Viqueira Pak, 250 mg (12.5 mg+75 mg+50 mg), film-coated tablets, 112 pcs.
Clinical research experience
If Vikeira Pak is used with ribavirin: for information about adverse reactions of ribavirin, you should read its instructions for use.
The safety assessment is based on pooled data from phase 2 and 3 clinical trials in more than 2,600 patients treated with Viqueira Pak with or without ribavirin.
Viqueira Pak in combination with ribavirin (including in patients with cirrhosis)
In patients receiving Viqueira Pak in combination with ribavirin, the most common adverse reactions observed (in more than 20% of patients) were fatigue and nausea. The number of patients who completely discontinued treatment due to adverse reactions was 1.2% (25/2044), 1.3% (27/2044) of patients interrupted (with the possibility of further resumption) treatment due to side effects. 7.7% (158/2044) of patients required a dose reduction of ribavirin due to adverse reactions.
The safety profile of Viqueira Pak and ribavirin in patients with cirrhosis was the same as in patients without cirrhosis.
Using Viqueira Pak without ribavirin
In patients in a clinical study receiving Viqueira Pak without ribavirin, the only reported adverse reaction was itching. The number of patients who completely discontinued treatment due to adverse reactions was 0.3% (2/588). 0.5% (3/588) of patients had treatment interruptions due to adverse reactions.
Table 3 lists adverse events, related or not related to the use of Vikeyra Pak, recorded in two randomized placebo-controlled studies (SAPPHIRE I and SAPPHIRE II) that were observed at an incidence of at least 5% higher than in patients receiving Viqueira Pak in combination with ribavirin compared with patients receiving placebo. In addition, Table 3 includes a list of these adverse reactions in three studies in which patients received Viqueira Pak with or without ribavirin (PEARL II, PEARL III and PEARL IV), and an analysis of these adverse reactions in studies in patients with cirrhosis livers receiving Viqueira Pak in combination with ribavirin for 12 or 24 weeks (TURQUOISE II).
Table 3. Summary table of the incidence of adverse events identified in phase 3 clinical trials 1,2
SAPPHIRE I and II studies PEARL II, III and IV studies TURQUOISE II study (patients with cirrhosis) Adverse reaction Viqueira Pak + ribavirin 12 weeks N=770 n (%) Placebo 12 weeks N=255 n (%) Viqueira Pak + ribavirin 12 weeks N=401 n (%) Viqueira Pak 12 weeks N=509 n (%) Viqueira Pak + ribavirin 12 or 24 weeks N=380 n (%) Fatigue 263 (34) 67 (26.3) 120 (29.9) 135 (26.5) ) 148 (38.9) Nausea 172 (22.3) 38 (14.9) 63 (15.7) 43 (8.4) 72 (18.9) Itching 3 121 (15.7) 11 (4.3) 48 (12.0) 31 (6.1) 71 (18.7) Other manifestations from the skin 4 (16) (9) Insomnia 108 (14.0) 19 (7.5) 49 (12.2) 26 (5.1) 63 (16.6) Weakness 104 (13.5) 17 (6.7) 36 (9.0) 20 (3.9) 51 ( 13.4) Anemia 41 (5.3) 0 30 (7.5) 1 (0.2) 34 (8.9) 1 - the listed adverse reactions occurred with an incidence of more than 5% among patients receiving Viqueira Pak in combination with ribavirin compared with patients receiving placebo in SAPPHIRE I and II. 2 - the layout of the table columns is provided to simplify the presentation; Direct comparisons should not be made for results from studies that differ in design. 3—The grouping term “itch” includes the preferred term “itch” and “generalized itch.” 4 - grouping term includes: rash, erythema, eczema, maculopapular rash, macular rash, dermatitis, etc. allergic and contact, papular rash, exfoliative phenomena, rash accompanied by itching, erythematous rash, generalized rash, photosensitivity reactions, psoriasis, skin reactions, ulcerations, urticaria.
