One tablet to be taken orally once daily with or without food. Renal impairment: Significantly increased drug exposures occurred when emtricitabine or tenofovir DF were administered to patients with moderate to severe renal impairment. Patients with lowered creatinine clearance (30 to 49 ml/min) should receive one tablet every 48 hours. This product should not be prescribed for patients with reduced renal function (creatinine clearance less than 30 ml/min or requiring hemodialysis).
Hypersensitivity to any of the components of the product.
The most frequently reported adverse effects of emtricitabine are mild to moderate headache, nausea, diarrhea, and skin rash. Skin discoloration on palms and soles was reported with higher frequency in emtricitabine-treated patients than in controls, but the mechanism of skin discoloration is unknown. In some patients coinfected with HIV and hepatitis B, exacerbation of hepatitis has been reported after discontinuing treatment with emtricitabine. Treatment-emergent grade 3 or 4 laboratory abnormalities have been reported in at least 1% of patients receiving emtricitabine. These abnormalities include triglycerides greater than 750 mg/dl and creatine kinase over four times the upper limit of normal. The most common adverse effects associated with tenofovir DF are asthenia, diarrhea, nausea, and vomiting. Less common side effects of tenofovir DF are hepatotoxicity, including lactic acidosis; abdominal pain; anorexia; and flatulence. Some side effects of tenofovir DF occurring with undetermined incidence include allergic reaction, dyspnea, Fanconi's syndrome, hypophosphatemia, pancreatitis, proximal tubulopathy, renal failure or insufficiency, and acute tubular necrosis. 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 in clinical practice. 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.
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.
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.