Viekira Pak 250mg tablets kit + (12.5 mg + 75mg + 50mg) 112 pcs

The drug Vikeyra Pak combines three antiviral agents of direct action for the treatment of hepatitis C virus (HCV), with different mechanisms of action and non-overlapping resistance profile, which allows to deal with the hepatitis C virus at different stages of its life cycle, and ritonavir. < / p>

The antiviral drug active against hepatitis C.

dasabuvir

dasabuvir is a non-nucleoside inhibitor of RNA-dependent RNA viral polymerase encoding gene NS5B, which is required for replication of the viral genome. According to biochemical research dasabuvir inhibits the NS5B polymerase activity of the recombinant enzyme genotype Ia and Ib HCV IS30 with values ​​2.8 and 10.7 nM, respectively.

Ombitasvir

Ombitasvir is an inhibitor of HCV NS5A protein, required for viral replication. In studies in cell culture replicon EC50 values ​​for ombitasvira were 14.1 and 5.0 nM for the genotypes of HCV Ia and Ib, respectively.

Paritaprevir

Paritaprevir is an inhibitor of HCV NS3 / 4A protease, which is necessary for proteolytic cleavage of the encoded HCV polyprotein (in the mature forms of proteins NS3, NS4A, NS4B, NS5A and NS5B) and is essential for viral replication. According to biochemical analysis, paritaprevir inhibits proteolytic NS3 / 4A protease activity of the recombinant HCV genotype Ia and Ib with IC50 values ​​of 0.18 and 0.43 nM, respectively.

Ritonavir

Ritonavir does not possess antiviral activity against HCV. Ritonavir pharmacokinetic acts as an amplifier which increases paritaprevira peak concentration in plasma and the concentration paritaprevira measured immediately before taking it next dose, and increases the total drug exposure (i.e., area under “concentration-time” curve).

Active substance:
Dasabuvir; Ombitasvir+Paritaprevir+Ritonavir…

Manufacturer

EbbVi Ltd., Russia

Composition

2. Tablets, film-coated pink, oblong, biconvex, engraved with “AV1” on one side.

1 tablet contains:

• ombitasvira hydrate – 13.6 mg, which corresponds to the content ombitasvira – 12.5 mg
• paritaprevira dihydrate – 78.5 mg, which corresponds to the content paritaprevira – 75 mg
• ritonavir – 50 mg

Excipients: copovidone – 849.2 mg, D-alpha-tocopheryl succinate macrogol – 42.5 mg, colloidal silicon dioxide – 10.8 mg, propylene glycol monolaurate – 10 mg Sorbitan laurate – 33.3 mg
.

Composition of film-coating: Opadry II pink – 32.5 mg, incl polyvinyl alcohol – 46.94% Macrogol 3350 – 23.7% talc – 17.36% titanium dioxide – 11.9% iron oxide red – 0.1%

…

Complex antiviral Vikeyra Pak contains two types of tablets.

1. Tablets, film-coated light brown color, oval, engraved “AV2” on one side.

1 tablet contains sodium monohydrate dasabuvir – 270.26 mg which corresponds to the content dasabuvir – 250 mg

.

Excipients: microcrystalline cellulose PH101 – 103.04 mg microcrystalline cellulose PH102 – 104.72 mg lactose monohydrate – 47.3 mg, copovidone – 101.35 mg Croscarmellose sodium – 33.78 mg, colloidal silicon dioxide – 4.5 mg magnesium stearate – 11.15 mg. Composition of film-coating: Opadry II beige – 21 mg, incl polyvinylalcohol – 40% titanium dioxide – 21.55% macrogol 3350 – 20.2% talc – 14.8%, yellow iron oxide – 3%, iron red oxide -.. 0.35%, iron oxide black – 0.1%

.

Indications

Chronic hepatitis C, 1 st genotype, including patients with compensated cirrhosis, with or without ribavirin him.