The majority of adverse reactions in phase 3 clinical studies were mild (grade 1). The safety profile of Viqueira Pak when used in combination with ribavirin is consistent with the existing safety profile of ribavirin.
Adverse reactions by organs and systems according to frequency of occurrence
Determination of the frequency of adverse reactions: very often (≥1/10), often (≥1/100 to <1/10), infrequently (≥1/1000 to <1/100), rarely (≥1/10,000 <1/ 1000) or very rarely (<1/10,000).
Listed below are adverse reactions that occurred at an incidence of at least greater than 5% in patients receiving Viqueira Pak with or without ribavirin compared to patients receiving placebo.
Frequency of occurrence of adverse reactions in patients taking Viqueira Pak with ribavirin (N = 2044). Data include all patients with genotype 1 in phase 2 and 3, incl. patients with cirrhosis
From the hematopoietic and lymphatic system: often - anemia.
From the mental side: very often - insomnia.
From the digestive system: very often - nausea.
From the skin and subcutaneous tissues: very often - itching.
General reactions: very often - weakness, fatigue.
Incidence of adverse reactions in patients taking Viqueira Pak without ribavirin (N=588)
From the skin and subcutaneous tissues: often - itching.
Skin reactions
In the PEARL II, III and IV studies, 7% of patients receiving Vikeira Pak monotherapy and 10% of patients receiving Vikeira Pak in combination with ribavirin experienced dermatitis in the form of rash. In the SAPPHIRE I and II studies, 16% of patients receiving Viqueira Pak with ribavirin and 9% of patients receiving placebo experienced skin adverse events. In the TURQUOISE II study, 18% and 24% of patients receiving Viqueira Pak in combination with ribavirin for 12 or 24 weeks experienced skin adverse events. The severity of most events is classified as mild. No serious events or severe skin reactions have been reported, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug-associated allergic dermatitis (with eosinophilia and systemic symptoms).
Deviations from normal laboratory parameters
Changes in selected laboratory parameters are shown in Table 4.
Table 4. Selected laboratory abnormalities that occurred during treatment 2
Laboratory parameters SAPPHIRE studies I and II PEARL studies II, III and IV TURQUOISE II study (patients with cirrhosis) Viqueira Pak+ribavirin 12 weeks N=770 n (%) Placebo 12 weeks N=255 n (%) Viqueira Pak+ribavirin 12 weeks N=401 n (%) Viqueira Pak 12 weeks N=509 n (%) Viqueira Pak + ribavirin 12 or 24 weeks N=380 n (%) ALT >5-20×ULN 1 (grade 3) 6/765 ( 0.8%) 10/254 (3.9%) 3/401 (0.7%) 1/509 (0.2%) 4/380 (1.1%) >20×ULN (grade 4) 3/765 (0.4%) 0 0 0 2 /380 (0.5%) Hemoglobin <10-8 g/dl (grade 2) 41/765 (5.4%) 0 23/401 (5.7%) 0 30/380 (7.9%) <8-6.5 g/dl (3 degree) 1/765 (0.1%) 0 2/401 (0.5%) 0 3/380 (0.8%) <6.5 g/dl (grade 4) 0 0 0 0 1/380 (0.3%) Total bilirubin >3- 10×ULN (grade 3) 19/765 (2.5%) 0 23/401 (5.7%) 2/509 (0.4%) 37/380 (9.7%) > 10×ULN (grade 4) 1/765 (0.1% ) 0 0 0 0 1 — ULN in accordance with laboratory data. 2 - the layout of the table columns is provided to simplify the presentation; Direct comparisons should not be made for results from studies that differ in design.
Increased ALT activity in blood serum
In clinical studies using Viqueira Pak with and without ribavirin, approximately 1% of patients experienced a transient increase in ALT greater than 5 times the ULN after initiation of treatment.
In women, with concomitant use of drugs containing ethinyl estradiol, the incidence of increased ALT activity increased to 25% (4/16). The incidence of clinically significant increases in ALT among women receiving estrogens other than ethinyl estradiol (e.g., estradiol and conjugated estrogens) for hormone replacement therapy was 3% (2/59) (see Contraindications).
