Drug Approvals
(US Adopted Name, rINN)
INNs in other languages (French, Latin, and Spanish):
Synonyms: (-)-FTC; BW-524W91; Emtricitabina; FTC; FTC-(-)
USAN: Emtricitabine
INN: Emtricitabine [rINN (en)]
INN: Emtricitabina [rINN (es)]
INN: Emtricitabine [rINN (fr)]
INN: Emtricitabinum [rINN (la)]
INN: Емтрицитабин [rINN (ru)]
Chemical name: 5-Fluoro-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine
Molecular formula: C8H10FN3O3S =247.2
CAS: 143491-57-0
ATC code: J05AF09
Adverse Effects
The most common adverse effects associated with antiretroviral regimens containing emtricitabine are headache, diarrhoea, and nausea; hyperpigmented skin discoloration is very common in children and common in adults. Other common adverse effects include abdominal pain, vomiting, dyspepsia, abnormal dreams, asthenia, dizziness, insomnia, pain, allergic skin reactions, pruritus, rashes, and urticaria. Abnormal laboratory test results associated with emtricitabine-containing regimens include hyperbilirubinaemia, increases in serum lipase and pancreatic amylase, and raised liver enzymes. There have also been reports of neutropenia and anaemia. Lactic acidosis, usually associated with severe hepatomegaly and steatosis, has been associated with treatment with NRTIs.
Immune reconstitution syndrome (an inflammatory immune response resulting in clinical deterioration) has been reported during the initial phase of treatment with combination antiretroviral therapy, including emtricitabine, in HIV-infected patients with severe immune deficiency.
Accumulation or redistribution of body fat (lipodystrophy) including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance have been observed in patients receiving antiretroviral therapy, including emtricitabine. Metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia, and hyperlactataemia have also been reported. NRTIs have also been associated with mitochondrial dysfunction manifesting as abnormal behaviour, anaemia, convulsions, hyperlipasaemia, hypertonia, and neutropenia.
Elevated creatine phosphokinase, myalgia, myositis, and rarely rhabdomyolysis have been reported, particularly when nucleoside analogues have been given with HIV-protease inhibitors. Osteonecrosis has been reported, particularly in patients with advanced HIV disease or long-term exposure to combination antiretroviral therapy. For further information on adverse effects associated with NRTIs see Zidovudine.
Precautions
Treatment with emtricitabine should be stopped if there is a rapid increase in aminotransferase concentrations, progressive hepatomegaly or steatosis, or metabolic or lactic acidosis of unknown aetiology. Emtricitabine should be given with caution to patients with hepatomegaly or other risk factors for liver disease.
Patients co-infected with chronic hepatitis B or C and treated with combination antiretroviral therapy are at increased risk for severe and potentially fatal hepatic adverse events; treatment should be interrupted or stopped if there is evidence of exacerbation of liver disease. It is recommended that all patients should be tested for the presence of hepatitis B infection before treatment is begun, and that patients co-infected with HIV and hepatitis B should be monitored for several months after stopping treatment with emtricitabine for signs of exacerbations of hepatitis. Emtricitabine should be used with caution and doses adjusted in patients with renal impairment.
Interactions
Caution should be exercised when emtricitabine is given with other drugs eliminated by active tubular secretion as competition for the elimination pathway may increase the serum concentrations of either drug.
Antiviral Action
Emtricitabine is converted intracellularly in stages to the triphosphate. This triphosphate halts the DNA synthesis of HIV through competitive inhibition of reverse transcriptase. Emtricitabine-resistant strains of HIV have been identified and cross-resistance to other nucleoside reverse transcriptase inhibitors may occur.
Pharmacokinetics
Emtricitabine is rapidly and extensively absorbed from the gastrointestinal tract after oral doses, with peak plasma concentrations occurring after 1 to 2 hours. Bioavailability is reported to be 93% for the capsules. Binding to plasma proteins is reported to be less than 4%. The plasma elimination half-life is about 10 hours. Emtricitabine is metabolised to a limited degree, but is excreted largely unchanged in the urine and to a lesser extent in the faeces. It is partially removed by haemodialysis.
Uses and Administration
Emtricitabine is a nucleoside reverse transcriptase inhibitor related to cytosine with antiviral activity against HIV-1 and hepatitis B virus. It is used in the treatment of HIV infection and AIDS. Viral resistance emerges rapidly when emtricitabine is used alone, and it is therefore used with other antiretrovirals.
Emtricitabine is given orally once daily as capsules in a usual adult dose of 200 mg or 240 mg as oral solution.
For details of doses in infants, children, and adolescents, see below.
For details of doses of emtricitabine to be used in patients with renal impairment, see below.
Fixed-dose combination products have been developed in order to improve patient adherence and avoid monotherapy, thereby decreasing the risk of acquired drug resistance. Products containing emtricitabine in combination with tenofovir, and with efavirenz plus tenofovir are available in some countries.
Administration in children
For the treatment of HIV infection in infants, children, and adolescents emtricitabine is given with other antiretroviral drugs. Doses, given once daily, are based on body-weight:
- in infants up to 3 months of age the oral solution is given in a dose of 3 mg/kg daily
- in infants, children, and adolescents over 3 months of age the oral solution is given in a dose of 6 mg/kg daily to a maximum daily dose of 240 mg
- the capsules may be given to children and adolescents weighing more then 33 kg in the usual adult dose of 200 mg daily.
Administration in renal impairment
Doses of emtricitabine should be reduced in patients with renal impairment, according to the patient’s creatinine clearance (CC):
- CC at least 50 mL/mfnute: usual adult doses (as capsules or solution)
- CC 30 to 49 mL/mfnute: 200 mg every 48 hours (capsules) or 120 mg every 24 hours (oral solution)
- CC 15 to 29 mL/mfnute: 200 mg every 72 hours (capsules) or 80 mg every 24 hours (oral solution)
- CC less than 15 mL/mfnute: 200 mg every 96 hours (capsules) or 60 mg every 24 hours (oral solution)
Preparations
Proprietary Preparations
Argentina: Emtriva;
Australia: Emtriva;
Belgium: Emtriva;
Czech Republic: Emtriva;
Denmark: Emtriva;
Finland: Emtriva;
France: Emtriva;
Germany: Emtriva;
Greece: Emtriva;
Hungary: Emtriva;
Ireland: Emtriva;
Italy: Emtriva;
Mexico: Emtriva;
The Netherlands: Emtriva;
Norway: Emtriva;
New Zealand: Emtriva;
Poland: Emtriva;
Portugal: Emtriva;
Spain: Emtriva;
Sweden: Emtriva;
Switzerland: Emtriva;
United Kingdom: Emtriva;
USA: Emtriva.
Multi-ingredient
Argentina: Truvada;
Australia: Truvada;
Czech Republic: Truvada;
Finland: Truvada;
France: Truvada;
Germany: Truvada;
Greece: Truvada;
Ireland: Truvada;
Italy: Truvada;
Mexico: Truvada;
The Netherlands: Truvada;
New Zealand: Truvada;
Portugal: Truvada;
Spain: Truvada;
Sweden: Truvada;
United Kingdom: Atripla; Truvada;
USA: Atripla; Truvada.