Zeffix
Zeffix: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Drug interactions
- 14. Analogs
- 15. Terms and conditions of storage
- 16. Terms of dispensing from pharmacies
- 17. Reviews
- 18. Price in pharmacies
Latin name: Zeffix
ATX code: J05AF05
Active ingredient: Lamivudine (Lamivudine)
Manufacturer: Glaxo Wellcome Operation Ltd. (United Kingdom)
Description and photo update: 18.10.2018
Prices in pharmacies: from 810 rubles.
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Zeffix is an antiviral drug.
Release form and composition
Zeffix dosage forms:
- film-coated tablets: biconvex, capsule-shaped, yellowish-brown in color, engraved with "GX GG5" on one side of the tablet (14 pieces in a blister strip, 1, 2 or 6 packs in a cardboard box);
- oral solution: from colorless to pale yellow, transparent, has a fruit smell (in 240 ml vials with a dosing syringe and syringe adapter, 1 pc. in a box).
Composition of 1 Zeffix tablet:
- active substance: lamivudine - 100 mg;
- excipients: microcrystalline cellulose - 116.55 mg, sodium carboxymethyl starch (type A) - 6.75 mg, magnesium stearate - 1.7 mg;
- shell: yellow-brown opadry (titanium dioxide, hypromellose, red and yellow iron oxide, macrogol 400, polysorbate 80) - 5.6 mg.
Composition of 1 ml Zeffix solution:
- active substance: lamivudine - 5 mg;
- excipients: methyl parahydroxybenzoate, sucrose, propyl parahydroxybenzoate, propylene glycol, citric acid, sodium citrate, banana and strawberry flavors, purified water.
Pharmacological properties
Pharmacodynamics
Lamivudine is metabolized in infected and uninfected cells to lamivudine triphosphate, which is the active form of the parent compound. In vitro, the intracellular half-life of this metabolite in hepatocytes ranges from 17–19 hours. For hepatitis B virus DNA polymerase, lamivudine triphosphate is a substrate. It has high antiviral activity against the hepatitis B virus (HBV). Lamivudine triphosphate is a weak inhibitor of mammalian α- and β-DNA polymerases; it does not affect the normal cellular metabolism of deoxynucleotides. No significant toxic effects were found in the studies. Lamivudine has a weak ability to reduce the content of mitochondrial DNA, is briefly included in its chain and does not inhibit mitochondrial DNA γ-polymerase.
Pharmacokinetics
Absorption from the gastrointestinal tract is rapid; in adults, after oral administration, bioavailability is approximately 80–85%. The maximum concentration of lamivudine in the blood is reached within about 1 hour after taking the drug in the recommended doses and is 1.1–1.5 μg / ml. The degree of absorption of lamivudine does not change depending on food intake, at the same time, C max decreases (by 47%) and T max increases.
The average volume of distribution is 1.3 l / kg with IV. The degree of binding to plasma proteins is insignificant, since when taken in the recommended doses, lamivudine has linear pharmacokinetics. There are limited data on the ability of lamivudine to penetrate the cerebrospinal fluid and the central nervous system (after 2-4 hours after taking the drug, the concentration ratio in the cerebrospinal fluid and serum is approximately 0.12).
Biotransformation in the liver is negligible. T 1/2 - about 5-7 hours. Systemic clearance of lamivudine - about 0.3 l / h / kg. The kidneys, unchanged, excrete most (70%) of lamivudine by active secretion using the transport system of organic cations and glomerular filtration.
The clearance of lamivudine in children is higher than in adults, and therefore their AUC is reduced. The highest clearance of lamivudine is observed in children aged 2 years and by the age of 12 it becomes similar to that in adults.
In patients with creatinine clearance less than 50 ml / min, a dose reduction of lamivudine is required. In the course of the study, it was found that in patients with renal insufficiency, impaired renal function affects the elimination of lamivudine from the body.
Decreased renal function in elderly patients has no clinical effect on the elimination of lamivudine with creatinine clearance less than 50 ml / min.
Lamivudine is well tolerated by patients with hepatic impairment who are not infected with HIV and HBV and does not cause changes in the lamivudine adverse reaction profile or laboratory parameters. The pharmacokinetics of lamivudine does not change with impaired liver function, however, there is limited information that patients after liver transplantation have a slight effect on the pharmacokinetics of the drug (only in the absence of renal failure).
Indications for use
Zeffix is used to treat chronic hepatitis B, including:
- compensated liver disease with signs of active viral replication, histological signs of an active inflammatory process in the liver and / or fibrosis, and a constant increase in serum alanine aminotransferase activity;
- decompensated liver disease in combination with a second medication that is not cross-resistant to lamivudine.
