Epivir, 10 mg/ml 240 ml

Indications

Treatment of HIV infection as part of combination antiretroviral therapy for adults and children.

Active ingredient

Composition

1 ml of the solution for oral administration contains:

active ingredient:

lamivudine 10 mg,

excipients:

sucrose; methyl and propyl parahydroxybenzoate;

citric acid (anhydrous);

propylene glycol;

sodium citrate;

purified water;

aromatic additives.

How to take, the dosage

Treatment with the drug Epivir, oral solution, should be conducted by a physician experienced in managing patients with HIV infection.
The drug Epivir, oral solution, can be taken regardless of meals.
Epivir oral solution is not intended as a monotherapy drug.
Epivir oral solution is intended for children and patients who have difficulty swallowing tablets.

Adults and adolescents with a body weight of at least 30 kg

The recommended daily dose of lamivudine is 300 mg (30 ml), which can be divided into 2 doses of 150 mg (15 ml) or taken in one dose of 300 mg (30 ml).

Interaction

The probability of lamivudine metabolic interaction with other drugs is extremely low, since lamivudine is very poorly metabolized, binds only slightly with plasma proteins and is excreted mainly unchanged by the kidneys.
Lamivudine is excreted mainly by active tubular secretion through the organic cation transport system. You should consider the possibility of interaction of lamivudine with drugs that have the same excretion mechanism, such as trimethoprim. Other drugs (e.g. ranitidine, cimetidine) are only partially excreted by this mechanism and do not interact with lamivudine.

Drugs that are primarily excreted by active renal secretion through the organic anion transport system or by glomerular filtration do not appear to have any clinically relevant interactions with lamivudine.

Zidovudine. With concomitant use of lamivudine and zidovudine there is a moderate (28%) increase in Cmax of zidovudine in plasma, while AUC is not significantly changed. Zidovudine does not affect the pharmacokinetics of lamivudine.

Trimethoprim/sulfamethoxazole. Concomitant use of trimethoprim/sulfamethoxazole at a dose of 160/800 mg (co-trimoxazole) increases the plasma concentration of lamivudine by approximately 40% (due to interaction with trimethoprim). However, there is no need to reduce the dose of lamivudine in the absence of renal dysfunction. Pharmacokinetics of trimethoprim and sulfamethoxazole is not affected by lamivudine. Interaction of lamivudine with high doses of co-trimoxazole prescribed for the treatment of pneumocystis pneumonia and toxoplasmosis has not been studied.

Salcitabine. When lamivudine and zalcitabine are administered concomitantly, lamivudine may inhibit the intracellular phosphorylation of the latter. In this regard, this combination of drugs is not recommended.

Special Instructions

The treatment with the drug Epivir, oral solution, should be carried out by a physician experienced in managing patients with HIV infection.
In children under 3 years of age it is not recommended to use tablet dosage forms, so for the treatment of children and those patients who have difficulty swallowing tablets, the drug form solution for oral administration is designed.
Patients should be warned that treatment with antiretroviral drugs, including lamivudine, does not prevent the risk of HIV transmission to others through sexual contact or blood transfusion. Therefore, patients must take appropriate precautions.

Patients receiving lamivudine or other antiretrovirals may develop opportunistic infections or other complications, so they should be closely monitored by a physician experienced in treating HIV infection.

Renal impairment

In patients with moderate to severe renal impairment, plasma concentrations of lamivudine are increased due to decreased clearance of the drug, so dose adjustments are required.

Pancreatitis

There have been several cases of pancreatitis in patients treated with lamivudine. However, it remains unclear whether this complication is caused by lamivudine or by HIV infection itself. If abdominal pain, nausea, vomiting or characteristic changes in biochemical parameters occur in a patient receiving lamivudine, pancreatitis should be excluded. The drug should be suspended until the diagnosis of pancreatitis is excluded.

Lactoacidosis/ pronounced hepatomegaly with fatty liver dystrophy

. In HIV-infected patients (predominantly women) who have taken nucleoside analogues antiretroviral drugs as monotherapy or in combination with lamivudine, cases of lactoacidosis have been described, usually accompanied by severe hepatomegaly and fatty liver dystrophy, including death.

The symptoms that may indicate the development of lactoacidosis include: general weakness, loss of appetite, sudden unexplained weight loss, disorders of the gastrointestinal tract and respiratory system (shortness of breath and rapid breathing).
Treatment with lamivudine always requires caution, especially if the patient has risk factors for liver disease. In the case of clinical or laboratory signs of lactoacidosis or liver dysfunction (including hepatomegaly and fatty liver dystrophy even in the absence of a marked increase in liver transaminases) lamivudine should be stopped.

Distribution of subcutaneous fat

In some patients, combination antiretroviral therapy may be accompanied by redistribution/accumulation of subcutaneous fat, including decreased peripheral fat and increased visceral fat, weight loss in extremities and face, increased breast/milk gland and fat deposits on the back of the neck and inter-scapular area of the back (“buffalo hump”) and elevated serum lipid and blood glucose concentrations.

