Tenofovir Disoproxil Fumarate is an antiviral drug that is used to treat patients with chronic Hepatitis B and HIV infections.

Indications of Tenofovir:

• Chronic hepatitis B:

  • It is used for the treatment of chronic hepatitis B virus in patients ≥2 years of age weighing ≥10 kg.

• Treatment of HIV-1 infection:

  • It is indicated for the treatment of HIV-1 infection in patients ≥2 years of age weighing ≥10 kg, in combination with other antiretroviral agents.

• Off Label Use of Tenofovir disoproxil fumarate in Adults:

  • HIV-1 nonoccupational postexposure prophylaxis; HIV-1 occupational postexposure prophylaxis.

Tenofovir disoproxil fumarate dose in Adults

• Hepatitis B infection:

  • 300 mg per oral once daily.

• Treatment duration:

  • Tenofovir is influenced by HBeAg status, duration of HBV suppression, and presence of cirrhosis/decompensation.

Tenofovir Disoproxil Fumarate use in patients without cirrhosis:

• Hepatitis B e antigen-positive immune-active chronic hepatitis:

  • The duration of therapy is generally a minimum of 12 months of persistently normal ALT and undetectable serum HBV DNA levels after HBeAg seroconversion

• HBeAg-negative immune-active chronic hepatitis:

  • Duration of therapy is indefinite, discontinuation may be considered in patients with loss of HBsAg.

Tenofovir Disoproxil Fumarate in Patients with Cirrhosis:

• HBeAg-positive immune-active chronic hepatitis:

  • Treatment should be continued indefinitely in seroconversion unless there is a strong reason for discontinuation.

• HBeAg-negative immune-active chronic hepatitis:

  • Treatment discontinuation is not recommended due to the potential for decompensation and death.

Tenofovir Disoproxil Fumarate Dose in HIV-1 infection:

• Treatment:

  • 300 mg per oral once-daily concurrently with other antiretrovirals.

• HIV-1 nonoccupational postexposure prophylaxis (off-label use):

  • 300 mg per oral once daily for 28 days concurrently with other antiretroviral agents.
  • Therapy should be started within 72 hours of exposure.

• HIV-1 occupational postexposure, prophylaxis (off-label use):

  • 300 mg per oral once daily in combination with emtricitabine and raltegravir.
  • Therapy should be started within 72 hours and continued for one month.

Tenofovir Disoproxil Fumarate Dose in Children:

Tenofovir Disoproxil Fumarate Dose in HIV-1 infection:

• Treatment - Weight-directed dosing:

  • Children ≥2 years weighing ≥10 kg and Adolescents: 8 mg/kg per oral once daily
  • maximum daily dose: 300 mg/day

• Dosage form specific fixed dosing:

  • Oral powder: Children ≥2 years weighing ≥10 kg and Adolescents:

Note: Only measure with the provided scoop. One level scoop = 40 mg tenofovir disoproxil fumarate

• 10 to <12 kg:

  • 80 mg (2 scoops)per oral once daily

• 12 to <14 kg:

  • 100 mg (2.5 scoops) per oral once daily

• 14 to <17 kg:

  • 120 mg (3 scoops) per oral once daily

• 17 to <19 kg:

  • 140 mg (3.5 scoops) per oral once daily

• 19 to <22 kg:

  • 160 mg (4 scoops) per oral once daily

• 22 to <24 kg:

  • 180 mg (4.5 scoops) per oral once daily

• 24 to <27 kg:

  • 200 mg (5 scoops) per oral once daily

• 27 to <29 kg:

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  • 220 mg (5.5 scoops)per oral once daily

• 29 to <32 kg:

  • 240 mg (6 scoops) per oral once daily

• 32 to <34 kg:

  • 260 mg (6.5 scoops) per oral once daily

• 34 to <35 kg:

  • 280 mg (7 scoops) per oral once daily

• ≥35 kg:

  • 300 mg (7.5 scoops)per oral once daily

• Oral tablets: Children ≥2 years weighing ≥17 kg and Adolescents:

  • 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:

  • Children ≥2 years:

    • Oral: Age- and weight-appropriate dosing (see HIV-1 infection, treatment above) for 28 days in combination with other antiretroviral agents.
    • Initiate therapy within 72 hours of exposure.

