Tenofovir Disoproxil FumaratePronunciation
(ten OF oh vir dye soe PROX il FUE ma rate)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Powder, Oral, as disoproxil fumarate:
Viread: 40 mg/g (60 g)
Tablet, Oral, as disoproxil fumarate:
Viread: 150 mg, 200 mg, 250 mg
Viread: 300 mg [contains fd&c blue #2 aluminum lake]
Brand Names: U.S.
- Antihepadnaviral, Reverse Transcriptase Inhibitor, Nucleotide (Anti-HBV)
- Antiretroviral, Reverse Transcriptase Inhibitor, Nucleotide (Anti-HIV)
Tenofovir disoproxil fumarate (TDF), a nucleotide reverse transcriptase inhibitor, is an analog of adenosine 5'-monophosphate; it interferes with the HIV viral RNA dependent DNA polymerase resulting in inhibition of viral replication. TDF is first converted intracellularly by hydrolysis to tenofovir and subsequently phosphorylated to the active tenofovir diphosphate. Tenofovir inhibits replication of HBV by inhibiting HBV polymerase.
Vd: 1.2-1.3 L/kg
Tenofovir disoproxil fumarate (TDF) is converted intracellularly by hydrolysis (by non-CYP enzymes) to tenofovir, then phosphorylated to the active tenofovir diphosphate
Urine (70% to 80%) via filtration and active secretion, primarily as unchanged tenofovir
Time to Peak
Serum: Fasting: 36-84 minutes; With high-fat meal: 96-144 minutes
<7% to serum proteins
Special Populations: Renal Function Impairment
In patients with CrCl <50 mL/minute or with ESRD requiring dialysis, Cmax and AUC of tenofovir were increased. Following a single 300 mg dose, a 4-hour hemodialysis session removed ~10% of the administered tenofovir dose.
Use: Labeled Indications
Chronic hepatitis B: Treatment of chronic hepatitis B virus (HBV) in patients ≥12 years of age
HIV infection: In combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients ≥2 years of age
U.S. labeling: There are no contraindications listed in the manufacturer's labeling.
Canadian labeling: Hypersensitivity to tenofovir or any component of the formulation; concurrent use with fixed-dose combination products that contain tenofovir (Truvada, Atripla, Complera, or Stribild); concurrent use with adefovir (Hepsera)
Oral: Note: Concurrent use with adefovir and/or tenofovir combination products should be avoided. Canadian labeling does not approve of use in children <12 years with HIV or patients <18 years with chronic HBV.
Children 2 to <12 years: HIV infection: 8 mg/kg once daily (maximum: 300 mg once daily) (in combination with other antiretrovirals)
Dosing recommendations based on body weight if using the oral powder: Note: One level scoop of powder = 40 mg tenofovir
10 to <12 kg: 80 mg once daily
12 to <14 kg: 100 mg once daily
14 to <17 kg: 120 mg once daily
17 to <19 kg: 140 mg once daily
19 to <22 kg: 160 mg once daily
22 to <24 kg: 180 mg once daily
24 to <27 kg: 200 mg once daily
27 to <29 kg: 220 mg once daily
29 to <32 kg: 240 mg once daily
32 to <34 kg: 260 mg once daily
34 to <35 kg: 280 mg once daily
≥35 kg: 300 mg once daily
Dosing recommendations based on body weight if using the oral tablets:
17 to <22 kg: 150 mg once daily
22 to <28 kg: 200 mg once daily
28 to <35 kg: 250 mg once daily
≥35 kg: 300 mg once daily
Children ≥12 years (and ≥35 kg), Adolescents, and Adults:
Hepatitis B infection: 300 mg once daily; Note: Tenofovir is recommended for first-line treatment of HBV (Lok 2009)
Treatment duration (AASLD practice guidelines 2009):
Note: Patients not achieving <2 log decrease in serum HBV DNA after at least 6 months of therapy should either receive additional treatment or be switched to an alternative therapy (Lok 2009).
