Severe acute exacerbations of hepatitis B virus (HBV) have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in HBV-infected patients who discontinue anti-hepatitis B therapy. If appropriate, resumption of anti-hepatitis B therapy may be warranted.
HIV-1 infection, treatment: Note: Gene mutation and antiretroviral (ARV) resistance patterns should be evaluated (refer to https://www.iasusa.org/ for more information) when necessary.
Weight-directed dosing: Children ≥2 years weighing ≥10 kg and Adolescents: Oral: 8 mg/kg/dose once daily; maximum daily dose: 300 mg/day
Dosage form specific fixed dosing:
Oral powder: Children ≥2 years weighing ≥10 kg and Adolescents: Oral:
Note: Only measure with the provided scoop. One level scoop = 40 mg tenofovir disoproxil fumarate
10 to <12 kg: 80 mg (2 scoops) once daily
12 to <14 kg: 100 mg (2.5 scoops) once daily
14 to <17 kg: 120 mg (3 scoops) once daily
17 to <19 kg: 140 mg (3.5 scoops) once daily
19 to <22 kg: 160 mg (4 scoops) once daily
22 to <24 kg: 180 mg (4.5 scoops) once daily
24 to <27 kg: 200 mg (5 scoops) once daily
27 to <29 kg: 220 mg (5.5 scoops) once daily
29 to <32 kg: 240 mg (6 scoops) once daily
32 to <34 kg: 260 mg (6.5 scoops) once daily
34 to <35 kg: 280 mg (7 scoops) once daily
≥35 kg: 300 mg (7.5 scoops) once daily
Oral tablets: Children ≥2 years weighing ≥17 kg and Adolescents: Oral:
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
HIV-1 nonoccupational postexposure prophylaxis (nPEP) (HHS [nPEP] 2016):
Children ≥2 years: Oral: Age- and weight-appropriate dosing (see HIV-1 infection, treatment above) for 28 days in combination with other antiretroviral agents. Initiate therapy within 72 hours of exposure.
Adolescents: The combination product is recommended (see Emtricitabine and Tenofovir Disoproxil Fumarate monograph)
Hepatitis B infection, chronic: Children ≥2 years weighing ≥10 kg and Adolescents: Oral: 8 mg/kg/dose once daily; maximum daily dose: 300 mg/day; see HIV treatment dosing for product-specific dosing. In trials, oral antivirals were continued for 1 to 4 years; Hepatitis B e antigen (HBeAg) seroconversion has been suggested as a therapeutic endpoint followed by an additional 12 months of consolidation (AASLD [Terrault 2016]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥2 years and Adolescents: There are no dosage adjustments provided in manufacturer's labeling. Dosage should be decreased in patients with CrCl <50 mL/minute (HHS [pediatric] 2018).
Children ≥2 years and Adolescents: No dosage adjustment required.
(For additional information see "Tenofovir disoproxil fumarate: Drug information")
Hepatitis B infection: Oral: 300 mg once daily
Note: Concurrent use with adefovir and/or tenofovir combination products should be avoided.
Treatment duration (AASLD practice guidelines): Treatment duration for nucleos(t)ide analog-based therapy (eg, tenofovir) is variable and influenced by HBeAg status, duration of HBV suppression, and presence of cirrhosis/decompensation (AASLD [Terrault 2016]):
Patients without cirrhosis:
Hepatitis B e antigen (HBeAg) positive immune-active chronic hepatitis: Treat until HBeAg seroconversion; after seroconversion, prolonged duration of therapy is often required in patients treated with nucleos(t)ide analogues. Optimal duration is unknown; however, consolidation therapy is generally a minimum of 12 months of persistently normal ALT and undetectable serum HBV DNA levels after HBeAg seroconversion.
HBeAg-negative immune-active chronic hepatitis: Indefinite antiviral therapy is suggested unless there is competing rationale for discontinuation (risk/benefit decision); treatment discontinuation may be considered in patients with loss of HBsAg; however, there is insufficient evidence to guide decisions in these patients.
