Version July 2025
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.
Note: International considerations: Doses are expressed as tenofovir disoproxil fumarate salt, consistent with US and Canadian labeling; in some other countries, dosing may be expressed as tenofovir disoproxil base. Tenofovir disoproxil fumarate 300 mg is equivalent to tenofovir disoproxil base 245 mg.
Hepatitis B virus infection, treatment: Tenofovir disoproxil fumarate: Oral: 300 mg once daily.
Treatment duration: Treatment duration is variable and influenced by hepatitis B e antigen (HBeAg) status, duration of hepatitis B virus (HBV) suppression, and presence of cirrhosis/decompensation (Ref).
Patients without cirrhosis:
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 (Ref).
HBeAg-negative immune-active chronic hepatitis: Indefinite antiviral therapy is suggested unless there is compelling 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 (Ref).
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 (Ref).
HBeAg-negative immune-active chronic hepatitis: Treatment discontinuation is not recommended due to potential for decompensation and death (limited data) (Ref).
Viral breakthrough: Patients with confirmed viral breakthrough (HBV DNA ≥100 IU/mL with previously undetectable levels [<10 IU/mL] or >1 log increase in HBV DNA compared to nadir) should either be switched to an alternative antiviral monotherapy agent with a high genetic barrier to resistance or receive a second antiviral agent with a complementary resistance profile; consult current clinical practice guidelines for recommended agents (Ref).
Hepatitis B virus reactivation prophylaxis, immunocompromised patients (off-label use): Tenofovir disoproxil fumarate: Oral: 300 mg once daily (Ref).
Hepatitis B virus reinfection prophylaxis, post liver transplant (off-label use): Tenofovir disoproxil fumarate: Oral: 300 mg once daily (Ref).
Hepatitis B/HIV coinfection, treatment (in patients with both infections requiring treatment): Tenofovir disoproxil fumarate: Oral: 300 mg once daily, in combination with lamivudine or emtricitabine and other appropriate antiretrovirals (Ref).
HIV-1 infection, treatment: Tenofovir disoproxil fumarate: Oral: 300 mg once daily in combination with other antiretrovirals.
HIV-1 nonoccupational postexposure prophylaxis (nPEP) (off-label use): Tenofovir disoproxil fumarate: 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 (Ref).
HIV-1 occupational postexposure prophylaxis (oPEP) (off-label use): Tenofovir disoproxil fumarate: 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 (Ref).
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 A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: International considerations: Doses are expressed as tenofovir disoproxil fumarate salt, consistent with US and Canadian labeling; in some other countries, dosing may be expressed as tenofovir disoproxil base. Tenofovir disoproxil fumarate 300 mg is equivalent to tenofovir disoproxil base 245 mg.
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 (Ref). If tenofovir disoproxil fumarate cannot be avoided, the following dose adjustments are recommended:
Altered kidney function:
CrCl ≥50 mL/minute: No dosage adjustment necessary (Ref).
CrCl 30 to <50 mL/minute: Tenofovir disoproxil fumarate: 300 mg every 48 hours (Ref) or 150 mg once daily (Ref).
CrCl 10 to <30 mL/minute: Tenofovir disoproxil fumarate: 300 mg twice weekly (every 72 to 96 hours) (Ref).
CrCl <10 mL/minute: Tenofovir disoproxil fumarate: 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 (Ref).
Hemodialysis, intermittent (thrice weekly): Tenofovir disoproxil fumarate: 300 mg following dialysis every 7 days; use with caution and close monitoring (Ref). 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 (Ref).
Peritoneal dialysis: Tenofovir disoproxil fumarate: 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 (Ref). 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 (Ref).
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 (Ref).
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]) (Ref).
No dosage adjustment necessary.
Refer to adult dosing.
(For additional information see "Tenofovir disoproxil fumarate: Pediatric drug information")
Note: International Considerations: Doses are expressed as tenofovir disoproxil fumarate salt, consistent with US and Canadian labeling; in some other countries, dosing may be expressed as tenofovir disoproxil base. Tenofovir disoproxil fumarate 300 mg is equivalent to tenofovir disoproxil base 245 mg.
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: Tenofovir disoproxil fumarate: Oral: 8 mg/kg/dose once daily; maximum dose: 300 mg/dose.