Contraindications

• severe degree of liver failure (class C Child-Pugh);
• hypersensitivity to ombitasviru, paritapreviru, ritonavir dasabuvir or any of the excipients of the drug;
• known hypersensitivity to ritonavir (e.g., toxic epndermalny necrolysis or Stevens-Johnson syndrome);
• contraindications to the use of Ribavirin (co-use of the drug Vikeyra Pak and ribavirin). you must familiarize yourself with the instructions for use for information on contraindications to ribavirin;
• the use of ribavirin in women during pregnancy, as well as men whose partner pregnant;
• simultaneous use of drugs, which increase in concentration and blood plasma can bring severe adverse reactions and clearance are significantly dependent on metabolism by isozyme CYP3A;
• simultaneous use of drugs, which are potent inhibitors of CYP2C8 (as this could lead to a significant increase dasabuvir concentration in plasma and the risk of QT interval elongation);
  simultaneous application of drugs – powerful inducers isoenzyme CYP3A (can substantially reduce the concentration of paritaprevira, ombitasvira dasabuvir and plasma);
• simultaneous use of drugs that are potent inducers isoenzyme CYP2C8 (as this could lead to a significant reduction dasabuvir concentration in plasma);
• the simultaneous application of medications: alfuzosin; carbamazepine; phenytoin, phenobarbital; efavirenz; ergot alkaloids (ergotamine, dihydroergotamine, zrgometrin, metilergometrin); gemfibrozil, lovastatin, simvastatin; midazolam and triazolam (in dosage forms for oral administration); pimozide; rifampin; salmeterol; preparations Hypericum (St. John’s wort, Hypericum perforatum); sildenafil (when used for treating pulmonary arterial hypertension) rilpivirine; lopinavir / ritonavir; darunavir / ritonavir; preparations containing ethinylestradiol (e.g., combined oral contraceptives); atazanavir / ritonavir in fixed combination;
• Children under 18 years of age;
• lactase deficiency, galactose intolerance, glucose-galactose malabsorption.

Caution

• The combined use of the drug Vikeyra Pak and fluticasone or other glucocorticoids that are metabolized by the izofermepta CYP3A4.


• The combined use of antiarrhythmic drugs.


• Liver failure of moderate severity.


• Application of pregnancy and breastfeeding

Side effects

Vikeyra Pak drug in combination with ribavirin (including in patients with cirrhosis) security assessment is based on the combined data of phase 2 and 3 clinical studies in over 2600 patients receiving the drug Vikeyra Pak with or without ribavirin him. < / p>

If the drug Vikeyra Pak used with ribavirin: to get information about adverse reactions to ribavirin, you must familiarize yourself with the instructions for use

.

In patients receiving the drug Vikeyra Pak in combination with ribavirin, the most commonly observed adverse reactions (greater than 20% of patients) were fatigue and tishnota. The number of patients .lechenie completely discontinued due to adverse reactions was 1.2% (25/2044), 1.3% (27/2044) of patients discontinued (with the possibility of the resumption) treatment due to side effects. 7.7% (158/2044) patients required a dose reduction of ribavirin due to adverse reactions.
The safety profile of the drug Vikeyra Pak and ribavirin in patients with cirrhosis was the same as in patients without cirrhosis.

Use of the drug Vikeyra Pak without ribavirin

Patients in a clinical trial who received the drug Vikeyra Pak without ribavirin only recorded adverse event was pruritus. The number of patients completely discontinued treatment due to adverse reactions was 0.3% (2/588). 0.5% (3/588) of patients did treatment interruptions due to adverse reactions.