Hepatitis Be antigen (HBeAg) positive chronic hepatitis: Treat ≥1 year until HBeAg seroconversion and undetectable serum HBV DNA; continue therapy for ≥6 months after HBeAg seroconversion
HBeAg negative chronic hepatitis: Treat >1 year until hepatitis B surface antigen (HBsAg) clearance
Decompensated liver disease: Lifelong treatment is recommended
HIV infection: 300 mg once daily (in combination with other antiretrovirals). Note: Tenofovir is a component of recommended initial regimens in adult and adolescent treatment-naive patients (when coadministered with emtricitabine plus dolutegravir, with emtricitabine plus darunavir/ritonavir, or with emtricitabine plus raltegravir; lamivudine may be substituted for emtricitabine in any of these regimens) and is a component of a recommended initial regimen in adult and adolescent treatment-naive patients with pre-ART CrCl >70 mL/minute (when coadministered with emtricitabine plus elvitegravir/cobicistat) (HHS [adult] 2015).
Dosage adjustment in renal impairment:
Children: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Adults: Note: Use of powder formulation has not been evaluated in renal impairment.
CrCl ≥50 mL/minute: No dosage adjustment necessary
CrCl 30-49 mL/minute: 300 mg every 48 hours
CrCl 10-29 mL/minute: 300 mg every 72-96 hours
CrCl <10 mL/minute without hemodialysis: No dosage adjustment provided in manufacturer’s labeling; has not been studied.
Hemodialysis: 300 mg following dialysis every 7 days or after a total of ~12 hours of dialysis (usually once weekly assuming 3 dialysis sessions lasting about 4 hours each)
Alternate recommendations (IDSA [Lucas 2014]):
CrCl <50 mL/minute (and not on hemodialysis) or GFR <60 mL/minute/1.73 m2: Avoid use
Peritoneal dialysis: Use with caution; dose reduction recommended (no specific adjustment provided)
Dosage adjustment in hepatic impairment: No dosage adjustment necessary.
Tablets may be administered without regard to meals. Powder should be mixed with 2-4 ounces of soft food (applesauce, baby food, yogurt) and swallowed immediately (avoids bitter taste); do not mix in liquid (powder may float on top of the liquid even after stirring). Measure powder using only the supplied dosing scoop.
Consider calcium and vitamin D supplementation.
Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Dispense only in original container.
Acyclovir-Valacyclovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Acyclovir-Valacyclovir. Monitor therapy
Adefovir: May diminish the therapeutic effect of Tenofovir Products. Adefovir may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Adefovir. Avoid combination
Aminoglycosides: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Monitor therapy
Atazanavir: Tenofovir Disoproxil Fumarate may decrease the serum concentration of Atazanavir. Atazanavir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Management: Must use ritonavir-boosting in adults; give combo (atazanavir/ritonavir 300mg/100mg and tenofovir 300mg) as a single daily dose with food. Pediatric patients, pregnant patients, and users of H2-blockers require other dose changes. Consider therapy modification
Cidofovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Cidofovir. Monitor therapy
Cobicistat: May enhance the adverse/toxic effect of Tenofovir Products. More specifically, cobicistat may impair proper tenofovir monitoring and dosing. Monitor therapy
Darunavir: Tenofovir Disoproxil Fumarate may increase the serum concentration of Darunavir. Darunavir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy
Diclofenac (Systemic): May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to this combination whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. Consider therapy modification
Didanosine: Tenofovir Disoproxil Fumarate may diminish the therapeutic effect of Didanosine. Tenofovir Disoproxil Fumarate may increase the serum concentration of Didanosine. Management: Avoid concomitant treatment with tenofovir disoproxil fumarate and didanosine. Consider altering even existing, stable treatment to avoid this combination. Avoid combination
Ganciclovir-Valganciclovir: Tenofovir Products may increase the serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase the serum concentration of Tenofovir Products. Monitor therapy
Ledipasvir: May increase the serum concentration of Tenofovir Disoproxil Fumarate. Management: Avoidance of this combination is recommended under some circumstances. Refer to full monograph for details. Consider therapy modification
Lopinavir: May enhance the nephrotoxic effect of Tenofovir Disoproxil Fumarate. Lopinavir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. Consider therapy modification
Simeprevir: Tenofovir Disoproxil Fumarate may decrease the serum concentration of Simeprevir. Simeprevir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy
Telaprevir: May increase the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy
Tipranavir: Tenofovir Disoproxil Fumarate may decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Includes data from both treatment-naive and treatment-experienced HIV patients and in chronic hepatitis B.
