Free lookups today: 0/3 · Unlimited with Pro Subscribe from KES 99

Free lookups: 0/3 Unlimited with Pro → Browse by class Interactions · Tip: type at least 2 letters, then pick a result

← New search | Disoproxil

Classes Check interactions

INN monograph

Disoproxil

Therapeutic agent (verify pharmacological class) · POM

POM Source-linked Grade perfect

Source-linked · Updated 03 Aug 2026 · Source: FDA drug label via OpenFDA/DailyMed; Local active-ingredient clinical extract; Professional class pharmacology (Therapeutic agent (verify pharmacological class))

Patient advice Interactions

Kenya market

Wholesale / list prices where loaded

From

—

Median

—

Brands

BOXED WARNING WARNING: POSTTREATMENT EXACERBATION OF HEPATITIS Severe acute exacerbations of hepatitis have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy, including tenofovir disoproxil fumarate tablets. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including tenofovir disoproxil fumarate tablets. If appropriate, resumption of anti-hepatitis B therapy may be warranted [See Warnings and Precautions ( 5.1 )]. WARNING: POSTTREATMENT EXACERBATION OF HEPATITIS See full prescribing information for complete boxed warning. Severe acute exacerbations of hepatitis have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy, including tenofovir disoproxil fumarate tablets. Hepatic function should be monitored closely in these patients. If appropriate, resumption of anti-hepatitis B therapy may be warranted. (5.1)

Risk first

Contraindications

Hypersensitivity to the active substance or excipients.
Additional absolute contraindications are indication- and product-specific — consult SmPC.

Precautions

5 WARNINGS AND PRECAUTIONS • New onset or worsening renal impairment: Can include acute renal failure and Fanconi syndrome.
Assess estimated creatinine clearance before initiating treatment with tenofovir disoproxil fumarate tablets.
In patients at risk for renal dysfunction, assess estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein before initiating treatment with tenofovir disoproxil fumarate tablets and periodically during treatment.
Avoid administering tenofovir disoproxil fumarate tablets with concurrentor recent use of nephrotoxic drugs.
(5.2) • Lactic acidosis/severe hepatomegaly with steatosis: Discontinue treatment in patients who develop symptoms or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.
(5.3) • Coadministration with other products: Do not use with other tenofovir-containing products (e.g., ATRIPLA, BIKTARVY, COMPLERA, DESCOVY, GENVOYA, ODEFSEY, STRIBILD, TRUVADA, or VEMLIDY).
Do not administer in combination with HEPSERA.
(5.4) • HIV testing: HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with tenofovir disoproxil fumarate tablets.
Tenofovir disoproxil fumarate tablets should only be used as part of an appropriate antiretroviral combination regimen in HIV-infected patients with or without HBV coinfection.
(5.5) • Decreases in bone mineral density (BMD): Consider assessment of BMD in patients with a history of pathologic fracture or other risk factors for osteoporosis or bone loss.
(5.6) • Immune reconstitution syndrome: Observed in HIV-infected patients.
May necessitate further evaluation and treatment.

