Vikeira Pak

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Vikeira Pak: 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. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Viekira Pak

ATX code: J05AX66

Active ingredient: Dasabuvir (Dasabuvir); Ombitasvir + Paritaprevir + Ritonavir (Ombitasvir + Paritaprevir + Ritonavir)

Manufacturer: Dasabuvir tablets - AbbVi Ireland NL B. V. (AbbVie Ireland NL V. W.) / Manorhamilton Road, Sligo (Ireland); Tablets (Ombitasvir + Paritaprevir + Ritonavir) - Foumier Laboratories Ireland Limited / Engrove, Carrigtwohill, Co. Cork (Anngrove, Carrigtwohill, Co. Cork) (Ireland)

Description and photo updated: 25.12.2018

Prices in pharmacies: from 79,500 rubles.

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Vikeira Pak is an antiviral complex drug containing three active components with different mechanisms of action and non-overlapping resistance profiles for the treatment of HCV (viral hepatitis C) at different stages of its life cycle in combination with ritonavir as a pharmacokinetic enhancer of paritaprevir.

Release form and composition

Vikeira Pak is available as a set of film-coated tablets:

tablets 1 - pink, oblong, biconvex, engraved "AV1" on one side;
tablets 2 - light brown, oval, engraved "AV2" on one side.

2 pink and 2 light brown tablets each in blisters of PVC / PE / PCTFE and Al foil, 7 blisters in a cardboard box, in a cardboard box 4 packs and instructions for use of Vikeira Pak.

Composition for 1 pink film-coated tablet (ombitasvir + paritaprevir + ritonavir):

active ingredients: ombitasvir hydrate (1 ÷ 4.5) - 13.6 mg, in terms of ombitasvir - 12.5 mg; paritaprevir dihydrate - 78.5 mg, in terms of paritaprevir - 75 mg; ritonavir - 50 mg;
auxiliary components: D-α-tocopherol macrogol succinate - 42.5 mg; copovidone - 849.2 mg; colloidal silicon dioxide - 10.8 mg; sorbitan laurate - 33.3 mg; propylene glycol monolaurate - 10 mg;
film coating: Opadry II pink (Opadry II Pink) - 32.5 mg (polyvinyl alcohol - 46.94%; macrogol 3350 - 23.7%; talc - 17.36%; titanium dioxide - 11.9%; iron oxide red - 0.1%).

Composition for 1 light brown film-coated tablet (dasabuvir):

active substance: dasabuvir sodium monohydrate - 270.26 mg, in terms of dasabuvir - 250 mg;
auxiliary components: microcrystalline cellulose (Avicel PH102) - 104.72 mg; microcrystalline cellulose (Avicel PH101) - 103.04 mg; lactose monohydrate - 47.3 mg; croscarmellose sodium - 33.78 mg; copovidone - 101.35 mg; magnesium stearate - 11.15 mg; colloidal silicon dioxide - 4.05 mg;
film shell: Opadry II beige (Opadry II Beige) - 21 mg (polyvinyl alcohol - 40%; titanium dioxide - 21.55%; macrogol 3350 - 20.2%; talc - 14.8%; iron oxide yellow - 3%; iron oxide red - 0.35%; iron oxide black - 0.1%).

Pharmacological properties

Pharmacodynamics

The therapeutic effect of Vikeira Pak combines the activity of three direct-acting antiviral substances aimed at the treatment of hepatitis C virus (HCV), with various ways of interacting with specific binding sites and with non-overlapping resistance profiles (which makes it possible to fight the hepatitis C virus at different stages of its life cycle), as well as a protease inhibitor, which is a pharmacokinetic enhancer for one of the antiviral components.

Pharmacodynamic properties of Vikeira Pak components:

