Virolam - instructions for use, dose, side effects, contraindications

An antiviral agent. Selectively suppresses HIV replication-1 and HIV-2 in vitro. Penetrates into cells, induced by the virus, passes into the active form - lamivudine-5'-triphosphate, which is a weak inhibitor of RNA and DNA-dependent reverse transcriptase of HIV. Suppresses alpha, beta and gamma-DNA polymerases. Does not interfere with the metabolism of cellular deoxynucleotides, having a weak effect on DNA content.

Stable strains of the virus appear 12 weeks after the onset of monotherapy; the resistance is due to the replacement in 184 of the position of the reverse transcriptase of isoleucine on valine.

It is active against HIV strains resistant to zidovudine. Has a higher than zidovudine, therapeutic index in vitro (weaker than zidovudine, oppresses bone marrow precursor cells, a also has a less pronounced cytotoxic effect on peripheral blood lymphocytes, lymphocytic and monocyte-macrophage cell lines).

Suppresses the replication of the hepatitis B virus, preventing the appearance of reverse transcriptase activity.

Pharmacokinetics:

Absorption is high, bioavailability in adults and adolescents is 80-85%, in children 60-68%. Maximum concentration (C_max) after oral administration 4 mg / kg is 1.75 μg / ml, the time to reach the maximum concentration (TC_max) - 1 h. Presence of food in the stomach slows absorption (3-3.5 times lengthened TC_max and on 40% its value decreases, but it does not have a significant effect on bioavailability).

Connection with plasma proteins - 35%; on the surface of erythrocytes is adsorbed up to 57% of the dose. The volume of distribution is 1.3 l / kg. Penetrates into the central nervous system (CNS) and cerebrospinal fluid (CSF) 2-4 hours after oral administration. In children, the concentration in the cerebrospinal fluid (CSF) is 10-17% of the corresponding unstable concentration in the blood serum.

It is subject to an insignificant (5%) metabolism in the liver with the formation of an inactive metabolite of transulfoxide.

Metabolized in cells before the formation of 5-triphosphate, half-life (T_1/2)which is 10.5-15.5 h.

System clearance - 0,32 l / kg / h; T_1/2- 5-7 hours.

70% of the drug is excreted by the kidneys unchanged (by secretion in the tubules), 10% - liver. Excretion is reduced in chronic renal failure (CRF).

In children from 3 months to 12 years of age, plasma concentrations are lower, at the use of appropriate doses, which is associated with a lower bioavailability - 65% and increased clearance - 0.52 l / kg / h. In newborn infants at the age of 1 week, the systemic clearance for ingestion is lower compared with children from 3 months to 12 years.

Indications:Progressing HIV infection the adults and children, as part of a combined therapy.

Contraindications:

- Hypersensitivity

- Children under 12 years of age with a body weight of less than 30 kg (due to the impossibility of dosing this dosage form)

- Pregnancy (1st trimester)

Carefully:

Renal insufficiency, pancreatitis (including in the anamnesis), peripheral neuropathy (including in the anamnesis).

Pregnancy and lactation:

Data on the safety of lamivudine during pregnancy is not enough. Lamivudine penetrates the placenta. The concentration of lamivudine in the serum of newborns at the time of birth is the same as in the serum of the mother and in the blood from the umbilical cord. The use of lamivudine in pregnancy in II and III trimester is possible only if the expected benefit to the mother exceeds the possible risk to the fetus. If it is necessary to use the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

Inside.

Adults and children over 12 years of age with a body weight of 30 kg and above: 150 mg twice a day in combination with zidovudine (600 mg / day for 2 or 3 appointments).

Table 1

Creatinine clearance (ml / min)	Adults and children over 12 years of age with a body weight of 30 kg and above
Creatinine clearance (ml / min)	Initial dose	Maintenance dose
≥50	150 mg	150 mg twice daily
50-30	150 mg	150 mg once daily
30-15	150 m	Not Applicable
5-15	-	-
<5	-	-

In patients on hemodialysis (dialysis sessions 2-3 times a week for at least 4 hours), after the initial dose reduction in accordance with from TOK, In the future throughout the period of hemodialysis, additional dose adjustment is not required.

With hepatic insufficiency and compensated renal function, dose adjustment Virolama is not required.