Table 2 lists the adverse events associated or not associated with drug Vikeyra Pak recorded in two randomized planebo-controlled trials (SAPPHIRE I and SAPPHIRE II), which were observed at a frequency of at least 5% higher than that patients receiving drug Vikeyra Pak plus ribavirin compared to patients receiving placebo. In addition, Table 2 includes a listing of these side reactions in three studies in which patients received the drug Vikeyra Pak with ribavirin or without (PEARL II, PEARL III and PEARL IV), and analysis of these side reactions in studies in patients with cirrhosis liver receiving Vikeyra Pak drug in combination with ribavirin for either 12 or 24 weeks (TURQUOISE II).

Table 2. Summary of the frequency of adverse events identified in phase 3 clinical study 1,2
 

Studies SAPPHIRE I and IIIssledovaniya PEARL II, III and IVIssledovanie TURQUOISE II (patients with cirrhosis) Incidental reaktsiyaVikeyra Pak plus ribavirin 12 weeks N = 770 n (%) Placebo 12 weeks N = 255 n (%) Vikeyra Pak plus ribavirin 12 weeks N = 401 n (%) Vikeyra Pak 12 weeks N = 509 n (%) Vikeyra Pak plus ribavirin 12 or 24 weeks N = 380 n (%) Ustalost263 (34) 67 (26.3) 120 (29.9) 135 (26.5) 148 (38.9 ) Toshnota172 (22.3) 38 (14.9) 63 (15.7) 43 (8.4) 72 (18.9) Zud3121 (15.7) 11 (4.3) 48 (12.0) 31 (6.1) 71 (18.7) Other manifestations by kozhi4 (16) ( 9)

Bessonnitsa108 (14.0) 19 (7.5) 49 (12.2) 26 (5.1) 63 (16.6) Slabost104 (13.5) 17 (6.7) 36 (9.0) 20 (3.9) 51 (13.4) Anemiya41 (5.3) 030 (7.5) 1 ( 0.2) 34 (8.9) 1 – listed adverse reactions occurred with a frequency of more than 5% among patients treated Vikeyra Pak plus ribavirin compared to those treated with placebo in SAPPHIRE I and II
.
2 – The location of the count table is provided for ease of presentation; direct comparisons should not be made to the research results, which differ in design.
3 – grouping the term “itching” includes the preferred term “itching” and “generalized itching”
.
4 – grouping term includes: rash, erythema, eczema, makulo-papular rash, dermatitis, including allergic and contact, maculopapular rash, exfoliative phenomenon, rash, accompanied by itching, erythematous rash, generalized rash, photosensitivity reactions, psoriasis, skin reactions, ulceration, urticaria.

Most adverse events were mild in phase 3 clinical trials (class 1). The safety profile of the drug Vikeyra Pak when combined with ribavirin is consistent with the safety profile of ribavirin available.

Skin reactions

The studies PEARL-II, -III, and -IV, 7% of patients receiving the drug Vikeyra Pak monotherapy and 10% of patients receiving the drug Vikeyra Pak in combination with ribavirin, dermatitis symptoms were observed in the form of a rash. < / p>

The studies SAPPHIRE-I and II in 16% of patients receiving drug Vikeyra Pak with ribavirin and 9% of patients receiving placebo were noted undesirable phenomena of the skin.

The TURQUOISE II study, 18% and 24% of patients receiving drug Vikeyra Pak plus ribavirin for 12 weeks or 24 noted undesirable phenomena of the skin.

The severity of most of the phenomena classified as mild. Not Registered serious phenomena and severe skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, dermatitis, allergic associated with taking drugs (with eosinophilia and systemic symptoms).

Abnormal laboratory values ​​

Changes in individual laboratory parameters are summarized in Table 3.

Table 3. Selected laboratory abnormalities that occurred during treatment 2.
 