dasa6uvir: a non-nucleoside inhibitor of viral RNA replicase (RNA-dependent RNA polymerase) encoded by the NS5B gene (non-structural protein 5A) required for viral genome replication. According to biochemical studies, dasabuvir inhibits the polymerase activity of the recombinant protein NS5B of HCV genotype 1a viruses with an inhibitory concentration of IC ₅₀ = 2.8 nM and genotype 1b with an IC ₅₀ value of 10.7 nM;
ombitasvir: an inhibitor of the HCV NS5A protein, which is essential for viral replication. In studies using replicon cell cultures, the EC ₅₀ values of ombitasvir for HCV genotype 1a were 14.1 nM, for genotype 1b - 5.0 nM;
paritaprevir: an inhibitor of HCV protease NS3 / 4A, which is necessary in the process of proteolytic cleavage of the HCV polyprotein encoded by the non-structural zone RNA (into mature forms of non-structural proteins NS3, NS4A, NS4B, NS5A, NS5B) plays an important role in viral replication. According to biochemical analyzes, paritaprevir inhibits the proteolytic activity of the NS3 / 4A protease with a value for the recombinant HCV genotype 1a EC ₅₀ = 0.18 and for genotype 1b EC ₅₀ = 0.43 nM;
ritonavir: having no antiviral activity against HCV, it acts as a pharmacokinetic enhancer that increases the peak concentration of paritaprevir in blood plasma and its level, measured immediately before taking the next dose, thereby increasing the total exposure of the drug (AUC - area under the pharmacokinetic curve "concentration - time").

Pharmacokinetics

Studies of the pharmacokinetic characteristics of the combination of ombitasvir + paritaprevir + ritonavir with dasabuvir were carried out in a control group of healthy adult volunteers and in a group of patients with chronic hepatitis C.

In a group of healthy volunteers, the mean values of the maximum concentration (Cmax) and AUC of ombitasvir, paritaprevir, ritonavir in combination with dasabuvir, obtained after taking several doses with food, were:

dasabuvir (250 mg twice daily): Cmax - 1030 ng / ml [CV (coefficient of variation) 31%]; AUC - 6840 ng × h / ml (CV 32%);
ombitasvir (25 mg once a day): Cmax - 127 ng / ml (CV 31%); AUC - 1420 ng × h / ml (CV 36%);
paritaprevir (150 mg once a day): Cmax - 1470 ng / ml (CV 87%); AUC - 6990 ng × h / ml (CV 96%);
ritonavir (100 mg once a day): Cmax - 1600 ng / ml (CV 40%); AUC - 9470 ng × h / ml (CV 41%).

Note: AUC ₂₄ - ombitasvir, paritaprevir and ritonavir; AUC ₁₂ - dasabuvir.

Absorption in the gastrointestinal tract

After taking the drug, all active components of Vikeira Pak are absorbed inside with an average Tmax (time to reach Cmax in blood plasma) of 4-5 hours. An increase in the exposure of ombitasvir and dasabuvir is equivalent to the dose taken, their cumulation coefficient is minimal. The exposure of paritaprevir and ritonavir increases more than proportionally to the dose, the cumulation coefficient is from 1.5 to 2. The equilibrium concentration of the drug components in the blood (Css) is reached approximately 12 days after the start of therapy.

When using Vikeira Pak, the absolute bioavailability of ombitasvir, paritaprevir and dasabuvir is ~ 50%, for dasabuvir ~ 70%.

Taking the drug with food increases the AUC of ombitasvir by 82%, paritaprevir by 211%, ritonavir by 49% and dasabuvir by almost 30%, in relation to fasting. The increase in exposure is independent of diet or calorie content (ranging from 600 to 1000 kcal). Vikeira Pak is required to be taken with food, regardless of its fat / calorie content, in order to maximize the bioavailability of the components.

The metabolic processes of the active substances in Vikeira Pak were studied by the method of tagged atoms using the radioactive isotope of carbon C ¹⁴, based on the identification, fixation and measurement of the radiation of radioactive isotopes. That allows you to track the absorption, movement in the body, cumulation in individual tissues, biochemical transformations and excretion of the studied components from the body.

In all clinical trials, Vikeira Pak was taken simultaneously with food.

Distribution to tissues and organs

All active components of Vikeira Pak actively bind to blood plasma proteins. Impaired renal / liver function practically does not affect the degree of binding. The ratio of levels in the blood and in the blood plasma indicates the predominant distribution of substances in the blood plasma and is in humans: ombitasvir - 0.49; paritaprevir - 0.7; ritonavir - 0.6; dasabuvir - 0.7.

Connection of active substance with human blood plasma proteins ÷ concentration range:

dasabuvir: more than 99.9% ÷ 0.15-5 mcg / ml;
ombitasvir: approximately 99.5% ÷ 0.09-9 mcg / ml;
paritaprevir: approximately 97–98.6% ÷ 0.08–8 mcg / ml;
ritonavir: more than 99% ÷ 0.007-22 mcg / ml.