Central nervous system: Insomnia (3% to 18%), headache (5% to 14%), pain (12% to 13%), dizziness (8% to 13%), depression (4% to 11%)
Dermatologic: Skin rash (includes maculopapular, pustular, or vesiculobullous rash; pruritus; or urticaria: 5% to 18%), pruritus (16%)
Endocrine & metabolic: Hypercholesterolemia (19% to 22%), increased serum triglycerides (1% to 4%)
Gastrointestinal: Abdominal pain (4% to 22%), nausea (8% to 20%), diarrhea (9% to 16%), vomiting (2% to 13%)
Neuromuscular & skeletal: Decreased bone mineral density (28%; ≥5% at spine or ≥7% at hip), increased creatine phosphokinase (2% to 12%), weakness (6% to 11%)
Miscellaneous: Fever (4% to 11%)
1% to 10%:
Cardiovascular: Chest pain (3%)
Central nervous system: Fatigue (9%), anxiety (6%), peripheral neuropathy (1% to 5%)
Dermatologic: Diaphoresis (3%)
Endocrine & metabolic: Weight loss (2% to 4%), glycosuria (grades 3/4: ≤3%), hyperglycemia (grades 3/4: 2% to 3%), lipodystrophy (1%)
Gastrointestinal: Increased serum amylase (grades 3/4: 4% to 9%), anorexia (3% to 4%), dyspepsia (3% to 4%), flatulence (3% to 4%)
Genitourinary: Hematuria (≤grades 3/4: 3% to 7%)
Hematologic & oncologic: Neutropenia (3%)
Hepatic: Increased serum ALT (2% to 10%), increased serum AST (3% to 5%), increased serum transaminases (2% to 5%), increased serum alkaline phosphatase (1%)
Neuromuscular & skeletal: Back pain (4% to 9%), arthralgia (5%), myalgia (4%)
Renal: Increased serum creatinine (9%), renal failure (7%)
Respiratory: Sinusitis (8%), upper respiratory tract infection (8%), nasopharyngitis (5%), pneumonia (2% to 5%)
Postmarketing and/or case reports: Angioedema, exacerbation of hepatitis B (following discontinuation), Fanconi’s syndrome, hepatitis, hypersensitivity reaction, hypokalemia, hypophosphatemia, immune reconstitution syndrome, increased gamma-glutamyl transferase, interstitial nephritis, lactic acidosis, myopathy, nephrogenic diabetes insipidus, nephrotoxicity, osteomalacia, pancreatitis, polyuria, proteinuria, proximal tubular nephropathy, renal insufficiency, renal tubular necrosis, rhabdomyolysis, severe hepatomegaly with steatosis
Concerns related to adverse effects:
• Decreased bone mineral density: In clinical trials, use has been associated with decreases in bone mineral density in HIV-1 infected adults and increases in bone metabolism markers. Serum parathyroid hormone and 1,25 vitamin D levels were also higher. Decreases in bone mineral density have also been observed in clinical trials of HIV-1 infected pediatric patients. Observations in chronic hepatitis B infected pediatric patients (aged 12-18 years) were similar. In all pediatric clinical trials, skeletal growth (height) appears unaffected. Consider monitoring of bone density in adult and pediatric patients with a history of pathologic fractures or with other risk factors for bone loss or osteoporosis. Consider calcium and vitamin D supplementation for all patients; effect of supplementation has not been studied but may be beneficial. Long-term bone health and fracture risk unknown. If abnormalities are suspected, expert assessment is recommended.
• Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance).
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.
• Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with tenofovir and other nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged nucleoside exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
• Osteomalacia and renal dysfunction: May cause osteomalacia with proximal renal tubulopathy. Bone pain, extremity pain, fractures, arthralgias, weakness and muscle pain have been reported. In patients at risk for renal dysfunction, persistent or worsening bone or muscle symptoms should be evaluated for hypophosphatemia and osteomalacia.
