Tenofovir Disoproxil Fumarate

What is Tenofovir Disoproxil Fumarate?

11 DESCRIPTION Tenofovir disoproxil fumarate tablet a prodrug of tenofovir which is a fumaric acid salt of bis-isopropoxycarbonyloxymethyl ester derivative of tenofovir. In vivo tenofovir DF is converted to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5’-monophosphate. Tenofovir exhibits activity against HIV-1 reverse transcriptase. The chemical name of tenofovir DF is 9-[(R)-2-[[bis[[(isopropoxycarbonyl)oxy]methoxy]phosphinyl]methoxy]propyl] adenine fumarate (1:1). It has a molecular formula of C 19 H 30 N 5 O 10 P • C 4 H 4 O 4 and a molecular weight of 635.52. It has the following structural formula: Tenofovir DF is a white to off-white crystalline powder with a solubility of 13.4 mg/mL in distilled water at 25°C. It has an octanol/phosphate buffer (pH 6.5) partition coefficient (log p) of 1.25 at 25 °C. Tenofovir disoproxil fumarate is available as tablets. Tenofovir disoproxil fumarate tablets are for oral administration. Each tablet contains 300 mg of tenofovir DF, which is equivalent to 245 mg of tenofovir disoproxil. Each tablet contains the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, micro

Uses of Tenofovir Disoproxil Fumarate

Established uses

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 t

How Tenofovir Disoproxil Fumarate works

In more detail: 12.1 Mechanism of Action Tenofovir disoproxil fumarate is an antiviral drug [See Microbiology ( 12.4 )].

How to take Tenofovir Disoproxil Fumarate

2 DOSAGE & 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 an

Dosage

Follow the dose prescribed by your doctor or pharmacist. The ranges below are general information, not a personal prescription.

Adults: 2 DOSAGE & 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 an

Side effects of Tenofovir Disoproxil Fumarate

Common

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.

Warnings and who should not take it

Who should NOT take Tenofovir Disoproxil Fumarate?

4 CONTRAINDICATIONS None.
None.
(4)

Overdose

10 OVERDOSAGE Limited clinical experience at doses higher than the therapeutic dose of tenofovir disoproxil fumarate tablets 300 mg are available. In Study 901, 600 mg tenofovir DF was administered to 8 subjects orally for 28 days. No severe adverse reactions were reported. The effects of higher doses are not known. If overdose occurs the patient must be monitored for evidence of toxicity and standard supportive treatment applied as necessary. 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.

Safety at a glance

PregnancyCaution

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.

BreastfeedingAvoid / Unsafe

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.

Children and elderly

Children

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 tenofovi

Elderly

8.5 Geriatric Use Clinical trials of tenofovir disoproxil fumarate tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for the elderly patient should be cautious, keeping in mind the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Interactions

Medicine and medicine

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.

Frequently asked questions

What is Tenofovir Disoproxil Fumarate used for?

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 t.

How should I take Tenofovir Disoproxil Fumarate?

2 DOSAGE & 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 an

What are the common side 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..

Who should not take Tenofovir Disoproxil Fumarate?

4 CONTRAINDICATIONS None.; None.; (4).

Can I take Tenofovir Disoproxil Fumarate during 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.

Can I take Tenofovir Disoproxil Fumarate while breastfeeding?

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.

Can children take Tenofovir Disoproxil Fumarate?

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 tenofovi

Does Tenofovir Disoproxil Fumarate interact with other medicines?

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..