Epivir^® (Tablets, Solution) Instructions for Use

ATC Code

J05AF05 (Lamivudine)

Active Substance

Lamivudine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antiviral drug active against HIV

Pharmacotherapeutic Group

Systemic antiviral drugs; direct-acting antiviral drugs; nucleosides and nucleotides – reverse transcriptase inhibitors

Pharmacological Action

Antiviral agent, nucleoside reverse transcriptase inhibitor. Penetrating into cells, it is metabolized to 5-triphosphate, which inhibits HIV reverse transcriptase, leading to suppression of viral replication.

It is active against strains resistant to zidovudine, and when used in combination with it, it slows down the development of viral resistance to zidovudine (in previously untreated patients).

It has a higher therapeutic index in vitro than zidovudine (it suppresses bone marrow progenitor cells less strongly than zidovudine and also has a less pronounced cytotoxic effect on peripheral blood lymphocytes, lymphocytic and monocytic-macrophage cell lines).

It has little effect on the metabolism of cellular deoxynucleotides and the DNA content in the mitochondria of intact cells.

Lamivudine is highly active against hepatitis B virus (HBV) in all studied cell lines and in all experimentally infected animals.

Pharmacokinetics

Rapidly absorbed from the gastrointestinal tract. Bioavailability is 80-88%. C_max in blood plasma is reached 1 hour after administration.

Lamivudine penetrates the blood-brain barrier and the placental barrier. Plasma protein binding is 36%. It is metabolized by phosphorylation to form 5-triphosphate. T_1/2 is 5-7 hours.

68-71% is excreted unchanged in the urine.

Indications

Treatment of HIV infection in adults and children (as part of combination therapy with other antiretroviral drugs).

Chronic viral hepatitis B with HBV replication in patients aged 16 years and older.

ICD codes

Dosage Regimen

Determine the dosage and regimen based on the indication: HIV infection or chronic hepatitis B.

For HIV infection in adults and adolescents (over 12 years and body weight ≥50 kg), administer 300 mg daily as a single dose or 150 mg twice daily.

For pediatric patients with HIV infection, base the dose on body weight. Administer 4 mg/kg twice daily, up to a maximum of 150 mg per dose. For children weighing ≥14 kg, the standard dose is 150 mg twice daily. For children weighing less than 14 kg, use the oral solution.

For chronic hepatitis B in adults and adolescents (aged 16 years and older), administer 100 mg once daily.

Perform dose adjustment for renal impairment based on creatinine clearance (CrCl). For HIV infection: if CrCl is 30-49 mL/min, give 150 mg once daily; if CrCl is 15-29 mL/min, give 150 mg first dose then 100 mg once daily; if CrCl is 5-14 mL/min, give 150 mg first dose then 50 mg once daily; if CrCl is less than 5 mL/min, give 50 mg first dose then 25 mg once daily.

For chronic hepatitis B with renal impairment (CrCl less than 50 mL/min), consider a reduced dose or increased dosing interval.

Administer tablets and oral solution without regard to meals.

Do not use the single-dose, 300 mg tablet for hepatitis B treatment or for pediatric patients requiring less than 300 mg daily.

For patients with co-infection of HIV and HBV, use the higher HIV dosage as part of a complete antiretroviral regimen.

Adverse Reactions

From the digestive system: pain and discomfort in the epigastric region, nausea, vomiting, diarrhea, decreased appetite, increased activity of liver transaminases. Development of autoimmune hepatitis is possible.

From the central nervous system: increased fatigue, headache.

From the respiratory system: respiratory tract infections.

Other: general malaise.

Contraindications

Hypersensitivity to lamivudine.

Use in Pregnancy and Lactation

Despite the absence of direct indications of teratogenic effects and changes in reproductive function, Lamivudine should be used during pregnancy only after careful assessment of the expected benefits and the potential risk of side effects.

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

Use in Hepatic Impairment

No dose adjustment is required in patients with impaired liver function.

However, it should be used with caution in patients with severe cirrhosis of the liver caused by hepatitis B virus, given the risk of exacerbation of the disease after discontinuation of lamivudine.

Use in Renal Impairment

Use with caution in case of impaired renal function. If creatinine clearance is less than 50 ml/min, dose adjustment is necessary.

Pediatric Use

There is no experience with the use of lamivudine in children under 3 months of age. In children with impaired renal function, dose adjustment is recommended in the same proportions as in adults.

Special Precautions

Use with caution in case of impaired renal function. If creatinine clearance is less than 50 ml/min, dose adjustment is necessary.

Given that Lamivudine is excreted almost exclusively by the kidneys, no dose adjustment is required in patients with impaired liver function.

However, it should be used with caution in patients with severe cirrhosis of the liver caused by hepatitis B virus, given the risk of exacerbation of the disease after discontinuation of lamivudine.

Lamivudine is not used in combination with zidovudine in case of neutropenia (neutrophil count less than 750/µl) or anemia (hemoglobin less than 7.5 g/dl or 4.65 mmol/l).

If abdominal pain, nausea, vomiting, or an increase in the level of pancreatic enzymes in the blood plasma occurs, Lamivudine should be discontinued and its use should not be resumed until the diagnosis of pancreatitis is ruled out.

The use of lamivudine does not prevent the possibility of infection through sexual contact or through blood.

During treatment, the possibility of developing a secondary infection should be kept in mind.

Use in pediatrics

There is no experience with the use of lamivudine in children under 3 months of age. In children with impaired renal function, dose adjustment is recommended in the same proportions as in adults.

Drug Interactions

With simultaneous use, Lamivudine increases the duration of action of zidovudine by 13%, and its C_max in blood plasma by 28%. Zidovudine does not affect the pharmacokinetics of lamivudine.

Synergism with zidovudine and other antiviral agents used in the treatment of HIV infections has been noted with respect to HIV replication in cell culture.

With simultaneous use with didanosine, sulfonamides, zalcitabine, the risk of developing pancreatitis increases.

With simultaneous use with dapsone, didanosine, isoniazid, stavudine, zalcitabine, the risk of developing peripheral neuropathy increases.

Trimethoprim increases the concentration of lamivudine in blood plasma.

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.