Dosage form-specific fixed dosing: Tenofovir disoproxil fumarate:
Oral powder: Children ≥2 years weighing ≥10 kg and Adolescents: Oral:
|
Patient Weight |
Dose (mg) of Tenofovir Disoproxil Fumarate Once Daily |
Scoops of Powder (One Level Scoop = 40 mg Tenofovir Disoproxil Fumarate) |
|---|---|---|
|
10 to <12 kg |
80 mg once daily |
2 scoops |
|
12 to <14 kg |
100 mg once daily |
2.5 scoops |
|
14 to <17 kg |
120 mg once daily |
3 scoops |
|
17 to <19 kg |
140 mg once daily |
3.5 scoops |
|
19 to <22 kg |
160 mg once daily |
4 scoops |
|
22 to <24 kg |
180 mg once daily |
4.5 scoops |
|
24 to <27 kg |
200 mg once daily |
5 scoops |
|
27 to <29 kg |
220 mg once daily |
5.5 scoops |
|
29 to <32 kg |
240 mg once daily |
6 scoops |
|
32 to <34 kg |
260 mg once daily |
6.5 scoops |
|
34 to <35 kg |
280 mg once daily |
7 scoops |
|
≥35 kg |
300 mg once daily |
7.5 scoops |
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) (Ref):
Children ≥2 years: Tenofovir disoproxil fumarate: 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 monograph).
Chronic hepatitis B: Children ≥2 years weighing ≥10 kg and Adolescents: Tenofovir disoproxil fumarate: Oral: 8 mg/kg/dose once daily; maximum dose: 300 mg/dose; see HIV treatment dosing for product-specific dosing (Ref). In trials, oral antivirals were continued for 1 to 4 years; hepatitis B e antigen (HBeAg) seroconversion has been suggested as a therapeutic end point followed by an additional 12 months of consolidation (Ref).
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 (Ref).
Children ≥2 years and Adolescents: No dosage adjustment necessary.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported with monotherapy in treatment-experienced HIV infected adults and chronic hepatitis B virus (HBV) adults unless otherwise specified.
>10%:
Endocrine & metabolic: Increased serum triglycerides (11%)
Gastrointestinal: Diarrhea (11% to 16%), nausea (8% to 11%)
Nervous system: Asthenia (7% to 11%), pain (12%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (grades 3/4: 2% to 12%)
1% to 10%:
Cardiovascular: Chest pain (3%)
Dermatologic: Diaphoresis (3%), skin rash (5% to 7%, including maculopapular rash, pruritus, pustular rash, urticaria, vesiculobullous dermatitis)
Endocrine & metabolic: Increased serum glucose (grades 3/4: 3%), weight loss (2% to 4%)
Gastrointestinal: Abdominal pain (4% to 7%), anorexia (3% to 4%), dyspepsia (3% to 4%), flatulence (3% to 4%), increased serum amylase (grades 3/4: 4% to 7%), vomiting (4% to 7%)
Genitourinary: Glycosuria (grades 3/4: 3%)
Hematologic & oncologic: Increased serum neutrophils (grades 3/4: 2%)
Hepatic: Increased serum alanine aminotransferase (grades 3/4: 10%), increased serum aspartate aminotransferase (grades 3/4: 4%)
Nervous system: Depression (4% to 8%), dizziness (3%), fatigue (≥5%), headache (8%), insomnia (3% to 4%), peripheral neuropathy (5%)
Neuromuscular & skeletal: Back pain (4%), myalgia (4%)
Respiratory: Nasopharyngitis (≥5%), pneumonia (2% to 3%)
Miscellaneous: Fever (4%)
Frequency not defined: Neuromuscular & skeletal: Decreased bone mineral density (≥4% decrease: children and adolescents with HBV)
Postmarketing (any indication):
Dermatologic: Lichenoid eruption (Gupta 2015), skin photosensitivity (Verma 2012)
Endocrine & metabolic: Hyperparathyroidism (Zeng 2023), hypokalemia (Fioroti 2022), hypophosphatemia (Fioroti 2022), lactic acidosis (Jung 2017), nephrogenic diabetes insipidus (Zilwa 2023)
Gastrointestinal: Pancreatitis
Genitourinary: Polyuria, proteinuria (Fioroti 2022)
Hepatic: Exacerbation of hepatitis B (following discontinuation), liver steatosis, hepatitis, hepatomegaly with steatosis, increased gamma-glutamyl transferase
Hypersensitivity: Hypersensitivity reaction (including angioedema) (Sousa 2018)
Nervous system: Myasthenia
Neuromuscular & skeletal: Bone fracture (Fioroti 2022), ostealgia (Fioroti 2022), osteomalacia (Iatan 2021), osteopenia (Li 2022), osteoporosis (Zeng 2023), myopathy, rhabdomyolysis
Renal: Increased serum creatinine (Fioroti 2022), nephrotoxicity (including acute kidney injury, Fanconi syndrome, interstitial nephritis, kidney failure, proximal tubular nephropathy, renal tubular necrosis) (Cho 2016; Li 2023; Zilwa 2023)
Respiratory: Dyspnea
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 in adults with HIV-1, use has been associated with decreases in bone mineral density 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.