According to the results of experiments carried out on animals, the level of paritaprevir in the liver was significantly lower than its concentration in the blood plasma (for mice, this ratio was more than 300 ÷ 1). These in vitro results confirm that paritaprevir is a substrate for hepatic transporters of the OATP ₁ B ₁ and OATP ₁ B ₃ subfamilies.

Metabolism

dasabuvir: metabolized mainly by the CYP2C8 isoenzyme, to a lesser extent by the CYP3A isoenzyme. As a result of taking 400 mg in blood plasma in humans, unchanged dasabuvir was the main component of ~ 60%, in addition to it, seven metabolites were found. The most common metabolite, M1 - 21% of AUC, in vitro showed properties similar to the parent drug (including binding to blood plasma proteins) in relation to HCV genotype 1;
ombitasvir: Metabolism occurs through amide hydrolysis followed by oxidation. As a result of taking a single dose of 25 mg (without other drugs) in the form of an unchanged substance in the blood plasma, 8.9% of the total volume was found, in addition, 13 metabolites were identified that did not exhibit either antiviral or other pharmacological activity;
paritaprevir: metabolized mainly by the CYP3A4 isoenzyme, to a lesser extent by the CYP3A5 isoenzyme. As a result of taking a single dose of 200/100 mg paritaprevir / ritonavir, unchanged paritaprevir was the main component in blood plasma ~ 90%. In addition to it, at least 5 insignificant metabolites (~ 10%), which do not have antiviral activity, have been identified;
ritonavir: metabolized predominantly by the CYP3A isoenzyme, to a lesser extent by the CYP2D6 isoenzyme. As a result of oral administration at a single dose of 600 mg, up to 100% unchanged ritonavir was found in blood plasma.

Excretion

dasabuvir: After oral administration of Vikeira Pak, the mean elimination half-life (T _1/2) of dasabuvir is ~ 5.5-6 hours. When dasabuvir was taken at a dose of 400 mg, ~ 94.4% of the substance was found in feces and a small amount (~ 2%) in urine. Including unchanged up to 26% in feces and 0.03% in urine;
Ombitasvir: After taking an ombitasvir / paritaprevir / ritonavir tablet with or without a dasabuvir tablet, the average T1 _{/ 2 of} ombitasvir is about 21-25 hours. When taking ombitasvir at a dose of 25 mg, up to 90.2% of the dose taken was found in feces, a small amount in urine - 1.91%. Including unchanged form up to 87.8% in feces and 0.03% in urine;
paritaprevir: after taking an ombitasvir / paritaprevir / ritonavir tablet with or without a dasabuvir tablet, the mean T _{1/2 of} paritaprevir from blood plasma is ~ 5.5 hours. After the combined use of 200 mg of paritaprevir with 100 mg of ritonavir, up to 88% of the dose taken was found in the feces, and a small amount in the urine - 8.8%. Including in unchanged form up to 1.1% of paritaprevir was found in feces and 0.05% in urine;
ritonavir: after taking the ombitasvir / paritaprevir / ritonavir tablet, the mean plasma T1 _{/ 2 of} ritonavir was ~ 4 hours. When ritonavir was taken as a solution for oral administration at a dose of 600 mg, up to 86.4% of the dose taken was found in feces, and 11.3% in urine.

Pharmacokinetic characteristics in special patient groups

Age, sex, body weight, race and ethnicity of patients do not affect the pharmacokinetics of Vikeira Pak and do not require dosing regimen correction.

In pediatric practice, the safety and efficacy of the drug has not been studied.

Changes in the main pharmacokinetic characteristics with impaired hepatic function in comparison with patients with normal liver function, when taking a combination that includes paritaprevir - 200 mg, ritonavir - 100 mg, ombitasvir - 25 mg, dasabuvir - 400 mg:

mild hepatic failure (class A on the Child-Pugh scale): average Cmax and AUC decreased in paritaprevir - by 29–48%, ritonavir - by 34–40%, ombitasvir - up to 8%; for dasabuvir, the average Cmax and AUC increased by 17-24%;
the average degree of hepatic failure (class B on the Child-Pugh scale): the average Cmax and AUC increased for paritaprevir - by 26–62%; mean Cmax and AUC decreased for ombitasvir - by 29–30%, ritonavir - by 30–33%, dasabuvir - by 16–39%;
severe hepatic impairment (class C on the Child-Pugh scale): mean values of Cmax and AUC increased for paritaprevir by 3.2–9.5 times, for dasabuvir by 0.3–3.3 times; for ritonavir, Cmax was 35% lower and AUC was 13% higher; for ombitasvir Cmax decreased by 68%, AUC decreased by 54%.