Contraindications
Pills
- high sensitivity to drug components;
- age up to 18 years.
In addition, Zeffix tablets are not prescribed for patients with impaired renal function whose creatine clearance is less than 50 ml / min.
Oral solution
- hypersensitivity to the components of the drug;
- I trimester of pregnancy.
Diseases / conditions in which Zeffix solution should be taken with caution:
- renal failure;
- pancreatitis (including a history);
- peripheral neuropathy;
- II – III trimesters of pregnancy;
- lactation period;
- age up to 2 years.
Instructions for the use of Zeffix: method and dosage
Zeffix is administered orally (by mouth), regardless of food intake.
Pills
The recommended dose of the drug is 100 mg once a day.
The duration of therapy is set by the attending physician on an individual basis.
Patients with HBeAg-positive chronic hepatitis B (CHB) without cirrhosis should receive therapy for 6–12 months after confirmation of HBeAg seroconversion (disappearance of HBeAg and HBV DNA with HBeAb detection) to limit the risk of recurrent viremia or until HBsAg seroconversion or efficacy decreases. Serum ALT and HBV DNA should be monitored regularly after treatment discontinuation to detect late recurrence of viremia.
Patients with HBeAg-negative CHB (prenuclear mutation) without cirrhosis should be treated until HBs seroconversion or signs of decreased efficacy. With long-term therapy, regular evaluation should be carried out to confirm the chosen treatment.
It is not recommended to discontinue treatment in patients with liver cirrhosis, decompensated disease, or with liver transplant. If the drug is discontinued, it is necessary to systematically monitor patients for signs of recurrence of hepatitis.
The development of a YMDD (tyrosine-methionine-aspartate-aspartate) mutant HBV variant can lead to a decrease in the therapeutic response to Zeffix in patients with HBeAg-positive or HBeAg-negative CHB, as evidenced by an increase in HBV DNA and ALT activity compared to those before therapy. To reduce the risk of resistance in patients receiving Zeffix monotherapy, treatment modification should be considered if serum HBV DNA remains detectable for 24 weeks or longer. The likelihood of adding an alternative medication without cross-resistance to lamivudine in patients with YMDD mutant HBV should be investigated. When treating patients with concomitant HIV infection,currently receiving or planning to start treatment with Zeffix or a combination of lamivudine and zidovudine, it is necessary to maintain the dose of lamivudine prescribed for the treatment of HIV infection (150 mg 2 times a day in combination with other antiretroviral drugs).
In elderly patients, the usual age-related decline in renal function does not have a clinically significant effect on lamivudine exposure, with the exception of patients with creatinine clearance below 50 ml / min.
Oral solution
- from 2 to 11 years: 3 mg / kg once a day (no more than 100 mg per day);
- 12 years and older: 100 mg once a day.
Side effects
- central nervous system: fatigue, headache;
- hematopoietic system: thrombocytopenia;
- immune system: angioedema, respiratory tract infections;
- digestive system: nausea, vomiting, diarrhea, discomfort and pain in the abdomen;
- liver and biliary tract: increased enzyme activity;
- musculoskeletal and connective tissue: muscle disorders (including spasms and myalgia), rhabdomyolysis;
- allergic reactions: rash, itchy skin.
Cases of development of peripheral neuropathy (or paresthesia) and pancreatitis have been reported in HIV-infected patients, the relationship of these complications with lamivudine treatment has not been identified. 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 HIV-infected patients who received joint therapy with nucleoside analogs, there were precedents of lactic acidosis, which were most often accompanied by fatty degeneration of the liver and severe hepatomegaly. There is information about the same undesirable effects in patients with hepatitis B with decompensated liver failure, but there is no information confirming the relationship of these complications with taking Zeffix.
Overdose
At the moment, there have been no cases of Zeffix overdose.
special instructions
Spontaneous exacerbations of chronic hepatitis B, characterized by a transient increase in serum ALT activity, are relatively frequent. In some patients, ALT activity may increase in serum after starting antiviral treatment with a decrease in HBV DNA concentration. In patients with compensated liver disease, such an increase in serum ALT activity is usually not accompanied by an increase in serum bilirubin concentration or signs of hepatitis decompensation.
At the beginning and during therapy, it is necessary to carefully and regularly monitor the patient's condition. In patients with moderate or severe renal impairment, AUC increases due to reduced renal clearance, therefore, Zeffix is not recommended for the treatment of patients with creatinine clearance less than 50 ml / min.
