Maviret - a new drug for the treatment of hepatitis C

Maviret is an innovation in the treatment of chronic hepatitis C.

This combination of two direct-acting antiviral drugs can be used to treat ChGS infection of all major genotypes for 8 weeks and is highly effective, including for treatment-resistant variants of the virus, said Dr. Michael Severino, executive vice president for research and development and chief science officer of AbbVie. - A new short 8-week course of therapy is able to meet the diverse needs of patients in Europe.

Maviret can be used in difficult treatment groups of patients, including patients with chronic hepatitis C with compensated liver cirrhosis, advanced advanced chronic kidney disease, or chronic hepatitis C genotype 3 (GT3). Maviret is a pangenotypic combination approved for use in patients with chronic hepatitis C and concomitant chronic kidney disease of any stage.

Composition and release form

Oblong biconvex tablets, film-coated pink color with "NXT" engraving on one side.

  1. Active ingredients: Glekaprevir 100.0 mg, pibrenthasvir 40.0 mg
  2. Excipients: copovidone K 28, D-alpha-tocopherol macrogol succinate, colloidal silicon dioxide, croscarmellose sodium. sodium fumarate, propylene glycol monocaprylate type II; film coating Opadry II pink (Opadryu II 32F240023) '. hypromellose 2910. lactose monohydrate, titanium dioxide, macrogol 3350, iron oxide red.

Indications for use

According to the instructions, absolutely all patients with HCV 1-6 genotypes can purchase a combination drug for the purpose of treatment. Direct indications for its use are:

  • hepatitis C in chronic forms of the course, provided that an infected person at the time of initiation of therapy is already eighteen years old;
  • cirrhosis in the stage of compensation;
  • relapse of pathology after a previously completed therapeutic course;
  • genotype mutations in connection with previously used active substances, which are the basis of drugs.

Maviret does not contain gluten. Therefore, it is suitable for the treatment of those people who are forced to be on a specific diet.

Mechanism of action

Maviret is a combination of two fixed-dose pangenotypic antivirals of fixed effect, glekapsrsira (protease inhibitor NS3 / 4A) and pibrentasvir (NS5A inhibitor), affecting different stages of the life cycle of the hepatitis C virus.

  1. Glekaprevir. It is an inhibitor of the protease of the hepatitis C virus (HCV) NS3 / 4A. which is necessary for the proteolytic cleavage of the hepatitis C virus-encoding polyprotein (for further transformation of the NS3, NS4A, NS4B, NS5A, and NS5B proteins into mature forms) and is essential for viral replication. In biochemical studies, glakprevir inhibited the proteolytic activity of recombinant proteases of the hepatitis C virus NS3 / 4A from clinical isolates of the virus of the la, lb, 2a, 2b, Za, 4a genotypes. 5a and 6a with IC50 values ​​from 3.5 to 11.3 nM.
  2. Pybrentasvir. It is a pangenotypic inhibitor of the NS5A protein of the hepatitis C virus, which is necessary for viral RNA replication and virion assembly. The mechanism of action of pibrentasvir was studied in the course of antiviral activity studies on cell cultures and studies to determine the nature of drug resistance.

As a result of this tandem, the main vital function of the hepatitis C virus of all genotypes in people who are carriers of the disease is blocked. Consequently, the pathogen loses the ability to reproduce itself and further infect healthy liver cells.

Instructions for use

Tablets are taken orally, once a day with food. The components of the drug do not react with food, act exclusively on the liver cells affected by the virus, and are quickly excreted in the urine without causing intoxication.

To compile the optimal treatment regimen, a competent specialist will need the results of PCR studies on genotyping. Depending on the identified genotype (1, 2, 3, 4, 5 or 6), an individual course of treatment is developed. If you suspect cirrhosis of the liver, it is necessary to conduct elastography - the only hardware technique that allows to obtain reliable information about the presence of cirrhosis and its degree. Ultrasound in this situation is not informative, so its implementation is not appropriate.

Contraindications

The drug has certain contraindications:

  1. Hypersensitivity to any active substance of the drug or to any of the excipients.
  2. Patients with severe hepatic impairment (class C on the Child-Pugh scale).
  3. Children's age up to 18 years.
  4. Lactase deficiency, lactose deficiency, glucose-galactose malabsorption.
  5. Combined use with the following drugs: atazanavir. atorvastatin, simvastatin, dabigatran etexilate, preparations containing estradiol, strong inducers of P-glycoprotein and CYP3A, for example, rifampicin, carbamazepine, drugs of Hypericum perforated Hypericum perjoratum, phenobarbital, phenytoin, martiromas, patterns, patterns, patterns, marines, phenytocaphene, phenytoin, marts, Hypericum perjoratum; .

Maviret is not recommended for use in combination with omeprazole (40 mg), darunavir / ritonavir, efavirenz, lopinavir / ritonavir, lovastatin, cyclosporine (> 100 mg per day).

