Tenofovir Disoproxil Fumarate
Pronouncation: (teh-NOE-fo-veer DIE-so-prox-ill FYU-mah-rate)Class: Nucleotide analog reverse transcriptase inhibitor
Trade Names:
Viread
- Tablets 300 mg (equivalent to tenofovir disoproxil 245 mg)
Pharmacology
Feedback for Tenofovir Disoproxil Fumarate
Compare with other drugs.
| ||||||||||||
Tenofovir disoproxil fumarate is a prodrug of tenofovir, which inhibits the activity of HIV-1 reverse transcriptase by competing with deoxyadenosine 5′-triphosphate and by DNA chain termination after incorporation into DNA.
Pharmacokinetics
Absorption
Tenofovir C max is approximately 296 ng/mL and approximately 326 ng/mL in fasting and fed states, respectively. AUC is approximately 2,287 ng•h/mL and approximately 3,324 ng•h/mL in fasting and fed states, respectively. T max is about 1.5 h and bioavailability is approximately 25%. Administration following a high-fat meal increases the oral bioavailability, with an increase in AUC of about 40% and C max increase of about 14%.
Distribution
Vd of tenofovir is approximately 1.3 L/kg.
Metabolism
Tenofovir is not a P450 substrate.
Elimination
Elimination of tenofovir is by glomerular filtration and tubular secretion. Approximately 70% to 80% is recovered in urine as unchanged drug.
Special Populations
Renal Function ImpairmentIn patients with CrCl less than 50 mL/min or with end-stage renal disease requiring dialysis, C max and AUC of tenofovir were increased to approximately 372 to 601 ng/mL and 6,008 to 15,984 ng•h/mL, respectively. It is recommended that the dosing interval be modified in these patients.
Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%. Following a single 300 mg dose, a 4-h hemodialysis session removed approximately 10% of the administered tenofovir dose.
Indications and Usage
Treatment of HIV-1 infection in combination with other antiretroviral agents.
Contraindications
Standard considerations.
Dosage and Administration
AdultsPO 300 mg/day without regard to food.
Renal Function ImpairmentAdults
PO CrCl at least 50 mL/min, give 300 mg every 24 h; CrCl 30 to 49 mL/min, give 300 mg every 48 h; CrCl 10 to 29 mL/min, give 300 mg twice weekly.
HemodialysisGive 300 mg every 7 days or after a total of about 12 h of dialysis.
Storage/Stability
Store tablets at controlled room temperature (59° to 86°F).
Drug Interactions
AtazanavirMay increase tenofovir plasma levels. Tenofovir may decrease AUC and C min of atazanavir, decreasing the therapeutic effect. Do not administer atazanavir without ritonavir in patients receiving tenofovir.
DidanosinePlasma concentrations of didanosine may be increased, increasing the risk of adverse reactions.
Drugs that reduce renal function or compete for active tubular secretion (eg, acyclovir, adefovir, dipivoxil, ganciclovir)May increase serum levels of tenofovir, and/or increase the levels of other renally eliminated drugs.
Lopinavir/ritonavirMay increase tenofovir plasma levels.
Laboratory Test Interactions
None well documented.
Adverse Reactions
CNS
Asthenia (11%); headache, depression (8%); peripheral neuropathy (5%); insomnia (4%); dizziness (3%).
Dermatologic
Rash (including pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash) (7%); sweating (3%).
GI
Diarrhea (16%); nausea (11%); abdominal pain, vomiting (7%); anorexia, dyspepsia, flatulence (4%); hepatitis, increased liver enzymes, pancreatitis (postmarketing).
Genitourinary
Renal insufficiency, renal failure, acute renal failure, Fanconi syndrome, proximal tubulopathy, proteinuria, acute tubular necrosis, nephrogenic diabetes insipidus (postmarketing).
Lab Tests
Increased amyolase, increased creatinine (postmarketing).
Metabolic-Nutritional
Weight loss (4%); hypophosphatemia, lactic acidosis (postmarketing).
