Tenofovir disoproxil fumarate.
Each film-coated tablet contains Tenofovir disoproxil fumarate 300 mg.
Excipients/Inactive Ingredients: Lactose monohydrate, microcrystalline cellulose, maize starch, sodium croscarmellose, magnesium stearate, opadry blue.
Pharmacotherapeutic group: Nucleoside and nucleotide reverse transcriptase inhibitors. ATC Code: J05AF07.
Pharmacology: Pharmacodynamics: Tenofovir disoproxil fumarate is an acyclic nucleoside phosphonate diester analog of adenosine monophosphate and has a molecular structure related to adefovir dipivoxil. Tenofovir disoproxil fumarate requires initial diester hydrolysis for conversion to tenofovir and subsequent phosphorylations by cellular enzymes to form tenofovir diphosphate. Tenofovir diphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with the natural substrate deoxyadenosine 5'-triphosphate and, after incorporation into DNA, by DNA chain termination. Beside, tenofovir disoproxil fumarate also works by blocking hepatitis B virus (HBV) DNA polymerase, the enzyme that is necessary for the virus to replicate in liver cell.
Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases, and mitochondrial DNA polymerase.
Pharmacokinetics: Tenofovir disoproxil fumarate is rapidly absorbed and converted to tenofovir following oral administration, with peak plasma concentrations occurring after 1 to 2 hours. Bioavailability in fasting patients is reported to be 25%, but this is enhanced when tenofovir disoproxil fumarate is taken with a high fat meal.
Tenofovir is widely distributed into body tissues, particularly the kidneys and liver. Binding to plasma proteins is reported to be less than 1% and that to serum proteins about 7%.
Tenofovir disoproxil fumarate is a water soluble ester prodrug which is rapidly converted in vivo to tenofovir and formaldehyde.
Tenofovir is converted intracellularly to tenofovir monophosphate and to the active component, tenofovir diphosphate.
The terminal elimination half-life of tenofovir is 12 to 18 hours. Tenofovir is excreted mainly in the urine by both active tubular secretion and glomerular filtration. Tenofovir is removed by haemodialysis.
Tenofovir disoproxil fumarate is used in conjunction with other antiretroviral agents (but should not be used alone) in the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults.
Tenofovir disoproxil fumarate is used in conjunction with other antiretroviral agents for postexposure prophylaxis of HIV infection (occupational exposure or nonoccupational exposure) in individuals associated with a risk for transmission of the virus.
Tenofovir disoproxil fumarate is also used in the treatment of chronic hepatitis B in adults. Like adefovir, tenofovir is also active against lamivudine-resistant mutant HBV.
Dosage: Adults: Treatment of HIV infection: 1 tablet once daily, in conjunction with other antiretrovirals.
Postexposure prophylaxis following occupational exposure to HIV: 1 tablet once daily in conjunction with other antiretrovirals (usually in conjunction with lamivudine or emtricitabine). Postexposure prophylaxis should be started as soon as possible following occupational exposure (preferably within hours rather than days) and continued for 4 weeks, if tolerated.
Postexposure prophylaxis following nonoccupational exposure to HIV: 1 tablet once daily in conjunction with at least 2 other antiretrovirals. Postexposure prophylaxis should be initiated as soon as possible following nonoccupational exposure (preferably within 72 hours) and continued for 28 days.
Treatment of chronic hepatitis B: The recommended dosage is 1 tablet once daily past 48 weeks.
Renal impairment patients: Doses of tenofovir disoproxil fumarate should be modified by adjustment of the dosing interval in patients with renal impairment according to their creatinine clearance (ClCr ): ClCr 50 ml or more per minute: Usual once-daily dosage.
ClCr 30 to 49 ml/minute: Every 48 hours.
ClCr 10 to 29 ml/minute: Every 72 to 96 hours.
Haemodialysis patients: A dose every 7 days or after a cumulative total of 12 hours of dialysis.
Because safety and efficacy of these dosages have not been evaluated in clinical studies, clinical response to treatment and renal function should be closely monitored.
Hepatic impairment patients: Dosage adjustment is not necessary in patients with hepatic impairment.
Method of Administration: Tefostad T300 is administered orally once daily without regard to meals.
The effects of higher doses are not known.
If overdose occurs the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary.
Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%. Following a single 300 mg dose, a four-hour hemodialysis session removed approximately 10% of the administered tenofovir dose.
Known hypersensitivity to tenofovir disoproxil fumarate or any ingredient in the formulation.
Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) have been reported rarely in patients receiving nucleoside reverse transcriptase inhibitors alone or in conjunction with other antiretroviral agents (tenofovir).
Adipogenic effects: Redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement ("buffalo hump'), peripheral wasting, facial wasting, breast enlargement, and general Cushingoid appearance, has been reported with antiretroviral therapy.
Bone effects: Decreases in bone mineral density at the lumbar spine, increases in levels of 4 biochemical markers of bone metabolism, and increased serum parathyroid hormone levels were reported in HIV infected patients receiving tenofovir concomitantly with lamivudine and efavirenz.
