Lamivudine + Didanosine + Efavirenz

Indications

Lamivudine + Didanosine + Efavirenz is used for: HIV infection

Adult Dose

Oral HIV infection Adult: 1 tab once daily

Child Dose

Renal Dose

Administration

Should be taken on empty stomach at least 2 hours after a meal and at night, preferably taken at bed time.

Contra Indications

Severe hepatic impairment; hypersensitivity; lactation.

Precautions

Hepatic impairment; not recommended for patients with moderate or severe hepatic impairment because there are insufficient data to determine whether dose adjustment is necessary Monitor liver function tests before and during treatment in patients with underlying hepatic disease, including hepatitis B or C coinfection, marked transaminase elevations, or who are taking medications associated with liver toxicity; among reported cases of hepatic failure, a few occurred in patients with no pre-existing hepatic disease; weigh risk/benefit if AST/ALT >5 xULN Use caution in history of seizures Total cholesterol and triglyceride elevations may occur; monitor before therapy and periodically thereafter Women should avoid pregnancy; use 2 forms of contraception including a barrier method

Pregnancy-Lactation

Interactions

It can be interacted with allopurinol, atazanavir, ciprofloxacin, darunavir, ethanol, febuxostat, fluconazole, ganciclovir, gemifloxacin, hydroxyurea.

Adverse Effects

Side effects of Lamivudine + Didanosine + Efavirenz : Pancreatitis, Peripheral Neuropathy, Hyperuricaemia, Hepatic failure, Retinal depigmentation, Neuritis. Rash including Stevens-Johnson syndrome and erythema multiforme; CNS effects e.g. dizziness, headache, insomnia, somnolence, abnormal dreams, fatigue, impaired concentration. Nausea, less frequently, vomiting, diarrhoea, hepatitis, depression, anxiety, psychosis, amnesia and ataxia, stupor, vertigo, abdominal pain, hepatic failure, convulsions, gynaecomastia, pruritus, blurred vision.

Mechanism of Action

Lamivudine is a synthetic nucleoside analogue and is phosphorylated intracellularly to its active 5'-triphosphate metabolite, lamivudine triphosphate (L-TP). This nucleoside analogue is incorporated into viral DNA by HIV reverse transcriptase and HBV polymerase, resulting in DNA chain termination. Didanosine (ddI) is metabolized intracellularly by a series of cellular enzymes to its active moiety, dideoxyadenosine triphosphate (ddATP), which inhibits the HIV reverse transcriptase enzyme competitively by competing with natural dATP. It also acts as a chain terminator by its incorporation into viral DNA as the lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated. Efavirenz inhibits the activity of viral RNA-directed DNA polymerase (i.e., reverse transcriptase). Antiviral activity of Efavirenz is dependent on intracellular conversion to the active triphosphorylated form. The rate of Efavirenz phosphorylation varies, depending on cell type. It is believed that inhibition of reverse transcriptase interferes with the generation of DNA copies of viral RNA, which, in turn, are necessary for synthesis of new virions.