While all drugs in the classes of protease inhibitors and nucleoside reverse transcriptase inhibitors can cause one or more of the above adverse reactions associated with the common syndrome often referred to as lipodystrophy, accumulating evidence suggests that there are differences between individual members of these drug classes in their ability to cause these adverse reactions.
It should also be noted that lipodystrophy syndrome has a multifactorial etiology: for example, the stage of HIV infection, advanced age, and duration of antiretroviral therapy play an important, possibly synergistic role in the development of this complication.
The long-term effects of these adverse reactions are currently unknown.

The clinical evaluation of patients should include assessment of physical signs of adipose tissue redistribution. Serum lipid concentrations and blood glucose concentrations should also be measured. Lipid metabolism disorders should be corrected, guided by their clinical manifestations.

Immune reconstitution syndrome

In HIV-infected patients with severe immunodeficiency during initiation of antiretroviral therapy, inflammation due to asymptomatic or silent opportunistic infection may worsen, causing serious deterioration or exacerbation of symptoms. As a rule, such reactions were observed in the first weeks or months after the start of ART. The most significant examples are cytomegalovirus retinitis, generalized and/or focal mycobacterial infection, and pneumocystis pneumonia. Any symptoms of inflammation should be identified immediately and treatment started without delay.

Mixed infection caused by HIV and hepatitis B virus

Some patients with chronic hepatitis B may have clinical or laboratory signs of hepatitis recurrence after withdrawal of lamivudine, which can have severe consequences if liver function is decompensated. Biochemical parameters of liver function and markers of hepatitis B virus replication should be monitored after lamivudine therapy in patients with co-infection caused by HIV and hepatitis B virus.

Diabetes

When prescribing oral solution in patients with concomitant diabetes mellitus, remember that the recommended dose for adults contains 3 g of sucrose.

Prophylaxis after probable HIV infection

According to international guidelines (Center for Disease Control, June 1998), if infection is likely to occur through the blood of an HIV-infected person (for example, through an injection needle), the combination therapy zidovudine and lamivudine should be given promptly (within 1-2 hours of infection). If there is a high risk of infection, a drug from the protease inhibitor group should be included in the antiretroviral therapy regimen. Prophylactic treatment is recommended for 4 weeks. There is insufficient data on the effectiveness of prophylactic treatment after accidental HIV infection, and no controlled studies have been conducted. Despite rapid initiation of antiretroviral treatment, seroconversion cannot be ruled out.

Impact on the ability to operate vehicles, machinery

There have been no specific studies on the effect of lamivudine on the ability to operate vehicles/mechanisms. However, based on the pharmacological properties of lamivudine, this effect is unlikely. Nevertheless, when assessing the ability to drive / mechanisms, the general condition of the patient, as well as the nature of adverse reactions of lamivudine should be taken into account.

Contraindications

Hypersensitivity to lamivudine or any other component of Epivir. Under 3 months of age due to limited data on the use of the drug in this age group.

With caution

Must be used with caution in patients with renal impairment; pancreatitis (including history); peripheral neuropathy; pregnancy and lactation.

Side effects

Overdose

Symptoms: there are few data on the effects of acute lamivudine overdose in humans. There have been no fatal outcomes, and the condition of all patients has normalized. No specific signs or symptoms of lamivudine overdose have been identified.

Treatment: it is recommended to monitor the patient’s condition and provide standard supportive therapy if necessary. Since lamivudine is excreted from the body by dialysis, continuous hemodialysis may be used, but no special studies have been conducted.

Pregnancy use

Pregnancy

There are currently insufficient data on the safety of lamivudine during pregnancy. Lamivudine should be used in pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus. Although the results of animal experiments cannot always be extrapolated to humans, data from rabbit studies suggest a possible risk of spontaneous abortion in early pregnancy.

In infants and children less than 1 year of age whose mothers received nucleoside reverse transcriptase inhibitors during pregnancy and delivery, there have been reports of transient increases in serum lactic acid concentrations apparently due to mitochondrial dysfunction. The clinical significance of a transient increase in serum lactic acid concentration has not been established. In addition, very rare cases of developmental delay, seizure syndrome, and other neurological abnormalities have been reported. However, the association of these complications with the intake of nucleoside reverse transcriptase inhibitors during pregnancy and their effects on postnatal development have not been proven. Therefore, it is recommended that HIV-infected women take antiretroviral drugs during pregnancy to prevent vertical transmission of HIV.

Lactation

According to experts, all HIV-infected women should avoid breastfeeding if possible to avoid transmitting the virus to the baby through breast milk. After ingestion, lamivudine is excreted with breast milk; its concentration in breast milk is virtually the same as in serum (1-8 µg/mL). Women taking lamivudine are not recommended to breastfeed.

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