Point of care

Dosing

Adult

& ADMINISTRATION • Recommended dose for the treatment of HIV-1 or chronic hepatitis B in adults and pediatric patients 12 years of age and older (35 kg or more): 300 mg once daily taken orally without regard to food. (2.1) • Recommended dose for the treatment of HIV-1 in pediatric patients (2 to less than 12 years of age): o Tablets: For pediatric patients weighing greater than or equal to 17 kg who can swallow an intact tablet, one tenofovir disoproxil fumarate tablet (300 mg based on body weight) once daily taken orally without regard to food. (2.2) • Dose recommended in renal impairment in adults: o Creatinine clearance 30 to 49 mL/min: 300 mg every 48 hours. (2.3) o Creatinine clearance 10 to 29 mL/min: 300 mg every 72 to 96 hours. (2.3) o Hemodialysis: 300 mg every 7 days or after approximately 12 hours of dialysis. (2.3) 2.1 Recommended Dose in Adults and Pediatric Patients 12 Years of Age and Older (35 kg or more) For the treatment of HIV-1 or chronic hepatitis B: The dose is one 300 mg tenofovir disoproxil fumarate tablet once daily taken orally, without regard to food. In the treatment of chronic hepatitis B, the optimal duration of treatment is unknown. Safety and efficacy in pediatric patients with chronic hepatitis B weighing less than 35 kg have not been established. 2.2 Recommended Dose in Pediatric Patients 2 Years to Less than 12 Years of Age HIV-1 Infection For the treatment of HIV-1 in pediatric patients 2 years of age and older, the recommended oral dose of tenofovir disoproxil fumarate tablet is 8 mg of tenofovir disoproxil fumarate (tenofovir DF) per kilogram of body weight (up to a maximum of 300 mg) once daily administered as tablets. Tenofovir disoproxil fumarate is available as tablets in 300 mg strength for pediatric patients who weigh greater than or equal to 17 kg and who are able to reliably swallow intact tablets. The dose is one tablet once daily taken orally, without regard to food. Table 2 contain dosing recommendations for tenofovir disoproxil fumarate tablets based on body weight. Weight should be monitored periodically and the tenofovir disoproxil fumarate tablets dose adjusted accordingly. Table 2 Dosing Recommendations for Pediatric Patients 2 Years of Age and Older and Weighing At Least 17 kg Using Tenofovir Disoproxil Fumarate Tablets Body Weight Kilogram (kg) Tablets Once Daily 17 to less than 22 150 mg 22 to less than 28 200 mg 28 to less than 35 250 mg 35 or greater 300 mg Chronic Hepatitis B Safety and efficacy of tenofovir disoproxil fumarate tablets in patients younger than 12 years of age have not been established. 2.3 Dose Adjustment for Renal Impairment in Adults Significantly increased drug exposures occurred when tenofovir disoproxil fumarate tablets were administered to subjects with moderate to severe renal impairment [See Clinical Pharmacology (12.3)] . Therefore, the dosing interval of tenofovir disoproxil fumarate tablets 300 mg should be adjusted in patients with baseline creatinine clearance below 50 mL/min using the recommendations in Table 3. These dosing interval recommendations are based on modeling of single-dose pharmacokinetic data in non-HIV and non-HBV infected subjects with varying degrees of renal impairment, including end-stage renal disease requiring hemodialysis. The safety and effectiveness of these dosing interval adjustment recommendations have not been clinically evaluated in patients with moderate or severe renal impairment; therefore, clinical response to treatment and renal function should be closely monitored in these patients [See Warnings and Precautions (5.2)] . No dose adjustment of tenofovir disoproxil fumarate tablets 300 mg is necessary for patients with mild renal impairment (creatinine clearance 50 to 80 mL/min). Routine monitoring of estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein should be performed in patients with mild renal impairment [See Warnings and Precautions (5.2)] . Table 3 Dosage Adjustment for Patients with Altered Creatinine Clearance Cre atinine Clearan ce (mL/min) a Hemodial ysis Patients 50 or greater 30- 49 10- 29 Recomm en ded 300 mg Dosing Inte r v al Every 24 hours Every 48 hours Every 72 to 96 hours Every 7 days or after a tot al of approximate ly 12 hours of dialysis a. Calculated using ideal (lean) body weight. b. Generally once weekly assuming three hemodialysis sessions a week of approximately 4 hours duration. Tenofovir disoproxil fumarate tablets should be administered following completion of dialysis. The pharmacokinetics of tenofovir have not been evaluated in non-hemodialysis patients with creatinine clearance below 10 mL/min; therefore, no dosing recommendation is available for these patients. No data are available to make dose recommendations in pediatric patients with renal impairment.

