Tenofovir Disoproxil FumaratePronunciation
Pronunciation: ten-OF-oh-vir DYE-soe-PROX-il FUE-ma-rate
Class: Nucleotide analog reverse transcriptase inhibitor
- Tablets, oral 150 mg
- Tablets, oral 200 mg
- Tablets, oral 250 mg
- Tablets, oral 300 mg
- Powder, oral 40 mg/g
Tenofovir disoproxil fumarate is a prodrug of tenofovir that inhibits the activity of HIV-1 reverse transcriptase and hepatitis B virus (HBV) reverse transcriptase by competing with deoxyadenosine 5′-triphosphate and by DNA chain termination after incorporation into DNA.
Tenofovir C max is approximately 0.3 mcg/mL and AUC is approximately 2.29 mcg•h/mL. T max is approximately 1 h, and bioavailability is approximately 25%. Administration following a high-fat meal increases the oral bioavailability, with an increase in AUC of approximately 40% and an increase in C max of approximately 14%.
Vd of tenofovir is approximately 1.3 L/kg. Binding to plasma or serum proteins is less than 0.7% and 7.2%, respectively.
Tenofovir is not a CYP-450 substrate.
Elimination of tenofovir is by glomerular filtration and active tubular secretion. Approximately 70% to 80% is recovered in urine as unchanged drug. Elimination half-life is approximately 17 h.
Special PopulationsRenal Function Impairment
In patients with CrCl less than 50 mL/min or with ESRD requiring dialysis, C max and AUC of tenofovir were increased. It is recommended that the dosing interval be modified in these patients. Following a single 300 mg dose, a 4-h hemodialysis session removed approximately 10% of the administered tenofovir dose.Hepatic Function Impairment
No substantial alterations in tenofovir pharmacokinetics were observed in patients with hepatic impairment.Elderly
Pharmacokinetic studies have not been performed.Children
Tenofovir exposures in pediatric patients 12 to younger than 18 y of age are similar to exposures achieved in adults. Pharmacokinetic studies have not been performed in pediatric patients younger than 12 y of age.Gender
Tenofovir pharmacokinetics are similar in men and women.Race
There were insufficient numbers from racial and ethnic groups other than white patients to adequately determine potential pharmacokinetic differences among these populations.
Indications and Usage
Treatment of HIV-1 infection in adults and children 2 y and older in combination with other antiretroviral agents; treatment of chronic hepatitis B infection in adults.
None well documented.
Dosage and AdministrationAdults
PO 300 mg/day. The optimal duration of therapy for chronic hepatitis B is not known.Children 2 y and older
PO 8 mg/kg once daily (max, 300 mg/day).Renal Function Impairment
PO CrCl at least 50 mL/min, 300 mg every 24 h; CrCl 30 to 49 mL/min, 300 mg every 48 h; CrCl 10 to 29 mL/min, 300 mg every 72 to 96 h; CrCl less than 10 mL/min and on hemodialysis, 300 mg every 7 days or after a total of approximately 12 h of dialysis (administer following completion of dialysis); CrCl 10 mL/min and nonhemodialysis, no recommendation is available.Children 2 y and older
PO No data available to make recommendations.
- Instruct patients to take with or without food.
- Use in combination with other antiretroviral agents for the treatment of HIV.
- One level scoop of the oral powder delivers 1 g of powder containing tenofovir 40 mg.
- Mix oral powder in a container with 2 to 4 oz of soft food not requiring chewing (eg, applesauce, baby food, yogurt). The entire mixture should be ingested immediately to avoid a bitter taste.
- Do not administer tenofovir oral powder in a liquid because the powder may float on top of the liquid even after stirring.
- Only measure tenofovir powder with the supplied dosing scoop.
Store between 59° and 86°F. Dispense only in the original container.
Coadministration increased abacavir C max 12%.Atazanavir, indinavir, lopinavir/ritonavir, tacrolimus
May increase tenofovir plasma levels. Tenofovir may decrease plasma levels of atazanavir and indinavir. Do not administer atazanavir without ritonavir in patients receiving tenofovir.Didanosine
Plasma concentrations of didanosine may be increased, increasing the risk of adverse reactions. Reduce the didanosine dose to 250 mg when administered with tenofovir in adults weighing more than 60 kg. Monitor patients closely for didanosine-associated adverse reactions.Drugs that reduce renal function or compete for active tubular secretion (eg, acyclovir, adefovir, cidofovir, ganciclovir, valacyclovir, valganciclovir)
May increase serum levels of tenofovir and/or increase the levels of other renally eliminated drugs. Avoid coadministration with adefovir.Entecavir
Coadministration increased entecavir AUC 13%.Lamivudine
Concurrent use decreased lamivudine C max 24%, but the AUC remained unchanged.Nephrotoxic agents (eg, amphotericin B)
Risk of nephrotoxicity may be increased; avoid tenofovir in patients who are currently receiving or have recently received nephrotoxic agents.NSAIDs (eg, ibuprofen)
May increase the pharmacologic and toxic effects of tenofovir. Coadminister with caution.Saquinavir/Ritonavir
Concurrent use increased saquinavir AUC 29% and C max 22%. These changes are not expected to be clinically relevant.
