Tenofovir disoproxil fumarate is a nucleotide reverse transcriptase inhibitor that interferes with viral RNA dependent DNA polymerase, inhibiting HIV replication. It also inhibits HBV replication by inhibiting HBV polymerase. It is used to treat the following conditions:

• Chronic hepatitis B in patients weighing more than 10 kgs and older than 2 years of age

• HIV-1 infection in combination with other antiretroviral agents in patients weighing more than 10 kgs and older than 2 years of age

• Postexposure prophylaxis of HIV-1 infection as off label Use.

Tenofovir disoproxil fumarate Dose in Adults

Dose in the treatment of Chronic Hepatitis B infection:

• 300 mg orally once a day

Note: It should not be used with adefovir

Treatment duration depends on the following factors:

• Patients without cirrhosis:

  •  Immune-active chronic hepatitis and Hepatitis B e antigen (HBeAg) positive:
    • Treatment should continue until HBeAg seroconversion
    • The optimal duration following seroconversion is not known, however, therapy is generally given for a minimum of 12 months of persistently normal ALT and undetectable HBV DNA.
  • Immune-active chronic hepatitis and HBeAg-negative :
    • Treatment should be continued indefinitely.
    • Treatment discontinuation may be considered in patients with HBsAg negativity, however, data is limited in this regard.

• Patients with cirrhosis:

  •  Immune-active chronic hepatitis and HBeAg-positive:
    • Treatment should continue indefinitely in patients who seroconvert on therapy due to concerns with decompensation and death.
  •  Immune-active chronic hepatitis and HBeAg-negative:
    • Treatment should be continued indefinitely due to the potential for decompensation and death.

Dose in the treatment of HIV-1 infection:

• • 300 mg orally once a day in combination with other antiretroviral agents.

Note: The initial regimens in treatment-naive patients should consist of

• Tenofovir coadministered with emtricitabine plus dolutegravir or
• Tenofovir, emtricitabine plus raltegravir

Lamivudine may be used as a substitute for emtricitabine in either of these regimens.

Off-label use for HIV-1 occupational and nonoccupational Postexposure prophylaxis:

• 300 mg orally once a day for 28 days in combination with other antiretroviral agents (emtricitabine and raltegravir).
• Treatment should be initiated within 72 hours of exposure.

Tenofovir disoproxil fumarate Dose in Childrens

Dose in the treatment of HIV-1 infection:

• Weight-adjusted dosing:
  • Children older than 2 years weighing more than 10 kgs and Adolescents:
    • 8 mg/kg/dose orally once a day to a maximum daily dose of 300 mg/day

Dosage form specific fixed dosing:

• Oral powder: Children older than 2 years weighing more than10 kgs and Adolescents:

Note: One scoop (provided by the manufacturer) = 40 mg of tenofovir disoproxil fumarate

• 10 to less than 12 kgs:
  • 2 scoops or 80 mg orally once a day
• 12 to less than 14 kgs:
  • 2.5 scoops or 100 mg orally once a day.
• 14 to less than 17 kg:
  • 3 scoops or 120 mg orally once a day.
• 17 to less than 19 kg:
  • 3.5 scoops or 140 mg orally once a day.
• 19 to less than 22 kg:
  • 4 scoops or 160 mg orally once a day.
• 22 to less than 24 kg:
  • 4.5 scoops or 180 mg orally once a day.
• 24 to less than 27 kg:
  • 5 scoops or 200 mg orally once a day.
• 27 to less than 29 kg:
  • 5.5 scoops or 220 mg orally once a day.
• 29 to less than 32 kg:
  • 6 scoops or 240 mg orally once a day.
• 32 to less than 34 kg:
  • 6.5 scoops or 260 mg orally once a day.
• 34 to less than 35 kg:
  • 7 scoops or 280 mg orally once a day.
• More than 35 kgs:
  • 7.5 scoops or 300 mg orally once a day.

Oral tablets: Children older than 2 years weighing more than 17 kg and Adolescents:

• 17 to less than 22 kgs:
  • 150 mg orally once a day
• 22 to less than 28 kg:
  • 200 mg orally once a day.
• 28 to less than 35 kg:
  • 250 mg orally once a day.
• more than 35 kgs:
  • 300 mg orally once a day.

Use in the  non-occupational postexposure prophylaxis (nPEP) of HIV-1 infection:

• Children older than 2 years and adolescents:
  • Treatment should be initiated as soon as possible and within the first 72 hours.
  • Age and weight-adjusted dosing should be used.
  • Tenofovir should be advised as a combination therapy with emtricitabine and raltegravir).
  • Treatment should be given for four weeks.