Patients with cirrhosis:
HBeAg-positive immune-active chronic hepatitis: In patients who seroconvert on therapy, continue antiviral therapy indefinitely due to concerns with decompensation and death, unless there is a strong competing rationale for discontinuation.
HBeAg-negative immune-active chronic hepatitis: Treatment discontinuation is not recommended due to potential for decompensation and death (limited data).
HIV-1 infection, treatment: Oral: 300 mg once daily (in combination with other antiretrovirals).
HIV-1 nonoccupational postexposure prophylaxis (nPEP) (off-label use): Oral: 300 mg once daily for 28 days (in combination with other antiretroviral agents). Initiate therapy within 72 hours of exposure. Note: The fixed dose emtricitabine and tenofovir disoproxil fumarate combination product is recommended for these components of the 3-drug regimen (HHS [nPEP] 2016)
HIV-1 occupational postexposure, prophylaxis (oPEP) (off-label use): Oral: 300 mg once daily in combination with emtricitabine and raltegravir; initiate therapy as soon as possible after occupational exposure (and within 72 hours) and continue for 4 weeks. Note: The fixed dose emtricitabine and tenofovir disoproxil fumarate combination product is recommended for these components of the 3-drug regimen (Kuhar 2013)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Chronic kidney disease prior to treatment:
Note: Tenofovir is associated with proximal tubular injury, Fanconi syndrome, and progression of chronic kidney disease (CKD). Avoid use in patients with preexisting CKD (GFR <60 mL/minute/1.73 m2 or CrCl <50 mL/minute), especially if the patient has any proximal tubular impairment (IDSA [Lucas 2014]). If tenofovir disoproxil fumarate cannot be avoided, the following dose adjustments are recommended:
Altered kidney function:
CrCl ≥50 mL/minute: No dosage adjustment necessary (Kearney 2006; manufacturer's labeling).
CrCl 30 to <50 mL/minute: 300 mg every 48 hours (Bregigeon 2017; Fung 2014; HHS [adult] 2021; IDSA [Lucas 2014]; Kearney 2006; Langness 2013; Liem 2021; Swanepoel 2018; manufacturer's labeling) or 150 mg once daily (Cressey 2015).
CrCl 10 to <30 mL/minute: 300 mg twice weekly (every 72 to 96 hours) (HHS [adult] 2021; IDSA [Lucas 2014]; Kearney 2006; Swanepoel 2018; manufacturer's labeling).
CrCl <10 mL/minute: Has not been studied; avoid use. If no alternative therapy is available, then may consider 300 mg every 7 days; use with caution and close monitoring (Swanepoel 2018; expert opinion)
Hemodialysis, intermittent (thrice weekly): 300 mg following dialysis every 7 days; use with caution and close monitoring (Aomura 2020; Dams 2020; Di Biagio 2004; HHS [adult] 2021; Izzedine 2003; Kearney 2006; Swanepoel 2018; manufacturer's labeling). Note: One small study in patients with HIV on hemodialysis receiving 300 mg once weekly reported elevated steady-state tenofovir plasma and intracellular peripheral blood mononuclear cell concentrations compared to healthy volunteers; less frequent or lower doses may be effective, although more research is needed (Slaven 2016).
Peritoneal dialysis: Avoid use if possible (has not been studied). If no alternative therapy is available, then may consider 300 mg every 7 days; use with caution and close monitoring (expert opinion). Note: One case report noted a serum trough level above the accepted therapeutic window with once-weekly dosing; adjustment of dose to 300 mg every 2 weeks resulted in a serum trough level within the accepted therapeutic window (Aleman 2015).
CRRT: Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted.
Dose as for CrCl 10 to <30 mL/minute (expert opinion derived from a single case report [Dams 2020]).
Acute kidney injury during treatment: Infectious Diseases Society of America 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]).
No dosage adjustment necessary.
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]
Generic: 300 mg
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as disoproxil fumarate:
Viread: 300 mg [contains fd&c blue #2 aluminum lake]
Generic: 300 mg
Oral:
Powder: Must administer with food. Measure dose only using the supplied dosing scoop (1 level scoop = 40 mg tenofovir disoproxil fumarate. Mix powder well with 2 to 4 ounces of soft food that does not require chewing (applesauce, baby food, yogurt) and swallow immediately (avoids bitter taste); ensure that entire mixture is ingested. Do not mix in liquid (powder may float on top of the liquid even after stirring).
