Victrelis

The effectiveness of Viktrelis in chronic hepatitis C (genotype 1) was evaluated in approximately 1.5 thousand patients who had not previously received therapy, or with ineffective previous therapy, at the 3rd stage of clinical testing. [1]

During both tests, the use of a drug in addition to the existing treatment regimen (ribavirin with peginterferon-α) significantly increased the sustained virological response values (compared to using the standard therapeutic regimen exclusively). [2]

Indications Victrelis

It is used in the case of a chronic form of hepatitis C , developing under the influence of a virus of the 1st genotype, in combination with ribavirin and peginterferon-α (in persons with compensated hepatic impairment , with ineffective previous therapy or who have not received treatment before).

Release form

The release of the drug substance is made in capsules - 12 pieces inside the cell pack; inside the box - 7 such packs.

Pharmacodynamics

Boceprevir is a viral NS3 protease inhibitor (type C hepatitis). The substance is reversibly covalently synthesized with serine inside the active site (type 139) of the NS3 protease through the (α) -ketoamide functional category, slowing down viral replication inside the affected cells. [3]

Pharmacokinetics

Suction.

The average Tmax of boceprevir when administered orally is 2 hours. The equilibrium level of AUC, Cmax and Cmin increases in smaller values than proportionally to the dosage, and their separate exposures were sometimes superimposed (mainly at 0.8 and 1.2 g portions), which allows one to determine a decrease in absorption at higher dosages. The accumulation of the drug is minimal, equilibrium pharmacokinetic parameters are noted after about 1 day with the use of drugs 3 times a day.

Viktrelis is consumed with food. In the case of taking with food, the exposure values of boceprevir increase by 60% with a portion of 0.8 g 3 times per day (in comparison with taking on an empty stomach).

Distribution processes.

The average equilibrium values of the apparent distribution volume of boceprevir are 772 liters. With a single use of the drug in a 0.8 g portion, protein synthesis is approximately 75%.

Boceprevir is used as a combination of 2 diastereoisomers in approximately equal proportions; they are rapidly mutually transformed within the blood plasma. At equilibrium values, the ratio of the exposure level of diastereoisomers is approximately 2k1 (the diastereoisomer demonstrating therapeutic activity predominates).

Biotransformation.

In vitro tests demonstrate that boceprevir is mainly involved in metabolic processes with the help of AKP. As a result, ketone-reduced metabolic products are formed that are not active against the hepatitis C virus.

With a single oral administration of 0.8 g of 14C-labeled boceprevir, a diastereoisomeric combination of ketone-reduced degradation products was most often formed with an average exposure index approximately four times higher than the value of boceprevir. Boceprevir is less actively involved in oxidative metabolic processes carried out with the help of CYP3A4 / 5.

Excretion.

Boceprevir is excreted with an average plasma half-life of approximately 3.4 hours. The average values of the systemic clearance of the substance are approximately 161 l / h.

With a single oral administration of 0.8 g of 14C-labeled boceprevir, about 9% and 79% of the total dosage are excreted in urine and feces, respectively. Another 3% and 8% of the introduced radiocarbon is excreted in the form of boceprevir with urine and feces. Excretion of Viktrelis is mainly realized through the liver.

Dosing and administration

The appointment of therapy and monitoring its progress should be carried out by a doctor who has experience in the treatment of chronic hepatitis type C.

Viktrelis is used together with ribavirin and peginterferon-α. The medicine is usually prescribed in 0.8 g portions, 3 times a day with food. A maximum of 2.4 g of the drug is allowed per day. When consumed outside of food, therapeutic efficacy may be diminished due to the lack of the required exposure index.

The recommended duration of treatment is 48 weeks. The cycle includes 1 month of 2nd treatment with PegIFN + RBV and 44 weeks of 3rd treatment with PegIFN + RBV and Viktrelis.

The duration of the 3rd treatment after the first month of the 2nd treatment should be at least 32 weeks. In connection with the increasing likelihood of developing negative signs of the drug (especially anemia), in cases where the patient is not able to tolerate therapy, it is possible to consider the option of carrying out the 2nd treatment instead of the 3rd one during the last 3 months.

Missed portions.

If you skip the use of drugs, if less than 2 hours are left before taking a new dosage, you do not need to use the missed one.

With an interval of more than 2 hours before using a new portion, the patient should take the missed dose with food and resume the standard regimen of medication.

• Application for children

You can not use the medicine in pediatrics.

Use Victrelis during pregnancy

It is forbidden to use the drug during pregnancy. If you need to use drugs during hepatitis B, you need to stop breastfeeding for the period of therapy.

Contraindications

The main contraindications of the drug in combination with ribavirin and peginterferon-α:

• high intolerance to the active and auxiliary elements of the drug;
• autoimmune hepatitis;
• administration together with drugs whose clearance is associated with CYP3A4 / 5, and the increased plasma values of which cause severe and life-threatening negative manifestations - taken orally triazolam with midazolam, halofantrine, bepridil and lumefantrine with pimozide, as well as substances that slow down tyrosine kinase ( ergonovine, dihydroergotamine and methylergonovine with ergotamine);
• all contraindications related to ribavirin and peginterferon-α;
• lack of Lapp lactase, hereditary galactosemia and glucose-galactose malabsorption.

Side effects Victrelis

Most often, with the complex use of Viktrelis with ribavirin and peginterferon-α, nausea, weakness, cephalalgia and anemia develop. The dosage must be reduced most often when anemia develops.

Overdose

An increase in the daily portion up to 3.6 g taken over a period of 5 days did not cause the development of negative manifestations.

The medicine has no antidote. In case of poisoning with Viktrelis, general supportive procedures are carried out, including monitoring the basic functions of the body and the clinical condition of the patient.

Interactions with other drugs

The drug greatly slows down the activity of CYP3A4 / 5. Substances that are involved in metabolic processes mainly with the help of CYP3A4 / 5 can receive an increased exposure when administered with Viktrelis, which can prolong or potentiate their side effects and therapeutic effect.

The drug is partially exposed to metabolic processes using CYP3A4 / 5. The introduction of drugs in combination with drugs that induce CYP3A4 / 5 can increase or decrease the level of its bioavailability.

The administration of a medication with rifampicin or anticonvulsants (among them phenobarbital, phenytoin or carbamazepine) can significantly reduce the parameters of its plasma bioavailability. It is forbidden to use boceprevir in combination with such medications.

It is necessary to combine the drug with great care with substances that prolong the QT-interval (among them methadone, amiodarone, pentamidine with quinidine and certain antipsychotics).

Storage conditions

Viktrelis must be kept in a place closed from the penetration of children. Temperature indicators are in the range of 2-8 ° C. For 3 months, the medicine can be stored in the original cell pack at temperatures up to 30 ° C.

Shelf life

Viktrelis can be used for a 24-month term from the date of manufacture of the medicinal product.

Analogs

Analogues of drugs are Presista, Kemeruvir with Aptivus, Kaletra and Arlansa with Sunvepra, and in addition, Atazanavir, Norvir with Ritonavir and Invirase. Also on the list is Shimanod with Telzir.