Abacavir (Ziagen) is used to treat HIV infections in combination with other antiretroviral agents. It should always be used as a component of a multidrug regimen. It should be used with caution in patients with a high HIV viral load defined as plasma HIV RNA levels ≥100,000 copies/mL because of treatment failure.

Abacavir Lamivudine single pill formulation:

The treatment of HIV infection includes the combination of two Nucleoside reverse transcriptase inhibitors and one non-nucleoside reverse transcriptase inhibitor or an integrase inhibitor or ritonavir-boosted protease inhibitor. Epzicom is a single pill combination of abacavir and lamivudine. It was initially considered as the first-line of treatment but because of severe allergic reactions and hepatotoxicity, other regimens especially Truvada (Tenofovir disoproxil fumarate/emtricitabine) was favored. In 2007, screening for the genetic marker HLA-B*5701 eliminated the severe allergic reactions associated with Epzicom combination. Epzicom and Truvada were considered comparable in terms of toxicity and efficacy. A study compared Tenofovir/ emtricitabine combination with abacavir/ lamivudine (Epzicom). Both the regimens were found to have similar efficacy, however, abacavir lamivudine treatment was associated with more non-aids related adverse events especially cardiovascular events [Ref]. The risks of myocardial infarction were not increased but there was an increased risk of overall cardiovascular disease which was a composite of myocardial infarction, coronary artery surgery, peripheral vascular disease, ischemic stroke, and deep venous thrombosis [Ref] Epzicom (Abacavir Lamivudine) is now considered as an alternative regimen because of its low potency at a high viral load (>100,000 copies/ml) and associated cardiovascular disease risks.

Abacavir/Lamivudine/Zidovudine (Trizivir):

Combination antiviral therapies make the backbone of HIV treatment. Trizivir is a single pill combination of abacavir/lamivudine/zidovudine. It was studied in patients with HIV infection in addition to efavirenz for 48 weeks followed by Trizivir therapy alone. Although a low rate of virological failure was seen in patients in the quadruple therapy, the percentage of drop-outs was quite high (37%). Furthermore, the four-drug regimen failed to improve the initial response to antiviral therapy compared to the Trizivir (three-drug regimen) [Ref].

 Abacavir Contraindications

• Patients with severe or moderate hepatic impairment and patients who have a hypersensitivity reaction.

Warnings and precautions

• Fat distribution
  • Abacavir can result in a cushingoid appearance, by redistributing fats
• Hypersensitivity reactions
  • Patients may develop serious and sometimes fatal hypersensitivity reactions especially individuals positive for HLA-B*5701.
  • Before starting therapy with abacavir, patients should be tested for HLA-B*5701. In 90% of patients, hypersensitivity reactions occur within six weeks.
  • However, most reactions occur within nine days.
  • Itching, skin rash, or respiratory symptoms such as a cough, shortness, difficulty breathing, nausea, vomiting, or a severe skin reaction should prompt the physician to discontinue administering the medication and notify them immediately.
  • Patients who have developed a hypersensitivity reaction should not restart the procedure.
  • Hypersensitivity reactions may be more common in 600 mg taken once daily.
• Immune reconstitution syndrome:
  • IRIS (immune reconstruction inflammatory syndrome) may occur in patients who have been treated with abacavir.
  • IRIS can be described as an inflammation response to an indolent disease like tuberculosis, or activation an autoimmune process such graves disease, polymysitis, and Guillain-Barre syndrome.
• Lactic acidosis and hepatomegaly [U.S Boxed Warning]:
  • Patients with liver disease should use it with caution. It can be associated with severe steatosis and Lactic acidosis.
• Coronary heart disease:
  • Patients at high risk for developing ischemic heart disease should not use it.
• Special populations
  • Children younger than 3 months old are not considered safe and effective.

Abacavir dosage in Adults:

• 300 mg twice daily orally or 600 mg once daily in combination with other antiretroviral agents.

Abacavir dose in Children:

• Infants younger than 3 months of age:

  • Not approved for use in younger children as safety, efficacy, and dosage is not established

• Infants older than 3 months, Children, and Adolescents younger than 16 years:

  • 8 mg/kg/dose twice daily to the maximum dose of 300 mg twice daily.

• Alternate dosing for patients greater than 14 kg who are able to swallow tablets (scored 300 mg tablets):

  • 14-21 kg: 150 mg ( 1 / 2 tablet) twice daily
  • more than 21 to less than 30 kg: 150 mg ( 1 / 2 tablet) in the morning and 300 mg (1 tablet) in the evening
  • more than 30 kg: 300 mg (1 tablet) twice daily

• Adolescents older than 16 years:

  • 300 mg twice daily or 600 mg once daily

Note: It should be used in combination with other antiretroviral agents

Abaacavir dose in Renal Disease:

The once-daily dosing and use in ESRD is not recommended.

Abaacavir dose in liver disease:

• Mild hepatic impairment (Child-Pugh score 5-6):

  • 200 mg twice daily (an oral solution is recommended)

• Moderate-to-severe hepatic impairment (Child-Pugh score >6):

  • Use is contraindicated by the manufacturer.

How to Administer Abaacavir?

Abacavir may be taken with or without food.

Pregnancy Risk Factor C

• Abacavir crosses the human placenta.
• No increased risk of overall birth defects has been observed following first trimester exposure according to data collected by the antiretroviral pregnancy registry.
• It has been linked to lactic acidosis, fatty steatosis, and other side effects.
• Pregnant women are at greater risk for developing HELLP syndrome and preeclampsia or eclampsia.
• These conditions should be closely monitored by patients.
• It is unknown if the drug can be found in breast milk.It is not recommended for use during breastfeeding.

Abacavir side effects:

• Life-threatening hypersensitivity reactions have been reported.
• These reactions are characterized by fever or rash and possibly nausea, vomiting, diarrhea, abdominal pain, dyspnoea, cough, lethargy, malaise, headache, and myalgia;
• Patients may develop mouth ulceration, edema, hypotension, sore throat, acute respiratory distress syndrome, anaphylaxis, paraesthesia, arthralgia, conjunctivitis, lymphadenopathy, lymphocytopenia, and renal failure and rarely myolysis;
• Children are more prone to develop a rash and gastrointestinal problems.
• Laboratory abnormalities may include raised liver function tests and creatine kinase.

Monitoring Parameters: 

• CBC with differential,
• serum creatine kinase,
• CD4 count,
• HIV RNA plasma levels,
• serum transaminases,
• triglycerides,
• serum amylase;
• HLA-B*5701 genotype status prior to initiation of therapy and prior to reinitiation of therapy in patients of unknown HLA-B*5701 status;
• Signs and symptoms of hypersensitivity, particularly in patients untested for the HLA-B*5701 allele.
• Monitor for symptoms of hypersensitivity reaction every 2 weeks for 2 months

Abacavir Mechanism of Action:

• Abacavir (Nucleoside reverse transcriptionase inhibitor) is an NRTI.
• It causes inhibition of viral replication by interfering with HIV-dependent DNA polymerase.

Orally, it is quickly and efficiently absorbed. 50% of the drug is bound with proteins.

It isMetabolizedIn the liver via alcohol and glucuronyl transfersase to inactive caroxylate and/or glucuronide metabolism.

It has been abioavailabilityA half-life of 1.5 hours and an average 83% concentration. It takes 0.7 to 1.7 hours to reach peak plasma concentration.

Abacavir Brands in Pakistan:

No brands available in Pakistan

Abacavir brands (International):

• Abamune
• Abavan
• Abec
• Ampi-quim
• Filabac
• Virol
• Zepril
• Ziagen
• Ziagenavir