Tablets: May be administered without regard to meals. Do not crush oral tablets (HHS [pediatric] 2018).
Tablets may be administered without regard to meals. Powder should be mixed with 2 to 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.
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.
Treatment of HIV-1 infection in combination with other antiretroviral agents (FDA approved in ages ≥2 years weighing ≥10 kg and adults); Note: HIV regimens consisting of 3 antiretroviral agents from at least 2 classes are strongly recommended; treatment of chronic hepatitis B virus (HBV) (FDA approved in ages ≥2 years weighing ≥10 kg and adults). Has also been used for HIV-1 nonoccupational postexposure prophylaxis (nPEP).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Includes data from both treatment-naive and treatment-experienced HIV patients and in chronic hepatitis B.
>10%:
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, dyspnea, 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, myasthenia, myopathy, nephrogenic diabetes insipidus, nephrotoxicity, osteomalacia, pancreatitis, polyuria, proteinuria, proximal tubular nephropathy, renal insufficiency, renal tubular necrosis, rhabdomyolysis, severe hepatomegaly with steatosis
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to tenofovir or any component of the formulation
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 were similar. In all pediatric clinical trials, skeletal growth (height) appears unaffected. Effects on long-term bone health and future fracture risk in adult and pediatric patients, including long-term effects on skeletal growth in pediatric patients and effects of extended duration in younger children, is unknown. 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. If abnormalities are suspected, expert assessment is recommended.
• 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: Lactic acidosis and severe hepatomegaly with steatosis, sometimes fatal, have been reported with the use of nucleoside analogs, alone or in combination with other antiretrovirals. Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (marked 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.
• 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 disoproxil fumarate and at risk for renal impairment. Assess serum creatinine, estimated creatinine clearance (CrCl), urine protein, and urine glucose prior to initiation of therapy and during therapy; in patients with chronic kidney disease, also assess serum phosphorus. Dosage adjustment required in patients with CrCl <50 mL/minute. 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]).
Disease-related concerns:
• Chronic hepatitis B: [US Boxed Warning]: Severe, acute exacerbation of hepatitis B may occur upon discontinuation. Monitor hepatic function several months after discontinuing treatment; reinitiation of antihepatitis B therapy may be required. Posttreatment hepatitis B exacerbation may lead to hepatic decompensation and hepatic failure, especially in patients with advanced hepatic disease or cirrhosis. 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: 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:
• Concomitant therapy: Do not use in combination with other tenofovir disoproxil fumarate or tenofovir alafenamide products, or with adefovir.
Other warnings/precautions:
• Appropriate use: Hepatitis B coinfection: 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.
Tenofovir disoproxil fumarate (TDF) disrupts vitamin D metabolism and has been associated with decreased bone mineral density (BMD) in adults and children. Plasma concentrations of the TDF metabolite plasma tenofovir (TFV) have been associated with endocrine disruption and low BMD; tenofovir alafenamide (TAF) is associated with lower TFV concentrations and less decline in BMD than TDF. Data suggest the impact may be greater in children who are less mature (eg, Sexual Maturity Ratings [SMRs] 1 to 2 [previously Tanner Stages]) than in those with more advanced pubertal development (SMR ≥3). The potential for BMD loss during the important period of rapid bone accrual in childhood and early adolescence is concerning and favors use of abacavir or TAF in children with SMRs 1 to 3 (children with perinatally-acquired HIV are already at risk for low peak bone mass). Prior to initiation of therapy, assessment of benefits versus potential risk should be assessed; with TDF therapy, monitor BMD; consider supplementation with calcium and vitamin D. Even in the absence of baseline vitamin D deficiency, improvement in lumbar spine BMD with vitamin D supplementation was observed in a group of young adults (18 to 25 years) receiving chronic TDF; therefore, some practitioners recommend vitamin D supplementation in all patients treated with TDF (HHS [pediatric] 2018).