• Kidney toxicity: May cause kidney 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 kidney impairment.
Disease-related concerns:
• Liver impairment: Use with caution in patients with liver impairment. Limited data supporting treatment of chronic hepatitis B in patients with decompensated liver disease; observe for increased adverse reactions, including kidney dysfunction.
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 tenofovir (TFV) have been associated with endocrine disruption and low BMD; tenofovir alafenamide (TAF) is associated with lower plasma 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 plasma vitamin D concentrations; supplement with vitamin D as needed; calcium carbonate supplementation may also be considered. Monitoring of BMD may be considered in patients with additional risk factors for decreased bone density (HHS [pediatric] 2022).
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 (indigo carm) aluminum lake]
Generic: 300 mg
May be product dependent
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
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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 (indigo carm) aluminum lake]
Generic: 300 mg
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.
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.
Hepatitis B virus infection, treatment: Treatment of hepatitis B virus (HBV) in patients ≥2 years of age weighing ≥10 kg.
HIV-1 infection, treatment: Treatment of HIV-1 infection in patients ≥2 years of age weighing ≥10 kg, in combination with other antiretroviral agents.
Hepatitis B virus reactivation prophylaxis, immunocompromised patients; Hepatitis B virus reinfection prophylaxis, post liver transplant; HIV-1 nonoccupational postexposure prophylaxis; HIV-1 occupational postexposure prophylaxis
TDF is an error-prone abbreviation (mistaken as tenofovir alafenamide)
Substrate of BCRP, OAT1/3, P-glycoprotein (Major with inhibitors), P-glycoprotein (Minor with inducers); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits MRP2;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Acyclovir-Valacyclovir: May increase serum concentration of Tenofovir Products. Tenofovir Products may increase serum concentration of Acyclovir-Valacyclovir. Risk C: Monitor
Adefovir: May decrease therapeutic effects of Tenofovir Products. Adefovir may increase serum concentration of Tenofovir Products. Tenofovir Products may increase serum concentration of Adefovir. Risk X: Avoid
Aminoglycosides: May increase serum concentration of Tenofovir Products. Tenofovir Products may increase serum concentration of Aminoglycosides. Risk C: Monitor
Aminosalicylic Acid: May decrease serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor
Asciminib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Atazanavir: Tenofovir Disoproxil Fumarate may decrease serum concentration of Atazanavir. Atazanavir may increase 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
Atidarsagene Autotemcel: Antiretroviral Agents may decrease therapeutic effects of Atidarsagene Autotemcel. Risk X: Avoid
Belumosudil: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid coadministration of belumosudil with these substrates of BCRP for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the BCRP substrate may be required. Risk D: Consider Therapy Modification
Betibeglogene Autotemcel: Antiretroviral Agents may decrease therapeutic effects of Betibeglogene Autotemcel. Risk X: Avoid
Cabozantinib: MRP2 Inhibitors may increase serum concentration of Cabozantinib. Risk C: Monitor
Cidofovir: May increase serum concentration of Tenofovir Products. Tenofovir Products may increase serum concentration of Cidofovir. Risk C: Monitor
Cladribine: Agents that Undergo Intracellular Phosphorylation may decrease therapeutic effects of Cladribine. Risk X: Avoid
Cobicistat: Tenofovir Disoproxil Fumarate may increase adverse/toxic effects of Cobicistat. More specifically, cobicistat may impair proper tenofovir disoproxil fumarate monitoring and dosing. Risk C: Monitor
Darolutamide: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Darunavir: Tenofovir Disoproxil Fumarate may increase serum concentration of Darunavir. Darunavir may increase serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor
Didanosine: Tenofovir Disoproxil Fumarate may decrease therapeutic effects of Didanosine. Tenofovir Disoproxil Fumarate may increase serum concentration of Didanosine. Management: When 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
Elacestrant: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Elivaldogene Autotemcel: Antiretroviral Agents may decrease therapeutic effects of Elivaldogene Autotemcel. Management: Avoid use of antiretroviral medications for at least one month, or for the amount of time required for elimination of the retroviral medication, prior to stem cell mobilization and until the all apheresis cycles are finished Risk X: Avoid
