Lamivudine
Lamivudine: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Lamivudine
ATX code: J05AF05
Active ingredient: lamivudine (lamivudine)
Producer: pharmaceutical company CJSC Obolenskoe (Russia), pharmaceutical company LLC Ozon (Russia), Aurobindo Pharma Ltd. (India), etc.
Description and photo updated: 22.11.2018
Prices in pharmacies: from 357 rubles.
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Lamivudine is an antiviral drug.
Release form and composition
Dosage form of Lamivudine - film-coated tablets: I manufacturer - from white to almost white, biconvex, round, with a dividing line, with a white or almost white core in cross section; Manufacturer II - from white to almost white, oblong shape, on one side - engraving C, on the other - engraving "63" (in a blister contour packaging 7, 10, 12, 15, 20, 25 or 30 pcs., In a cardboard box from 1 to 10 packs; in aluminum blisters 10 pcs., in a cardboard box 6 or 10 blisters; in a bottle of polyethylene terephthalate 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 pcs., in a cardboard box box 1 bottle).
Composition of one tablet:
- active substance: lamivudine - 150 mg;
- auxiliary components (core): microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate, additionally for manufacturer I - povidone, lactose monohydrate;
- shell: white opadry (hypromellose, titanium dioxide, polysorbate-80, macrogol-4000) or opadry II (macrogol, talc, polyvinyl alcohol, titanium dioxide).
Pharmacological properties
Pharmacodynamics
The antiviral drug Lamivudine belongs to the class of nucleoside reverse transcriptase inhibitors (NRTIs). Its mechanism of action is intracellular metabolism up to 5-triphosphate and competitive suppression of reverse transcriptase, an enzyme of the human immunodeficiency virus (HIV), which contributes to the suppression of viral replication. Lamivudine is active against strains resistant to zidovudine, and when used in combination with it, it slows down the development of resistance of viral pathogens to zidovudine (in previously untreated patients). Lamivudine has a higher in vitro therapeutic index than zidovudine - it weakly inhibits bone marrow progenitor cells, has a less pronounced cytotoxic effect on peripheral blood lymphocytes, as well as on monocyte-macrophage and lymphocytic cell lines,and other bone marrow stem cells. The drug practically does not affect the metabolism of deoxynucleotides in cells and the content of DNA (deoxyribonucleic acid) in the mitochondria of healthy cells.
Lamivudine is highly active against hepatitis B virus (HBV) in all tested cell lines and in all animals experimentally infected.
The drug is widely used as a component of combined antiretroviral treatment in combination with other NRTIs or drugs from other groups (non-nucleoside reverse transcriptase inhibitors, protease inhibitors). It has been established that combination antiretroviral therapy containing lamivudine is effective against HIV strains with mutations in the M184V codon, as well as in patients who have not previously received antiretroviral treatment.
Pharmacokinetics
Lamivudine is rapidly absorbed from the gastrointestinal tract. Bioavailability is from 80 to 88%. The maximum concentration (C max) in blood plasma occurs 1 hour after oral administration. Plasma proteins bind 36%.
Lamivudine is able to penetrate the blood-brain and placental barriers.
The substance is biotransformed by phosphorylation, forming 5-triphosphate. The half-life (T 1/2) is 5-7 hours. 68-71% of the active substance is excreted in the urine unchanged.
Indications for use
- HIV infection in adults and children (as part of combination antiretroviral therapy);
- viral chronic hepatitis B against the background of HBV replication in patients over 16 years of age.
Contraindications
Absolute:
- severe renal failure (creatinine clearance less than 30 ml / min);
- children under 3 years of age with a body weight of less than 14 kg;
- pregnancy and lactation;
- individual hypersensitivity to lamivudine or any auxiliary component of the drug.
According to the instructions, Lamivudine is prescribed with caution to patients with peripheral neuropathy (including a history), renal failure with creatinine clearance from 30 to 50 ml / min, as well as patients with pancreatitis (including a history).
Instructions for the use of Lamivudine: method and dosage
The prescription of the drug is allowed only by a specialist with experience in treating HIV infections.
Lamivudine tablets are taken orally, regardless of food intake. Dividing tablets into parts should be avoided in order to avoid impairment of the accuracy of dosing of the drug.
Dosage regimen depending on the age and weight of the patient:
- adults and adolescents weighing more than 25 kg: total daily dose - 300 mg. You can take 1 tablet (150 mg) twice a day or 2 tablets (300 mg) once a day;
- children weighing 20 to 25 kg: total daily dose - 225 mg - take 1 /2 tablets (75 mg) in the morning and one tablet (150 mg) in the evening or 1 1 /2 tablets (225 mg) once a day;
- children weighing from 14 to 20 kg: total daily dose - 150 mg. Can take 1 /2 tablets (75 mg) twice a day, morning and evening, or 1 tablet (150 mg) once a day.
