Introduction
Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used as part of highly active antiretroviral therapy (HAART) to treat HIV-1. For individuals who have not previously received HIV treatment, it serves as the preferred NNRTI-based regimen when combined with lamivudine and either zidovudine or tenofovir. Additionally, efavirenz is utilized in multi-drug post-exposure prophylaxis (PEP) regimens to prevent HIV transmission following high-risk exposures.
Uses
Efavirenz is a non-nucleoside reverse transcriptase inhibitor used to treat HIV infection or prevent the spread of HIV.
For use in combination treatment of HIV infection (AIDS)
Associated Conditions
Pharmacodynamics
Efavirenz (dideoxyinosine, ddI) is an oral non-nucleoside reverse transcriptase inhibitor (NNRTI). It is a synthetic purine derivative and, similar to zidovudine, zalcitabine, and stavudine. Efavirenz was originally approved specifically for the treatment of HIV infections in patients who failed therapy with zidovudine. Currently, the CDC recommends that Efavirenz be given as part of a three-drug regimen that includes another nucleoside reverse transcriptase inhibitor (e.g., lamivudine, stavudine, zidovudine) and a protease inhibitor or efavirenz when treating HIV infection.
Mechanism of Action
Similar to zidovudine, 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. Intracellular enzymes subsequently eliminate the HIV particle that previously had been uncoated, and left unprotected, during entry into the host cell. Thus, reverse transcriptase inhibitors are virustatic and do not eliminate HIV from the body. Even though human DNA polymerase is less susceptible to the pharmacologic effects of triphosphorylated efavirenz, this action may nevertheless account for some of the drug's toxicity.
Protein Binding
99.5-99.75%
Route of Elimination
Nearly all of the urinary excretion of the radiolabeled drug was in the form of metabolites.
Half Life
40-55 hours
Food Interactions
- Avoid excessive or chronic alcohol consumption. Alcohol may contribute to additive adverse effects when taken with efavirenz.
- Take on an empty stomach. Taking efavirenz with food increases efavirenz concentrations and may increase the frequency of adverse reactions. In patients who cannot swallow capsules, the capsule contents can be administered with a small amount of food or infant formula using the capsule sprinkle method of administration.
Dosage
Pediatric Patients: Following table describes the recommended dose of Efavirenz for pediatric patients 3 years of age or older and weighing between 10 and 40 kg. The recommended dosage of Efavirenz for pediatric patients weighing greater than 40 kg is 600 mg, once daily.
- 10 to <15 kg: 200 mg
- 15 to < 20 kg: 250 mg
- 20 to < 25 kg: 300 mg
- 25 to < 32.5 kg: 350 mg
- 32.5 to < 40 kg: 400 mg
- 40 kg: 600 mg