Eltrombopag: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Encorafenib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Futibatinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Ganciclovir-Valganciclovir: Tenofovir Products may increase serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase serum concentration of Tenofovir Products. Risk C: Monitor
Gilteritinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Lazertinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Ledipasvir: May increase 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
Leflunomide: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Leniolisib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Lonafarnib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Risk C: Monitor
Lopinavir: May increase nephrotoxic effects of Tenofovir Disoproxil Fumarate. Lopinavir may increase serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor
Lovotibeglogene Autotemcel: Antiretroviral Agents may decrease therapeutic effects of Lovotibeglogene Autotemcel. Risk X: Avoid
Lumacaftor and Ivacaftor: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may decrease serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Topical): May increase nephrotoxic effects of Tenofovir Products. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents: May increase nephrotoxic effects 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
Orlistat: May decrease serum concentration of Antiretroviral Agents. Risk C: Monitor
Osimertinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Oteseconazole: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
P-glycoprotein/ABCB1 Inhibitors: May increase serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor
Pretomanid: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Regorafenib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Rolapitant: May increase serum concentration of 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
Selpercatinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Sparsentan: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Tacrolimus (Systemic): Tenofovir Products may increase nephrotoxic effects of Tacrolimus (Systemic). Risk C: Monitor
Tafamidis: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Taurursodiol: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Tedizolid: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Teriflunomide: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Tipranavir: Tenofovir Disoproxil Fumarate may decrease serum concentration of Tipranavir. Tipranavir may decrease serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor
Vadadustat: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Vanzacaftor, Tezacaftor, and Deutivacaftor: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Vimseltinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Management: Avoid concomitant use of vimseltinib and P-gp substrates when possible. If combined, administer vimseltinib at least 4 hours before the P-gp substrate. Risk D: Consider Therapy Modification
Voxilaprevir: Tenofovir Disoproxil Fumarate may increase serum concentration of Voxilaprevir. Voxilaprevir may increase serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor
Fatty meals may increase the bioavailability of tenofovir. Management: May administer with or without food.
Contraception is not required to initiate or continue antiretroviral therapy (ART).
Tenofovir disoproxil fumarate a preferred nucleoside reverse transcriptase inhibitor for patients with HIV who are not yet pregnant but are trying to conceive.
Tenofovir disoproxil fumarate is a recommended component for preexposure prophylaxis (PrEP) in patients at risk for HIV infection who are sexually active and is a preferred component for PrEP in patients who have receptive vaginal sex and are planning to become pregnant. Up to 20 days of therapy are required in the partner without HIV to achieve protective drug concentrations in cervicovaginal tissue; therefore, continued use of condoms to prevent HIV exposure is recommended during this time. Continue PrEP for 7 to 28 days after the last potential vaginal exposure. Perform pregnancy testing at baseline, then as indicated. PrEP with tenofovir disoproxil fumarate may continue if pregnancy occurs.
Maximum viral suppression sustained below the limits of detection prior to conception is recommended for all persons with HIV who are planning a pregnancy. Prior to pregnancy, select or make changes to a specific antiretroviral regimen as part of a shared decision-making process. In most cases, recommendations based on data obtained from cisgender women can be applied to transgender and gender diverse people assigned female sex at birth.
Health care providers caring for couples planning a pregnancy when one or both partners are diagnosed with HIV may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2024).
Treatment for hepatitis B infection in patients without HIV coinfection should be evaluated prior to pregnancy. Tenofovir disoproxil fumarate is recommended for use in pregnant patients (AASLD [Terrault 2018]). Algorithms are available for assessing antiviral prophylaxis and treatment of hepatitis B infection in persons who could become pregnant (WHO 2024).