  • Adolescents:

    • The combination product is recommended (see Emtricitabine and Tenofovir Disoproxil Fumarate monograph)

Tenofovir Disoproxil Fumarate dose in the treatment of Chronic Hepatitis B infection:

• Children ≥2 years weighing ≥10 kg and Adolescents:

  • 8 mg/kg per oral once daily
  • The maximum daily dose: 300 mg/day

Pregnancy Risk Category: B

• Tenofovir can cross the human placenta, increasing the risk of stillbirth, preterm delivery, low birth weight and small for gestational infants.
• If viral suppression is successful and the regimen is well tolerated, Tenofovir may be continued during pregnancy.
• It should be administered postpartum, with dose modification in HIV.
• It can be administered at 28-32 weeks gestation, and stopped between 1 and 3 months after delivery. Continuous monitoring of ALT is recommended.
• Infants who have been exposed to antiretroviral medication should be followed up for a long time.
• Children with heart or CNS abnormalities and children with mitochondrial dysfunction should also be evaluated.
• Mothers who gave birth to tenofovir disoproxil fumarate during pregnancy could have lactic acidosis or hepatic steroids, and decreased bone mineral content.

Tenofovir disoproxil fumarate use during breastfeeding:

• Tenofovir can be excreted in milk but is not recommended for acute HIV infection in breastfeeding women.
• If the infection is confirmed, breastfeeding should be stopped.
• Postnatal HIV transmission is still possible even with maternal antiretroviral treatment.
• Besides, a multi-class-resistant virus has been detected in breastfeeding infants despite maternal therapy.

Tenofovir Disoproxil Fumarate Dose adjustment in renal disease:

• Manufacturer's labeling:

  • Creatinine clearance ≥50 mL/minute:

    • No dosage adjustment necessary.

  • Creatinine clearance 30 to 49 mL/minute:

    • 300 mg every 48 hours

  • Creatinine clearance 10 to 29 mL/minute:

    • 300 mg every 72 to 96 hours

  • Creatinine clearance <10 mL/minute:

    • There are no dosage adjustments provided in the manufacturer's labeling.

  • Hemodialysis:

    • 300 mg following dialysis every 7 days or after a total of 12 hours of dialysis (usually once weekly assuming 3 dialysis sessions lasting about 4 hours each).

• Alternate recommendations (IDSA):

  • Creatinine clearance <50 mL/minute (and not on hemodialysis) or GFR <60 mL/minute/1.73 m²:

    • Avoid use.

  • Peritoneal dialysis:

    • Use with caution; dose reduction recommended.

Tenofovir Disoproxil Fumarate Dose adjustment in liver disease:

No dosage adjustment is necessary.

Common Side Effects of Tenofovir Disoproxil Fumarate:

• Central Nervous System:

  • Insomnia
  • Headache
  • Pain
  • Dizziness
  • Depression

• Dermatologic:

  • Skin Rash
  • Pruritus

• Endocrine & Metabolic:

  • Hypercholesterolemia
  • Increased Serum Triglycerides

• Gastrointestinal:

  • Abdominal Pain
  • Nausea
  • Diarrhea
  • Vomiting

• Neuromuscular & Skeletal:

  • Decreased Bone Mineral Density
  • Increased Creatine Phosphokinase
  • Weakness

• Miscellaneous:

  • Fever

Rare Side Effects of Tenofovir Disoproxil Fumarate:

• Cardiovascular:

  • Chest Pain

• Central Nervous System:

  • Fatigue
  • Anxiety
  • Peripheral Neuropathy

• Dermatologic:

  • Diaphoresis

• Endocrine & Metabolic:

  • Weight Loss
  • Glycosuria
  • Hyperglycemia
  • Lipodystrophy

• Gastrointestinal:

  • Increased Serum Amylase
  • Anorexia
  • Dyspepsia
  • Flatulence

• Genitourinary:

  • Hematuria

• Hematologic & Oncologic:

  • Neutropenia

• Hepatic:

