Zeffix tablets 100mg, No. 28

Chronic viral hepatitis B against the background of hepatitis B virus replication.

Zeffix is ??taken orally, regardless of the time of the meal.

For adults and children aged 12 years and older, the drug is prescribed at a dose of 100 mg 1 time / day. D

For children aged 2 to 11 years - 3 mg / kg 1 time / day, but not more than 100 mg / day. In renal failure in patients with CC less than 50 ml / min, the dose of the drug should be reduced. The degree of dose reduction in children with renal insufficiency is the same as in adults. If a dose of less than 100 mg / day is required, Zeffix should be used in the form of an oral solution. The degree of dose reduction in children with renal insufficiency is the same as in adults.

Data on patients on hemodialysis (dialysis sessions 2-3 times a week for 4 hours or less) show that after the initial dose reduction of Zeffix in accordance with QC, further dose adjustment is not required throughout the entire period of hemodialysis. In liver failure, unless it is accompanied by renal failure, no dose adjustment of lamivudine is required.

The tablets are yellowish-brown coated, capsule-shaped, biconvex, with the inscription 'GX CG5' engraved on one side of the tablet.

1 tab. lamivudine 100 mg

Excipients: microcrystalline cellulose, sodium starch glycolate, magnesium stearate.

• I trimester of pregnancy;

• hypersensitivity to lamivudine and other components of the drug.

• Zeffix should be prescribed with caution in case of renal failure, pancreatitis (including history), peripheral neuropathy, in the II and III trimesters of pregnancy, during lactation and children under 2 years of age.

pharmachologic effect

Antiviral drug is an analogue of nucleosides. Highly active against the hepatitis B virus.

In both infected and uninfected cells, lamivudine is metabolized to lamivudine triphosphate, which is the active form of the drug and serves as a substrate for hepatitis B virus DNA polymerase. Incorporation of lamivudine triphosphate into the viral DNA chain and subsequent chain termination blocks further viral DNA formation.

Lamivudine triphosphate does not interfere with normal cellular DNA metabolism. It is also a weak inhibitor of mammalian ?- and ?-DNA polymerases. Lamivudine triphosphate has no significant effect on the DNA content in cells.

Lamivudine showed no significant toxic effects on the structure of mitochondria, as well as on the content and function of DNA. Lamivudine has a very weak ability to reduce the content of mitochondrial DNA, is not included in its chain and does not inhibit ?-polymerase.

Pharmacokinetics

Suction

After oral administration, lamivudine is well absorbed from the gastrointestinal tract. Bioavailability in adults after oral administration is usually 80-85%. Cmax in blood serum is reached on average after about 1 hour. When the drug is prescribed in therapeutic doses (100 mg 1 time / day), Cmax is 1.1-1.5 ?g / ml, Cmin is 0.015-0.2 ?g / ml.

Taking Zeffix with food leads to an increase in the time to reach Cmax and a decrease in its value (up to 47%). However, food intake did not affect the overall absorption of lamivudine (calculated from the concentration-time curve).

Distribution

With IV administration of lamivudine, Vd averaged 1.3 L / kg. In the therapeutic dose range, lamivudine has linear pharmacokinetics and is slightly associated with blood plasma proteins.

Lamivudine enters the central nervous system and cerebrospinal fluid. 2-4 hours after oral administration, the CSF to serum concentration ratio of lamivudine was approximately 0.12.

Metabolism

To an insignificant extent (5-10%) it is metabolized in the liver.

Withdrawal

The systemic clearance of lamivudine is, on average, about 0.3 L / h / kg. T1 / 2 - approximately 5-7 hours. Most of lamivudine is excreted unchanged by the kidneys through glomerular filtration and active secretion (organic cation transport system). Renal clearance accounts for about 70% of the elimination of lamivudine.

Pharmacokinetics in special clinical situations

In patients with renal insufficiency, the elimination of lamivudine from the body is slowed down. For patients with creatinine clearance less than 50 ml / min, the dose of Zeffix should be reduced.

Patients with hepatic impairment (not infected with HIV and hepatitis B virus) tolerate lamivudine well. Liver dysfunction does not affect the pharmacokinetics of lamivudine, unless combined with renal failure.

In elderly patients, the age-related decrease in renal function does not significantly affect the elimination of lamivudine with a CC of more than 50 ml / min.