Paediatric

8.4 Pediatric Use Pediatric Patients 2 Years of Age and Older with HIV-1 infection The safety of tenofovir disoproxil fumarate tablets in pediatric patients aged 2 to less than 18 years is supported by data from two randomized trials in which tenofovir disoproxil fumarate tablets were administered to HIV-1 infected treatment-experienced subjects. In addition, the pharmacokinetic profile of tenofovir in patients 2 to less than 18 years of age at the recommended doses was similar to that found to be safe and effective in adult clinical trials [See Clinical Pharmacology ( 12.3)]. In Study 352, 92 treatment-experienced subjects 2 to less than 12 years of age with stable, virologic suppression on stavudine- or zidovudine-containing regimen were randomized to either replace stavudine or zidovudine with tenofovir disoproxil fumarate tablets (N=44) or continue their original regimen (N=48) for 48 weeks. Five additional subjects over the age of 12 were enrolled and randomized (tenofovir disoproxil fumarate tablets N=4, original regimen N=1) but are not included in the efficacy analysis. After 48 weeks, all eligible subjects were allowed to continue in the study receiving open-label tenofovir disoproxil fumarate tablets. At Week 48, 89% of subjects in the tenofovir disoproxil fumarate treatment group and 90% of subjects in the stavudine or zidovudine treatment group had HIV-1 RNA concentrations less than 400 copies/mL. During the 48 week randomized phase of the study, 1 subject in the tenofovir disoproxil fumarate tablets group discontinued the study prematurely because of virologic failure/lack of efficacy and 3 subjects (2 subjects in the tenofovir disoproxil fumarate tablets group and 1 subject in the stavudine or zidovudine group) discontinued for other reasons. In Study 321, 87 treatment-experienced subjects 12 to less than 18 years of age were treated with tenofovir disoproxil fumarate tablets (N=45) or placebo (N=42) in combination with an optimized background regimen (OBR) for 48 weeks. The mean baseline CD4 cell count was 374 cells/mm 3 and the mean baseline plasma HIV-1 RNA was 4.6 log 10 copies/mL. At baseline, 90% of subjects harbored NRTI resistance-associated substitutions in their HIV-1 isolates. Overall, the trial failed to show a difference in virologic response between the tenofovir disoproxil fumarate tablets and placebo treatment groups. Subgroup analyses suggest the lack of difference in virologic response may be attributable to imbalances between treatment arms in baseline viral susceptibility to tenofovir disoproxil fumarate tablets and OBR. Although changes in HIV-1 RNA in these highly treatment-experienced subjects were less than anticipated, the comparability of the pharmacokinetic and safety data to that observed in adults supports the use of tenofovir disoproxil fumarate tablets in pediatric patients 12 years of age and older who weigh greater than or equal to 35 kg and whose HIV-1 isolate is expected to be sensitive to tenofovir disoproxil fumarate tablets. [See Warnings and Precautions (5.6), Adverse Reactions (6.1), and Clinical Pharmacology ( 12.3)]. Safety and effectiveness of tenofovir disoproxil fumarate tablets in pediatric patients younger than 2 years of age with HIV-1 infection have not been established. Pediatric Patients 12 Years of Age and Older with Chronic Hepatitis B In Study 115, 106 HBeAg negative (9%) and positive (91%) subjects aged 12 to less than 18 years with chronic HBV infection were randomized to receive blinded treatment with tenofovir disoproxil fumarate tablets 300 mg (N=52) or placebo (N=54) for 72 weeks. At study entry, the mean HBV DNA was 8.1 log10 copies/mL and mean ALT was 101 U/L. Of 52 subjects treated with tenofovir disoproxil fumarate tablets, 20 subjects were nucleos(t)ide-naïve and 32 subjects were nucleos(t)ide-experienced. Thirty-one of the 32 nucleos(t)ide-experienced subjects had prior lamivudine experience. At Week 72, 88% (46/52) of subjects in the tenofovir disoproxil fumarate tablets group and 0% (0/54) of subjects in the placebo group had HBV DNA <400 copies/mL (69 IU/mL). Among subjects with abnormal ALT at baseline, 74% (26/35) of subjects receiving tenofovir disoproxil fumarate tablets had normalized ALT at Week 72 compared to 31% (13/42) in the placebo group. One tenofovir disoproxil fumarate-treated subject experienced sustained HBsAg-loss and seroconversion to anti-HBs during the first 72 weeks of study participation. Safety and effectiveness of tenofovir disoproxil fumarate tablets in pediatric patients younger than 12 years of age or less than 35 kg with chronic hepatitis B have not been established.

Renal

Review renal impairment dosing; many agents need CrCl/eGFR adjustment.

CrCl 0–120: Confirm renal dosing in product SmPC / primary label.

Hepatic

Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.

Safety

Drug interactions

Open checker →

Professional use: confirm indication, dose, duration, monitoring and patient counselling points against current Kenya STG / EML and the product SmPC.
Document allergy status and key interactions.