Vikeira Pak should not be prescribed to patients with moderate to severe hepatic impairment (classes B and C on the Child-Pugh scale).

Changes in the main pharmacokinetic characteristics in case of impaired renal function, depending on the CC value (creatinine clearance), in comparison with patients with normal renal function, when taking a combination including paritaprevir - 200 mg, ritonavir - 100 mg, ombitasvir - 25 mg with dasabuvir c dose of 400 mg or without:

mild renal failure (CC 60–89 ml / min): the average Cmax and AUC were comparable for paritaprevir (above ~ 19%) and ombitasvir (below ~ 7%); the average Cmax and AUC values for ritonavir were higher by 26–42%, for dasabuvir - by 5–21%;
the average degree of renal failure (CC 30-59 ml / min): for paritaprevir, the average Cmax values were comparable (higher than less than 1%), the average AUC values were 33% higher; the average Cmax and AUC values for ombitasvir were comparable (down to 12%), for ritonavir they were higher by 48–80%, for dasabuvir they were higher by 9–37%;
severe renal failure (CC 15-29 ml / min): for paritaprevir, the average Cmax values were comparable (higher than less than 1%), the average AUC values were 45% higher; the average Cmax and AUC values for ombitasvir were comparable (down to 15%), for ritonavir they were 66-114% higher, for dasabuvir they were 12-50% higher.

Patients with mild, moderate or severe renal insufficiency do not need to adjust the Vieira Pak dosage regimen, since the exposure of the main active components of the drug (paritaprevir + ombitasvir + dasabuvir and ritonavir) changes clinically insignificantly.

Indications for use

A set of tablets Vikeira Pak is used for the treatment of chronic hepatitis C genotype 1, including in patients with compensated cirrhosis of the liver, as monotherapy or in combination with ribavirin.

Contraindications

Absolute contraindications for using Vikeira Pak:

liver failure of moderate and severe degree (classes B and C on the Child-Pugh scale);
children and adolescents up to 18 years old;
galactose intolerance, secondary lactase deficiency, glucose-galactose malabsorption;
hypersensitivity to ombitasvir, paritaprevir, ritonavir and dasabuvir, as well as to any auxiliary components of the drug, the manifestation of which, for example, can be toxic epidermal necrolysis or Stevens-Johnson syndrome.

It is contraindicated to take Vikeira Pak simultaneously with the following substances / preparations:

drugs, an increase in the plasma level of which in the blood can cause serious adverse reactions and the clearance of which largely depends on metabolism through the CYP3A isoenzyme;
potent inhibitors of CYP2C8 (the combination can significantly increase the level of dasabuvir in blood plasma and the risk of prolongation of the QT interval);
powerful and moderate inducers of the CUR3A isoenzyme (a significant decrease in plasma levels of paritaprevir, ombitasvir and dasabuvir is possible);
powerful inducers of the CUR2C8 isoenzyme (a significant decrease in the level of dasabuvir in blood plasma is possible);
drugs containing ethinyl estradiol (combined oral contraceptives);
substrates of the CUR3A4 isoenzyme: amiodarone, alfuzosin, dronedarone, ranolazine, terfenadine, astemizole, colchicine (for renal / hepatic failure), ergot alkaloids (dihydroergotamine, methylergometrine, ergometrinator, ergidotinic acid, simatamidine / lovate) oral dosage forms), lurasidone, pimozide, quetiapine, quinidine, ticagrelor, cisapride, salmeterol, sildenafil (only for the treatment of pulmonary arterial hypertension);
inducers of the CUR3A4 isoenzyme: mitotane, rifampicin, phenytoin, carbamazepine, efavirenz, nevirapine, phenobarbital, etravirine, enzalutamide, St. John's wort (Hypericum perforatum);
inhibitors of the isoenzyme CUR3A4: cobicistat, indinavir, tipranavir, saquinavir, lopinavir / ritonavir, ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin, conivaptan;
inhibitor of isoenzyme CUR2C8: gemfibrozil;
drugs metabolized by the CUR3A4 isoenzyme: rilpivirine;
protease inhibitors, drugs for the treatment of human immunodeficiency virus (HIV): darunavir / ritonavir and atazanavir / ritonavir, used in a fixed combination.