• Pancreatitis: Pancreatitis has been reported; use with caution in patients with a prior history or risk factors for pancreatitis. Discontinue if pancreatitis is suspected.
• Renal toxicity: May cause renal toxicity (acute renal failure and/or Fanconi syndrome); avoid use with concurrent or recent nephrotoxic therapy (including high dose or multiple NSAID use). Acute renal failure has occurred in HIV-infected patients with risk factors for renal impairment who were on a stable tenofovir regimen to which a high dose or multiple NSAID therapy was added. Consider alternatives to NSAIDS in patients taking tenofovir and at risk for renal impairment. Calculate estimated creatinine clearance prior to initiation of therapy and monitor renal function (including recalculation of creatinine clearance and serum phosphorus) during therapy. In patients at risk for renal dysfunction, including patients who have experienced renal events while taking adefovir, assess serum phosphorus, urine glucose, and urine protein prior to and periodically during treatment. Dosage adjustment required in patients with CrCl <50 mL/minute. Use with caution in patients with low body weight or concurrent medications that increase tenofovir levels. IDSA guidelines recommend discontinuing tenofovir (and substituting with alternative antiretroviral therapy) in HIV-infected patients who develop a decline in GFR (a >25% decrease in GFR from baseline and to a level of <60 mL/minute/1.73 m2) during use, particularly in presence of proximal tubular dysfunction (eg, euglycemic glycosuria, increased urinary phosphorus excretion and hypophosphatemia, proteinuria [new onset or worsening]) (IDSA [Lucas 2014]).
• Chronic hepatitis B: [U.S. Boxed Warning]: Severe, acute exacerbation of hepatitis B may occur upon discontinuation. Monitor liver function several months after discontinuing treatment; reinitiation of antihepatitis B therapy may be required. Treatment of HBV in patients with unrecognized/untreated HIV may lead to HIV resistance; patients should be tested for presence of HIV infection prior to initiating therapy
• Hepatic impairment: Use with caution in patients with hepatic impairment. Limited data supporting treatment of chronic hepatitis B in patients with decompensated liver disease; observe for increased adverse reactions, including renal dysfunction.
• Renal impairment: Tenofovir is predominately eliminated renally. Use with caution in patients with renal impairment (CrCl <50 mL/minute); dosage adjustment required. IDSA guidelines recommend avoiding tenofovir in HIV patients with preexisting kidney disease (CrCl <50 mL/minute and not on hemodialysis or GFR <60 mL/minute/1.73 m2) when other effective HIV treatment options exist because data suggest risk of chronic kidney disease (CKD) is increased (IDSA [Lucas 2014]).
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Tenofovir combination products: Do not use concurrently with tenofovir combination products (ie, Atripla, Complera, Stribild, Truvada).
• Elderly: Use with caution in the elderly. Dosage adjustment based on renal function may be required.
• Pediatric: Decreases in bone mineral density may occur; long term effects are unknown. Skeletal growth (height) appears to be unaffected in tenofovir-treated children and adolescents.
• Appropriate use: Hepatitis B coinfection: Treatment of HIV in patients with unrecognized/untreated hepatitis B virus (HBV) may lead to rapid HBV resistance. Patients should be tested for presence of chronic hepatitis B infection prior to initiation of therapy. In patients coinfected with HIV and HBV, an appropriate antiretroviral combination should be selected due to HIV resistance potential; these patients should receive tenofovir dosed for HIV therapy.
• Appropriate use: HIV treatment: Do not use as monotherapy in treatment of HIV. Clinical trials in HIV-infected patients whose regimens contained only three nucleoside reverse transcriptase inhibitors (NRTI) show less efficacy, early virologic failure and high rates of resistance substitutions. Use three NRTI regimens with caution and monitor response carefully. Triple drug regimens with two NRTIs in combination with a non-nucleoside reverse transcriptase inhibitor or a HIV-1 protease inhibitor are usually more effective.