In women in late pregnancy, the pharmacokinetics of lamivudine after oral administration were similar to those in non-pregnant women.

The pharmacokinetics of lamivudine in children does not differ from the pharmacokinetics in adults. However, in children, the clearance of lamivudine, adjusted for body weight, is higher than in adults, which is reflected in a decrease in the AUC. The highest clearance of lamivudine is observed in children aged 2 years and decreases by 12 years, when its values ??become similar to those in adults.

The recommended dose for children from 2 to 11 years old is 3 mg / kg 1 time / day (up to a maximum of 100 mg / day) is able to provide an exposure of lamivudine comparable to the adult dose (100 mg / day). Data on the pharmacokinetics of lamivudine in children under 2 years of age are few.

Side effect

From the digestive system: discomfort and pain in the abdomen, nausea, vomiting, diarrhea; very often - an increase in ALT.

An increase in ALT levels was more often observed after treatment with Zeffix than after taking a placebo. It should be noted, however, that in controlled clinical trials involving patients with compensated liver function, there was no significant difference between the Zeffix and placebo groups in the incidence of clinically significant post-therapeutic ALT elevations associated with elevated bilirubin levels and / or signs of liver failure. The relationship between these manifestations of recurrent hepatitis with Zeffix treatment or with preexisting HIV infection has not been established.

From the musculoskeletal system: often - an increase in CPK; very rarely - muscle disorders, including myalgia and spasms.

From the hematopoietic system: very rarely - thrombocytopenia.

Others: general malaise, fatigue, headache, respiratory tract infections.

In patients with HIV infection, cases of pancreatitis and peripheral neuropathy (or paresthesia) have been observed, but the relationship of these complications with lamivudine therapy has not been proven. There was no significant difference in the incidence of these complications in the groups of patients with chronic hepatitis B who took Zeffix or placebo.

In patients with HIV infection who received combination therapy with nucleoside analogs, there were cases of lactic acidosis, which was usually accompanied by severe hepatomegaly and fatty liver disease. There are separate reports of the same side effects in patients with viral hepatitis B and liver failure, but there is no data to support the association of these complications with Zeffix.

Zeffix is ??well tolerated by patients with chronic hepatitis B

Application during pregnancy and lactation

There are insufficient data on the safety of lamivudine use during pregnancy.

Lamivudine crosses 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 drug is contraindicated for use in the first trimester of pregnancy.

The use of lamivudine during pregnancy in the II and III trimesters is possible only if the expected benefit to the mother outweighs the possible risk to the fetus.

If pregnancy occurs during treatment with Zeffix, then it should be borne in mind that after discontinuation of the drug, an exacerbation of hepatitis B may develop.

After oral administration, the concentration of lamivudine in breast milk does not differ significantly from its concentration in serum (1 ?g / ml). Animal studies suggest that the concentration of lamivudine in human breast milk is not toxic to infants who are breastfed.

There is no information on transplacental transmission of hepatitis B virus in pregnant women receiving Zeffix. Routine newborn immunization against hepatitis B is recommended.

In experimental studies on animals, lamivudine did not show signs of teratogenicity and effects on fertility. Data from studies in rabbits indicate a possible risk of spontaneous abortion in early pregnancy.

Application for violations of liver function

In liver failure , unless it is accompanied by renal failure, no dose adjustment of lamivudine is required.

Application for impaired renal function

Zeffix should be used with caution in case of renal failure.

In renal failure in patients with CC less than 50 ml / min, the dose of the drug should be reduced. The degree of dose reduction in children with renal insufficiency is the same as in adults. If a dose of less than 100 mg / day is required, Zeffix should be used in the form of an oral solution. The degree of dose reduction in children with renal insufficiency is the same as in adults.

Data on patients on hemodialysis (dialysis sessions 2-3 times a week for 4 hours or less) show that after the initial dose reduction of Zeffix in accordance with QC, further dose adjustment is not required throughout the entire period of hemodialysis.

Application in children

The drug should be prescribed with caution to children under 2 years of age.

For children aged 12 years and older, the drug is prescribed at a dose of 100 mg 1 time / day.

Children aged 2 to 11 years - 3 mg / kg 1 time / day, but not more than 100 mg / day.

special instructions

Zeffix in the form of an oral solution is used to treat children and those patients who cannot take the drug in the form of tablets.

During treatment with Zeffix, patients should be regularly monitored by a physician experienced in the treatment of chronic hepatitis B.

Discontinuation of Zeffix therapy is possible in patients with normal biochemical parameters (ALT, AST), absence of hepatitis B virus DNA in the blood and HBeAg and / or HBsAg seroconversion (no earlier than 3 months after the onset of seroconversion). Cancellation of Zeffix is ??also possible if further treatment is ineffective (no positive dynamics within 6 months of treatment or symptoms of exacerbation of hepatitis).

When Zeffix is ??canceled, patients should be under medical supervision to detect symptoms of exacerbation of hepatitis.

Discontinuation of therapy is not recommended in the presence of symptoms of hepatic failure. There is currently insufficient data on the persistence of long-term seroconversion after Zeffix discontinuation.

After stopping treatment with Zeffix, it is necessary to periodically monitor the general condition of patients, as well as monitor the indicators of functional liver tests (activity of hepatic transaminases and the content of bilirubin) for 4 months to identify signs of a possible exacerbation of hepatitis; in the future, patients should be observed according to indications. Currently, there is no convincing data on the effectiveness of repeated treatment with Zeffix in those patients who have exacerbated hepatitis after stopping the course of therapy.

Patients should be under medical supervision for at least 6 months after stopping treatment for any reason. The condition of patients with symptoms of liver failure should be monitored more closely.

There are few data on the use of lamivudine in patients receiving concomitant immunosuppressive therapy.

With long-term therapy with lamivudine, subpopulations of viral hepatitis B (YMDD strain) with reduced sensitivity to it have been identified. Sometimes this type of virus can cause an exacerbation of hepatitis.

When treating patients with HIV / hepatitis B virus co-infection who are or will receive antiretroviral therapy that includes lamivudine, the dose of lamivudine normally prescribed for HIV infection should be maintained.

Patients should be warned that Zeffix treatment does not reduce the risk of transmission of hepatitis B to others and therefore appropriate precautions should be taken.

If it is necessary to use the drug in patients with diabetes mellitus, it should be borne in mind that each dose of oral solution (100 mg / 20 ml) contains 4 g of sucrose.

Use in pediatrics

There are currently insufficient guidelines for determining an effective and safe dose in children under 2 years of age .

Influence on the ability to drive vehicles and use mechanisms

No specific research has been carried out. Based on the pharmacological properties of lamivudine, such an effect is unlikely.

Overdose

There were no specific symptoms of lamivudine overdose.

There is limited data on the effects of high doses of lamivudine in humans. There were no lethal outcomes, the condition of all patients returned to normal.

In experimental studies, administration of very high doses of lamivudine had no organ toxicity.

Treatment: gastric lavage, the appointment of activated charcoal, monitoring of the patient's condition and standard supportive therapy are recommended. Continuous hemodialysis can be used to eliminate lamivudine, but no specific studies have been conducted.

Drug interactions

The possibility of interaction of lamivudine with other drugs should be taken into account, especially with those whose main mechanism of excretion is active renal secretion through the organic cation transport system (trimethoprim). The simultaneous use of trimethoprim / sulfamethoxazole (160 mg / 800 mg) increases the plasma concentration of lamivudine by approximately 40%. Lamivudine does not alter the pharmacokinetics of trimethoprim and sulfamethoxazole (in the absence of renal failure, there is no need to reduce the dose of lamivudine). Other drugs (eg, ranitidine, cimetidine) are only partially eliminated by this mechanism and do not interact with lamivudine.

Drugs that are eliminated predominantly by active transport of organic anions or by glomerular filtration do not appear to enter into clinically significant interactions with lamivudine.

With the simultaneous use of lamivudine and zidovudine, there is a moderate (28%) increase in Cmax of zidovudine in plasma, while the AUC does not change significantly.

There was no pharmacokinetic interaction of Zeffix with interferon alpha, as well as with immunosuppressants (for example, with cyclosporin A).

With the simultaneous appointment of lamivudine and zalcitabine, lamivudine can inhibit the intracellular phosphorylation of the latter (the combination is not recommended).

Concomitant use of didanosine, pentamidine, sulfonamides and ethanol increases the risk of developing pancreatitis.

Dapsone, didanosine, isoniazid, and stavudine increase the risk of developing peripheral neuropathy.