Dosing and uses of Epzicom (lamivudine-abacavir)
Adult dosage forms and strengths
lamivudine/abacavir
tablet
- 300mg/600mg
HIV Infection
Indicated to treat HIV infection in combination with other antiretroviral drugs
1 tablet (300 mg lamivudine / 600 mg abacavir/) PO qDay
Dosage modifications
Fixed-dose combination product; do not prescribe for patients requiring a dosage adjustment (eg, CrCl <50 mL/min, hepatic impairment)
Pediatric dosage forms and strengths
lamivudine/abacavir
tablet
- 300mg/600mg
HIV Infection
Indicated to treat HIV infection in combination with other antiretroviral drugs
<25 kg: Safety and efficacy not established
≥25 kg: 1 tablet (300 mg lamivudine / 600 mg abacavir/) PO qDay
Assess child's ability to swallow the tablet whole
Dosage modifications
Fixed-dose combination product; do not prescribe for patients requiring a dosage adjustment (eg, CrCl <50 mL/min, hepatic impairment)
Warnings
Black box warnings
Severe acute exacerbations of hepatitis B reported in patients co-infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) and have discontinued lamivudine; monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment
abacavir
- Severe and sometimes fatal hypersensitivity reactions (discontinue immediately if hypersensitivity reaction suspected)
- Never restart after suspected hypersensitivity reaction as more severe symptoms can occur within hours and may include life-threatening hypotension and death
- Reintroduction of abacavir or any other abacavir containing product, even in patients who have no identified history or unrecognized symptoms of hypersensitivity to abacavir therapy, can result (within hours) in serious or fatal hypersensitivity reactions
- Hypersensitivity reaction to this drug is a multiorgan clinical syndrome usually characterized by a sign or symptom in 2 or more of the following groups: 1) fever, 2) rash, 3) gastrointestinal (including nausea, vomiting, diarrhea, or abdominal pain, 4) constitutional (eg, generalized malaise, fatigue, achiness), and 5) respiratory (eg, pharyngitis, dyspnea, cough); HLA-B*5701 allele carriers at high risk for hypersensitivity reaction, Prior to initiating therapy, screen for the HLA-B*5701 allele; this approach decreases risk of hypersensitivity reaction
- Screening also recommended prior to reinitiation in patients of unknown HLA-B*5701 status who have previously tolerated abacavir therapy
- HLA-B*5701 allele negative patients may develop hypersensitivity reaction; although frequency significantly less than in HLA-B*5701 positive patients
- Regardless of HLA-B*5701 status, permanently discontinue if hypersensitivity cannot be ruled out, even when other diagnoses are possible
- Lactic acidosis and hepatomegaly with steatosis (including fatal cases) reported with nucleoside analogues alone or in combination
lamivudine
- Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals
- Not FDA approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of this drug have not been established in patients coinfected with HBV and HIV
- Tablets and oral solution formulations used to treat HIV infection contain a higher dose of lamivudine than formulations indicated for chronic hepatitis B infection; HIV patients should receive only formulation specific for HIV
Contraindications
Hypersensitivity (hypersensitivity reaction to abacavir is potentially lethal)
CrCl <50 mL/min; may use adjusted doses of abacavir & lamivudine instead
Patients requiring individual dose adjustments for each drug component
Hepatic impairment
Cautions
Review medical history for hypersensitivity to abacavir before administration; discontinue at first signs of hypersensitivity
(All NRTIs): Risk of potentially fatal lactic acidosis & severe hepatomegaly with steatosis
Exacerbation of hepatitis B may occur on discontinuation
Risk of immune reconstitution syndrome
May cause redistribution of fat (cushingoid appearance)
Use caution in patients with risks for coronary heart disease
Concomitant administration of emtricitabine with lamivudine-containing products not recommended
Hepatic decompensation, some fatal, reported in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy and interferon alfa with or without ribavirin; discontinue therapy as medically appropriate and consider dose reduction or discontinuation of interferon alfa, ribavirin, or both
Pregnancy and lactation
Pregnancy category: C
If pregnant woman exposed to abacavir, report to the Antiretroviral Pregnancy Registry 1-800-258-4263
Lactation: do not nurse if taking this drug
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Epzicom (lamivudine-abacavir)
Pharmacogenomics
Patients who carry the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction
Prior to initiating therapy with abacavir, screening for the HLA-B*5701 allele is recommended
For HLA-B*5701-positive patients, treatment with an abacavir-containing regimen is not recommended
Genetic testing laboratories
- The following companies provide genetic testing for HLA variants
- Kashi Clinical Laboratories (www.kashilab.com)
- LabCorp (https://www.labcorp.com/)
- Specialty Laboratories (https://www.specialtylabs.com)
- Quest (https://www.questdialgnotics.com)
Mechanism of action
Lamivudine: NRTI; following phosphorylation, inhibits HIV reverse transcriptase by viral DNA chain termination; cytosine analog
Abacavir: NRTI; following phosphorylation, inhibits HIV reverse transcriptase by inhibiting viral replication; guanosine analogue