The drug Maviret should be used with caution with the following drugs: digoxin, pravastatin, rosuvastatin, fluvastatin, pitavastatin, tacrolimus.

Use during pregnancy and breastfeeding

Data on the use of glekapsrsvira or pibrentasvir in pregnant women is limited or absent. During the study there were less than 300 cases of pregnancy. Studies of Glekaprsvir and Pibrentasvir in rats and mice did not demonstrate the presence of a direct toxic effect on the reproductive function. The presence of toxic effects on the pregnant female with a subsequent miscarriage was observed in rabbits when using glekapsrsira. which excluded the possibility of further research. As a precaution, the drug Maviret is not recommended for use during pregnancy.

It is not known whether Glekprevir or Pybrentasvir is excreted in breast milk. The available data from pharmacokinetic studies in animals have shown the excretion of Glekapsirsira and Pibrentasvir with milk, therefore the risk for newborns and children of the first year of life cannot be excluded. A decision should be made either to stop breastfeeding, or to stop or refrain from therapy with Maviret, taking into account the ratio of benefits of breastfeeding to the child and the benefits of therapy for the woman. Fertility

Studies on the effect of Glekapsrsvir and / or Pibrentasvir on fertility in humans have not been conducted. Studies in animals did not show a negative effect of Glecapsvir or Pibrentasvir on fertility with exposure exceeding the values ​​achieved in patients as a result of taking the recommended doses of drugs.

Side effects

Despite the almost complete safety of this drug, it is characteristic in isolated cases and side effects. Usually patients during the course of the course noted:

  • increased fatigue and fatigue in 11% of all;
  • dizziness and headache (10%);
  • violations in the gastrointestinal tract (3%);
  • nausea (6%);
  • elevated bilirubin (3%).

Overdose

The highest documented dose taken by healthy volunteers was 1200 mg once a day for 7 days for glekapsrsira and 600 mg once a day for 10 days for pibrentasvir. An asymptomatic increase in serum ALT (> 5 times VGN) was observed in 1 of 70 healthy volunteers after taking several doses of glekapsrsira (700 mg or 800 mg) 1 time per day for> 7 days.

In case of overdose, it is necessary to monitor the patient's condition for signs of toxic damage (see the “Side Effects” section). Appropriate symptomatic treatment should be started immediately. Hemodialysis to a small extent contributes to the release of glekapsrsira and pybentasvir from the body.

Special instructions

Reactivation of viral hepatitis B. During treatment with direct-acting antiviral drugs, reactivation of the hepatitis B virus has been reported, in some cases fatal. Before starting therapy, all patients should be screened for HBV. Patients with HBV / HCV co-infection are at risk of HBV reactivation. therefore, they should be monitored and maintained in accordance with current guidelines.

Patients after liver transplantation. The safety and efficacy of the use of the drug Maviret in patients undergoing liver transplantation have not been evaluated. Treatment with Maviret in accordance with the recommended route of administration and dosage (see section “Dosage and administration”) should be based on an assessment of the potential benefits and risks for each individual patient.

Liver dysfunction. The drug Maviret is not recommended for patients with moderate hepatic insufficiency (grade B on the Child-Pugh scale) and is contraindicated in patients with severe hepatic insufficiency (Grade C on the Child-Pugh scale) (see "Dosage and administration", "Contraindications ").

Patients who did not respond to a previous treatment regimen, including NS5A and / or NS3 / 4A inhibitors. The likelihood of the development of resistance to glecaprevir / pibrentasvir in patients infected with the genotype 1 virus and a limited number of patients infected with the genotype 4 virus who did not respond to the previous treatment regimen was studied. As expected, the risk of treatment failure was higher in patients with prior therapy involving both classes of drugs (NS5A and NS3 / 4A inhibitors). The methodology for predicting treatment failure based on baseline data on resistance to therapy has not been determined. The development of resistance to both classes of drugs was a major finding in patients who did not respond to therapy with glecaprevir / pibrentasvir. Data on the re-treatment of patients infected with genotypes 2, 3, 5 and 6 are absent. Use of the drug Maviret is not recommended for re-treatment of patients previously treated with NS3 / 4A and / or NS5A inhibitors.

Price per course of treatment Maviret

In Moscow, the price Maviret is at 360.000 rubles. for 1 box (84 tablets. glecaprevir 100 mg / pibrentasvir 40 mg). It is enough for 4 weeks of treatment. In Europe, the cost of the drug in the region of 15 000 euros.

Storage conditions

Storage of the drug does not take complexity: Maviret retains all the properties at temperatures up to + 25 ° C with low humidity. Shelf life 2 years. Do not use after the expiration date printed on the package.

Terms of sale

Prescription.

Organization authorized to accept claims

  • LLC EbBVi, Russia
  • 125047, Moscow, st. Lesnaya, 7,
  • BC "White Gardens" building "A"
  • tel. (495) 258 42 77
  • fax (495) 258 42 87

Watch the video: Hepatitis C. Nucleus Health (December 2019).

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