Substrate of BCRP/ABCG2, P-glycoprotein/ABCB1 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits MRP2
Acyclovir-Valacyclovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Acyclovir-Valacyclovir. Risk C: 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. Risk X: Avoid combination
Aminoglycosides: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Risk C: Monitor therapy
Aminosalicylic Acid: May decrease the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Asciminib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Atazanavir: Tenofovir Disoproxil Fumarate may decrease the serum concentration of Atazanavir. Atazanavir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Management: Use boosted atazanavir in adults; give combo (atazanavir/ritonavir or atazanavir/cobicistat with tenofovir) as a single daily dose with food. Pediatric patients, pregnant patients, and use of H2-blockers require dose changes. See Lexi Interact monograph. Risk D: Consider therapy modification
Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Risk C: Monitor therapy
Cidofovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Cidofovir. Risk C: Monitor therapy
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
Cobicistat: Tenofovir Disoproxil Fumarate may enhance the adverse/toxic effect of Cobicistat. More specifically, cobicistat may impair proper tenofovir disoproxil fumarate monitoring and dosing. Risk C: Monitor therapy
Darunavir: Tenofovir Disoproxil Fumarate may increase the serum concentration of Darunavir. Darunavir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Didanosine: Tenofovir Disoproxil Fumarate may diminish the therapeutic effect of Didanosine. Tenofovir Disoproxil Fumarate may increase the serum concentration of Didanosine. Management: Avoid use of tenofovir disoproxil fumarate and didanosine when possible. If combined in adults with CrCL greater than 60 mL/min, decrease didanosine to 250 mg daily if 60 kg or more or to 200 mg if less than 60 kg. Avoid if CrCL is less than 60 mL/min. Risk D: Consider therapy modification
Eltrombopag: May increase the serum concentration of BCRP/ABCG2 Substrates BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Encorafenib: May increase the serum concentration of BCRP/ABCG2 Substrates BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Ganciclovir-Valganciclovir: Tenofovir Products may increase the serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase the serum concentration of Tenofovir Products. Risk C: Monitor therapy
Gilteritinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Gilteritinib: May increase the serum concentration of BCRP/ABCG2 Substrates BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Lasmiditan: May increase the serum concentration of BCRP/ABCG2 Substrates BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Ledipasvir: May increase the serum concentration of Tenofovir Disoproxil Fumarate. Management: Avoid this combination if TDF is used as part of the elvitegravir/cobicistat/emtricitabine/TDF product. Consider alternatives when TDF is used with a ritonavir or cobicistat boosted protease inhibitor. Monitor for increased TDF toxicities if combined. Risk D: Consider therapy modification
Lopinavir: May enhance the nephrotoxic effect of Tenofovir Disoproxil Fumarate. Lopinavir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Lumacaftor and Ivacaftor: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may decrease the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Risk C: Monitor therapy
Mitapivat: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Risk C: 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 due to a potential risk of acute renal failure. Diclofenac appears to confer the most risk. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the nephrotoxic effect of Tenofovir Products. Risk C: Monitor therapy
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy
Osimertinib: May increase the serum concentration of BCRP/ABCG2 Substrates BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Regorafenib: May increase the serum concentration of BCRP/ABCG2 Substrates BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Rolapitant: May increase the serum concentration of BCRP/ABCG2 Substrates BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Management: Monitor patients receiving rolapitant for increased exposure to and/or effects of BCRP/ABCG2 substrates. Use the lowest effective rosuvastatin dose when used in combination with rolapitant. Risk C: Monitor therapy
Tafamidis: May increase the serum concentration of BCRP/ABCG2 Substrates BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Tedizolid: May increase the serum concentration of BCRP/ABCG2 Substrates BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Teriflunomide: May increase the serum concentration of BCRP/ABCG2 Substrates BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Tipranavir: Tenofovir Disoproxil Fumarate may decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Voxilaprevir: Tenofovir Disoproxil Fumarate may increase the serum concentration of Voxilaprevir. Voxilaprevir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Fatty meals may increase the bioavailability of tenofovir. Management: May administer with or without food.