With caution, Vikeira Pak is used in conjunction with fluticasone, other glucocorticosteroids, in the metabolism of which the CUR3A4 isoenzyme takes part; with antiarrhythmic drugs; and also with bepridil, disopyramide, flecainidine, lidocaine (with systemic administration), mexiletine, propafenone, erythromycin, dabigatran, diltiazem, fluvastatin, repaglinide, sulfasalazine, trazodone, fexofenadine, and deferifluxine.

In the case of a joint appointment of Vikeira Pak with ribavirin, it is necessary to take into account all contraindications to the use of ribavirin, which should be obtained by reading its instructions for use. The use of ribavirin for women during pregnancy is strictly prohibited, as well as for men whose partners are pregnant.

Vikeira Pak, instructions for use: method and dosage

Vikeira Pak tablets should be taken orally with food, regardless of its fat content or calorie content.

Recommended dose for adult patients: 1 time per day (in the morning) 2 tablets of ombitasvir / paritaprevir / ritonavir and 2 times a day (morning and evening) 1 tablet of dasabuvir. It is necessary to take pills in the recommended course, without interruption.

In some patient groups, Vieira Pak is used in combination with ribavirin.

Before starting the course of therapy, it is required to exclude decompensation of liver function on the basis of laboratory data and the study of clinical symptoms.

Recommended regimens and duration of treatment for different groups of patients (starting treatment for the first time or after using interferon):

genotype 1a without cirrhosis: Vieira Pak + ribavirin combination therapy, course duration - 12 weeks;
genotype 1a with cirrhosis: combination therapy with Vikeira Pak + ribavirin, course duration - 24 weeks (for some patients it is permissible to consider reducing the course duration to 12 weeks based on previous treatment);
genotype 1b, without cirrhosis: Vikeira Pak monotherapy, course duration - 12 weeks; a course of 8 weeks can be used in previously untreated patients with genotype 1b without severe fibrosis (stages F3 on the METAVIR scale) and cirrhosis (stages F4 on the METAVIR scale);
genotype lb with compensated cirrhosis, class A according to the Child-Pugh classification: Vikeira Pak monotherapy, course duration - 12 weeks.

When treating an unknown subtype of genotype 1 or genotype 1 mixed type, a dosing regimen for genotype 1a may be used.

The recommended dose of ribavirin in combination with Vikeira Pak depends on the patient's body weight and is: 1000 mg / day with a weight of ≤ 75 kg, 1200 mg / day with a weight> 75 kg. The daily dose of ribavirin is divided in half and taken simultaneously with food; correction, if necessary, is carried out in accordance with the instructions for use of ribavirin. The duration of use in combination treatment is the same for ribavirin and Vieira Pak.

If you miss taking an ombitasvir + paritaprevir + ritonavir tablet, the prescribed dose can be taken within 12 hours after the scheduled time. If you miss a tablet containing dasabuvir, the prescribed dose can be taken within 6 hours of the scheduled time. If more than 12 hours have passed since the scheduled time of taking the ombitasvir + paritaprevir + ritonavir tablet, or more than 6 hours for the dasabuvir tablet, do not take the missed doses. The following tablets are taken according to the usual schedule.

Side effects

Undesirable side effects from organs and systems (data from the results of clinical observations of patients taking Vikeira Pak as monotherapy or with ribavirin, compared with patients receiving placebo, in which adverse reactions occurred with a frequency of ≥ 5%):

skin and subcutaneous tissue: very often - itching;
hematopoietic and lymphatic systems: often - anemia;
digestive system: very often - nausea;
psyche: very often - insomnia;
general reactions: very often - weakness, fatigue;
laboratory parameters: deviations from the norm - an increase in the activity of alanine aminotransferase (ALT), a decrease in hemoglobin levels and an increase in total bilirubin.

When taking Vickeira Pak tablets in combination with ribavirin, you should read the information on side reactions of ribavirin in the instructions for its use.