Dose in the treatment of chronic Hepatitis B infection:

• Children older than 2 years weighing less than 10 kg and Adolescents:
  • 8 mg/kg/dose orally once a day to a maximum daily dose of 300 mg/day.
  • Hepatitis B e antigen (HBeAg) seroconversion may be used as a therapeutic endpoint followed by an additional twelve months of consolidation therapy.

Tenofovir disoproxil fumarate Pregnancy Risk Factor: B

• Although Tenofovir crosses into the placental barriers, there is no increased risk of birth defects in pregnant women exposed to it during their first trimester.
• Antiretroviral therapy has been linked to stillbirths, preterm births, low birth weight, small for gestational years, and stillbirths. However, the data is inconsistent and limited.
• Children who have significant toxicities should be tested for mitochondrial dysfunction.
• Another adverse effect observed in infants born to mothers who took ART is a decrease of bone mineral density, lactic acidsosis, and hepatic steatosis.
• According to the HHS (Health and Human Services), Perinatal HIV Guidelines, tenofovir is a preferred NRTI in HIV-infected pregnant women.
• The HHS recommends that tenofovir be used in combination with lamivudine or emtricitabine to be preferred dual-NRTI as initial therapy for ART-naive pregnant women and patients with HIV/HBV coinfection.
• Tenofovir disoproxil fumarate is also recommended for pre-exposure prevention in discordant couples who are trying to conceive.
• AASLD guidelines recommend antiviral treatment to prevent perinatal transmission in pregnant HBsAg-positive women with an HBV genome of more than 200,000 units/ml.
• Tenofovir can be started at 28-32 weeks gestation to prevent perinatal transmission. It may also be stopped at 3 months gestation.

Tenofovir disoproxil fumarate use during breastfeeding:

• Tenofovir is minimally absorbed into breastmilk. It is recommended as part of a combination treatment for HIV infection in breastfeeding mothers.
• If HIV infection has been confirmed, it is important to stop breastfeeding because the baby could be HIV-infected.
• The AASLD guidelines don't consider antiviral treatment as a contraindication for breastfeeding in hepatitis B-infected women who are not HIV coinfected.

Tenofovir disoproxil fumarate Dose in Renal Disease:

Dose adjustment in kidney disease as per the manufacturer's labeling:

• CrCl of 50 mL/minute or more:
  • Adjustment in the dose is not necessary.
• CrCl 30 - 49 mL/minute:
  • 300 mg every 48 hours
• CrCl 10 - 29 mL/minute:
  • 300 mg every 72 - 96 hours
• CrCl of less than 10 mL/minute:
  • Adjustment in the dose has not been provided in the manufacturer's labeling.
• Hemodialysis:
  • 300 mg after dialysis every 7 days or after a total of 12 hours of dialysis
  • The usual dose is once a week assuming three dialysis sessions lasting about four hours each.

Dose adjustment in kidney disease as per IDSA guidelines:

• CrCl of less than 50 mL/minute or GFR less than 60 mL/minute/1.73 m²:
  • Avoid its use.
• Peritoneal dialysis:
  • It should be used with caution and the dose should be reduced. No specific recommendation has been made regarding dose adjustment).

Tenofovir disoproxil fumarate Dose in Liver Disease:

• Adjustment in the dose is not required in patients with liver disease.

Common Side Effects of Tenofovir disoproxil fumarate Include:

• 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

Less Common Side Effects Of Tenofovir Disoproxil Fumarate Include:

• 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 Include:

• Contraindications are not listed on the label.
• Patients who have severe allergic reactions to any ingredient of the drug should be advised not to use it.