Safety

Adverse effects

6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: • Severe Acute Exacerbation of Hepatitis [See Boxed Warning, Warnings and Precautions ( 5.1 )]. • New Onset or Worsening Renal Impairment [See Warnings and Precautions ( 5.2 )]. • Lactic Acidosis/Severe Hepatomegaly with Steatosis [See Warnings and Precautions ( 5.3 )]. • Bone Effects [See Warnings and Precautions ( 5.6 )]. • Immune Reconstitution Syndrome [See Warnings and Precautions ( 5.7)]. • In HIV-infected adult subjects: Most common adverse reactions (incidence greater than or equal to 10%, Grades 2 to 4) are rash, diarrhea, headache, pain, depression, asthenia, and nausea.
(6.1) • In HBV-infected subjects with compensated liver disease: Most common adverse reaction (all grades) was nausea (9%).
(6.1) • In pediatric subjects: Adverse reactions in pediatric subjects were consistent with those observed in adults.
(6.1) • In HBV-infected subjects with decompensated liver disease: Most common adverse reactions (incidence greater than or equal to 10%, all grades) were abdominal pain, nausea, insomnia, pruritus, vomiting, dizziness, and pyrexia.
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact NorthStar Rx LLC at 1-800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Adverse Reactions from Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Clinical Trials in Adult Patients with HIV-1 Infection More than 12,000 subjects have been treated with tenofovir disoproxil fumarate tablets alone or in combination with other antiretroviral medicinal products for periods of 28 days to 215 weeks in clinical trials and expanded access programs.
A total of 1,544 subjects have received tenofovir disoproxil fumarate tablets 300 mg once daily in clinical trials
over 11,000 subjects have received tenofovir disoproxil fumarate tablets in expanded access programs.
The most common adverse reactions (incidence greater than or equal to 10%, Grades 2 to 4) identified from any of the 3 large controlled clinical trials include rash, diarrhea, headache, pain, depression, asthenia, and nausea.
Treatment-Naïve Patients Study 903 - Treatment-Emergent Adverse-Reactions: The most common adverse reactions seen in a double-blind comparative controlled trial in which 600 treatment-naïve subjects received tenofovir disoproxil fumarate tablets (N=299) or stavudine (N=301) in combination with lamivudine and efavirenz for 144 weeks (Study 903) were mild to moderate gastrointestinal events and dizziness.
Mild adverse reactions (Grade 1) were common with a similar incidence in both arms and included dizziness, diarrhea, and nausea.
Selected treatment-emergent moderate to severe adverse reactions are summarized in Table 4.
Table 4 Selected Treatment-Emergent Adverse Reactionsa (Grades 2 to 4) Reported in ≥5% in Any Treatment Group in Study 903 (0 to 144 Weeks) Tenofovir disoproxil fumarate Tablets +3TC+EFV d4T+3TC+EFV N=299 N=301 Body as a Whole Headache Pain Fever Abdominal pain Back pain Asthenia 14% 13% 8% 7% 9% 6% 17% 12% 7% 12% 8% 7% Digestive System Diarrhea Nausea Dyspepsia Vomiting 11% 8% 4% 5% 13% 9% 5% 9% Metabolic Disorders Lipodystrophy b 1% 8% Musculoskeletal Arthralgia Myalgia 5% 3% 7% 5% Nervous System Depression Insomnia Dizziness Peripheral neuropathy c Anxiety 11% 5% 3% 1% 6% 10% 8% 6% 5% 6% Respiratory Pneumonia 5% 5% Skin and Appendages Rash event d 18% 12% a.
Frequencies of adverse reactions are based on all treatment-emergent adverse events, regardless of relationship to study drug. b.

Use

Indications

1 INDICATIONS & USAGE Tenofovir disoproxil fumarate tablets are a nucleotide analog HIV-1 reverse transcriptase inhibitor and an HBV reverse transcriptase inhibitor. • Tenofovir disoproxil fumarate tablets are indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 2 years of age and older.
(1) • Tenofovir disoproxil fumarate tablets are indicated for the treatment of chronic hepatitis B in adults and pediatric patients 12 years of age and older.
(1) 1.1 HIV-1 Infection Tenofovir disoproxil fumarate tablets are indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 2 years of age and older.
The following points should be considered when initiating therapy with tenofovir disoproxil fumarate tablets for the treatment of HIV-1 infection: • Tenofovir disoproxil fumarate tablets should not be used in combination with ATRIPLA ® , BIKTARVY ® , COMPLERA ® , DESCOVY ® , GENVOYA ® , ODEFSEY ® , STRIBILD ® , TRUVADA ® , or VEMLIDY ® [See Warnings and Precautions (5.4)]. 1.2 Chronic Hepatitis B Tenofovir disoproxil fumarate tablets are indicated for the treatment of chronic hepatitis B in adults and pediatric patients 12 years of age and older.
The following points should be considered when initiating therapy with tenofovir disoproxil fumarate tablets for the treatment of chronic hepatitis B infection: • The indication in adults is based on safety and efficacy data from treatment of subjects who were nucleoside-treatment-naïve and subjects who were treatment-experienced with documented resistance to lamivudine.
Subjects were adults with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease [See Clinical Studies (14.2)]. • Tenofovir disoproxil fumarate tablets were evaluated in a limited number of subjects with chronic hepatitis B and decompensated liver disease [See Adverse Reactions (6.1), Clinical Studies (14.2)]. • The numbers of subjects in clinical trials who had adefovir resistance-associated substitutions at baseline were too small to reach conclusions of efficacy [See Microbiology (12.4), Clinical Studies ( 14.2)].

Pharmacology

Mode of action

12.

1 Mechanism of Action Tenofovir disoproxil… → Mechanism is agent-specific. → At receptor, enzyme, ion channel, transpor…

Full mechanism text

12.1 Mechanism of Action Tenofovir disoproxil fumarate is an antiviral drug [See Microbiology ( 12.4 )]. Mechanism is agent-specific. At receptor, enzyme, ion channel, transporter or microbial target level, the drug alters a physiological or pathological pathway to produce its therapeutic effect. Confirm precise molecular mechanism in current SmPC / pharmacology reference for this INN before high-stakes decisions.