Overdose

The highest documented single doses given to healthy volunteers were: paritaprevir - 400 mg (+100 mg ritonavir); ritonavir - 200 mg (+100 mg paritaprevir), ombitasvir - 350 mg; dasabuvir 2000 mg

In case of overdose, continuous monitoring of any signs / symptoms of adverse reactions is recommended, if necessary, appropriate symptomatic treatment is carried out immediately.

special instructions

Risk of increased ALT enzyme activity

A transient asymptomatic increase in ALT activity above the upper limit of normal (ULN) ≥ 5 times was observed in approximately 1% of cases.

Significantly more often, an increase in ALT activity was noted in women who took ethinylestradiol-containing drugs (combined oral contraceptives, contraceptive patches and vaginal rings). Usually, an increase in ALT activity is observed within 4 weeks from the start of therapy and decreases with continued administration of Vikeira Pak (with or without ribavirin) for 2-8 weeks from the start of the increase. Therefore, the use of drugs containing ethinyl estradiol is discontinued before the start of antiviral treatment and alternative methods of contraception (progestin-based oral contraceptives, non-hormonal contraceptives) are used all the time Vieira Pak is taken. You can resume protection with drugs containing ethinyl estradiol approximately 2 weeks after the end of the course.

In patients who received drugs containing other estrogens (estradiol, conjugated estrogens) as hormone replacement therapy, ALT activity indices correspond to the data recorded in women who did not receive estrogens. However, the use of other estrogens in combination with Vikeira Pak should also be used with caution due to the limited number of observational data.

During the first 4 weeks of treatment, it is necessary to measure the biochemical parameters of the liver, and in case of a clinically significant excess of VGN in the parameters of serum ALT activity, a second study should be carried out and then:

monitor ALT activity on a regular basis;
inform patients about the need for immediate consultation with the attending physician if symptoms such as weakness, fatigue, loss of appetite, nausea / vomiting, jaundice, discoloration of feces appear;
consider the feasibility of further use of Vikeira Pak in the case when the ALT activity in serum exceeds VGN 10 times or more.

The risk of worsening liver failure and the transition of the disease to the stage of decompensation in patients with liver cirrhosis

According to the results of post-marketing observations, episodes of liver failure in the stage of decompensation up to the need for liver transplantation or death were noted in patients receiving Vikeira Pak. Most of the severe outcomes showed signs of advanced liver cirrhosis before starting therapy. Registration of such conditions, as a rule, occurred from the 1st to the 4th week from the start of therapy, was characterized by an acute increase in the serum concentration of direct bilirubin without an increase in the activity of the ALT enzyme, and was accompanied by clinical symptoms of liver decompensation. It is not possible to establish the reliability and assess the frequency or cause-and-effect relationship with the drug intake.

In the case of moderate to severe impairment of liver function, belonging to classes B and C on the Child-Pugh scale, Vikeira Pak should not be used.

Patients with liver cirrhosis are advised to:

monitor the appearance of symptoms of decompensation of liver function (hepatic encephalopathy, bleeding from varicose veins, ascites);
to assess before the start of treatment, during the first 4 weeks of the course and further, if there are clinical indications, laboratory parameters of liver function, including the serum concentration of direct bilirubin;
stop taking Vikeira Pak if there are signs of liver decompensation.

Risk of Hepatitis B Virus (HBV) Reactivation

During the treatment of viral hepatitis C with the use of direct-acting antiviral drugs in patients with co-infection with viral hepatitis B / C, episodes of HBV reactivation were observed, sometimes leading to liver failure, in some cases fatal.

A sign of reactivation is a sudden increase in HBV replication, manifested by an increase in the HBV DNA content in the blood serum. HBsAg negative (HBsAg) negative patients with anti-HBc antibodies against hepatitis B virus that have previously been successfully treated for HBV infection may have a secondary appearance of HBsAg.

First of all, HBV reactivation is accompanied by deviations in liver function tests, for example, an increase in the activity of hepatic transaminases and / or an increase in the concentration of bilirubin. Therefore, all patients should be screened for HBV prior to treatment. Patients with co-infection with viral hepatitis B / C (including a history of HBV infection) due to the risk of HBV reactivation require monitoring and treatment in accordance with current clinical guidelines.