Consider calcium and vitamin D supplementation.
The Health and Human Services perinatal HIV guidelines consider tenofovir disoproxil fumarate a preferred nucleoside reverse transcriptase inhibitor for patients living with HIV who are not yet pregnant but are trying to conceive.
Tenofovir disoproxil fumarate is one of the agents recommended for preexposure prophylaxis (PrEP) in couples with discordant HIV status who are planning a pregnancy. The partner without HIV should begin therapy 20 days prior to attempting conception. Up to 20 days of therapy are required to achieve protective drug concentrations in cervicovaginal tissue, therefore continued use of condoms to prevent HIV exposure is recommended during this time. PrEP should continue for 28 days after attempting conception or condomless sex exposure.
Viral suppression sustained below the limits of detection with antiretroviral therapy (ART) and modification of therapy (if needed) is recommended in patients of all genders who are living with HIV and planning a pregnancy. Optimization of the health of the person who will become pregnant and a discussion of the potential risks and benefits of ART during pregnancy is also recommended prior to conception.
Health care providers caring for couples planning a pregnancy when one or both partners are living with HIV may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2020).
Tenofovir has a high level of transfer across the human placenta following maternal use of tenofovir disoproxil fumarate.
No increased risk of overall teratogenic effects has been observed following first trimester exposure according to data collected by the antiretroviral pregnancy registry. Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes, including preterm delivery, stillbirth, low birth weight, and small-for-gestational-age infants. Actual risks may be influenced by maternal factors such as disease severity, gestational age at initiation of therapy, and specific ART regimen; therefore, close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children not diagnosed with HIV infection but who were exposed to ART in utero or as a neonate and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction.
The Health and Human Services (HHS) perinatal HIV guidelines consider tenofovir disoproxil fumarate a preferred nucleoside reverse transcriptase inhibitor (NRTI) for pregnant patients living with HIV who are antiretroviral naive, who have had ART therapy in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). In addition, patients who become pregnant while taking tenofovir disoproxil fumarate may continue if viral suppression is effective and the regimen is well tolerated.
The HHS perinatal HIV guidelines consider tenofovir disoproxil fumarate in combination with emtricitabine or lamivudine to be preferred dual NRTI backbone for initial therapy in antiretroviral-naive patients who are pregnant . The guidelines also consider tenofovir disoproxil fumarate plus emtricitabine or lamivudine as recommended dual NRTI backbone for HIV/hepatitis B virus coinfected pregnant patients. Hepatitis B flare may occur if tenofovir disoproxil fumarate is discontinued.
Tenofovir disoproxil fumarate is one of the agents recommended for preexposure prophylaxis (PrEP) in couples with discordant HIV status; PrEP may be considered for uninfected pregnant patients who have a partner with HIV. Tenofovir disoproxil fumarate is also a preferred component of a regimen when acute HIV infection is detected during pregnancy. Maternal exposure is modestly decreased during the third trimester; dose adjustments are not needed.
ART is recommended for all patients who are pregnant and living with HIV to maintain the viral load below the limit of detection and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Monitoring of patients who are pregnant is more frequent than in patients who are not pregnant. ART should be continued postpartum for all patients living with HIV and can be modified after delivery.
The American Association for the Study of Liver Diseases (AASLD) chronic hepatitis B treatment guidelines provide recommendations for the management of hepatitis B-infected pregnant patients (not coinfected with HIV). Patients meeting standard indications for HBV therapy should be treated; patients without standard indications but with an HBV DNA >200,000 units/mL in the second trimester should consider treatment to reduce the risk of perinatal transmission. Tenofovir disoproxil fumarate is the preferred antiviral for use in pregnancy, with most studies initiating antiviral therapy at 28 to 32 weeks gestation and discontinuing antiviral therapy between birth to 3 months postpartum (monitor for ALT flares every 3 months for 6 months following discontinuation). There are insufficient long-term safety data in infants born to patients who took antiviral agents during pregnancy (AASLD [Terrault 2018]).
Health care providers are encouraged to enroll patients exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or http://www.APRegistry.com). Health care providers caring for pregnant patients who are living with HIV and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2020).