Side effects
The incidence of side effects from systems and organs according to a special scale (> 0.1% - very often; 0.01-0.1% - often; 0.001-0.01% - infrequently; 0.0001-0.001% - rarely; <0.0001% - extremely rare):
- central nervous system: often - insomnia, headache, increased fatigue; extremely rare - paresthesia. There have been cases of development of peripheral neuropathy, but the relationship of this complication with the use of lamivudine has not been proven;
- hematopoietic organs: infrequently - anemia, neutropenia, thrombocytopenia; extremely rare - aplasia of the erythroid lineage of the bone marrow;
- metabolism: often - an increase in the content of lactic acid in the blood serum; rarely - lactic acidosis, accumulation / redistribution of subcutaneous fat (the frequency of occurrence depends on a number of factors, including the combination of antiretroviral drugs used);
- gastrointestinal tract: often - decreased appetite, nausea, diarrhea, vomiting, pain and discomfort in the epigastric region; rarely - pancreatitis (the connection with the use of lamivudine has not been proven), increased serum amylase activity;
- hepatobiliary system: infrequently - a transient increase in the enzymatic activity of hepatic transaminases; rarely - hepatitis;
- skin and its derivatives: often - skin rash, alopecia;
- musculoskeletal system and connective tissue: often - muscle disorders, arthralgia; rarely - rhabdomyolysis;
- respiratory system and mediastinal organs: often - nasal symptoms, cough;
- the body as a whole: a feeling of fatigue, general malaise, fever.
There have been cases of osteonecrosis in patients with risk factors such as long-term combination antiretroviral therapy or advanced stages of HIV infection (incidence unknown).
Overdose
At this time, there is not enough information about the consequences of an overdose of lamivudine in humans. No specific symptoms or signs of acute drug overdose have been identified. It was noted that the condition of all patients returned to normal, no deaths were recorded.
In the case of using high doses of lamivudine, systematic monitoring of the patient's condition and standard maintenance therapy are recommended. To remove the drug from the body, it is possible to carry out continuous hemodialysis, however, there is no special experimental data on the effectiveness of this method.
special instructions
The use of lamivudine as monotherapy is not recommended.
Patients should be warned about the need to observe appropriate precautions, since during the period of treatment with antiretroviral drugs, including lamivudine, the risk of transmitting HIV infection to others through blood transfusion or sexual intercourse remains.
During drug therapy, the patient should be closely monitored by a specialist qualified and experienced in the treatment of HIV-associated diseases, since antiretroviral drugs (including lamivudine) can lead to the development of opportunistic infections or other complications of HIV infection.
In case of severe and moderate renal impairment, the content of lamivudine in the blood plasma increases due to a decrease in drug clearance, therefore, dose adjustment is required.
There are reports of rare cases of pancreatitis with the use of lamivudine. It has not been established, however, whether this complication is caused by an underlying medical condition (HIV infection) or a drug. If clinical symptoms or laboratory test data appear, indicating the development of pancreatitis (nausea, abdominal pain, vomiting or increased biochemical parameters), the use of lamivudine should be stopped immediately. The drug should not be taken until the diagnosis of pancreatitis has been ruled out.
In rare cases, the development in patients, mainly in women, of lactic acidosis and severe hepatomegaly with steatosis (including fatal outcomes), as a result of therapy with antiretroviral drugs that are analogs of nucleosides (including lamivudine and its combinations) is noted. Symptoms of developing lactic acidosis are: anorexia, general weakness, disruption of the gastrointestinal tract, unexplained rapid weight loss, impaired respiratory function (shortness of breath, tachypnea).
Care must be taken when treating any patient (especially obese women) with lamivudine with hepatitis, hepatomegaly, or other known risk factors for liver disease and hepatic steatosis, including alcohol and certain medications. Patients with hepatitis C co-infection and receiving treatment with ribavirin and interferon alpha may be at particular risk. In the event of clinical and / or laboratory signs of hepatotoxicity or lactic acidosis, the drug should be canceled.
During the period of clinical examination, it is important to pay attention to signs of redistribution of subcutaneous fat. Close monitoring of serum lipids and blood glucose is required. In case of lipid metabolism disorders, appropriate treatment is necessary.
In patients with chronic hepatitis B or C, when receiving combination antiretroviral therapy, the risk of developing severe (up to lethal) adverse reactions from the liver is significantly increased. When using lamivudine with other antiviral agents for the treatment of hepatitis B and C, you must strictly follow the appropriate medical instructions for the use of these drugs.
There is evidence based on clinical studies and post-marketing observations that in some cases, patients with concomitant hepatitis B virus (HBV) taking lamivudine may experience clinical and / or laboratory signs of hepatitis recurrence after the end of drug therapy, which have more severe consequences in patients with uncompensated liver damage. Therefore, after stopping treatment with lamivudine, patients with co-infection (HIV and hepatitis B virus) require careful monitoring of biochemical parameters of liver function and markers of hepatitis B virus replication.