Risks of negative side effects due to the simultaneous use of Vikeira Pak with other drugs

When used in combination with a number of drugs, known or potentially significant drug interactions are possible, the result of which may be:

a clinically significant decrease in therapeutic efficacy with the likelihood of developing resistance;
clinically significant undesirable side effects associated with an increase in the exposure of drugs used in combination with the active components of Vikeira Pak, or with its excipients.

In complex therapy with ribavirin, it is necessary to take into account the contraindications and special instructions for its use, presented in the instructions for the drug, especially in terms of its teratogenic and / or embryocidal action.

The greatest possible measures should be taken to avoid pregnancy for female patients and female partners of male patients. An HCV regimen with ribavirin should not be used until a negative pregnancy test is obtained immediately before starting treatment. During the course of treatment and for at least seven months after its completion, women of reproductive age and their partners, male patients and their partners should use at least two effective methods of protection at the same time. Women should have routine pregnancy tests every month.

The possibility of the development of drug interactions should be assessed before starting the use of Vikeira Pak, as well as during therapy by constant monitoring of the patient's condition.

The efficacy and safety of Vickeira Pak in relation to the treatment of HCV genotypes other than genotype 1 have not been established.

In the course of experimental studies, no clinically significant effect of dasabuvir and ombitasvir + paritaprevir + ritonavir on the patient's ECG and prolongation of the QTc interval was found.

Influence on the ability to drive vehicles and complex mechanisms

Vikeira Pak in combination with ribavirin can cause fatigue, which affects the ability to perform activities that require increased concentration of attention and speed of reactions, including driving.

Application during pregnancy and lactation

There are no high-quality and well-controlled studies on the use of Vikeira Pak in pregnant women. According to the results of animal studies using ombitasvir + paritaprevir + ritonavir and its main inactive metabolites (M29, M36), as well as dasabuvir, no effect on the development of the embryo and fetus was noted. Despite the fact that animal tests were carried out using maximum doses (from 4 to 98 times the recommended clinical dose in humans), it is impossible to draw conclusions on the safety and efficacy of the drug in pregnant women based on the data obtained in this way. Vickeira Pak should be used during pregnancy only when there is a justified clinical situation when necessary.

The concomitant use of Vikeira Pak with ribavirin is contraindicated in pregnant women and men whose partners are pregnant, since ribavirin can cause fetal malformations / death. Patients receiving ribavirin in combination with Vikeira Pak should read the instructions for its use.

There is no data on the penetration of ombitasvir, paritaprevir, ritonavir or dasabuvir during lactation, as well as their metabolites into the breast milk of a woman. According to the results of animal studies, paritaprevir, its metabolite M13, ombitasvir and dasabuvir were found unchanged in the milk of lactating rats. Their effect on the reared calves was not revealed. Due to the alleged adverse reactions due to the effect of Vikeira Pak on infants, it is necessary to stop breastfeeding during therapy or interrupt treatment during lactation. The choice should be based on an assessment of the mother's health status.

Pediatric use

There are no data on the efficacy and safety of Vikeira Pak for the treatment of children and adolescents under 18 years of age.

With impaired renal function

Patients with mild, moderate and severe renal failure, as well as patients with end-stage renal failure (grade 4–5) on dialysis, do not need a dose adjustment of Vikeira Pak.

If ribavirin must be included in the therapeutic regimen, be sure to read the instructions for its use.

For violations of liver function

In patients with mild hepatic impairment (class A on the Child-Pugh scale), dose adjustment of Vikeira Pak is not necessary. In moderate and severe liver failure (classes B and C on the Child-Pugh scale), the drug is contraindicated.

During the first four weeks of treatment, liver function indicators should be monitored.

Use in the elderly

In elderly patients, dose adjustment of Vikeira Pak is not necessary, but the likelihood of hypersensitivity to the drug components in people of this age category should be taken into account.