HIV: General recommendations: Management of HIV infection requires extensive monitoring; refer to current guidelines (https://aidsinfo.nih.gov/) for additional guidance. Antiretroviral (ARV) drug-resistance testing is recommended before initiation of therapy in treatment-naive patients. After initiation of or change in ARV therapy regimen, pediatric patients should be evaluated for clinical adverse effects and treatment adherence at 1 to 2 weeks, and laboratory testing for drug toxicity should occur at 2 to 4 weeks; monitor for therapy adherence, effectiveness, and toxicities every 3 to 4 months.
Drug-specific monitoring: Frequency may vary based on several factors including age, concomitant therapy, and clinical response; refer to current guidelines for additional information.
Screen for hepatitis B prior to starting therapy (in patients who previously demonstrated no immunity to hepatitis B). For patients with hepatitis B coinfection, monitor hepatic function and hepatitis B viral load for several months after therapy with tenofovir is stopped. Serum electrolytes (including anion gap), 25-OH-Vitamin D levels, serum phosphate, SCr, lipid profiles, urine protein and glucose and/or urinalysis, serum lactate (if clinical presentation indicates need).
Urine albumin to protein ratio may be helpful in identifying the nonalbumin proteinuria seen in tenofovir disoproxil fumarate-associated nephrotoxicity. Some experts recommend obtaining a DXA scan prior to therapy and every 6 to 12 months during therapy for patients in pre- and early puberty (Sexual Maturity Rating [SMR] stages 1 and 2), adolescent women receiving medroxyprogesterone, and children with compelling indications (eg, cerebral palsy).
Hepatitis B: Test patients for HIV prior to starting therapy. Serum electrolytes (including anion gap), 25-OH-Vitamin D levels, serum phosphate, SCr, lipid profiles, urine protein and glucose and/or urinalysis, hepatic function tests, serum lactate (if clinical presentation indicates need).
Urine albumin to protein ratio may be helpful in identifying the nonalbumin proteinuria seen in tenofovir disoproxil fumarate-associated nephrotoxicity. Some experts recommend obtaining a DXA scan prior to therapy and every 6 to 12 months during therapy for patients in pre- and early puberty (SMR stages 1 and 2), adolescent women receiving medroxyprogesterone, and children with compelling indications (eg, cerebral palsy).
Liver enzymes and HBV RNA plasma levels should be monitored as part of routine hepatitis B disease monitoring. Children with hepatitis B who stop antiviral therapy should be monitored every 3 months for at least 1 year for recurrent viremia, ALT flares, and clinical decompensation (AASLD [Terrault 2016]).
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.
Distribution: Vd: 1.2 to 1.3 L/kg
Protein binding: <7% to serum proteins
Metabolism: Tenofovir disoproxil fumarate (TDF) is converted intracellularly by hydrolysis (by non-CYP enzymes) to tenofovir, then phosphorylated to the active tenofovir diphosphate
Bioavailability:
Tablets: ~25% (fasting); increases ~40% with high-fat meal
Powder: Peak serum concentrations are 26% lower compared to tablet, but the mean AUCs are similar
Half-life elimination: Serum: 17 hours; intracellular: 10 to 50 hours
Time to peak, serum: Fasting: 36 to 84 minutes; With high-fat meal: 96 to 144 minutes
Excretion: Urine (70% to 80%) via filtration and active secretion, primarily as unchanged tenofovir within 72 hours; after multiple oral doses (administered with food): 32% ± 10% is excreted in the urine within 24 hours
Clearance: Total body clearance is decreased in patients with renal impairment
Renal function impairment: In patients with CrCl <50 mL/minute or with ESRD requiring dialysis, Cmax and AUC of tenofovir were increased.
Powder (Viread Oral)
40 mg/g (per gram): $13.67
Tablets (Tenofovir Disoproxil Fumarate Oral)
300 mg (per each): $3.65 - $40.53
Tablets (Viread Oral)
150 mg (per each): $46.47
200 mg (per each): $46.47
250 mg (per each): $46.47
300 mg (per each): $50.14
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