Side effects:

In patients with HIV infection who received a combination therapy with nucleoside analogs, there were cases of lactic acidosis, usually accompanied by severe hepatomegaly and fatty liver dystrophy.

From the nervous system:

Fatigability, headache, dizziness, weakness, insomnia, peripheral neuropathy, paresthesia (sensation of tingling, burning, numbness and pain in hands, hands, feet or feet), most often in children.

From the respiratory system:

Respiratory tract infections, cough, flu-like syndrome.

From the digestive system:

Gastralgia, abdominal pain,anorexia, nausea, vomiting, diarrhea, necrotizing pancreatitis(sometimes with lethal outcome), increased activity of "hepatic" transaminase.

From the system of blood and blood-forming organs:

Neutropenia, leukopenia, anemia, thrombocytopathy, aplasia of the erythroid bone marrow.

From the side of the musculoskeletal and connective tissue:

Rhabdomyolysis.

From the side of metabolism and nutrition:

Redistribution / accumulation of subcutaneous fat.

Laboratory and instrumental data:

Increase the concentration of lactic acid in the serum, increase activity serum amylase.

Allergic reactions:

Skin rash, etc.

Other: myalgia, arthralgia, hyperthermia, sweating, rarely - alopecia.

Overdose:

Symptoms: increased dose-dependent side effects.

Treatment: gastric lavage, Activated carbon, forced diuresis, symptomatic therapy.

Interaction:

Increases the duration of zidovudine by 13%, C_m_Oh - by 28%; zidovudine does not affect the pharmacokinetics of lamivudine.

Trimethoprim increases the concentration of lamivudine in plasma by 40% (interaction at the level of excretion, in the absence of renal dysfunction, dose adjustment is not required).

Use in combination with retrovir slows the appearance of zidovudine-resistant strains in patients who have not previously received antiretroviral therapy. There is synergy with other drugs used to treat HIV infection (especially with zidovudine), with respect to HIV replication in cell culture. Simultaneous administration of didanosine, pentamidine, sulfonamides, zalcitabine, ethanol increases the risk of developing pancreatitis.

Dapson, didanosine, isoniazid, stavudine, zalcitabine increase the risk of developing peripheral neuropathy.

Whensimultaneous administration of lamivudine and zalcitabine lamivudine can inhibit intracellular phosphorylation of the latter (a combination of these drugs is not recommended).

Special instructions:

During treatment with Virolam, blood tests are monitored: 1 time per 2 weeks for the first 3 months of therapy, then 1 time per month. Changes in peripheral of blood appear 4-6 weeks from the start of therapy: anemia and neutropenia develop more often in patients receiving large doses of the drug, with late stage of HIV infection (with reduced reserve of bone marrow before the start of therapy), neutropenia, anemia, vitamin B deficiency₁₂. With a decrease in hemoglobin content by more than 25%, or a decrease in the number of neutrophils by more than 50% compared to the baseline level, control of blood tests is performed more often.

During the treatment period it is necessary to control the level of alanine aminotransferase (ALT), aspartate aminotransferase (ACT),amylase, lipase, thyroglobulin (TG) in serum. In patients with impaired renal function, monitoring of nitrogen values, urea and creatinine in the blood serum.

On the background of therapy, opportunistic infections and other complications of HIV infection can develop, so patients should remain under the supervision of doctors.

Antiretroviral therapy does not prevent the transmission of HIV through sexual contact and through infected blood. If resistance to lamivudine appears, zidovudine-resistant strains of the virus may again appear susceptible to zidovudine.

Effect on the ability to drive transp. cf. and fur:

Not studied.

Form release / dosage:Film coated tablets 150 mg.

Packaging:60 tablets in a vial of high-density polyethylene with a protective film of foil under the lid; 1 bottle with instructions for use in a cardboard box. 10 tablets in a blister of aluminum foil and PVC / PVDC; 3 or 6 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

In a dry place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:PL-000618

Date of registration:21.09.2011

Expiration Date:21.09.2016

The owner of the registration certificate:Ranbaxy Laboratories LimitedRanbaxy Laboratories Limited India

Manufacturer: & nbsp

RANBAXY LABORATORIES, Ltd. India

Representation: & nbspRABBAYS LABORATORY LIMITEDRABBAYS LABORATORY LIMITED

Information update date: & nbsp19.02.2017

Illustrated instructions

Instructions

Virolam (Virolam)