Drug interactions

Established drug interactions based on research data:

antiarrhythmic drugs: digoxin - does not affect the plasma concentration, there is no need to adjust the dose, but it is advisable to monitor its concentration in the blood serum; bepridil, amiodarone, disopyramide, lidocaine (systemic administration), flecainide, mexiletine, quinidine, propafenone - their plasma concentration increases, it should be used with caution, controlling the plasma content if possible;
the anticoagulant warfarin: does not affect the plasma concentration, there is no need for dose adjustment, but it is advisable to monitor the international normalized ratio (INR);
antifungal agents: voriconazole - Vieira Pak reduces its concentration, is used together only when the benefits of therapy exceed the potential risks; ketoconazole - its plasma concentration increases, should not be used in a daily dose of more than 200 mg;
blocker of slow calcium channels amlodipine: the content of Vikeira Pak in plasma increases significantly, it is recommended to reduce the dose by 50% and monitor the patient's condition;
inhalation / nasal glucocorticosteroid fluticasone: a decrease in the concentration of cortisol in serum is possible, it is recommended to evaluate the possibility of using other glucocorticosteroids, especially with prolonged use;
the diuretic furosemide: an increase in the maximum plasma concentration (C _max) is likely, it is recommended to reduce the dose to 50% and monitor the patient's condition;
sedative / hypnotic alprazolam: an increase in its concentration is likely, depending on the clinical response to therapy, a dose reduction and patient monitoring may be required;
antiviral drugs for HIV therapy: atazanavir + ritonavir, darunavir + ritonavir, lopinavir + ritonavir and rilpivirin - it is contraindicated to use in conjunction with Vikeira Pak;
inhibitors of HMG-CoA (hydroxymethylglutaryl-coenzyme A) -reductase: an increase in plasma concentration is possible; rosuvastatin - the daily dose should not be more than 10 mg; pravastatin - the daily dose should not be more than 40 mg;
immunosuppressants: an increase in plasma concentration is possible, it is required to monitor the concentration and, as necessary, adjust the frequency of use and / or dose; cyclosporine - at the beginning of joint use, 20% of the required daily dose is prescribed at one time; tacrolimus - 0.5 mg taken once a week; everolimus - its exposure significantly increases, joint use with Vikeira Pak is not recommended; sirolimus - 0.2 mg is taken once every 3 or 4 days (twice a week on the same days), under the control of the concentration of the substance and correction, if necessary, of the dose / frequency of use;
long-acting β-adrenergic receptor agonist salmeterol: increased risk of adverse events from the cardiovascular system (increased QT interval, increased heart rate and sinus tachycardia), concomitant use with Vieira Pak is contraindicated;
narcotic analgesics buprenorphine + naloxone, buprenorphine + norbuprenorphine: no dose adjustment of buprenorphine / naloxone is necessary, but monitoring of sedation and cognitive impairment is recommended;
proton pump inhibitor omeprazole: a decrease in the plasma concentration of omeprazole is possible, it is recommended to monitor patients for the timely detection of a decrease in its effectiveness, with an increase in the dose (but not more than 40 mg per day) in patients whose symptoms are insufficiently controlled;
oral contraceptives: ethinyl estradiol + norgestimate, ethinyl estradiol + norethindrone - combined use with Vieira Pak is contraindicated.

No clinically significant interactions of dasabuvir and ombitasvir + paritaprevir + ritonavir with buprenorphine, methadone, naloxone, duloxetine, escitalopram, norethisterone, tenofovir, emtricitabine, raltegravir, zolpidem, and the most commonly prescribed drugs were found. Dose adjustments are not required for their complex use.

Analogs

There is no information about Vikeira Pak analogues.

Terms and conditions of storage

Store at temperatures up to 25 ° C. Keep out of the reach of children.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Vikeira Pak

Experts emphasize that for the treatment of HCV genotype 1a today Vikeira Pak is the drug of choice, since it is an original and officially registered drug in the Russian Federation, has a direct antiviral effect, inhibiting all stages of viral RNA replication, is well tolerated, practically does not cause side reactions … After two weeks of therapy, an aviremia can be observed with a sustained virological response.

Patients in the reviews of Vikeira Pak claim that the drug is effective, since analyzes after a course of therapy show the absence of a virus in the body, and it is quite easily tolerated. Minor side reactions do not cause severe discomfort.

The only limitation to the widespread use of Vikeira Pak is its price. According to both patients and specialists, it is very expensive.

Price for Vikeira Pak in pharmacies

Price range for Vikeira Pak, for a set of tablets 250 mg + (12.5 mg + 75 mg + 50 mg) 112 pcs. in the package - from 157 to 233 thousand rubles.

Vikeira Pak: prices in online pharmacies

Drug name

Price

Pharmacy

Vikeira Pak 250 mg (12.5 mg + 75 mg + 50 mg) film-coated tablets 112 pcs.

RUB 79,500

Buy

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, 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!