Tenof^® 300 (Tablets) Instructions for Use

Marketing Authorization Holder

Hetero Labs, Limited (India)

Manufactured By

Hetero Labs, Limited (India)

Or

Makiz-Pharma, LLC (Russia)

ATC Code

J05AF07 (Tenofovir disoproxil)

Active Substance

Tenofovir (Rec.INN registered by WHO)

Dosage Form

Tenof® 300

Film-coated tablets, 300 mg: 30, 60, 100, 500, or 1000 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets blue in color, biconvex, triangular in shape with rounded ends, engraved with “H” on one side and “123” on the other side; on cross-section, two layers: a white or almost white core and a blue coating.

Excipients: croscarmellose sodium – 40 mg, lactose monohydrate – 153.66 mg, microcrystalline cellulose MCC-102 – 133.34 mg, pregelatinized starch – 33.33 mg, magnesium stearate – 6.67 mg.

Coating composition Opadry II light blue Y-30-10671 (hypromellose – 28%, titanium dioxide – 22.51%, lactose monohydrate – 40%, triacetin – 8%, aluminum lake based on indigo carmine dye – 1.49%) – 32 mg.

30 pcs. – polyethylene bottles (1) – cardboard packs.
60 pcs. – polyethylene bottles (1) – cardboard packs.
100 pcs. – polyethylene bottles (1) – cardboard packs.
500 pcs. – polyethylene bottles (1) – cardboard packs.
1000 pcs. – polyethylene bottles (1) – cardboard packs.
30 pcs. – polyethylene jars (1) – cardboard packs.

Clinical-Pharmacological Group

Antiviral drug active against HIV

Pharmacotherapeutic Group

Antiviral agent

Pharmacological Action

Antiviral agent, nucleotide reverse transcriptase inhibitor. Tenofovir is converted in vivo to tenofovir, an analog of nucleoside monophosphate (nucleotide) adenosine monophosphate.

Tenofovir is subsequently converted to the active metabolite, tenofovir diphosphate, which inhibits the activity of HIV-1 reverse transcriptase by incorporating into the viral DNA molecule and disrupting DNA chain synthesis.

Tenofovir is a weak inhibitor of mammalian DNA polymerases α, β, and mitochondrial DNA polymerase γ.

Pharmacokinetics

When taken on an empty stomach, the bioavailability of tenofovir is approximately 25% and up to 40% (with food); it improves when taken with food, especially high-fat meals.

Food intake does not have a clinically significant effect on the efficacy of tenofovir.

After a single oral dose of 300 mg, C_max in blood serum is reached in 1±0.4 hours.

The pharmacokinetics of tenofovir are dose-dependent. T_1/2 from the cell > 60 hours.

After a single oral dose, the T_1/2 of tenofovir is approximately 17 hours.

After multiple oral doses of 300 mg once daily (under non-fasting conditions), 32±10% of the administered dose is determined in the urine over more than 24 hours.

Tenofovir is excreted by the kidneys, through glomerular filtration and active tubular secretion.

Indications

Treatment of HIV-1 infection as part of combination antiretroviral therapy in adults.

ICD codes

Dosage Regimen

Take orally, with or without food.

The recommended adult dose is 300 mg once daily.

For patients with renal impairment, adjust the dosing interval based on creatinine clearance (CrCl).

For CrCl 30-49 mL/min, administer 300 mg every 48 hours.

For CrCl 10-29 mL/min, administer 300 mg every 72 to 96 hours.

For patients on hemodialysis, administer 300 mg every 7 days; give the dose after the hemodialysis session is completed.

Determine CrCl before initiating therapy.

Monitor renal function and serum phosphorus regularly, especially in patients with risk factors for renal impairment.

Avoid concomitant use with other nephrotoxic drugs.

Adverse Reactions

Metabolism: very common – hypophosphatemia; rare – lactic acidosis; possible – hypokalemia.

Digestive system: very common – diarrhea, vomiting, nausea; common – flatulence; rare – pancreatitis, increased transaminase activity; very rare – hepatitis; possible – hepatic steatosis.

Musculoskeletal system: possible – rhabdomyolysis, osteomalacia, muscle weakness, myopathy.