ADME

Pharmacokinetics & PD

Onset	Product-specific
Duration	Product-specific
Route	See product SmPC
Absorption	Tenofovir disoproxil fumarate tablets are a water soluble diester prodrug of the active ingredient tenofovir. The oral bioavailability of tenofovir from tenofovir disoproxil fumarate tablets in fasted subjects is approximately 25%. Following oral administration of a single dose o...
Distribution	In vitro binding of tenofovir to human plasma or serum proteins is less than 0.7 and 7.2%, respectively, over the tenofovir concentration range 0.01 to 25 mcg/mL. The volume of distribution at steady-state is 1.3 ± 0.6 L/kg and 1.2 ± 0.4 L/kg, following intravenous administration...
Elimination	In vitro studies indicate that neither tenofovir disoproxil nor tenofovir are substrates of CYP enzymes. Following IV administration of tenofovir, approximately 70 to 80% of the dose is recovered in the urine as unchanged tenofovir within 72 hours of dosing. Following single dose...
Half-life	of tenofovir is approximately 17 hours. After multiple oral doses of tenofovir disoproxil fumarate tablets 300 mg once daily (under fed conditions), 32 ± 10% of the administered dose is recovered in urine over 24 hours. Tenofovir is eliminated by a combination of glomerular filtr...