As a rule, this phenomenon was asymptomatic, appeared during the first 4 weeks of treatment and resolved as therapy continued. An increase in ALT activity is usually not associated with an increase in bilirubin concentration. Cirrhosis was not a risk factor for elevated ALT levels.
Anemia/decreased hemoglobin levels
Across all phase 3 studies, the mean change from baseline in hemoglobin concentrations in patients treated with Vikeira Pak in combination with ribavirin was -2.4 g/dL and the mean change in patients treated with Vikeira Pak without ribavirin was -0.5 g/dL. A decrease in hemoglobin content occurred at the beginning of treatment (1–2 weeks) with a further decrease during the 3rd week of therapy. Hemoglobin concentrations remained low for the remainder of treatment and returned to baseline values at 4 weeks after completion of therapy. Less than 1% of patients treated with Viqueira Pak with ribavirin experienced a decrease in hemoglobin concentration of less than 8.0 g/dL during therapy. In 7% of patients treated with Viqueira Pak in combination with ribavirin, a ribavirin dose reduction was required due to a decrease in hemoglobin levels. 3 patients required blood transfusion and 5 patients required erythropoietin administration. One patient discontinued therapy due to anemia. There were no cases of decrease in hemoglobin concentration less than 10 g/dL during therapy with Viqueira Pak without ribavirin.
Increased bilirubin concentration
A temporary increase in bilirubin concentrations (mainly indirect) was observed in patients receiving Viqueira Pak in combination with ribavirin, which is associated with inhibition of the bilirubin transporters OATP1B1/1B3 by paritaprevir and due to hemolysis caused by the use of ribavirin. Increases in bilirubin concentrations occurred after initiation of treatment, peaked at week 1 of the study, and resolved completely as therapy continued. The increase in bilirubin concentration was not associated with an increase in aminotransferase concentrations. The incidence of increased indirect bilirubin was lower among patients who did not receive ribavirin.
Use of Vikeyra Pak in patients with HCV/HIV-1 co-infection
Viqueira Pak in combination with ribavirin was evaluated in 63 patients with HCV/HIV-1 co-infection who were receiving antiretroviral therapy on a stable basis. The most common adverse events reported in at least 10% of patients: weakness (48%), insomnia (19%), nausea (17%), headache (16%), itching (13%), cough (11%), irritability (10%), scleral icterus (10%).
The overall safety profile in patients co-infected with HCV genotype 1 and HIV-1 was similar to the safety profile in patients with HCV genotype 1 without concomitant HIV-1 infection. Short-term increases in total bilirubin >3×ULN (mostly indirect) occurred in 17 (27.0%) patients; 15 of these patients received atazanavir. None of the patients with hyperbilirubinemia had a concomitant increase in aminotransferase.
In patients with hyperbilirubinemia, there was no concomitant increase in aminotransferase activity.
In 7 patients (11%), at least one case of a decrease in hemoglobin concentration below 10 g/dL was recorded; 6 of them underwent dose adjustment of ribavirin. In these cases, blood transfusion and erythropoietin administration were not required.
At the end of 12 and 24 weeks of therapy, there was a decrease in the average number of CD4 + T cells to a concentration of 47 cells/mm 3 and 62 cells/mm 3, respectively; in most cases, after completion of the course of therapy, the indicators returned to the original values. In 2 patients, during the course of therapy, a decrease in the number of CD4 + T cells to a concentration of less than 200 cells/mm 3 without a decrease in CD4 + was recorded. There were no cases of AIDS-associated opportunistic infections reported.
Use of Vikeyra Pak without ribavirin in patients with HCV genotype 1b with compensated liver cirrhosis
In the TURQUOISE III clinical trial of 60 patients with hepatitis C genotype 1b with compensated cirrhosis who took Viqueira Pak without ribavirin for 12 weeks, the most common adverse events (20% or more) were fatigue and diarrhea.