  • Increased Serum ALT
  • Increased Serum AST
  • Increased Serum Transaminases
  • Increased Serum Alkaline Phosphatase

• Neuromuscular & Skeletal:

  • Back Pain
  • Arthralgia
  • Myalgia

• Renal:

  • Increased Serum Creatinine
  • Renal Failure

• Respiratory:

  • Sinusitis
  • Upper Respiratory Tract Infection
  • Nasopharyngitis
  • Pneumonia

Contraindication to Tenofovir Disoproxil Fumarate:

Hypersensitivity to tenofovir and any component of the formulation

Warnings and precautions

• Reduced bone mineral density

  • Tenofovir has been associated with decreases in bone mineral density and increased serum parathyroid hormone and 1,25 vitamin D levels in adults and children were also higher.
  • Supplementation with Vitamin D and calcium should be provided. It is also important to monitor bone density in adults and children who have had a history of fractures.

• Immune reconstitution syndrome:

  • Immune reconstitution syndrome can occur in patients who have an inflammatory response to residual HIV infection.
  • Patients may also develop autoimmune disorders like Graves' disease or polymyositis later in therapy.

• Lactic acidosis/ hepatomegaly:

  • Life-threatening conditions include severe hepatomegaly and lactic acidosis.

• Osteomalacia, renal dysfunction

  • Osteomalacia may be caused by proximal renal tubeopathy. This can manifest as bone pain, extreme pain, fractures and weakness.

• Toxicity in the renal system:

  • May cause renal toxicity such as acute renal failure and/or Fanconi syndrome and the risk factor is increased with NSAIDs.
  • Guidelines from IDSA recommend replacing tenofovir by alternate therapy for HIV-infected persons with a >25% decrease of GFR from baseline.
  • This includes a level of 60mL/minute/1.73m2 during treatment, as well as euglycemic, increased urinary and phosphorus excretion, hypophosphatemia and proteinuria.

• Chronic Hepatitis B: [US-Boxed Warning]

  • Hepatitis B exacerbation may occur after treatment has been stopped.
  • This can lead to hepatic dysfunction and hepatic failure in patients with advanced hepatic diseases or cirrhosis.
  • After stopping therapy, LFTs should continue to be monitored for longer periods.

Monitoring parameters:

• CBC
• LFTS
• RFTS
• Creatinine kinase
• Urine glucose and protein
• Serum phosphorus
• CD4 count/HIV RNA levels
• bone density
• testing for HBV
• HIV status

How to administer Tenofovir disoproxil fumarate (Viread)?

• Tablets can be given without regard to food.
• The powder should be mixed with 2 to 4 ounces of soft food (applesauce, baby food, yogurt) and swallowed immediately, do not mix in liquid (powder may float on top of the liquid even after stirring).
• The powder should be measured using only the supplied dosing scoop.

Mechanism of action of Tenofovir disoproxil fumarate:

• Tenofovir diproxil fumarate, also known as TDF, is a nucletide reverse transcriptase inhibitor.
• It is analogous to adenosine 5’-monophosphate. It inhibits viral replication by interfering the HIV viral DNA dependent polymerase. 
• Hydrolysis converts tenofovir disoproxil fumarate to tenofovir, and then phosphorylates it to the active form of tenofovir. Tenofovir inhibits HBV replication by inhibiting HBV polymerase.

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 the tablet, but the mean AUCs are similar

Half-life elimination:

• Serum: 17 hours
• intracellular: 10 to 50 hours

Time to peak serum concentration:

• 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

Tenofovir disoproxil fumarate Brand Names (International):

• APO-Tenofovir
• Auro-Tenofovir
• JAMP-Tenofovir
• MYLAN-Tenofovir Disoproxil
• NAT-Tenofovir
• PMSTenofovir
• TEVA-Tenofovir
• Viread
• Dipovir
• Forvic
• Foviral
• Glonovir
• Ricovir
• Tefostad T300
• Tenof
• Tenofir
• Tenofo-B
• Tenolam
• Tenozet
• Tenvir
• Tenvira
• Tenvor
• Viraday
• Viread
• Xynovir

Tenofovir disoproxil fumarate Brand Names in Pakistan:

Brands in Pakistan will be updated later.