Full PK/PD text

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Tenofovir disoproxil fumarate is an antiviral drug [See Microbiology ( 12.4 )]. 12.3 Pharmacokinetics The pharmacokinetics of tenofovir DF have been evaluated in healthy volunteers and HIV-1 infected individuals. Tenofovir pharmacokinetics are similar between these populations. Absorption Tenofovir disoproxil fumarate tablets are a water soluble diester prodrug of the active ingredient tenofovir. The oral bioavailability of tenofovir from tenofovir disoproxil fumarate tablets in fasted subjects is approximately 25%. Following oral administration of a single dose of tenofovir disoproxil fumarate tablets 300 mg to HIV-1 infected subjects in the fasted state, maximum serum concentrations (C max ) are achieved in 1 ± 0.4 hrs. C max and AUC values are 0.30 ± 0.09 mcg/mL and 2.29 ± 0.69 mcg·hr/mL, respectively. The pharmacokinetics of tenofovir are dose proportional over a tenofovir disoproxil fumarate tablets dose range of 75 to 600 mg and are not affected by repeated dosing. Distribution In vitro binding of tenofovir to human plasma or serum proteins is less than 0.7 and 7.2%, respectively, over the tenofovir concentration range 0.01 to 25 mcg/mL. The volume of distribution at steady-state is 1.3 ± 0.6 L/kg and 1.2 ± 0.4 L/kg, following intravenous administration of tenofovir 1 mg/kg and 3 mg/kg. Metabolism and Elimination In vitro studies indicate that neither tenofovir disoproxil nor tenofovir are substrates of CYP enzymes. Following IV administration of tenofovir, approximately 70 to 80% of the dose is recovered in the urine as unchanged tenofovir within 72 hours of dosing. Following single dose, oral administration of tenofovir disoproxil fumarate tablets, the terminal elimination half-life of tenofovir is approximately 17 hours. After multiple oral doses of tenofovir disoproxil fumarate tablets 300 mg once daily (under fed conditions), 32 ± 10% of the administered dose is recovered in urine over 24 hours. Tenofovir is eliminated by a combination of glomerular filtration and active tubular secretion. There may be competition for elimination with other compounds that are also renally eliminated. Effects of Food on Oral Absorption Administration of tenofovir disoproxil fumarate 300 mg tablets following a high-fat meal (~700 to 1,000 kcal containing 40 to 50% fat) increases the oral bioavailability, with an increase in tenofovir AUC 0 to ∞ of approximately 40% and an increase in C max of approximately 14%. However, administration of tenofovir disoproxil fumarate tablets with a light meal did not have a significant effect on the pharmacokinetics of tenofovir when compared to fasted administration of the drug. Food delays the time to tenofovir C max by approximately 1 hour. C max and AUC of tenofovir are 0.33 ± 0.12 mcg/mL and 3.32 ± 1.37 mcg·hr/mL following multiple doses of tenofovir disoproxil fumarate tablets 300 mg once daily in the fed state, when meal content was not controlled. Special Populations Race: There were insufficient numbers from racial and ethnic groups other than Caucasian to adequately determine potential pharmacokinetic differences among these populations. Gender: Tenofovir pharmacokinetics are similar in male and female subjects. Pediatric Patients 2 Years of Age and Older: Steady-state pharmacokinetics of tenofovir were evaluated in 31 HIV-1 infected pediatric subjects 2 to less than 18 years (Table 12). Tenofovir exposure achieved in these pediatric subjects receiving oral once daily doses of tenofovir disoproxil fumarate tablets 300 mg up to a maximum dose of 300 mg was similar to exposures achieved in adults receiving once-daily doses of tenofovir disoproxil fumarate tablets 300 mg. Table 12 Mean (± SD) Tenofovir Pharmacokinetic Parameters by Age Groups for HIV-1- infected Pediatric Patients Dose and Formulation 300 mg tablet 12 to <18 Years (N=8) C max (mcg/mL) 0.38 ± 0.13 AUC tau (mcg•hr/mL) 3.39 ± 1.22 Tenofovir exposures in 52 HBV-infected pediatric subjects (12 to less than 18 years of age) receiving oral once-daily doses of tenofovir disoproxil fumarate 300 mg tablet were comparable to exposures achieved in HIV-1 infected adults and adolescents receiving once-daily doses of 300 mg. Geriatric Patients: Pharmacokinetic trials have not been performed in the elderly (65 years and older). Patients with Impaired Renal Function: The pharmacokinetics of tenofovir are altered in subjects with renal impairment [See Warnings and Precautions (5.2)]. In subjects with creatinine clearance below 50 mL/min or with end-stage renal disease (ESRD) requiring dialysis, C max , and AUC 0 to ∞ of tenofovir were increased (Table 13). It is recommended that the dosing interval for tenofovir disoproxil fumarate tablets be modified in patients with estimated creatinine clearance below 50 mL/min or in patients with ESRD who require dialysis [See Dosage and Administration ( 2.3)]. Table 13 Pharmacokinetic Parameters (Mean ± SD) of Tenofovira in Subjects with Varying Degrees of Renal Function Baseline Creatinine Clearance (mL/min) >80 ( N = 3 ) 50-80 (N=10) 30-49 ( N = 8 ) 12-29 (N=11) C max (mcg/mL) 0.34 ± 0.03 0.33 ± 0.06 0.37 ± 0.16 0.60 ± 0.19 AUC 0 to ∞ (mcg · hr/mL) 2.18 ± 0.26 3.06 ± 0.93 6.01 ± 2.50 15.98 ± 7.22 CL/F (mL/min) 1043.7 ± 115.4 807.7 ± 279.2 444.4 ± 209.8 177 ± 97.1 CL renal (mL/min) 243.5 ± 33.3 168.6 ± 27.5 100.6 ± 27.5 43 ± 31.2 a. 300 mg, single dose of tenofovir disoproxil fumarate tablets Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%. Following a single 300 mg dose of tenofovir disoproxil fumarate tablets, a four-hour hemodialysis session removed approximately 10% of the administered tenofovir dose. Patients with Hepatic Impairment: The pharmacokinetics of tenofovir following a 300 mg single dose of tenofovir disoproxil fumarate tablets have been studied in non-HIV infected subjects with moderate to severe hepatic impairment. There were no