Tenofovir Disoproxil, in combination with other antiretroviral agents, is used for the treatment of HIV-1 infection. It is also indicated for the treatment of chronic hepatitis B in adults.

Mechanism of Action: Tenofovir works by inhibiting HIV reverse transcriptase through competition with the natural substrate, deoxyadenosine 5-triphosphate. It acts as an analogue of naturally occurring deoxynucleotides required for viral DNA synthesis. By competing with these natural nucleotides, it becomes incorporated into the growing viral DNA chain and thereby interrupts further DNA elongation.

Pharmacokinetics: Tenofovir is a water-soluble diester prodrug of the active compound Tenofovir. Its oral bioavailability is approximately 25%. After a single oral dose of 245 mg in HIV-1 infected individuals under fasting conditions, peak serum concentration (Cmax) is reached within about 1.0 to 1.4 hours. The Cmax and AUC values are approximately 0.30 ± 0.09 µg/mL and 2.29 ± 0.69 µg·hr/mL, respectively. Protein binding is very low, with less than 0.7% binding to human plasma proteins and less than 7.2% to serum proteins. The elimination half-life is approximately 17 hours. Tenofovir is excreted through both glomerular filtration and active tubular secretion.

The size and frequency of the dosage must be adjusted to the needs of the individual patient. Tenofovir disoproxil 245 mg oral tablets should be administered once daily orally, without regard to food.

Recommended Dose in Adults: For the treatment of HIV-1 or chronic hepatitis B: The dose is 245 mg Tenofovir tablet once daily taken orally, without regard to food. In the treatment of chronic hepatitis B, the optimal duration of treatment is unknown.

Recommended Dose in Pediatric Patients (12 years of age and older and greater than or equal to 35 kg): For the treatment of HIV-1 in pediatric patients 12 years of age and older with body weight greater than or equal to 35 kg: The dose is one 245 mg Tenofovir tablet once daily taken orally, without regard to food.

Didanosine: Use with caution. Patients should be monitored for didanosine-related side effects.

Atazanavir: Patients taking Atazanavir and Tenofovir should be monitored for Tenofovir-related side effects.

Lopinavir/Ritonavir: Patients taking Lopinavir/Ritonavir and Tenofovir should be monitored for Tenofovir-related side effects.

Do not use Tenofovir in patients with: broken bones due to disease, fatty liver, severe liver disease, acute kidney disease, low bone density, breastfeeding mothers, low blood phosphate, high lactic acid levels, or overweight.

Like all medicines, Tenofovir may cause side effects. In most cases, these effects are mild and may not require treatment or can be easily managed by a healthcare provider. The most commonly reported side effects include headache, diarrhea, nausea, and weakness. Other possible effects include indigestion, heartburn, chest pain, and drowsiness. Although most side effects are mild, some serious conditions should be reported immediately to a healthcare provider, such as elevated cholesterol or triglyceride levels, kidney problems, depression, and anxiety.

Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. Tenofovir should be used during pregnancy only if clearly necessary.The Centers for Disease Control and Prevention recommend that HIV-1 infected mothers should not breastfeed, as there is a risk of postnatal transmission of HIV-1.Pediatric Use: For HIV-1 treatment in children aged 12 years and above with body weight ≥35 kg, the recommended dose is Tenofovir 245 mg once daily taken orally.Geriatric Use: Clinical studies have not included enough patients aged 65 years and above to determine differences in response. Dose selection in elderly patients should be done cautiously, considering possible reduced liver, kidney, or heart function, and the presence of other diseases or medications.

Lactic acidosis/severe hepatomegaly with steatosis: Cases of lactic acidosis and severe liver enlargement with fatty changes, including fatal outcomes, have been reported with nucleoside analogs like Tenofovir, especially when used with other antiretroviral drugs. These cases have been reported more frequently in women. Exacerbation of hepatitis after discontinuation: Stopping Tenofovir or other anti-HBV therapy may lead to severe worsening of hepatitis. Patients should be closely monitored clinically and through laboratory tests for several months after discontinuation. New onset or worsening renal impairment: Tenofovir is mainly eliminated by the kidneys. Cases of kidney damage, including acute renal failure and Fanconi syndrome (renal tubular dysfunction with severe hypophosphatemia), have been reported.

Coadministration with other products: Tenofovir should not be used together with fixed-dose combinations containing Tenofovir or with adefovir disoproxil.

Patients coinfected with HIV-1 and HBV: To prevent development of HIV resistance, Tenofovir should be used as part of a complete antiretroviral regimen in patients coinfected with HIV and HBV. Fat redistribution: In HIV-infected patients receiving combination antiretroviral therapy, changes in body fat distribution such as central obesity, buffalo hump, peripheral wasting, facial wasting, and breast enlargement have been observed.

Immune reconstitution syndrome: This condition has been reported in HIV-infected patients treated with combination antiretroviral therapy, including Tenofovir.

Dose Adjustment for Renal Impairment in Adults: In patients with moderate to severe renal impairment, increased drug exposure occurs. Therefore, the dosing interval should be adjusted: If creatinine clearance is 30–49 mL/min, 245 mg every 48 hours is recommended. If creatinine clearance is 10–29 mL/min, 245 mg every 72 to 96 hours is recommended. For hemodialysis patients, 245 mg is recommended every 7 days or after about 12 hours of dialysis. No dose adjustment is required for mild renal impairment (creatinine clearance 50–80 mL/min).

Antiretroviral, Hepatic viral infections (Hepatitis B)

Store below 25°C, in a cool, dry, light-protected place. Keep out of children’s reach.