Zeffix, 100 mg 28 pcs.

Zeffix is an antiviral drug.

It has high activity against hepatitis B virus (HBV).

In both infected and uninfected cells lamivudine is metabolized to lamivudine triphosphate, which is the active form of the drug. In vitro half-life of lamivudine triphosphate in hepatocytes is 17-19 h.

Lamivudine triphosphate is a substrate for DNA polymerase of hepatitis B virus. Incorporation of lamivudine triphosphate into viral DNA chain and subsequent chain breakage block further formation of viralDNA. Lamivudine is a weak inhibitor of mammalian α- and β-DNA polymerases.

In studies to determine possible effects on mitochondrial structure and DNA content and function, no significant toxic effects have been observed with lamivudine. Lamivudine has a very weak ability to reduce mitochondrial DNA content, is not normally incorporated into the mitochondrial DNA chain and does not inhibit mitochondrial DNA γ-polymerase.

Zeffix^® has marked antiviral activity in vivo and rapidly suppresses HBV replication after initiation of treatment.

Pharmacokinetics

It is well absorbed from the gastrointestinal tract, bioavailability in adults after oral administration is usually 80-85%. When taken orally in therapeutic doses (100 mg once daily), C_max is reached after approximately 1 h and is 1.1-1.5 mcg/ml.

Eating decreases C_max (by 47%) and prolongs T_max without changing the overall absorption of lamivudine (calculated based onAUC). When administered intravenously, the volume of distribution averages 1.3 L/kg.

In the therapeutic dose range, lamivudine has linear pharmacokinetics and binds only slightly to plasma proteins. According to limited data, lamivudine penetrates the CNS and the cerebrospinal fluid (2-4 h after oral administration, the ratio of concentrations in cerebrospinal fluid to serum is approximately 0.12).

It is slightly biotransformed in the liver. Systemic clearance of lamivudine averages about 0.3 L/h/kg. T_1/2 is approximately 5-7 h. 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 lamivudine elimination.

Particular groups of patients

In patients with renal impairment the excretion of lamivudine is delayed (patients with Cl creatinine

Patients with hepatic impairment (not infected with HIV and HBV), tolerate lamivudine well. Impaired hepatic function does not affect the pharmacokinetics of lamivudine unless combined with renal impairment.

In elderly patients, age-related reduction in renal function has no significant effect on lamivudine excretion at creatinine Cl above 50 mL/min.

In late pregnant women, the pharmacokinetics of lamivudine after oral administration was similar to that of non-pregnant women.

The pharmacokinetics of lamivudine in children is not different from that in adults, but lamivudine clearance, adjusted according to body weight, is higher than in adults, which is expressed by a decrease in AUC. Clearance of lamivudine is highest in children at the age of 2 years and decreases by the age of 12 years, when its values become similar to those of adults.

The recommended dose for children from 2 to 11 years of age is 2 mg/kg once daily (up to a maximum of 100 mg/day), capable of providing comparable exposure to lamivudine to an adult dose (100 mg/day). There are few data on lamivudine pharmacokinetics in children younger than 2 years of age.

Indications

Chronic hepatitis B against a background of hepatitis B virus replication.

Active ingredient

Composition

Active ingredient:

Lamivudine 100 mg;

Associates:

MCC;

Sodium starch glycolate;

Magnesium stearate;

Hypromellose;

titanium dioxide;

macrogol 400;

polysorbate 80;

iron oxides yellow and red

How to take, the dosage

Overly, regardless of meals.

Adults and children aged 12 years and older: 100 mg once daily.

In children from 2 to 11 years of age: 3 mg/kg once daily, but not more than 100 mg/day.

In children younger than 2 years of age: there are insufficient data to recommend dosages in this age group.

Interaction

The probability of metabolic interaction of lamivudine with other drugs is low due to limited metabolism, low degree of binding to plasma proteins and excretion of the drug mainly by the kidneys in unchanged form.

The possibility of interaction of lamivudine with other drugs whose main mechanism of excretion is active renal secretion through organic cation transport system, such as trimethoprim, should be considered. Other drugs (e.g. ranitidine, cimetidine) are only partially eliminated by this mechanism and do not interact with lamivudine.

Drugs that are eliminated primarily by active transport of organic anions or by glomerular filtration do not appear to have any clinically significant interactions with lamivudine.

The concomitant use of trimethoprim/sulfamethoxazole (co-trimoxazole) at a dose of 160 mg/800 mg results in a 40% increase in lamivudine exposure due to interaction with trimethoprim. However, in the absence of renal impairment, there is no need to reduce the dose of lamivudine. Lamivudine does not affect the pharmacokinetics of trimethoprim and sulfamethoxazole.

Concomitant use of lamivudine and zidovudine resulted in a moderate (28%) increase in peak plasma concentrations of zidovudine, but the area under the “plasma concentration – time” curve did not change significantly. Zidovudine has no clinically significant effect on the pharmacokinetics of lamivudine.

No pharmacokinetic interaction between lamivudine and α-interferon was observed when these drugs were used simultaneously. No clinically significant adverse interactions have been observed in patients receiving Zefix® and immunosuppressants (e.g., cyclosporine A) concomitantly; however, no specific studies have been performed. Lamivudine may inhibit intracellular phosphorylation of zalcitabine. Therefore, concomitant use of lamivudine and zalcitabine is not recommended.

Special Instructions

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

Contraindications

Hypersensitivity to lamivudine or any other component of the drug, pregnancy (1st trimester).

With caution: should be used in renal failure, pancreatitis (including anamnesis), peripheral neuropathy, pregnancy (II-III trimester), during lactation, in children (under 2 years).

Side effects

The most common side effects are general malaise and rapid fatigue, respiratory infections, headache, abdominal discomfort and pain, nausea, vomiting, and diarrhea.

The frequency of changes in laboratory parameters in patients with chronic hepatitis B is similar with Zefix® and placebo, with the exception of a more frequent increase in ALT levels after therapy with Zefix®. However, there is no significant difference in the frequency of elevated ALT levels combined with elevated bilirubin levels and/or signs of liver failure. It is unknown whether these cases of hepatitis exacerbation are related to treatment with Zeffix® or to the characteristics of the course of chronic hepatitis itself.

In patients with HIV infection, cases of pancreatitis and peripheral neuropathy (or paresthesias) have been observed, but the association of these complications with lamivudine therapy has not been proven. There was no significant difference in the incidence of these complications between the groups of patients with chronic hepatitis B receiving Zefix® and placebo.

In patients with HIV infection receiving combination therapy with nucleoside analogues, cases of lactic acidosis have been reported, usually accompanied by marked hepatomegaly and fatty liver dystrophy. There have been anecdotal reports of the same side effects in patients with viral hepatitis B and hepatic failure; however, there are no data to support a link between these complications and Zeffix®.

Overdose

Symptoms: no specific symptoms of lamivudine overdose have been identified.

Gastric lavage, administration of activated charcoal, monitoring the patient’s condition and standard supportive therapy are recommended.

The use of continuous hemodialysis is possible for lamivudine excretion, but no specific studies have been performed.

Similarities