Warnings and Precautions​​​​​​​

• Reduced bone mineral density
  • Tenofovir therapy for HIV patients has been associated with osteoporosis, decreased bone mineral density, increased bone metabolic markers, and osteopenia.
  • While the skeletal height does not change, children can also experience a decrease in bone mineral density.
  • All patients should consider taking vitamin D and calcium supplements.
  • Patients at high risk should have their bone mineral density, vitamin D and parathyroid hormone levels monitored.
• Immune reconstitution syndrome:
  • An autoimmune disorder such as Graves, polymyositis or Guillain Barre syndrome may cause an inflammatory response in patients.
  • This can lead to a worsening of the clinical condition.
  • The immune response can cause rapid deterioration in patients with an indolent, or opportunistic, infection such as tuberculosis.
• Lactic acidosis & hepatomegaly:
  • Patients can develop severe hepatomegaly and lactic acidosis with steatosis, which may sometimes be life-threatening.
  • Patients with lactic acidosis, hepatotoxicity or steatosis should not be treated.
• Osteomalacia, renal dysfunction
  • Osteomalacia may be caused by proximal renal tubeopathy.
  • This is characterized by bone pain, fractures and extremities pain.
  • Patients at high risk of renal dysfunction should be assessed for hypophosphatemia or osteomalacia, especially if they have persistent or worsening muscle or bone symptoms.
• Toxicity in the renal system:
  • Tenofovir can cause renal toxicities (acute renal failure, Fanconi syndrome).
  • Patients on other nephrotoxic medications should avoid it.
  • NSAIDs should also be avoided in patients on tenofovir therapy.
  • Before starting therapy, patients should have their serum creatinine, estimated creatinine clearance, and urine protein checked. This can also be done periodically thereafter.
  • If the GFR drops by more than 25% from baseline, and to a level below 60 ml/minute/1.73m2, the IDSA guidelines recommend that HIV-infected persons discontinue taking tenofovir (especially in the presence proximal tubular dysfunction).
• Chronic hepatitis B [US Boxed Warning]
  • Patients with chronic hepatitis B could experience a flare up, leading to hepatic impairment and decompensation.
  • After discontinuing treatment, patients should be monitored regularly for any changes in liver function.
  • HIV resistance may occur in patients receiving tenofovir treatment to treat chronic hepatitis B. Before starting treatment for hepatitis B, HIV testing is recommended.
• Hepatic impairment
  • Patients with hepatic impairment must be cautious when taking the drug.
• Renal impairment
  • Patients with impaired renal function should be advised to take the drug with caution.
  • The IDSA recommends that patients with a CrCl less than 50 mg/min, and not those on hemodialysis or less 60 mg/min/1.73m2, should avoid tenofovir.

Tenofovir disoproxil fumarate: Drug Interaction

Monitoring as per the manufacturer’s labeling:

• Patients with HIV infection:

  • CBC with differential counts
  • Reticulocyte count
  • Creatine kinase levels
  • CD4 count
  • Plasma HIV RNA levels
  • Serum phosphorus
  • Serum creatinine
  • Urine glucose
  • Urine protein
  • Liver function tests
  • Bone mineral density
  • HBV testing is recommended before the start of antiretroviral therapy
  • Weight in children.

• Patients with HBV:

  • HIV status before starting therapy
  • Serum phosphorus
  • Serum creatinine
  • Urine glucose
  • Urine protein
  • Bone mineral density
  • LFTs at 3 months interval and following discontinuation of tenofovir.

Alternate recommendations:

• Patients with chronic hepatitis B:

  • HBV DNA and ALT every 3 months until undetectable and then every 3 - 6 months thereafter
  • HBeAg
  • anti-HBe antibodies
  • HBsAg
  • Creatinine clearance
  • Serum phosphate
  • Urine glucose
  • Urine protein
  • Bone mineral density
  • Serum lactate levels
  • Monitor for viremia, ALT, seroreversion, and clinical features of decompensation every 3 months for at least one year
  • Monitor the patient for the development of hepatocellular carcinoma.

How to administer Tenofovir?

• The tablets may be taken without regard to meals.
• The powder should be mixed with 2 - 4 ounces of soft food and swallowed immediately.
• It should not be mixed with liquids and the dose should be measured only with the supplied dosing scoop.

Mechanism of action of Tenofovir disoproxil fumarate:

• Tenofovir dioproxil fumarate is a nucletide reverse transcriptase inhibitor.
• It's also an analog to adenosine 5-'-monophosphate.
• Tenofovir disoproxil fumarate is first converted intracellularly by hydrolysis to tenofovir and then phosphorylated into the active compound, tenofovir Diphosphate.
• It interferes with viral RNA dependent DNA Polymerase, which inhibits HIV replication. 
• It inhibits HBV polymerase, which in turn inhibits HBV replication.

Less than 7% of the drug is bound to serum proteins. It is metabolized intracellularly by hydrolysis to tenofovir and then to the active compound tenofovir diphosphate. Bioavailability of the tablets is about 25% that is increased with a high-fat meal Half-life elimination of the drug in the serum is 17 hours while inside the cells, it has a half-life of 10 - 50 hours. The time to reach the peak serum concentration is 36 - 84 minutes in the fasting state and 96 - 144 minutes if taken with a high-fat meal.

70 - 80% of the drug is excreted in the urine via filtration and active secretion within 72 hours as unchanged drug.

International Brands of Tenofovir disoproxil fumarate:

• APO-Tenofovir
• Auro-Tenofovir
• JAMP-Tenofovir
• MYLAN-Tenofovir Disoproxil
• NAT-Tenofovir
• PMS-Tenofovir
• TEVA-Tenofovir
• Viread
• Agifovir
• Dipovir
• Foviral
• Glonovir
• Ricovir
• Tenof
• Tenofir
• Tenolam
• Tenozet
• Tenvir
• Tenvira
• Tenvor
• Viraday
• Xynovir

Tenofovir Disoproxil Brands in Pakistan: