Lamivudine is an antiviral agent having activity against the hepatitis B virus (HS).
As in infected and in uninfected cells lamivudine metabolized to lamivudine triphosphate, which testosterone blend 400 is the active form of the drug and serves as a substrate for DNA polymerase of hepatitis B virus . The inclusion of lamivudine triphosphate into viral DNA chain and subsequent chain termination block further formation of viral DNA.
At lamivudine showed no significant toxic effects on mitochondrial structure and the maintenance and function of DNA. Lamivudine has very poor ability to reduce the content of mitochondrial DNA is not incorporated into the chain and it does not inhibit the γ-polymerase.
Special patient groups
In patients with renal insufficiency excretion from the body slows down lamivudine (patients with creatinine clearance less than 50 mL / min the dose of lamivudine should be reduced).
Patients with hepatic insufficiency (not infected with HIV and HS) are well tolerated lamivudine. Abnormal liver function has no effect on the pharmacokinetics of lamivudine unless combined with renal insufficiency.
In elderly patients, age-related decline of renal function did not significantly affect the excretion of lamivudine with creatinine clearance above 50 mL / min.
The women in the later stages of pregnancy pharmacokinetics of lamivudine at reception inside is similar to that in non-pregnant women.
The pharmacokinetics of lamivudine in children is not different from the pharmacokinetics in adults. However, infants lamivudine clearance adjusted depending on the weight, higher than in adults, resulting in reduction of AUC. The highest ground clearance of lamivudine in children aged 2 years and reduced to 12 years, when its values are similar to those in adults.
The recommended dose for children testosterone blend 400 2 to 11 years, 3 mg / kg once daily (up to a maximum of 100 mg per day ) is able to provide comparable to the adult dose (100 mg daily) exposure lamivudine. Data on the pharmacokinetics of lamivudine in children under 2 years are numerous.
Chronic hepatitis B on the background of replication of hepatitis B virus
- Hypersensitivity to lamivudine or to any other component of the drug.
- I trimester pregnancy.The caution
should be used in renal failure, pancreatitis (including history), peripheral neuropathy, pregnancy (II-III trimester), lactation, in children younger than 2 years.Dosing and Administration
Zeffiks can be taken regardless of meals. Adults and children aged 12 years and over 100 mg once a day. Children from 2 to 11 years, 3 mg / kg once a day, but not more than 100 mg per day . Children testosterone blend 400 under 2 years for dosage recommendations for this age group is not enough data. Renal insufficiency in patients with creatinine clearance less than 50 mL / min the dose should be reduced. If you need a dose of less than 100 mg per day should be used Zeffiks oral solution. The degree of dose reduction in children with renal failure is the same as that of adults. The data for patients on hemodialysis (2-3 dialysis sessions per week duration of 4 hours or less), show that after an initial decline Zeffiksa doses according to the clearance creatinine, hereinafter throughout the period of hemodialysis additional correction dose is not required. liver failure in liver failure, if it is not accompanied by renal insufficiency, lamivudine does not require dose adjustments.
Zeffiks well tolerated in patients with chronic hepatitis B. The most common side effects were malaise and fatigue, respiratory tract infections, headache, discomfort and abdominal pain, nausea, vomiting and diarrhea.
The following are the side effects of the different systems. Category frequency indicated only for those side effects, whose connection with the treatment Zeffiksom considered at possible.
According to the frequency side effects have been divided into the following categories: very common (> 1:10), frequent (> 1: 100 and <1:10) , infrequent (21: 1000 <1: 100), rare (> 1:10 000 and <1: 1000)., very rare (<1/10 000)
The following categories of adverse events are estimated frequency, as against most side effects are no data on the basis of which it was possible to calculate their frequency.
categories “very often” and “frequently” were determined on the basis of the results of clinical trials, it does not take into account the background incidence in placebo groups. Side effects identified during post-marketing use Zeffiksa, are considered rare or very rare.
Side effects identified in clinical studies Hepatobiliary disorders Very common: increased ALT levels. Increased levels of ALT often observed after treatment Zeffiksom than after placebo. It should be noted, however, that in controlled clinical trials, which included patients with compensated liver function, among Zeffiksa groups and the placebo group had no significant difference in the frequency of postterapevticheskogo clinically significant elevations of ALT, accompanied by increased bilirubin levels and / or signs of liver failure. The relationship between these manifestations of recurrent hepatitis C Zeffiksom treatment or pre-existing HIV infection has not been established. Violations of the musculoskeletal system, connective tissue and bones Frequent: increased levels of creatine kinase (CK). The side effects observed in clinical practice In addition to side effects, identified in clinical trials, in everyday clinical practice, observed the following side effects. violations of the blood and lymphatic systemVery rare: thrombocytopenia. violations of the musculoskeletal system, connective tissue and bones rare: muscle disorders, including myalgia and cramps. in patients with HIV infection have been cases of pancreatitis and peripheral neuropathy (or paresthesia), but no proven relationship between these complications with lamivudine therapy. There was no significant difference in the incidence of these complications in patients with chronic hepatitis B treated with Zeffiks or placebo. In patients with HIV infection treated with combination therapy with nucleoside analogs, there were cases of lactic acidosis, which is usually accompanied by severe hepatomegaly and steatosis. There are anecdotal reports of the same side effects in patients with HS and liver failure, but no data confirming the relationship of these complications with Zeffiksom.