substantial alterations in tenofovir pharmacokinetics in subjects with hepatic impairment compared with unimpaired subjects. No change in tenofovir disoproxil fumarate tablets dosing is required in patients with hepatic impairment. Assessment of Drug Interactions At concentrations substantially higher (~300-fold) than those observed in vivo, tenofovir did not inhibit in vitro drug metabolism mediated by any of the following human CYP isoforms: CYP3A4, CYP2D6, CYP2C9, or CYP2E1. However, a small (6%) but statistically significant reduction in metabolism of CYP1A substrate was observed. Based on the results of in vitro experiments and the known elimination pathway of tenofovir, the potential for CYP-mediated interactions involving tenofovir with other medicinal products is low. Tenofovir disoproxil fumarate tablets have been evaluated in healthy volunteers in combination with other antiretroviral and potential concomitant drugs. Tables 14 and 15 summarize pharmacokinetic effects of coadministered drug on tenofovir pharmacokinetics and effects of tenofovir disoproxil fumarate tablets on the pharmacokinetics of coadministered drug. TDF is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters. When TDF is coadministered with an inhibitor of these transporters, an increase in absorption may be observed. No clinically significant drug interactions have been observed between tenofovir disoproxil fumarate tablets and efavirenz, methadone, nelfinavir, oral contraceptives, ribavirin, or sofosbuvir. Table 14 Drug Interactions: Changes in Pharmacokinetic Parameters for Tenofovira in the Presence of the Coadministered Drug Coadministered Drug Dose of Coadministered Drug (mg) N % Change of Tenofovir Pharmacokinetic Parameters b (90% CI) C max AUC C min Atazanavir c 400 once daily × 14 days 33 ↑ 14 (↑ 8 to ↑ 20) ↑ 24 (↑ 21 to ↑ 28) ↑ 22 (↑ 15 to ↑ 30) Atazanavir/ Ritonavir c 300/100 once daily 12 ↑ 34 (↑ 20 to ↑ 51) ↑ 37 (↑ 30 to ↑ 45) ↑ 29 (↑ 21 to ↑ 36) Darunavir/ Ritonavir d 300/100 twice daily 12 ↑ 24 (↑ 8 to ↑ 42) ↑ 22 (↑ 10 to ↑ 35) ↑ 37 (↑ 19 to ↑ 57) Indinavir 800 three times daily × 7 days 13 ↑ 14 (↓ 3 to ↑ 33) Û Û Ledipasvir/ Sofosbuvir e,f 90/400 once daily x 10 days 24 ↑ 47 (↑ 37 to ↑ 58) ↑ 35 (↑ 29 to ↑ 42 ) ↑ 47 (↑ 38 to ↑ 57) Ledipasvir/ Sofosbuvir e,g 23 ↑ 64 (↑ 54 to ↑ 74) ↑ 50 (↑ 42 to ↑ 59) ↑ 59 (↑ 49 to ↑ 70) Ledipasvir/ Sofosbuvir h 90/400 once daily x 14 days 15 ↑ 79 (↑ 56 to ↑ 104) ↑ 98 (↑ 77 to ↑ 123) ↑ 163 (↑ 132 to ↑197) Lopinavir/ Ritonavir 400/100 twice daily × 14 days 24 Û ↑ 32 (↑ 25 to ↑ 38) ↑ 51 (↑ 37 to ↑ 66) Saquinavir/ Ritonavir 1,000/100 twice daily × 14 days 35 Û Û ↑ 23 (↑ 16 to ↑ 30) Sofosbuvir i 400 single dose 16 ↑ 25 (↑ 8 to ↑ 45) Û Û Sofosbuvir/ Velpatasvir j 400/100 once daily 24 ↑ 44 (↑ 33 to ↑ 55) ↑ 40 (↑ 34 to ↑ 46) ↑ 84 (↑ 76 to ↑ 92) Sofosbuvir/ Velpatasvir k 400/100 once daily 30 ↑ 46 (↑ 39 to ↑ 54) ↑ 40 (↑ 34 to ↑ 45) ↑ 70 (↑ 61 to ↑ 79) Sofosbuvir/ Velpatasvir/ Voxilaprevir l 400/100/100 + Voxilaprevirm 100 once daily 29 ↑ 48 (↑ 36 to ↑ 61) ↑ 39 (↑ 32 to↑ 46) ↑ 47 (↑ 38 to ↑ 56) Tacrolimus 0.05 mg/kg twice Daily × 7 days 21 ↑ 13 (↑ 1 to ↑ 27) Û Û Tipranavir/ Ritonavir n 500/100 twice daily 22 ↓ 23 (↓ 32 to ↓ 13) ↓ 2 (↓ 9 to ↑ 5) ↑ 7 (↓ 2 to ↑ 17) 750/200 twice daily (23 doses) 20 ↓ 38 (↓ 46 to ↓ 29) ↑ 2 (↓ 6 to ↑ 10) ↑ 14 (↑ 1 to ↑ 27) a. Subjects received tenofovir disoproxil fumarate tablets 300 mg once daily. b. Increase = ↑; Decrease = ↓; No Effect = Û c. Reyataz Prescribing Information. d. Prezista Prescribing Information. e Data generated from simultaneous dosing with HARVONI (ledipasvir/sofosbuvir). Staggered administration (12 hours apart) provided similar results. f. Comparison based on exposures when administered as atazanavir/ritonavir + emtricitabine/tenofovir DF. g. Comparison based on exposures when administered as darunavir/ritonavir + emtricitabine/tenofovir DF. h. Study conducted with ATRIPLA (efavirenz/emtricitabine/tenofovir DF) coadministered with HARVONI; coadministration with HARVONI also results in comparable increases in tenofovir exposure when TDF is administered as COMPLERA, or TRUVADA + dolutegravir. i. Study conducted with ATRIPLA coadministered with SOVALDI ® (sofosbuvir). j. Study conducted with COMPLERA coadministered with EPCLUSA; coadministration with EPCLUSA also results in comparable increases in tenofovir exposures when TDF is administered as ATRIPLA, STRIBILD, TRUVADA + atazanavir/ritonavir, or TRUVADA + darunavir/ritonavir. k. Administered as raltegravir + emtricitabine/tenofovir DF. l. Comparison based on exposures when administered as darunavir/ritonavir + emtricitabine/tenofovir DF. m. Study conducted with additional voxilaprevir 100 mg to achieve voxilaprevir exposures expected in HCV-infected patients. n. Aptivus Prescribing Information. No effect on the pharmacokinetic parameters of the following coadministered drugs was observed with tenofovir disoproxil fumarate: abacavir, didanosine (buffered tablets), emtricitabine, entecavir, and lamivudine. Table 15 Drug Interactions: Changes in Pharmacokinetic Parameters for Coadministered Drug in the Presence of Tenofovir disoproxil fumarate Tablets Coadministered Drug Dose of Coadministered Drug (mg) N % Change of Coadministered Drug Pharmacokinetic Parameters a (90% CI) C max A UC C min Abacavir 300 once 8 12 (¯ 1 to 26) Û NA Atazanavirb 400 once daily x 14 days 34 ¯21 (¯27 to ¯ 14) ¯25 (¯30 to ¯19) ¯ 40 (¯ 48 to ¯ 32) Atazanavirb Atazanavir/Ritonavir 300/100 once daily x 42 days 10 ¯28 (¯ 50 to 5) ¯25c (¯42 to ¯ 3) ¯23c (¯46 to 10) Darunavir d Darunavir/Ritonavir 300/100 once daily 12 16 (¯ to 42) 21 (¯ to 54) 24 (¯ to 69) Didanosine e 250 once, simultaneously with tenofovir disoproxil fumarate tablets and a light meal f 33 ¯ 20 g (¯ 32 to ¯ 7) Û g NA Emtricitabine 200 once daily x 7 days 17 Û Û 20 ( 12 to 29) Entecavir 1 mg once daily x 10 days 28 Û 13 ( to 15) Û Indinavir 800 three times daily x 7 days 12 ¯ 11 (¯ 30 t