Urinary system: rare – acute renal failure, proximal renal tubulopathy (including Fanconi syndrome), hypercreatininemia; very rare – acute tubular necrosis; frequency unknown – nephritis (including acute interstitial), nephrogenic diabetes insipidus.

Other: very common – dizziness; rare – rash; very rare – dyspnea, asthenia.

Contraindications

Hypersensitivity to tenofovir.

Use in Pregnancy and Lactation

If use during pregnancy is necessary, the expected benefit of therapy for the mother and the potential risk to the fetus should be weighed.

Due to identified changes in bone tissue during the use of tenofovir, and limited experience of use, it is recommended to use Tenofovir with caution during pregnancy.

Women of childbearing age should use reliable methods of contraception during treatment.

If use during lactation is necessary, breastfeeding should be discontinued.

Use in Renal Impairment

Tenofovir should be used with caution in renal failure with CrCl less than 50 ml/min, including patients on hemodialysis.

With CrCl less than 30 ml/min, the use of Tenofovir is not recommended; if use is necessary, renal function should be carefully monitored and the interval between drug administrations should be adjusted.

Newly occurring or progressive renal failure may lead to acute renal failure and Fanconi syndrome.

Determination of CrCl is necessary before starting treatment with tenofovir.

Monitoring of creatinine clearance and serum phosphorus is necessary in patients at increased risk of developing or progressing renal failure.

The use of tenofovir simultaneously with or after recent treatment with nephrotoxic drugs should be avoided.

Special Precautions

Tenofovir should be used with caution in renal failure with CrCl less than 50 ml/min, including patients on hemodialysis.

With CrCl less than 30 ml/min, the use of Tenofovir is not recommended; if use is necessary, renal function should be carefully monitored and the interval between drug administrations should be adjusted.

Newly occurring or progressive renal failure may lead to acute renal failure and Fanconi syndrome.

Determination of CrCl is necessary before starting treatment with tenofovir.

Monitoring of creatinine clearance and serum phosphorus is necessary in patients at increased risk of developing or progressing renal failure.

The use of tenofovir simultaneously with or after recent treatment with nephrotoxic drugs should be avoided.

The use of tenofovir simultaneously with combined antiviral drugs containing Tenofovir and adefovir dipivoxil should be excluded.

Tenofovir should be used only as part of appropriate antiretroviral combination therapy in HIV-1 infected patients.

During the use of tenofovir, the development of Fanconi syndrome, accompanied by hypophosphatemia, hypoglycemia, proteinuria, normoglycemic glucosuria, is possible; in some cases, acute renal failure may develop.

In the early stages, the course may be asymptomatic or accompanied by myalgias; in most cases, symptoms disappear after discontinuation of tenofovir.

Risk factors include low body weight, presence of kidney disease at the start of therapy.

The frequency of nephrotoxic side effects is extremely low in patients with initially normal renal function.

Drug Interactions

With simultaneous use of tenofovir with didanosine, the plasma concentration of didanosine increases (this combination is not recommended; if combination therapy is necessary, the dose of didanosine should be reduced).

With concomitant use, a decrease in the plasma concentration of atazanavir and an increase in the concentration of tenofovir occur.

Tenofovir should be used with atazanavir only with additional boosting of the latter with ritonavir.

With concomitant use of the lopinavir/ritonavir combination with tenofovir, the plasma concentration of tenofovir increases.

Darunavir increases the concentration of tenofovir by 20-25%.

With this combination, darunavir and Tenofovir should be used in standard doses, while careful monitoring of the nephrotoxic effect of tenofovir is necessary.

Tenofovir is mainly excreted from the body by the kidneys.

With concomitant use of tenofovir with drugs that reduce renal function or suppress/stop active tubular secretion, an increase in the serum concentration of tenofovir and/or an increase in the concentrations of other drugs excreted by the kidneys is possible.

Ganciclovir, valganciclovir, and cidofovir compete with tenofovir for active tubular secretion by the kidneys, resulting in an increase in the plasma concentration of tenofovir (clinical observation is necessary to monitor possible side effects).

Nephrotoxic drugs can increase the plasma concentration of tenofovir.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.