HBV viral subpopulations with reduced sensitivity to lamivudine (YMDD mutation HBV) have been observed with prolonged treatment. The emergence of HBV with the YMDD mutation may in some patients lead to an exacerbation of hepatitis, mainly determined by an increase in serum ALT activity and the reappearance of HBV DNA. In patients with the YMDD HBV mutation, the possibility of adding or switching to an alternative drug in the absence of cross-resistance to lamivudine should be analyzed based on therapeutic guidelines.
In patients who discontinued treatment for hepatitis B, an exacerbation of this disease was noted, usually determined by an increase in serum ALT activity and reappearance of HBV DNA. In phase III studies with a follow-up period without active therapy, the frequency of increased ALT activity after discontinuation of treatment (more than 3 times the baseline value) was higher in patients receiving lamivudine (21%) compared with patients receiving placebo (8%). The proportion of patients with an increase in ALT activity after discontinuation of therapy combined with an increase in bilirubin concentration was low and the same in both treatment groups. In lamivudine-treated patients, a higher incidence of elevated ALT activity after discontinuation of therapy occurred between 8 and 12 weeks after discontinuation of treatment. In most cases, the outcome was favorable,but several fatalities have been reported. In case of discontinuation of treatment with Zeffix, it is necessary to conduct regular monitoring of patients with an assessment of clinical signs and liver function tests (ALT activity and serum bilirubin concentration) for a period of at least four months and further according to clinical indications.
The risk of active viral replication is increased in patients with decompensated liver cirrhosis / after transplantation. Due to the minimal liver function in patients of this category, reactivation of hepatitis upon discontinuation of Zeffix treatment or loss of efficacy during treatment can lead to severe decompensation or even decompensation with a fatal outcome. This category of patients requires monitoring for virological, clinical and serological parameters associated with hepatitis B, kidney and liver function and antiviral response during treatment (at least monthly), as well as after its termination (due to various circumstances) even in for at least 6 months. Monitored laboratory parameters should include concentrations of albumin, bilirubin, urea nitrogen in the blood,serum ALT activity, creatinine and virological status: HBV antigens / antibodies and serum HBV DNA concentration, if possible. There are insufficient data on the beneficial effect of repeated treatment with Zeffix in patients with signs of recurrent hepatitis after treatment.
Patients with concomitant infection with chronic hepatitis B with a delta agent or hepatitis C should be used with caution Zeffix.
In HBeAg-negative patients, as well as in patients receiving concomitant immunosuppressive therapy, chemotherapy, data on the use of lamivudine are limited. Patients in this category are recommended to use the drug with caution.
During the period of treatment with Zeffix, it is necessary to regularly monitor the patient's condition. Serum HBV DNA and ALT should be monitored at 3-month intervals, and HBeAg levels in HBeAg-positive patients should be assessed every 6 months.
Patients with concurrent HIV infection without the need for antiretroviral treatment are at risk of HIV mutation when Zeffix monotherapy is used to treat chronic hepatitis B.
There is no information on mother-to-fetal transmission of hepatitis B virus in pregnant women undergoing lamivudine treatment. Standard procedures for immunizing infants to prevent hepatitis B should be followed.
Patients should be educated to take appropriate precautions, as lamivudine has not been shown to reduce the risk of transmission of hepatitis B virus to others.
Zeffix is not recommended for use in combination with emtricitabine and cladribine. There is information about cases of lactic acidosis (in the absence of hypoxemia), in some cases with a fatal outcome, usually with concomitant severe hepatomegaly and fatty liver, when using nucleoside analogues. Since lamivudine is a nucleoside analogue, this risk cannot be excluded. With a rapid increase in aminotransferase activity, progressive hepatomegaly, or the appearance of metabolic acidosis / lactic acidosis for an unknown reason, therapy with nucleoside analogs must be discontinued. Mild symptoms of indigestion, such as abdominal pain, vomiting, and nausea, can be signs of lactic acidosis. Severe cases, sometimes fatal, were accompanied by fatty degeneration of the liver,hepatic and renal failure, pancreatitis and increased serum lactate concentration. It is recommended to prescribe nucleoside analogs with caution to all patients (in particular overweight women) with hepatomegaly, hepatitis, or other known risk factors for liver disease and fatty liver disease (including the use of certain medications and alcohol consumption). Patients with co-infection with hepatitis C who are taking ribavirin and interferon-alpha may be at particular risk. It is recommended to monitor the condition of such patients with special attention.hepatitis or other known risk factors for liver disease and fatty liver disease (including the use of certain drugs and alcohol consumption). Patients with co-infection with hepatitis C who are taking ribavirin and interferon-alpha may be at particular risk. It is recommended to monitor the condition of such patients with special attention.hepatitis or other known risk factors for liver disease and fatty liver disease (including the use of certain drugs and alcohol consumption). Patients with co-infection with hepatitis C who are taking ribavirin and interferon-alpha may be at particular risk. It is recommended to monitor the condition of such patients with special attention.