Kenya

Brands & prices

0 listed

Brand	Company	Pack	KES
No brands linked yet.

Special populations

Pregnancy & lactation

Pregnancy

8.1 Pregnancy Pregnancy Category B There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, tenofovir disoproxil fumarate tablets should be used during pregnancy only if clearly needed. Antiretroviral Pregnancy Registry: To monitor fetal outcomes of pregnant women exposed to tenofovir disoproxil fumarate tablets, an Antiretroviral Pregnancy Registry has been established. Healthcare providers are encouraged to register patients by calling 1-800-258-4263. Risk Summary Animal Data Reproduction studies have been performed in rats and rabbits at doses up to 14 and 19 times the human dose based on body surface area comparisons and revealed no evidence of impaired fertility or harm to the fetus due to tenofovir.

Lactation

8.3 Nursing Mothers Nursing Mothers: The Centers for Disease Control and Prevention recommend that HIV-1 infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV-1. Samples of breast milk obtained from five HIV-1 infected mothers in the first post-partum week show that tenofovir is secreted in human milk. The impact of this exposure in breastfed infants is unknown. Because of both the potential for HIV-1 transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving tenofovir disoproxil fumarate tablets.

Diet

Food & alcohol

Drug & food interactions (label) 7 DRUG INTERACTIONS This section describes clinically relevant drug interactions with tenofovir disoproxil fumarate tablets. Drug interactions trials are described elsewhere in the labeling [See Clinical Pharmacology ( 12.3 )]. • Tenofovir disoproxil fumarate increases didanosine concentrations. Dose reduction and close monitoring for didanosine toxicity are warranted. (7.2) • Coadministration decreases atazanavir concentrations. When coadministered with tenofovir disoproxil fumarate, use atazanavir given with ritonavir. (7.2) • Coadministration of tenofovir disoproxil fumarate with certain HIV-1 protease inhibitors or certain drugs to treat HCV increases tenofovir concentrations. Monitor for evidence of tenofovir toxicity. (7.2) • Consult Full Prescribing Information prior to and during treatment for important drug interactions. (7.2) 7.1 Drugs Affecting Renal Function Tenofovir is primarily eliminated by the kidneys [see Clinical Pharmacology ( 12.3)]. Coadministration of tenofovir disoproxil fumarate tablets with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the coadministered drug. Some examples include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions ( 5.2)]. Drugs that decrease renal function may increase concentrations of tenofovir. In the treatment of chronic hepatitis B, tenofovir disoproxil fumarate tablets should not be administered in combination with HEPSERA (adefovir dipivoxil). 7.2 Established and Significant Interactions Table 11 provides a listing of established or clinically significant drug interactions. The drug interactions described are based on studies conducted with tenofovir DF [see Clinical Pharmacology (12.3)]. Table 11 Established and Significanta Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Trials Concomitant Drug Class: Drug Name Effect on Concentration b Clinical Comment NRTI: didanosine ↑ didanosine Patients receiving tenofovir disoproxil fumarate tablets and didanosine should be monitored closely for didanosine-associated adverse reactions. Discontinue didanosine in patients who develop didanosine-associated adverse reactions. Higher didanosine concentrations could potentiate didanosine-associated adverse reactions, including pancreatitis, and neuropathy. Suppression of CD4+ cell counts has been observed in patients receiving tenofovir disoproxil fumarate tablets with didanosine 400 mg daily. In patients weighing greater than 60 kg, reduce the didanosine dose to 250 mg when it is coadministered with tenofovir disoproxil fumarate tablets. In patients weighing less than 60 kg, reduce the didanosine dose to 200 mg when it is coadministered with tenofovir disoproxil fumarate tablets. When coadministered, tenofovir disoproxil fumarate tablets and Videx EC may be taken under fast

Trust

Sources & disclaimer

Source: FDA drug label via OpenFDA/DailyMed; Local active-ingredient clinical extract; Professional class pharmacology (Therapeutic agent (verify pharmacological class))

Open source link

Clinical review date not recorded.

Decision support only — not a substitute for clinical judgment, product SmPC, or Kenya STG/EML.