Victrelis

The efficacy of Victrelis in chronic hepatitis C (genotype 1) was assessed in approximately 1,500 patients who had not previously undergone therapy or had ineffective previous therapy, in the 3rd stage of clinical trials. [ 1 ]

In both trials, using the drug in addition to the existing treatment regimen (ribavirin with peginterferon-α) significantly increased SVR rates (compared to using the standard treatment regimen alone).[ 2 ]

Indications Victrelis

It is used in cases of chronic hepatitis C, developing under the influence of the 1st genotype virus, in combination with ribavirin and peginterferon-α (in individuals with compensated liver damage, with ineffective previous therapy or who have not undergone treatment previously).

Release form

The medicinal substance is released in capsules - 12 pieces inside a cell pack; inside a box - 7 such packs.

Pharmacodynamics

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

Pharmacokinetics

Suction.

The mean Tmax of boceprevir after oral administration is 2 hours. Steady-state AUC, Cmax, and Cmin increase less than proportionally with dose, and their individual exposures sometimes overlap (mostly with 0.8 and 1.2 g doses), suggesting decreased absorption at higher doses. Drug accumulation is minimal, with steady-state pharmacokinetic parameters observed after approximately 1 day of 3-times-daily dosing.

Victrelis is taken with food. When taken with food, boceprevir exposure values are increased by 60% with a 0.8 g dose 3 times daily (compared to taking on an empty stomach).

Distribution processes.

The mean apparent distribution volume at steady state for boceprevir is 772 L. With a single 0.8 g dose of the drug, protein synthesis is approximately 75%.

Boceprevir is administered as a combination of two diastereoisomers in approximately equal proportions; they rapidly interconvert within the blood plasma. At steady state, the diastereoisomer exposure ratio is approximately 2:1 (with the diastereoisomer demonstrating therapeutic activity predominating).

Biotransformation.

In vitro tests demonstrate that boceprevir is primarily metabolized by ACR, resulting in the formation of ketone-reduced metabolic products that are inactive against hepatitis C virus.

A single oral dose of 0.8 g of 14C-labeled boceprevir resulted in the formation of a diastereomeric combination of ketone-reduced degradation products with an average exposure approximately four times that of boceprevir. Boceprevir is less active in oxidative metabolism mediated by CYP3A4/5.

Excretion.

Boceprevir is excreted with a mean plasma half-life of approximately 3.4 hours. Mean systemic clearance values are approximately 161 L/hour.

Following a single oral dose of 0.8 g of 14C-labeled boceprevir, approximately 9% and 79% of the total dose is excreted in urine and faeces, respectively. An additional approximately 3% and 8% of the administered radiocarbon is excreted as boceprevir in urine and faeces. Victrelis is primarily eliminated via the liver.

Dosing and administration

Therapy should be prescribed and monitored by a physician experienced in treating chronic hepatitis C.

Victrelis is used together with ribavirin and peginterferon-α. The drug is usually prescribed in a dose of 0.8 g, 3 times a day with food. A maximum of 2.4 g of the drug is allowed per day. When used without food, the therapeutic efficacy may be weakened due to the lack of the required exposure rate.

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

The duration of the 3rd treatment after the first month of the 2nd treatment should be at least 32 weeks. Due to the increased likelihood of developing adverse effects of the drug (especially anemia), in cases where the patient is unable to tolerate therapy, the option of administering the 2nd treatment instead of the 3rd during the last 3 months can be considered.

Missed portions.

If you miss a dose of the medicine, if there are less than 2 hours left before taking the next dose, you do not need to take the missed dose.

If the interval is more than 2 hours before taking a new dose, the patient should take the missed dose with food and resume the standard regimen of taking the medication.

• Application for children

The medicine cannot be used in pediatrics.

Use Victrelis during pregnancy

It is prohibited to use the drug during pregnancy. If it is necessary to use the drug during breastfeeding, you should stop breastfeeding for the period of therapy.

Contraindications

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

• high intolerance to the active and auxiliary elements of the drug;
• autoimmune hepatitis;
• co-administration with drugs whose clearance is associated with CYP3A4/5 and whose increased plasma levels cause severe and life-threatening adverse effects - orally administered triazolam with midazolam, halofantrine, bepridil and lumefantrine with pimozide, as well as tyrosine kinase inhibitors and ergot derivatives (ergonovine, dihydroergotamine and methylergonovine with ergotamine);
• all contraindications related to ribavirin and peginterferon-α;
• Lapp lactase deficiency, hereditary galactosemia and glucose-galactose malabsorption.

Side effects Victrelis

The most common side effects of Victrelis combined with ribavirin and peginterferon-α are nausea, weakness, headache, and anemia. Dosage reduction is most often necessary when anemia develops.

Overdose

Increasing the daily dose to 3.6 g with intake over a period of 5 days did not cause the development of negative manifestations.

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

Interactions with other drugs

The drug significantly slows down the activity of CYP3A4/5. Substances that participate in metabolic processes mainly through CYP3A4/5 may have increased exposure when administered with Victrelis, which can prolong or potentiate their side effects and therapeutic effect.

The drug is partially metabolized by CYP3A4/5. Administration of the drug in combination with drugs that induce CYP3A4/5 may increase or decrease its bioavailability.

Administration of the drug with rifampicin or anticonvulsants (including phenobarbital, phenytoin or carbamazepine) may significantly reduce its plasma bioavailability. It is prohibited to use boceprevir in combination with such drugs.

The drug should be combined with substances that prolong the QT interval (including methadone, amiodarone, pentamidine with quinidine and certain neuroleptics) with great caution.

Storage conditions

Victrelis should be stored in a place closed to children. Temperature indicators are within 2-8 ° C. The medicine can be stored in the original blister pack for 3 months at temperatures up to 30 ° C.

Shelf life

Victrelis can be used for a period of 24 months from the date of manufacture of the medicinal product.

Analogues

The analogs of the drug are Prezista, Kemeruvir with Aptivus, Kaletra and Arlansa with Sunvepra, and in addition Atazanavir, Norvir with Ritonavir and Invirase. Also on the list are Simanod with Telzir.