Insomnia (18%); dizziness (13%); fatigue (more than 5%); asthenia (postmarketing).
Pruritus (16%); rash (postmarketing).
Nasopharyngitis (more than 5%).
Abdominal pain (22%); nausea (20%); diarrhea (16%); vomiting (13%); pancreatitis (postmarketing).
Acute renal failure, acute tubular necrosis, Fanconi syndrome, interstitial nephritis, nephrogenic diabetes insipidus, polyuria, proteinuria, proximal renal tubulopathy, renal failure, renal insufficiency (postmarketing).
Hepatic steatosis, hepatitis, increased liver enzymes (postmarketing).
Increased ALT (10%); increased serum creatinine (9%); increased AST, increased serum amylase (4%); glycosuria (3%); increased creatine kinase (2%).
Hypokalemia, hypophosphatemia, lactic acidosis (postmarketing).
Back pain (more than 5%); muscular weakness, myopathy, osteomalacia, rhabdomyolysis (postmarketing).
Fever (11%); allergic reaction, including angioedema (postmarketing).
Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) were reported with the use of nucleoside analogs in combination with other antiretrovirals.
Severe acute exacerbations of HBV have been reported in HBV-infected patients who have discontinued anti–hepatitis B therapy, including tenofovir. Monitor hepatic function closely with clinical and laboratory follow-up for at least several months in patients who discontinue tenofovir. If appropriate, resumption of anti–hepatitis B therapy may be warranted.
Monitor renal function and serum phosphorous in patients at risk of or with a history of renal dysfunction and in patients receiving nephrotoxic agents. Monitor bone density in HIV-infected patients with history of pathologic bone fracture or who are at risk of osteoporosis or bone loss. Monitor hepatic function closely with clinical and laboratory follow-up for at least several months in patients who discontinue tenofovir and are coinfected with HIV and HBV. Monitor patient for signs and symptoms of lactic acidosis. Test HIV patients for chronic HBV before starting antiretroviral therapy. Test HBV patients for HIV-1 before starting therapy.
Category B .
Excreted in breast milk. HIV-infected mothers should not breast-feed infants.
Safety and efficacy not established in children younger than 2 y with HIV.
Select dose with caution, reflecting greater frequency of decreased hepatic, renal, or cardiac function, and of comorbidity.
Dosing adjustments are required for patients with renal impairment.
Reduction in bone mineral density and fractures have been reported. Ensure that supplementation with calcium and vitamin D has been considered in patients with HIV-associated osteopenia or osteoporosis.
Early virologic failure
Early virologic failure and high rates of resistance substitutions have been reported in patients on triple nucleoside regimens. Use these regimens with caution and carefully monitor patients receiving these regimens, or consider therapy modification for these patients.
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.
Immune reconstitution syndrome
During the initial phase of therapy, a patient whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections. Autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution syndrome.
Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported.
None well documented.
- Inform patients that tenofovir is not a cure for HIV-1 infection and patients may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. Patients should remain under the care of a health care provider when using tenofovir.
- Inform patients that the use of tenofovir has not been shown to reduce the risk of transmission of HIV-1 or HBV to others through sexual contact or blood contamination. Advise patients to continue to practice safe sex and to use latex or polyurethane condoms to lower the chance of sexual contact with any body fluids, such as semen, vaginal secretions, or blood. Advise patients never to reuse or share needles.
- Inform patients that the long-term effects of tenofovir are unknown.
- Advise patients not to discontinue tenofovir without first informing their health care provider.
- Inform patients with HIV-1 infection, with or without HBV coinfection, that it is important to take tenofovir with combination therapy.
- Advise patients that it is important to take tenofovir on a regular dosing schedule and to avoid missing doses.
- Inform patients that lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported. Suspend treatment with tenofovir in any patient who develops clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity (including nausea, vomiting, unusual or unexpected stomach discomfort, and weakness).
- Advise patients with HIV-1 to be tested for HBV before initiating antiretroviral therapy.
- Inform patients with chronic hepatitis B to obtain HIV antibody testing prior to initiating therapy with tenofovir.
- Inform patients that severe acute exacerbations of hepatitis have been reported in patients who are infected with HBV or coinfected with HBV and HIV-1 and who have discontinued tenofovir.
- Inform patients that renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent. The dosing interval of tenofovir may need adjustment in patients with renal impairment.
- Advise patients not to coadminister tenofovir with the fixed-dose combination products emtricitabine/tenofovir, emtricitabine/rilpivirine/tenofovir, or efavirenz/emtricitabine/tenofovir because it is a component of these products.
- Advise patients not to administer tenofovir in combination with adefovir.
- Inform patients that decreases in bone mineral density have been observed with the use of tenofovir in patients with HIV and that supplementation with calcium and vitamin D may be beneficial.
- Inform patients that in the treatment of chronic hepatitis B, the optimal duration of treatment is unknown. The relationship between response and long-term prevention of outcomes such as hepatocellular carcinoma is not known.
- Advise HIV-infected mothers not to breast-feed to prevent infecting infant with HIV.
Copyright © 2009 Wolters Kluwer Health.