters: HIV viral load, CD4 count, liver function tests, renal function tests, signs and symptoms of hypersensitivity reaction.
Popular Combinations
- Abacavir/Lamivudine (Epzicom): This combination is convenient for once-daily dosing.
- Abacavir/Dolutegravir/Lamivudine (Triumeq): This three-drug combination simplifies treatment regimens.
Precautions
- General Precautions: Screen all patients for the HLA-B*5701 allele before initiating therapy. Educate patients on the signs and symptoms of hypersensitivity reaction. Closely monitor patients for potential adverse effects, particularly during the initial phase of therapy.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Abacavir?
A: Adults: 600 mg once daily or 300 mg twice daily. Children (≥3 months): Weight-based dosing (consult pediatric guidelines).
Q2: What is the most serious side effect of Abacavir?
A: A potentially fatal hypersensitivity reaction can occur. Patients must be screened for the HLA-B*5701 allele before starting abacavir.
Q3: Can Abacavir be used during pregnancy?
A: Yes, it can be used during pregnancy if the potential benefits outweigh the risks to the fetus. No dose adjustment is needed.
Q4: Is it safe to breastfeed while taking Abacavir?
A: No, breastfeeding is not recommended due to the potential for HIV transmission to the infant.
Q5: What should I do if a patient develops a hypersensitivity reaction to Abacavir?
A: Discontinue abacavir immediately and permanently. Do not rechallenge the patient with abacavir, as it can lead to more severe or even fatal reactions.
Q6: Does Abacavir cure HIV?
A: No, Abacavir does not cure HIV. It helps control viral replication and slows the progression of the disease.
Q7: What other medications should be avoided while taking Abacavir?
A: Several drug interactions can occur with Abacavir. Always consult a comprehensive drug interaction resource or pharmacist before co-prescribing any other medications with Abacavir.
Q8: Can Abacavir be used in patients with liver problems?
A: Abacavir requires dose adjustment in mild hepatic impairment and is contraindicated in moderate to severe hepatic dysfunction.
A: Abacavir is primarily metabolized in the liver by alcohol dehydrogenase and glucuronyl transferase.
Q10: What are the key monitoring parameters for patients on Abacavir?
A: Monitor HIV viral load, CD4 cell count, liver and renal function tests, and closely observe for any signs or symptoms of hypersensitivity reaction.