Patients with HIV: CBC with differential, reticulocyte count, creatine kinase, CD4 count, HIV RNA plasma levels, serum phosphorus; serum creatinine (prior to initiation and as clinically indicated during therapy), urine glucose and urine protein (in patients at risk for renal impairment or who experienced renal impairment while taking adefovir), hepatic function tests, bone density (patients with a history of bone fracture or have risk factors for bone loss); testing for HBV is recommended prior to the initiation of antiretroviral therapy; weight (children)
Patients with HBV: HIV status (prior to initiation of therapy); serum phosphorus; serum creatinine (prior to initiation and as clinically indicated during therapy), urine glucose and urine protein (in patients at risk for renal impairment or who experienced renal impairment while taking adefovir); bone density (patients with a history of bone fracture or have risk factors for bone loss); HBV DNA (every 3-6 months during therapy); HBeAg and anti-HBe; LFTs every 3 months during therapy and for several months following discontinuation of tenofovir; signs/symptoms of HBV relapse/exacerbation following discontinuation of therapy
Patients with HIV and HBV coinfection should be monitored for several months following tenofovir discontinuation.
Pregnancy Risk Factor
Adverse events were observed in some animal reproduction studies. Tenofovir has a high level of transfer across the human placenta. Intrauterine growth has not been affected in human studies, but one study found lower length and head circumference. Clinical studies in children have shown bone demineralization with chronic use. No increased risk of overall birth defects has been observed following first trimester exposure according to data collected by the antiretroviral pregnancy registry. Limited data indicate decreased maternal bioavailability during the third trimester; dose adjustments are not needed. Cases of lactic acidosis/hepatic steatosis syndrome related to mitochondrial toxicity have been reported in pregnant women with prolonged use of nucleoside analogues. It is not known if pregnancy itself potentiates this known side effect; however, women may be at increased risk of lactic acidosis and liver damage. In addition, these adverse events are similar to other rare but life-threatening syndromes which occur during pregnancy (eg, HELLP syndrome). Hepatic enzymes and electrolytes should be monitored in women receiving nucleoside analogues and clinicians should watch for early signs of the syndrome. In addition, mitochondrial dysfunction may develop in infants following in utero exposure. Renal function should also be monitored. The DHHS Perinatal HIV Guidelines consider tenofovir in combination with either emtricitabine or lamivudine to be a preferred NRTI backbone for use in antiretroviral-naive pregnant women. The DHHS Perinatal HIV Guidelines consider emtricitabine plus tenofovir, or lamivudine plus tenofovir as recommended dual NRTI/NtRTI backbones for HIV/HBV coinfected pregnant women. Hepatitis B flare may occur if tenofovir is discontinued postpartum.
Regardless of CD4 count or HIV RNA copy number, all HIV-infected pregnant women should receive a combination antiretroviral (ARV) drug regimen. A combination of antepartum, intrapartum, and infant ARV prophylaxis is recommended. ARV therapy should be started as soon as possible in women with symptomatic infection. Although earlier initiation may be more effective in reducing the perinatal transmission of HIV, also consider maternal conditions (eg, nausea and vomiting) and the potential risks of first trimester fetal exposure for specific agents. A scheduled cesarean delivery at 38 weeks' gestation is recommended for all women with HIV RNA >1000 copies/mL or unknown concentrations near delivery in order to decrease transmission. If ARV therapy must be interrupted for <24 hours during the peripartum period, stop then restart all medications simultaneously in order to decrease the chance of developing resistance. Long-term follow-up is recommended for all infants exposed to ARV medications. In couples who want to conceive, the HIV-infected partner should attain maximum viral suppression prior to conception.
Health care providers are encouraged to enroll pregnant women exposed to antiretroviral medications in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com). Health care providers caring for HIV-infected women and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2014).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, dizziness, nausea, diarrhea, or asthenia. Have patient report immediately to prescriber signs of renal impairment, signs of hepatic impairment, signs of lactic acidosis, depression, osteodynia, myalgia, painful extremities, lipodystrophy, or sign of infection (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
More about tenofovir
- Other brands: Viread