For the treatment of HIV-1 infection in adults.
One tablet to be taken orally once daily with or without food. This product should not be prescribed for patients with reduced renal function (creatinine clearance less than < 50 ml/min).
Hypersensitivity to any of the components of the product and concurrently with astemizole, cisapride, midazolam, triazolam, or ergot derivatives and voriconazole.
Headache, nausea, diarrhea, vomiting, nervous system symptoms, psychiatric symptoms and rash. Less common side effects are hepatotoxicity, lactic acidosis, abdominal pain, anorexia and flatulence. Other side effects reported are allergic reactions, asthenia, abnormal coordination, ataxia, convulsions, hypoesthesia, paraesthesia, neuropathy, tremor, gynaecomastia, constipation, malabsorption, flushing, palpitations, hepatic enzyme increase, hepatic failure, hypercholesterolaemia, hypertriglyceridaemia, arthralgia, myalgia, myopathy, aggressive reactions, agitation, delusions, emotional lability, mania, neurosis, paranoia, psychosis, suicide, dyspnoea, erythema multiforme, nail disorders, skin discoloration, Stevens-Johnson Syndrome, abnormal vision, tinnitus. Higher tenofovir concentrations could potentiate tenofovir DF-associated adverse events, including renal disorders.
Redistribution/accumulation of body fat, including central obesity and dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance," have been observed in patients receiving antiretroviral therapy. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including emtricitabine and tenofovir. Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. Careful monitoring for signs of toxicity, such as deterioration of renal function, and for changes in viral load is required in patients with pre-existing renal impairment once Emtricitabine and tenofovir has been started at prolonged dosing intervals. Renal events, which may include hypophosphataemia, have been reported with the use of tenofovir disoproxil fumarate. Use of this product should be avoided with concurrent or recent use of a nephrotoxic medicinal product. If bone abnormalities are suspected then appropriate consultation should be obtained. Exacerbations of hepatitis have been reported in patients after the discontinuation of emtricitabine or tenofovir disoproxil fumarate. The safety and efficacy of emtricitabine or tenofovir disoproxil fumarate have not been established in patients with significant underlying liver disorders. Serious psychiatric adverse experiences have been reported in patients treated with efavirenz. These include severe depression, suicidal ideation/attempts, aggressive behaviour, paranoid reactions and manic reactions. Patients with serious psychiatric adverse experiences should seek immediate medical evaluation to assess the possibility that the symptoms may be related to the use of efavirenz, and if so, to determine whether the risk of continued therapy outweighs the benefits. Efavirenz must be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement or fever. Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. Nervous system symptoms with efavirenz usually begin during the first one or two days of therapy and generally resolve after the first 2-4 weeks. Dosing at bedtime seems to improve the tolerability of these symptoms. Patients who experience central nervous system symptoms should avoid potentially hazardous tasks such as driving or operating machinery. Convulsions have been observed infrequently in patients receiving efavirenz, generally in the presence of known medical history of seizures. In patients with persistent elevations of serum transaminases to greater than 5 times the upper limit of normal range, the benefit of continued therapy with efavirenz needs to be weighed against the unknown risks of significant liver toxicity. Monitoring of cholesterol and triglycerides should be considered in patients treated with efavirenz.
Because renal elimination of emtricitabine is through glomerular filtration and active tubular secretion, there may be competition for elimination with other compounds that are also renally eliminated. Coadministration with other drugs that are eliminated by active tubular secretion, such as cidofovir, acyclovir, valacyclovir, ganciclovir, and valganciclovir, may increase serum concentrations of either tenofovir or the coadministered drug due to competition for this elimination pathway. Coadministration of tenofovir DF and didanosine should be undertaken with caution, and patients receiving this combination should be monitored closely for didanosine-associated adverse events. Didanosine should be discontinued in patients who develop didanosine-associated adverse events. Patients receiving atazanavir or lopinavir/ritonavir and tenofovir DF should be monitored for tenofovir-associated adverse events. Tenofovir DF should be discontinued in patients who develop tenofovir-associated adverse events. Tenofovir DF decreases the AUC and Cmin of atazanavir. Atazanavir without ritonavir should not be coadministered with this product. Coadministration of efavirenz with drugs primarily metabolized by CYP2C9, CYP2C19, and CYP3A4 may result in altered plasma concentrations of the coadministered drug. Clinically important pharmacokinetic interactions occur when efavirenz is used in conjunction with PIs (amprenavir, indinavir, lopinavir (in fixed dose combination with ritonavir, nelfinavir, saquinavir). Concurrent use of rifampin decreases efavirenz plasma concentrations; concurrent use of rifabutin does not effect efavirenz plasma concentrations but decreases rifabutin plasma concentrations. Efavirenz may decrease the plasma concentration of clarithromycin. Coadministration of methadone and efavirenz decreased the Cmax and AUC of methadone by 42% and 52%, respectively, and resulted in manifestations of opiate withdrawal. Anticonvulsant levels should be monitored in patients taking efavirenz and carbamazepine, phenobarbitol, or phenytoin. Administration of efavirenz in patients receiving psychoactive drugs may result in increased CNS effects. Plasma concentrations of ethinyl estradiol found in oral and other hormonal contraceptives may be increased by efavirenz; the addition of a reliable method of barrier contraception is recommended for patients taking efavirenz. Concurrent use of St. John's wort (Hypericum perforatum) or St. John's wort-containing products with efavirenz is expected to substantially decrease efavirenz plasma concentrations, which may result in suboptimal efavirenz levels and lead to loss of virologic response or resistance to efavirenz. Plasma concentrations and clinical effects of warfarin may be either increased or decreased when used concurrently with efavirenz.
Tenofovir, Emtricitabine: Category B; Efavirenz: Category D.
It is recommended that HIV-infected women do not breast feed their infants to avoid risking postnatal transmission of HIV.
If overdose occurs, the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary. Emtricitabine: Hemodialysis treatment removes approximately 30% of the emtrictabine dose over a 3-hour dialysis period starting within 1.5 hours of emtricitabine dosing (blood flow rate of 400 mL/min and a dialysate flow rate of 600 mL/min). It is not known whether emtricitabine can be removed by peritoneal dialysis. Tenofovir DF: Tenofovir is efficiently removed by haemodialysis with an extraction coefficient of approximately 54%. Following a single 300 mg dose of tenofovir DF, a 4-hour haemodialysis session removed approximately 10% of the administered tenofovir dose. Efavirenz: Administration of activated charcoal may be used to aid removal of unabsorbed Efavirenz. Since Efavirenz is highly protein bound, dialysis is unlikely to remove significant quantities from blood.