Version May 2024
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 infection, treatment: Tenofovir disoproxil fumarate: Oral: 300 mg once daily.
Treatment duration: Treatment duration for nucleos(t)ide analog-based therapy (eg, tenofovir disoproxil fumarate) is variable and influenced by HBeAg status, duration of hepatitis B virus (HBV) suppression, and presence of cirrhosis/decompensation (Ref).
Patients without cirrhosis:
Hepatitis B e antigen (HBeAg) positive immune-active chronic hepatitis: Treat until HBeAg seroconversion; after seroconversion, prolonged consolidation therapy is often required in patients treated with nucleos(t)ide analogues to prevent hepatitis flares. 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 compensated 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).
Patients with decompensated cirrhosis: For individuals with decompensated cirrhosis, indefinite therapy is recommended regardless of HBV DNA level, HBeAg status, or ALT level (Ref).
Viral breakthrough: For patients with confirmed viral breakthrough (HBV DNA ≥100 units/mL with previously undetectable levels [<10 units/mL] or >1 log increase in HBV DNA), either switch to an alternative antiviral monotherapy agent with a high genetic barrier to resistance or add 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).
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.
• 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:
• 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]).
Other warnings/precautions:
• Appropriate use: HIV/Hepatitis B coinfection: 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. 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 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
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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.
Chronic hepatitis B: Treatment of chronic 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
Substrate of BCRP/ABCG2, OAT1/3, P-glycoprotein/ABCB1 (major); 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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
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 BCRP/ABCG2 Substrates (Clinically Relevant 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
Betibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination
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
Darolutamide: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). 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
Elacestrant: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Elivaldogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect 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 combination
Eltrombopag: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Encorafenib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Futibatinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant 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 BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
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
Leflunomide: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Leniolisib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Lopinavir: May enhance the nephrotoxic effect of Tenofovir Disoproxil Fumarate. Lopinavir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Lovotibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination
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
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 (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Oteseconazole: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Pacritinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Pretomanid: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Regorafenib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Rolapitant: May increase the 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 therapy
Sparsentan: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Tacrolimus (Systemic): Tenofovir Products may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
Tafamidis: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Taurursodiol: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Tedizolid: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Teriflunomide: May increase the serum concentration of 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.
Contraception is not required to initiate or continue antiretroviral therapy (ART).
The US Department of Health and Human Services (HHS) perinatal HIV guidelines consider 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 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. Pregnancy testing should be done 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. Optimization of the health of the person who will become pregnant is recommended. Selection of or changes to a specific antiretroviral regimen prior to pregnancy should be done as part of a shared decision-making process. In most cases, recommendations from the HHS perinatal HIV guidelines (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] 2023).
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. 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 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 metabolic dysfunction.
The US Department of Health and Human Services (HHS) perinatal HIV guidelines consider tenofovir disoproxil fumarate 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). 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 or tenofovir alafenamide plus emtricitabine or lamivudine as recommended dual NRTI backbone for HIV/hepatitis B virus coinfected pregnant patients.
Tenofovir disoproxil fumarate is a recommended component for preexposure prophylaxis (PrEP) in uninfected patients at risk for HIV infection who are pregnant. 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 modestly decreased during pregnancy; 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 detection, and reduce the risk of perinatal transmission. Selection of or changes to a specific antiretroviral regimen during pregnancy should be done 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. Monitoring of patients who are pregnant is more frequent than in patients who are not pregnant. ART initiated during pregnancy can be modified after delivery. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender-diverse people assigned female sex at birth.
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]).
Data collection to monitor pregnancy and infant outcomes following exposure to ART is ongoing. Health care providers should enroll all patients exposed to antiretroviral medications during pregnancy in the Antiretroviral Pregnancy Registry (1-800-258-4263). Enrollment should be done as early in pregnancy as possible.
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] 2023).
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 recommended component for PrEP in uninfected patients at risk for HIV infection who are breastfeeding.
Tenofovir disoproxil fumarate is a recommended component of a regimen when early (acute/recent) HIV infection is detected in patients who are breastfeeding. Breastfeeding should be interrupted if acute HIV infection is suspected and not continued if infection is confirmed. Milk may be expressed and stored while waiting for confirmation.
Maintaining maximum viral suppression during pregnancy and postpartum decreases but does not eliminate the risk of HIV transmission via breast milk. In addition, multiclass-resistant virus has been detected in breastfeeding infants who acquire HIV despite maternal therapy. In the United States, where formula is usually accessible, affordable, safe, and sustainable, and the risk of infant mortality due to diarrhea and respiratory infections is low, the Health and Human Services perinatal HIV guidelines do not recommend breastfeeding for patients with HIV when safer infant feeding options are available. Persons with HIV who maintain an undetectable viral load while taking antiretroviral therapy (ART) should evaluate infant feeding options (formula, banked donor milk, or breastfeeding) as part of a shared decision-making process (if breastfeeding is being considered, see guidelines for measures to reduce the risk of HIV transmission). When the HIV status at delivery is not known, breast milk may be expressed and stored until a negative test is available. If HIV infection is diagnosed after breastfeeding has been initiated, breastfeeding should be discontinued immediately. Breastfeeding is not recommended for persons with HIV who are not taking ART and/or who do not have sustained viral suppression.
Information is available for counseling and managing patients with HIV who are considering breastfeeding (1-888-448-8765). In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender-diverse people assigned female sex at birth (HHS [perinatal] 2023).
The American Association for the Study of Liver Disease (AASLD) chronic hepatitis B treatment guidelines do not consider antiviral therapy a contraindication to breastfeeding in patients with hepatitis B infection not coinfected with HIV; antivirals are minimally excreted in breast milk and unlikely to cause significant toxicity. However, the unknown risk of low-level exposure to the infant should be discussed with mothers as well as the insufficient long-term safety data in infants born to mothers who took antiviral agents while breastfeeding (AASLD [Terrault 2018]). If nipples are cracked or bleeding, breastfeeding is not recommended (Tran 2016).
Consider calcium and vitamin D supplementation.
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).
Chronic hepatitis B: Hepatitis B virus (HBV) DNA and ALT (HBV DNA usually done every 3 months until undetectable and then every 3 to 6 months thereafter); HBeAg; anti-HBe (in patients who are HBeAg-positive to monitor for seroconversion); HBsAg; creatinine clearance (baseline); consider lactic acid levels (if clinical concern); following discontinuation, monitor for recurrent viremia, ALT flares, seroreversion, and clinical decompensation every 3 months for at least 1 year. As antivirals do not eliminate the risk of hepatocellular carcinoma, continued monitoring for this complication is recommended in at-risk patients (AASLD [Terrault 2018]).
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.
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