Lamivudin-Advansd (Tablets) Instructions for Use

Marketing Authorization Holder

Advanced Pharma, LLC (Russia)

ATC Code

J05AF05 (Lamivudine)

Active Substance

Lamivudine (Rec.INN registered by WHO)

Dosage Form

Lamivudine-Advansd

Film-coated tablets, 150 mg: 10, 30, 60, or 100 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, round, biconvex; the core on the cross-section is white or almost white.

Excipients: magnesium stearate – 1.5 mg, croscarmellose sodium – 5 mg, microcrystalline cellulose (type 102) – 123.5 mg.

Shell composition ready white coating WT-10019P white (polyvinyl alcohol – 45%, soy lecithin – 3%, macrogol 4000 – 11%, titanium dioxide – 30%, talc – 11%) – 7 mg.

10 pcs. – strips (1) – cardboard packs.
10 pcs. – strips (3) – cardboard packs.
10 pcs. – strips (6) – cardboard packs.
10 pcs. – strips (10) – cardboard packs.
10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (6) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.
10 pcs. – jars (1) – cardboard packs.
30 pcs. – jars (1) – cardboard packs.
60 pcs. – jars (1) – cardboard packs.
100 pcs. – jars (1) – cardboard packs.

Clinical-Pharmacological Group

Antiviral drug active against HIV

Pharmacotherapeutic Group

Systemic antiviral agents; direct-acting antiviral agents; nucleoside and nucleotide 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 virus 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 monocyte-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, patient’s renal function, and age.

For HIV infection in adults and adolescents (aged 12 years and older, with body weight ≥30 kg): administer 150 mg twice daily or 300 mg once daily.

For pediatric patients with HIV infection (aged 3 months and older): calculate the dose based on body weight. For patients weighing ≥30 kg: use the adult dose. For patients weighing 21-30 kg: administer 75 mg twice daily or 150 mg once daily. For patients weighing 14-21 kg: administer 75 mg once daily. For patients weighing <14 kg: administer 6 mg/kg twice daily or 12 mg/kg once daily.

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

Adjust the dosage in patients with renal impairment. For creatinine clearance (CrCl) 30-49 mL/min: administer 150 mg once daily for HIV or 100 mg first dose, then 50 mg once daily for hepatitis B. For CrCl 15-29 mL/min: administer 150 mg first dose, then 100 mg once daily for HIV or 100 mg first dose, then 25 mg once daily for hepatitis B. For CrCl 5-14 mL/min: administer 150 mg first dose, then 50 mg once daily for HIV or 35 mg first dose, then 15 mg once daily for hepatitis B. For CrCl <5 mL/min: administer 50 mg first dose, then 25 mg once daily for HIV or 35 mg first dose, then 10 mg once daily for hepatitis B.

Take tablets orally, with or without food. Do not discontinue therapy for hepatitis B without medical supervision due to the risk of severe acute exacerbation.

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 a careful assessment of the expected benefits and the potential risk of developing 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 liver cirrhosis 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 renal impairment. 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 renal impairment, dose adjustment is recommended in the same proportions as in adults.

Special Precautions

Use with caution in renal impairment. 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 liver cirrhosis 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 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 increased levels of pancreatic enzymes in the blood plasma occur, Lamivudine should be discontinued and not 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 considered.

Use in pediatrics

There is no experience with the use of lamivudine in children under 3 months of age. In children with renal impairment, 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 regarding 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 plasma concentration of lamivudine.

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.