Musculoskeletal
Myalgia, back pain (4%).
Respiratory
Pneumonia (3%), dyspnea (postmarketing).
Miscellaneous
Pain (12%); fever (4%); chest pain (3%); allergic reaction (postmarketing).
Precautions
WarningsLactic acidosis and severe hepatomegaly with steatosis (including fatal cases) were reported with the use of nucleoside analogs alone or in combination with other antiretrovirals. Tenofovir is not indicated for the treatment of chronic hepatitis B virus (HBV) infection, and the safety and efficacy of tenofovir have not been established in patients coinfected with HBV and HIV. Severe acute exacerbations of HBV have been reported in patients who are coinfected with HBV and HIV and have discontinued tenofovir. Hepatic function should be followed closely with clinical and laboratory follow-up for at least several months in patients who discontinue tenofovir and are coinfected with HIV and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted. |
MonitorMonitor renal function and serum phosphorous in patients at risk for, or with history of, renal dysfunction, and patients receiving nephrotoxic agents. Monitor bone density in HIV-infected patient with history of pathologic bone fracture or at risk for osteopenia. Ensure that liver enzymes are evaluated before starting therapy and periodically thereafter during prolonged treatment. Monitor patient for signs and symptoms of lactic acidosis. If patient develops profound weakness or tiredness, unexpected stomach discomfort, fatty diarrhea, feeling cold, dizzy or lightheaded, or slow or irregular heartbeat, withhold drug. |
Pregnancy
Category B .
Lactation
Undetermined. HIV-infected mothers should not breast-feed infants.
Children
Safety and efficacy not established.
Elderly
Select dose with caution, reflecting greater frequency of decreased hepatic, renal, or cardiac function and comorbidity.
Renal Function
See Route/Dosage section for recommended adjustments. Renal function impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia) has been reported. If possible, avoid using tenofovir in patients with concurrent or recent use of nephrotoxic agent.
Bone effects
Reduction in bone mineral density and fractures have been reported. Ensure that supplementation with calcium and vitamin D has been considered in patient with HIV-associated osteopenia or osteoporosis.
Fat redistribution
Accumulation and redistribution of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance, may occur.
Hepatitis B
Test HIV patients for chronic HBV before starting antiretroviral therapy.
Immune reconstitution syndrome
During initial phase of therapy, patients whose immune system responds may develop an inflammatory response to indolent of residual opportunistic infections.
Lactic acidosis/Severe hepatomegaly with stenosis
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported. Use with caution in patients with risk factors for liver disease.
Patient Information
- Advise patient or caregiver to review the patient information leaflet before starting therapy and with each refill.
- Advise patient to take tenofovir once daily without regard to meals but to take with food if stomach upset occurs.
- Instruct patient that if a dose is missed, to take it as soon as possible and take the next dose at the regularly scheduled time. If it is almost time for the next dose, advise patient to not take the missed dose and to take the next dose as scheduled. Caution patient not to double the next dose to catch up.
- Warn patient that this drug is not to be used by itself but is combined with other antiviral agents.
- Instruct patient to report these symptoms immediately to health care provider: abdominal swelling or enlargement, fatty diarrhea, profound weakness or tiredness, unexpected stomach discomfort, feeling cold, dizzy or lightheaded, or slow or irregular heartbeat.
- Inform patient that drug does not completely eliminate HIV virus and therefore does not reduce risk of transmitting HIV to others. Appropriate precautions must still be followed.
- Advise patient that drug is not a cure for HIV infection and that illnesses associated with HIV infection, including opportunistic infections, may continue to be acquired. Patients should remain under a physician's care.
- Advise patient with HIV-associated osteopenia or osteoporosis to discuss need for supplementation with calcium and vitamin D with health care provider
- Advise HIV-infected mothers not to breast-feed to prevent infecting infants with HIV.
 |
Link to Page |  |
Print Page |  |
Email Page |  | Add to List |
HIV Infection, Hepatitis B - Chronic, Nonoccupational Exposure