Experimental studies have shown that very high doses of lamivudine do not have a toxic effect. Data on the long-term effects of high doses of lamivudine in humans is not enough. However, deaths were observed, the condition of all patients returned to normal. Specific symptoms lamivudine overdose are not identified. It is recommended to wash out the stomach, activated charcoal to appoint, monitor the patient’s condition and perform standard maintenance therapy. For lamivudine elimination is possible to use a continuous hemodialysis, but special studies have not been conducted.
Interaction with other drugs
should take into account the interoperability of lamivudine with other drugs, especially with the likes of which the main mechanism of elimination is active renal secretion via the organic cation transport system, eg with trimethoprim. The simultaneous use of trimethoprim / sulfamethoxazole (160mg / 800mg) increases in the plasma concentration of lamivudine approximately 40% (in the absence of renal failure there is no need to reduce the dose). Other drugs (eg ranitidine, cimetidine) is only partially removed from the body via said mechanism and do not interact with lamivudine.
Drugs that are derived primarily by active transport of organic anions or by glomerular filtration, apparently do not come into clinically significant interactions with lamivudine .
with simultaneous use of lamivudine testosterone blend 400 and zidovudine observed (28%) increase in C max of AZT, while AUC is not significantly changed.
pharmacokinetic interaction with a combination of lamivudine with ɑ-interferon as well as immunosuppressive agents (e.g. cyclosporine a), apparently without is observed.
When concomitant administration of lamivudine and zalcitabine lamivudine may inhibit the intracellular phosphorylation of the latter (not recommended combination of drugs).
Co-administration of didanosine, pentamidine, sulfonamides and ethanol increases the risk of developing pancreatitis.
dapsone, didanosine, stavudine and isoniazid increase the risk of peripheral neuropathy.
Zeffiks in the form of a solution for oral administration is used to treat children and those patients who can not take the medication in tablet form.
Discontinuation of therapy Zeffiksom possible in patients with normal immunity after achieving HBeAg and / or HBsAg seroconversion. Cancel Zeffiksa is also possible with the ineffectiveness of further treatment (signs of acute hepatitis).
In case of cancellation Zeffiksa patients should be under medical observation for symptoms of hepatitis exacerbation.
Discontinuation of therapy is not recommended if there are signs of liver failure. At present, insufficient data on the long-term preservation of seroconversion after the abolition Zeffiksa.
During treatment, patients Zeffiksom state should regularly monitor the doctor having experience of treatment of chronic hepatitis B
after discontinuation of treatment Zeffiksom necessary to periodically monitor the general condition of patients, and also monitor the performance of the functional liver samples (activity of “liver” transaminases and bilirubin) during 4 months for signs of a possible exacerbation of hepatitis B; further, patients should be observed for indications. There is currently no conclusive data on the effectiveness of re-treatment with Zeffiks those patients after discontinuation of therapy there was an exacerbation of hepatitis.
In the case of discontinuation of treatment for any reason, patients should remain under medical supervision for at least 6 months after its cancellation. Condition of patients with symptoms of liver failure should be monitored frequently.
Data on the use of lamivudine in patients receiving concomitant immunosuppressive therapy, are scarce.
When long-term therapy with lamivudine have been identified subpopulations HS (YMDD strain) with reduced susceptibility to it. Sometimes this kind of virus can cause exacerbation of hepatitis.
In the treatment of patients with HIV co-infection and the HS, which are already receiving or will be receiving antiretroviral therapy, including amivudin and necessary to maintain the dose of lamivudine usually prescribed for the treatment of HIV infection.
Information on the transplacental transfer hepatitis B virus in pregnant women receiving Zeffiks missing. It is recommended that the standard procedure of neonatal immunization against hepatitis B.
Patients should be warned that treatment Zeffiksom not reduce the risk of transmission of hepatitis B to other people, and therefore it is necessary to comply with the appropriate precautions.
Pregnancy and lactation Pregnancy
Safety Data lamivudine during pregnancy is not enough.
Lamivudine crosses the placenta. Lamivudine concentration in neonatal serum at the time of birth is the same as in the mother’s serum and blood from the umbilical cord.
Animal studies have found no lamivudine signs of teratogenicity and effects on fertility.
These studies in rabbits suggest a possible risk of miscarriage in early pregnancy. Do not appoint Zeffiks in the first trimester of pregnancy. If the pregnancy during treatment Zeffiksom, it should be borne in mind that after the withdrawal of the drug may develop an exacerbation of hepatitis C.
The use of lamivudine in pregnancy during the second and third trimester is possible only if the expected benefit to the mother outweighs the potential risk to the fetus. lactation After oral administration of lamivudine concentration in human milk does not significantly differ from its concentration in serum (1 ug / ml). Studies in animals suggest that lamivudine concentration in human breast milk has no toxic effect on children through breastfeeding.
Effects on ability to drive and / or other mechanisms
Research on the effect of Zeffiksa on ability to drive and has not been moving mechanisms. However, based on the pharmacological properties of the drug, it can not be assumed that it violates these functions.
On 14 tablets in a blister pack of a double aluminum foil. At 1, 2, or 6 blisters with instruction on use in carton box.
Do not use the drug after the expiry date stated on the package.
at temperatures below 30 ° C.
Keep out of reach of children.