It has been proven in vitro and in vivo that nucleotide and nucleoside analogs contribute to mitochondrial damage of varying severity. There is evidence of cases of mitochondrial dysfunction in children who have been exposed to nucleoside analogs in utero and / or after birth. The main adverse reactions were hematological disorders (anemia, neutropenia) and metabolic disorders (hyperlipasemia, hyperlactatemia). Neurological disorders can be both permanent and transient. There is information about late manifestations of neurological disorders (convulsions, hypertonicity, inappropriate behavior). It is necessary to carry out follow-up laboratory and clinical observation of the health of all children exposed in utero to nucleotide and nucleoside analogs,and if characteristic symptoms / signs appear, conduct a full examination for possible mitochondrial dysfunction.
Influence on the ability to drive vehicles and complex mechanisms
The clinical condition of the patient and the profile of Zeffix's undesirable effects should be taken into account when driving vehicles and other potentially hazardous activities that require a high concentration of attention and speed of psychomotor reactions.
Application during pregnancy and lactation
In cases of pregnancy on the background of Zeffix therapy, when it is canceled, exacerbation of hepatitis B is possible.
Pills
Available information indicates that there is no toxicity associated with birth defects. In the presence of clinical indications, it is allowed to use Zeffix during pregnancy.
When mother-to-child transmission of HBV is concerned, the likelihood of stopping breastfeeding should be considered to reduce the risk of lamivudine resistance mutations in the newborn. The presence of hepatitis B in the mother is not a contraindication to breastfeeding if the newly born baby has adequate prevention of hepatitis B at birth. There is no evidence that low concentrations of lamivudine in breast milk cause side effects in breastfed babies. Breastfed infants whose mothers received HIV therapy have very low serum lamivudine concentrations (less than 4% of the mother's serum concentration), which slowly decline to levelsundetectable after 24 weeks. The total amount of lamivudine that a baby receives through breast milk is very low, which may result in exposure that is not effective antiviral.
Oral solution
There is limited information available on the safe use of lamivudine during pregnancy. Lamivudine crosses the placenta. Serum concentrations of lamivudine in neonates at birth are the same as in umbilical cord blood and maternal serum.
Before using Zeffix during pregnancy, it is necessary to balance the potential benefits to the mother and the possible risk to the fetus. After taking the drug, lamivudine concentrations in breast milk were similar to those in serum (1–8 μg / ml).
Pediatric use
According to the instructions, Zeffix in the form of tablets is contraindicated in children under 18 years of age.
The drug in the form of a solution for children under 2 years of age is prescribed only according to the strict indications of a doctor and under close medical supervision.
With impaired renal function
Zeffix in tablet form is contraindicated in patients with creatinine clearance less than 50 ml / min.
For violations of liver function
If liver failure is not accompanied by renal failure, dose adjustment of Zeffix is not required.
Drug interactions
- sulfamethoxazole (160 mg) + trimethoprim (800 mg): increases the exposure of lamivudine by approximately 40%;
- zidovudine: increased C max of zidovudine;
- interferon-alpha: no pharmacokinetic interaction of lamivudine with interferon-alpha with the simultaneous use of these drugs was observed;
- emtricitabine, cladribine: inhibits intracellular phosphorylation of the latter.
Analogs
Zeffix analogs are: Amiviren, Virolam, Heptavir-150, Lamivudin, Lamivudin Canon, Lamivudin-ZTS, Lamivudin-Vial, Lamivudin-Teva, Epivir.
Terms and conditions of storage
Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Shelf life:
- tablets - 3 years;
- solution - 2 years. After opening the bottle, use within 1 month.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Zeffix
At the moment, there are few reviews about Zeffix, indicating the effectiveness of the drug.
Price for Zeffix in pharmacies
The price of Zeffix in the form of tablets is approximately 3300 rubles, the cost of the drug in the form of a solution is not presented in this instruction.
Zeffix: prices in online pharmacies
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Drug name Price Pharmacy |
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Zeffix 100 mg film-coated tablets 28 pcs. RUB 810 Buy |
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Zeffix tablets p.o. 100mg 28 pcs. 1602 RUB Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
