Efavirenz/Emtricitabine/Tenofovir disoproxil
Efavirenz/Emtricitabine/Tenofovir disoproxil Uses, Dosage, Side Effects, Food Interaction and all others data.
Efavirenz, a synthetic antiretroviral agent, is a non- nucleoside reverse transcriptase inhibitor. While Efavirenz is pharmacologically related to other non nucleoside reverse transcriptase inhibitors, Efavirenz differs structurally from these drugs and also differs structurally from other currently available anti-retroviral agents.
Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against HIV-1. It blocks the RNA- and DNA-dependent polymerase activities including HIV-1 replication.
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.
Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) indicated for the treatment of HIV infection in adults or combined with tenofovir alafenamide for the prevention of HIV-1 infection in high risk adolescents and adults. Emtricitabine is a cytidine analogue. The drug works by inhibiting HIV reverse transcriptase, preventing transcription of HIV RNA to DNA.
Emtricitabine was granted FDA approval on 2 July 2003.
Emtricitabine is a cytidine analog that competes with the natural substrate of HIV-1 reverse transcriptase to be incorporated into newly formed DNA, terminating its transcription. It is administered once daily so it has a long duration of action. Patients should be counselled regarding the risk of lactic acidosis and hepatomegaly with steatosis.
| Trade Name | Efavirenz/Emtricitabine/Tenofovir disoproxil |
| Generic | efavirenz + emtricitabine + tenofovir disoproxil succinate |
| Type | Tablet |
| Therapeutic Class | |
| Manufacturer | Dr, Reddys Laboratories (UK) Ltd |
| Available Country | United Kingdom |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Efavirenz in combination with other antiretroviral agents is used for the treatment of HIV-1 infection. This indication is based on analyses of plasma HIV- RNA levels and CD4 cell counts in controlled studies of up to 24 weeks in duration. At present, there are no results from controlled trials evaluating long term suppression of HIVRNA with Efavirenz.
Emtricitabine is a nucleoside reverse transcriptase inhibitor used for the treatment and prophylaxis of HIV.
Emtricitabine is indicated in combination with other medications for the treatment of HIV-1 infections; treatment of HIV-1 infections in pediatric patients 25-35kg, treatment of HIV-1 infections in adult patients ≥35kg, for pre exposure prophylaxis of HIV-1 in adolescent and adult patients excluding those who have receptive vaginal sex; treatment of HIV-1 infections in pediatric and adult patients ≥17kg, pre exposure prophylaxis in adolescents and adults ≥35kg; treatment of HIV-1 in patients ≥12 years and ≥35kg; treatment of HIV-1 in patients weighing ≥35kg; treatment of HIV-1 in patients weighing ≥25kg; and treatment of HIV-1 in patients weighing ≥40kg.
Efavirenz/Emtricitabine/Tenofovir disoproxil is also used to associated treatment for these conditions: Human Immunodeficiency Virus Type 1 (HIV-1) InfectionHIV Transmission, Human Immunodeficiency Virus (HIV) Infections, Human Immunodeficiency Virus Type 1 (HIV-1), Human Immunodeficiency Virus Type 1 (HIV-1) Infection
How Efavirenz/Emtricitabine/Tenofovir disoproxil works
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.
Emtricitabine is a cytidine analog which, when phosphorylated to emtricitabine 5'-triphosphate, competes with deoxycytidine 5'-triphosphate for HIV-1 reverse transcriptase. As HIV-1 reverse transcriptase incorporates emtricitabine into forming DNA strands, new nucleotides are unable to be incorporated, leading to viral DNA chain termination. Inhibition of reverse transcriptase prevents transcription of viral RNA into DNA, therefore the virus is unable to incorporate its DNA into host DNA and replicate using host cell machinery. This reduces viral load.
Dosage
Efavirenz/Emtricitabine/Tenofovir disoproxil dosage
It is recommended that Efavirenz be taken on an empty stomach, preferably at bedtime.
Adults: The recommended dosage of Efavirenz is 600 mg orally, once daily, in combination with a protease inhibitor and/or nucleoside analogue reverse transcriptase inhibitors (NRTIs).
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
Side Effects
Rashes, psychiatric or CNS disturbances, amnesia, agitation, confusion, dizziness, vertigo, headache, euphoria, insomnia or somnolence, impaired concentration, abnormal thinking or dreaming, depersonalisation, convulsions, hallucinations, nausea, vomiting, diarrhoea, pancreatitis, fatigue, hepatic failure, photoallergic dermatitis; autoimmune disorders (e.g. Graves’ disease, polymyositis, Guillain-Barre syndrome), osteonecrosis. Accumulation or redistribution of body fat (lipodystrophy) including central obesity, peripheral and facial wasting, buffalo hump, breast enlargement, cushingoid appearance. Metabolic abnormalities e.g. hypercholesterolaemia, hyperglycaemia, hypertriglyceridaemia, hyperlactataemia, insulin resistance.
Toxicity
The LD50 of emtricitabine is not readily available.[9019,L9818]
Symptoms of emtricitabine toxicity include hepatotoxicity with steatosis, as well as lactic acidosis. Treat overdose with symptomatic and supportive measures, including hemodialysis.
Precaution
Patient with history of seizures and psychiatric disorders; acute porphyria. Patients receiving voriconazole or rifampicin (weighing ≥50 kg). Discontinue if severe rash or fever develops. Moderate hepatic and severe renal impairment. Childn. Pregnancy.
Interaction
Additive CNS effects w/ psychoactive drugs. May alter plasma warfarin concentrations. May reduce plasma concentrations of HIV integrase inhibitors (e.g. dolutegravir), other HIV NNRTIs (e.g. etravirine), HMG-CoA reductase inhibitors (e.g. simvastatin). Plasma concentrations of efavirenz is increased and that of voriconazole is reduced when given concomitantly. Reduced plasma concentrations w/ rifampicin.
Volume of Distribution
The apparent central volume of distribution is 42.3L and the peripheral volume of distribution is 55.4L.
Elimination Route
Emtricitabine reaches a Cmax of 1.8±0.7µg/mL with a Tmax of 1-2 hours, and has an AUC of 10±3.1µg*hr/mL. The bioavailability of emtricitabine capsules is 93% and the bioavailability of the oral solution is 75%. Taking emtricitabine with food decreases the Cmax by 29%.[L9019
Half Life
40-55 hours
The half life of emtricitabine is approximately 10 hours.
Clearance
Emtricitabine has an apparent elimination rate of 15.1L/h. This rate is closely linked to creatinine clearance.
Elimination Route
Nearly all of the urinary excretion of the radiolabeled drug was in the form of metabolites.
Emtricitabine is 86% recovered in the urine and 14% recovered in feces. 13% of the dose is recovered in the urine as metabolites; 9% as 3'-sulfoxide diastereomers and 4% as 2'-O-glucuronide.
Pregnancy & Breastfeeding use
Category D: There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Lactation: Efavirenz may pass through breast milk and cause serious harm to the baby. It should not be used during lactation.
Contraindication
Hypersensitivity. Severe hepatic impairment. Lactation. Concomitant admin with terfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, ergot alkaloids, St John’s wort.
Special Warning
Paediatric use: Efavirenz has not been studied in pediatric patients below 3 years of age or who weigh less than 10 kg.
Women taking hormone-based birth control: Women should not rely only on hormone-based birth control, such as pills, injections, or implants, because Efavirenz may make these contraceptives ineffective.
Acute Overdose
Symptoms: Increased adverse CNS effects including involuntary muscle contractions.
Management: Supportive and symptomatic treatment. May administer activated charcoal.
Storage Condition
Store at 25°C.
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