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 birth, low birth weight, and small for gestational age infants. High viral loads are also associated with adverse outcomes, including preterm birth and pregnancy loss. Treatment improves the health of the pregnant patient and reduces the risk of perinatal transmission. Do not withhold appropriate maternal ART due to concerns for adverse neonatal outcomes. Closely monitor for pregnancy complications. Document in utero ART exposure in the long-term medical record of a child born without HIV; evaluate for potential metabolic dysfunction if significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) develop.
Tenofovir disoproxil fumarate is a preferred nucleoside reverse transcriptase inhibitor (NRTI) for pregnant patients 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). Patients who become pregnant while taking tenofovir disoproxil fumarate may continue if viral suppression is effective and the regimen is well tolerated.
Tenofovir disoproxil fumarate in combination with emtricitabine or lamivudine is a preferred dual NRTI backbone for initial therapy in antiretroviral-naive patients who are pregnant. Tenofovir disoproxil fumarate or tenofovir alafenamide plus emtricitabine or lamivudine is a recommended dual NRTI backbone for pregnant patients who are HIV/hepatitis B virus coinfected. Tenofovir disoproxil fumarate is a preferred component for preexposure prophylaxis (PrEP) in uninfected patients at risk for HIV infection who have receptive vaginal sex during pregnancy. Tenofovir disoproxil fumarate is also a preferred component of a regimen when early (acute/recent) HIV infection is detected during pregnancy; genotyping may be required if the person had prior use of long acting cabotegravir for preexposure prophylaxis (PrEP).
Maternal exposure is decreased during the third trimester of pregnancy but trough levels are adequate; dose adjustments are not needed.
ART is recommended for all pregnant people with HIV to maximize their health, maintain the viral load below the limit of an ultrasensitive assay detection, and reduce the risk of perinatal transmission. Start ART prior to conception or as soon as possible during pregnancy. During pregnancy, select or make changes to a specific antiretroviral regimen as part of a shared decision-making process. Patients on fully suppressive regimens prior to pregnancy generally may continue the same regimen considering known pregnancy outcomes and pharmacokinetic data. Monitor pregnant patients more frequently than non-pregnant patients. ART initiated during pregnancy can be modified after delivery. In most cases, recommendations based on data obtained from cisgender women can be applied to transgender and gender diverse people assigned female sex at birth (HHS [perinatal] 2024).
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]). Algorithms are available for assessing antiviral prophylaxis and treatment of hepatitis B infection in pregnant patients (WHO 2024).
Data collection to monitor pregnancy and infant outcomes following exposure to ART is ongoing. Enroll all patients exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263).
Health care providers caring for pregnant patients with HIV and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2024).
Tenofovir is present in breast milk following use of tenofovir disoproxil fumarate.
Tenofovir was present in the breast milk of 50 women without HIV using tenofovir disoproxil fumarate for preexposure prophylaxis (PrEP); tenofovir serum concentrations were below the limits of quantification in all but 3 of 49 breastfed infants. Decreases in bone mineral density were observed in some lactating patients who received tenofovir disoproxil fumarate as a component of a long-term regimen for antiretroviral therapy.
Tenofovir disoproxil fumarate is a preferred component for PrEP in uninfected breastfeeding patients at risk for HIV infection who have receptive vaginal sex.
Tenofovir disoproxil fumarate is a recommended component of an initial regimen for early (acute/recent) HIV infection in postpartum patients. Interrupt breastfeeding immediately if seroconversion is suspected and do not continue if infection is diagnosed. Breast milk may be expressed and stored while waiting for test results.
Provide patient-centered evidence-based counseling for infant feeding options as early as possible in pregnancy.
Using properly prepared formula or pasteurized banked donor milk eliminates the risk of postnatal HIV transmission via breastfeeding.
Counsel patients on antiretroviral therapy (ART) who achieve and maintain a consistently undetectable plasma viral load during pregnancy and postnatally about feeding options, including breastfeeding, formula feeding, or banked donor milk. Maintaining maximum viral suppression decreases but does not eliminate the risk of HIV transmission via breast milk. Temporary discontinuation of breastfeeding and use of replacement feeding may be required if maternal viral load becomes detectable or if mastitis or bleeding nipples develop. Permanent discontinuation of breastfeeding is recommended if the maternal HIV RNA is ≥200 copies/mL.