One patient (2%) had a decrease (grade 2) in hemoglobin concentration in the blood.
An increase (grade 2) in total bilirubin was observed in 12 patients (20%).
There were not a single case of a decrease in hemoglobin of grade 3 or more from the initial value or an increase in total bilirubin from the initial value of grade 3 or more. One patient (2%) had a grade 3 increase in ALT activity. One patient (2%) experienced a serious adverse event. One patient (2%) temporarily interrupted therapy due to an adverse event. No patient discontinued therapy completely due to adverse events.
Use of Viqueira Pak in liver transplant recipients
Viqueira Pak in combination with ribavirin was evaluated in 34 liver transplant patients with relapsed HCV. Adverse events reported in more than 20% of patients: weakness (50%). headache (44%), cough (32%), diarrhea (26.5%), insomnia (26.6%), asthenia (23.5%), nausea (23.5%), anemia 20.6%, muscle cramps (20.6%), rash ( 20.6%). In 10 patients (29.4%) there was at least one case of a decrease in hemoglobin concentration to a concentration of less than 10 g/dL. In 10 of 34 patients (29.4%), a dose adjustment of ribavirin was performed due to a decrease in hemoglobin concentration; In 2.9% (1/34) of patients, ribavirin therapy was interrupted. Changing the dose of ribavirin did not affect the sustained virological response. 5 patients received erythropoietin; in all these patients, the initial dose of ribavirin was 1000-1200 mg/day. No blood transfusions were performed.
Use of Vikeyra Pak in patients with HCV genotype 1b with end-stage renal failure on dialysis
The RUBY-I clinical trial in 20 patients with chronic hepatitis C genotype 1b and end-stage renal disease on dialysis showed no difference in the efficacy and safety profile compared to a previous phase 3 trial without patients with severe renal disease. . An exception is for patients who discontinued therapy due to ribavirin-related adverse reactions (decreased hemoglobin concentration). In 9 of 13 cases of use of Vikeyra Pak in combination with ribavirin, temporary discontinuation of ribavirin was required, and in 4 of 13 cases, erythropoietin therapy was administered. One patient had a decrease in hemoglobin <8 g/dL. No patient required blood transfusion. No anemia was observed in 7 patients with hepatitis C genotype 1b who did not take ribavirin
Post-marketing adverse events
The following adverse reactions were identified during post-marketing use of Vikeyra Pak. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
From the immune system: hypersensitivity reactions (including angioedema).
From the hepatobiliary system: decompensation of liver function, liver failure.
Manufacturer
The manufacturer of the drug is the American biopharmaceutical company AbbVie, founded relatively recently, in 2013. But in practice, AbbVie is a subsidiary of the famous Abbot corporation, which occupies a leading position in the development and production of bioengineered drugs. The company produces one of the main drugs for the treatment of rheumatoid arthritis under the trade name Humira.
In addition to the drug Viekira Pak (proprietary name Viekira Pak, international nonproprietary name - ombitasvir/ritonavir/paritaprevir + dasabuvir), AbbVie also produces another latest-generation drug for the treatment of hepatitis C under the INN glecaprevir/pibrentasvir (trade name Mavyret). The company also cooperates with other pharmaceutical corporations. Thus, it was possible to develop and launch on the pharmacy market effective means to combat oncology and other potentially fatal diseases. AbbVie representative offices are open in the Russian Federation and the CIS countries, which makes it possible to implement government programs to provide patients with HCV with free drug care.
Price and where to buy
The medicine is registered in the Russian Federation, therefore it is allowed for official sale. But due to its high cost, the drug is easier to find in pharmacies in Moscow and St. Petersburg. Sometimes the medicine is available in other large cities of the country. Many pharmacies offer made-to-order delivery.
You can buy one package (28 tablets) for 140,000–190,000 rubles (the price in Russia is the same on average). Thus, the cost of a course of treatment will be at least 420,000–570,000 rubles (not counting ribavirin, hepatoprotectors, vitamins and other medications).