Bone monitoring should be considered for HIV-infected patients who have a history of pathologic bone fracture or are at substantial risk for osteopenia. Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation may be beneficial for all patients. If bone abnormalities are suspected, appropriate consultation should be obtained.
Patients with pre-existing liver dysfunction including chronic active hepatitis have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.
Severe acute exacerbations of HBV infection have been reported in HIV infected patients following discontinuance of tenofovir. Hepatic function should be closely monitored with clinical and laboratory follow up for at least several months after tenofovir is discontinued in patients with HBV and HIV coinfection. If appropriate, initiation of treatment for HBV infection may be warranted.
The clinical activity of tenofovir disoproxil fumarate has not been determined against hepatitis B virus (HBV) in humans. It is unknown whether treatment of patients co-infected with HIV-1 and HBV will result in the development of HBV resistance to tenofovir disoproxil fumarate or other medicinal products.
Immune reactivation syndrome: In HIV infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, such reactions have been observed within the first few weeks or months of initiation of CART. Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterium infections, and Pneumocystis carinii pneumonia. Any inflammatory symptoms should be evaluated and treatment instituted when necessary.
Tefostad T300 contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive or use machines have been performed. However, patients should be informed that dizziness has been reported during treatment with tenofovir disoproxil fumarate.
Pregnancy: No clinical data on exposed pregnancies are available for tenofovir disoproxil fumarate. Tenofovir disoproxil fumarate should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
However, given that the potential risks to developing human foetuses are unknown, the use of tenofovir disoproxil fumarate in women of childbearing potential must be accompanied by the use of effective contraception
Lactation: It is not known whether tenofovir is excreted in human milk. It is recommended that mothers being treated with tenofovir disoproxil fumarate do not breast-feed their infants. As a general rule, it is recommended that HIV infected women do not breast-feed their infants in order to avoid transmission of HIV to the infant.
The most common (1/100 ≤ ADR <1/10) adverse effects reported from the use of tenofovir disoproxil fumarate are mild gastrointestinal effects, particularly diarrhoea, nausea and vomiting, abdominal pain, flatulence, dyspepsia, and anorexia.
Serum-amylase concentrations may be raised and pancreatitis has been reported.
Hypophosphataemia occurs commonly (1/100 ≤ ADR <1/10).
Skin rashes may occur.
Other adverse effects occurring commonly (1/100 ≤ ADR <1/10) include peripheral neuropathy, headache, dizziness, insomnia, depression, asthenia, sweating, and myalgia.
Raised liver enzymes, hypertriglyceridaemia, hyperglycaemia, and neutropenia.
Renal impairment, acute renal failure, and effects on the renal proximal tubules, including Fanconi syndrome.
Lactic acidosis, usually associated with severe hepatomegaly and steatosis, has been associated with treatment with nucleoside reverse transcriptase inhibitors.
Drugs affecting or metabolized by hepatic microsomal enzymes: Pharmacokinetic interactions with drugs that are inhibitors or substrates of hepatic microsomal enzymes unlikely. Tenofovir and its prodrug are not substrates of cytochrome P-450 (CYP) isoenzymes, does not inhibit CYP isoenzymes 3A4, 2D6, 2C9, or 2E1, but may have a slight inhibitory effect on 1A.
Drugs affecting or eliminated by renal excretion: Interaction of tenofovir with drugs that reduce renal function or that may compete with tenofovir for active renal tubular secretion (i.e., acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir) increased plasma concentrations of tenofovir or the concomitantly administered drug may occur.
HIV protease inhibitors: Additive or synergistic effects between tenofovir and HIV protease inhibitors as amprenavir, atazanavir, indinavir, nelfinavir, ritonavir, saquinavir.
Nonnucleoside reverse transcriptase inhibitors: Additive or synergistic effects between tenofovir and nonnucleoside reverse transcriptase inhibitors as delavirdine, efavirenz, nevirapine.
Nucleoside reverse transcriptase inhibitors: Additive or synergistic effects between tenofovir and nucleoside reverse transcriptase inhibitors as abacavir, didanosine, emtricitabine, lamivudine, stavudine, zalcitabine, zidovudine.
Adefovir: Tenofovir should not be used with adefovir.
Didanosine: Tenofovir increases the plasma concentrations of didanosine.
Therefore, should not be combinations of these drugs.
Oral contraceptives: Pharmacokinetic interaction unlikely with oral contraceptives containing ethinyl estradiol and norgestimate.
Incompatibilities: In the absence of incompatibility studies, this medicinal product must not be mixed with other medicinal products.
Store in a well-closed container, in a dry place. Do not store above 30°C.
Shelf-Life: 36 months from the date of manufacturing.
J05AF07 - tenofovir disoproxil ; Belongs to the class of nucleoside and nucleotide reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.
FC tab 300 mg (almond-shape, light blue, engraved "STADA" on one side, plain on the other) x 3 x 10's, 30's.