Formula feeding or banked donor milk is recommended for persons with HIV who are not on ART and/or do not have sustained viral suppression. Provide the infant presumptive ART throughout breastfeeding and for up to 6 weeks after the last exposure to breast milk if the breastfeeding parent does not have sustained viral suppression but breastfeeding is continued; conduct infant virologic diagnostic testing at specified intervals.
When the HIV status at delivery is not known, breast milk may be expressed and stored until a negative test is available.
Discontinue breastfeeding immediately if HIV infection is diagnosed after breastfeeding has been initiated.
Evaluate and provide support for maternal conditions that would make adherence to postpartum ART difficult.
Information is available for counseling and managing patients with HIV who are considering breastfeeding (1-888-448-8765). In most cases, recommendations based on data obtained from cisgender women can be applied to transgender and gender diverse people assigned female sex at birth (HHS [perinatal] 2024).
Patients requiring antivirals for hepatitis B infection (who are not HIV coinfected) may breastfeed if the infant received immunoprophylaxis at birth. If nipples are cracked or bleeding, breastfeeding from the affected breast is not recommended (milk should be expressed and discarded until healed) (SMFM [Badell 2024]).
Consider calcium and vitamin D supplementation.
General monitoring: Serum phosphorus (baseline and as clinically indicated in patients with chronic kidney disease); serum creatinine, urine glucose, urine protein (baseline and as clinically indicated during therapy); hepatic function tests; bone density (patients with a history of bone fracture or have risk factors for bone loss); weight (children).
Hepatitis B virus infection:
Before initiating therapy: Baseline assessment of liver fibrosis or cirrhosis status (eg, aspartate aminotransferase-to-platelet ratio index [APRI] score); CBC, kidney function, INR, alpha-fetoprotein (AFP), gamma-glutamyl transferase, liver biochemistries, hepatitis B DNA levels and genotype, hepatitis B surface antigen, hepatitis B e antigen. Also screen for HIV, anti-hepatitis A antibodies, anti-hepatitis D antibodies (if considered at risk, such as endemic in country of origin), and hepatitis C RNA to determine need for cotreatment and/or vaccination. Obtain baseline bone mineral density for patients with known history or risk of bone fractures (AASLD [Terrault 2018]; WHO 2024).
During therapy:
Every visit: Treatment adherence (WHO 2024). Obtain lactic acid level if signs or symptoms of lactic acidosis are present; obtain urine protein, urine glucose, or bone mineral density if clinically indicated (AASLD [Terrault 2018].
Every 3 to 6 months for the first year, then at least annually thereafter: Liver biochemistries, kidney function, hepatitis B DNA levels, hepatitis B surface antigen, hepatitis B e antigen, tuberculosis (WHO 2024).
Every 6 to 12 months: Liver fibrosis, cirrhosis status; if cirrhosis or risk factors for hepatocellular carcinoma (eg, family history) are present, monitor AFP and abdominal ultrasound every 6 months to enable detection of hepatocellular carcinoma (AASLD [Terrault 2018]; WHO 2024).
Periodically monitor for treatment failure, which is defined as failure of antiviral regimen to reduce hepatitis B virus (HBV) viral load by >1 log10 IU/mL within 3 months, or rebound of HBV viral load of >1 log10 IU/mL from nadir at any time during therapy (WHO 2024).
If therapy discontinued:
Patients without cirrhosis: Monitor liver biochemistries and hepatitis B serologies every 3 months for 1 year (AASLD [Terrault 2016]; WHO 2024).
Patients with cirrhosis: Monitor liver biochemistries and hepatitis B serologies monthly for 6 months then every 3 months indefinitely to detect recurrence of hepatitis B (AASLD [Terrault 2016]; WHO 2024). Monitor AFP and abdominal ultrasound every 6 months to enable detection of hepatocellular carcinoma (WHO 2024).
HIV: CBC with differential, reticulocyte count, creatine kinase, CD4 count, HIV RNA plasma levels testing for HBV prior to the initiation of antiretroviral therapy.
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
Altered kidney function: In patients with CrCl <50 mL/minute or with ESRD requiring dialysis, Cmax and AUC of tenofovir were increased.