With pre-existing liver dysfunction, including active chronic hepatitis, the incidence of liver dysfunction during the period of combined antiretroviral therapy increases. Such patients should be under medical supervision with the possibility of suspending or discontinuing treatment in case of deterioration in liver function.
According to international recommendations, in the case of probable infection through the blood of an HIV-infected patient (through an injection needle, for example), it is urgently necessary, within 1–2 hours from the moment of infection, to begin a combination therapy with zidovudine and lamivudine. If the risk of infection is high, the antiretroviral therapy regimen should include a drug from the group of protease inhibitors. The recommended course of preventive treatment is 4 weeks.
Since no relevant controlled trials have been conducted, there is insufficient evidence of the effectiveness of preventive therapy following accidental exposure to HIV.
Influence on the ability to drive vehicles and complex mechanisms
During lamivudine therapy, when assessing a patient's ability to drive vehicles or perform actions that require a high concentration of attention and a quick physical / mental reaction, it is necessary to take into account his general condition, as well as the nature of the drug's adverse reactions.
Application during pregnancy and lactation
There are insufficient data on the safety of lamivudine in pregnant women. Experimental studies have shown that the active substance penetrates the placental barrier. The drug should be prescribed to pregnant women only after a careful assessment of the ratio of the expected benefits of therapy and potential risks to the fetus.
Since lamivudine passes into breast milk, if it is necessary to use it during lactation, breastfeeding should be discontinued.
Pediatric use
It is contraindicated to use the drug in children under 3 years of age with a body weight of up to 14 kg.
With impaired renal function
Severe renal failure (creatinine clearance less than 30 ml / min) is an absolute contraindication to the use of lamivudine.
In case of impaired renal function with creatinine clearance from 30 to 50 ml / min, the administration of the drug requires caution and dose adjustment.
For violations of liver function
In case of impaired liver function, there is usually no need to adjust the dosage regimen of lamivudine. However, in patients with severe liver cirrhosis caused by the hepatitis B virus, the drug should be used with caution, given the likelihood of an exacerbation of the disease after the end of therapy.
Use in the elderly
There is not enough information about the pharmacokinetics of the drug in elderly patients at this time. Patients in this category require special attention due to age-related changes in blood counts and a decrease in renal excretory function.
Drug interactions
Due to the fact that lamivudine is metabolized slightly, weakly binds to blood plasma proteins and is excreted mainly by the kidneys unchanged, the likelihood of its metabolic interaction with other drugs is extremely low.
With the combined use of lamivudine and zidovudine, there is a moderate (by 28%) increase in C max of zidovudine in blood plasma, AUC (area under the pharmacokinetic curve "concentration - time") does not change significantly. Zidovudine has no effect on the pharmacokinetics of lamivudine.
The simultaneous use of sulfamethoxazole / trimethoprim (co-trimoxazole) at a dose of 800/160 mg leads to an increase in the concentration of lamivudine in the blood plasma by about 40% (due to interaction with trimethoprim). However, with normal renal function, no dose reduction of lamivudine is required. Lamivudine has no effect on the pharmacokinetics of sulfamethoxazole and trimethoprim. Concomitant use of lamivudine with high doses of co-trimoxazole (for the treatment of toxoplasmosis and Pneumocystis pneumonia) is not recommended.
Lamivudine, when used simultaneously with zalcitabine or cladribine, can inhibit their intracellular phosphorylation, and therefore should not be combined with these drugs.
There is no data on the possible pharmacodynamic and pharmacokinetic interaction of ribavirin and lamivudine, however, fatal cases of liver dysfunction have been recorded in patients with co-infection (HIV and hepatitis C) who received antiretroviral therapy in combination with ribavirin and interferon alfa.
When used together, lamivudine is able to slow down the intracellular phosphorylation of emtricitabine. In addition, the path of development of resistance to emtricitabine and lamivudine is associated with a mutation in the same codon of the reverse transcriptase gene (M184V). Since the therapeutic efficacy of both drugs in combination therapy may be limited, the use of lamivudine in combination with emtricitabine or fixed dose combinations containing emtricitabine is not recommended.
Analogs
Analogues of Lamivudin are: Amiviren, Virolam, Zeffix, Lamivudin Canon, Lamivudin-Teva, Epivir and others.
Terms and conditions of storage
Store in a dark, dry place at a temperature not exceeding 25 ° C.
Keep out of the reach of children.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews of Lamivudine
Based on reviews of lamivudine, it is difficult to assess the degree of effectiveness of the drug. As a rule, it depends on the qualifications and personal experience of the attending physician, who must individually select a combination of antiviral drugs for each patient and prescribe the optimal dosage regimen.
The price of lamivudine in pharmacies
The price of Lamivudine (film-coated tablets, 150 mg) per bottle 60 pcs. is approximately 288 p.
Lamivudine: prices in online pharmacies
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Drug name Price Pharmacy |
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Lamivudine Canon 150 mg film-coated tablets 60 pcs. 357 r Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