Laboratory pokazateliIssledovaniya SAPPHIRE I and IIIssledovaniya PEARL II, III and IVIssledovanie TURQUOISE II (patients with tsirrolom) Vikeyra Pak plus ribavirin 12 weeks N = 770 n (%) Placebo 12 weeks N = 255 n (%) Vikeyra Pak plus ribavirin 12 weeks N = 401 n (%) Vikeyra Pak 12 weeks N = 509 n (%) Vikeyra Pak plus ribavirin 12 or 24 weeks N = 380 n (%) ALT (alannnaminotransferaza) > 5-20 × upper limit normy1 (grade 3 ) 6/765 (0.8%) 10/254 (3.9%) 3/401 (0.7%) 1/509 (0.2%) 4/380 (1.1%) > 20 × upper limit of normal (grade 4) 3/765 (0.4%) 0002/380 (0.5%) Gemoglobin41 / 765 (5.4%) 023/401 (07.05%) 030/380 (7.9%) 1/765 (0.1%) 02/401 (0.5%) 03/380 ( 0.8%) 00001/380 (0.3%) Total bilirubin > 3-10 × upper limit of normal (degree 3 v) 19/765 (2.5%) 023/401 (5.7%) 2/509 (0.4%) 37/380 (9.7%) > 10 × upper limit of normal (grade 4) 1/765 (0.1%) 00001 – the upper limit of normal, in accordance with laboratory data
.
2 – The location of the count table is provided for ease of presentation; direct comparisons should not be made for the results to explore different design.

Increase of ALT activity in serum

In the course of clinical trials with the drug Vikeyra Pak with ribavirin and without it, in less than 1% of patients who did not use estrogen-containing drugs, was found a temporary increase in ALT activity in more than 5 times the upper limit of normal after treatment. < / p>

In women with concomitant use of preparations containing ethinylestradiol improving incidence of ALT activity increased to 25% (4/16). The incidence of clinically significant increase in ALT activity in women receiving oestrogens other than ethinyl estradiol (e.g., estradiol, and conjugated estrogens) as hormone replacement therapy was 3% (2/59).
As a rule, this phenomenon was asymptomatic, occur within the first 4 weeks of treatment and were allowed to the extent of continued therapy.

Increase of ALT are generally not associated with increased bilirubin concentrations.

Cirrhosis was not a risk factor for the increase in ALT activity.

For most patients do not require special monitoring of biochemical parameters of liver.

Increasing the concentration of bilirubin

The temporary increase in the concentration of bilirubin (mainly indirect) was observed in patients receiving the drug Vikeyra Pak in combination with ribavirin, which is associated with inhibition paritaprevirom bilirubin transporter OATR1V1 / 1VZ and thus hemolysis caused by ribavirin. Increased bilirubin occurred after the start of treatment the concentration reached a peak in the week I study, and fully permitted as continuation of therapy.

Increasing the concentration of bilirubin was not associated with an increase in aminotransferase concentrations.

The frequency increase of indirect bilirubin was lower among patients who did not receive ribavirin.

Use of the drug Vikeyra Park in patients co-infected with HCV / HIV-1

Use of the drug Vikeyra Pak in combination with ribavirin was evaluated in 63 patients co-infected with HCV / HIV-1 which were receiving antiretroviral therapy on a stable basis. The most common adverse events were registered at least 10% of patients: weakness (48%), insomnia (19%), nausea (17%). headache (16%), pruritus (13%). cough (11%), irritability (10%), ikterichnost sclera (10%).

Increased total bilirubin concentration in 2 or more times the upper limit of normal (more often – at the expense of indirect bilirubin) was registered in 34 patients (54%). 15 of them in a period of increased bilirubin concentrations of atazanavir, 9 patients were also observed ikterichnost sclera, jaundice or hyperbilirubinemia.

In patients with hyperbilirubinemia were observed concomitant increase in transaminases. Cases increasing the activity of ALT grade 3 is not registered.

In 7 patients (11%) have been reported at least one case to reduce the hemoglobin concentration below 10 g / dL; 6 of them held dose adjustment of ribavirin. In these cases, blood transfusions and erythropoietin was not required.

After 12 and 24 weeks of treatment was a decrease in the average number of CD4 + T cells to a concentration of 47 cells / mm3 and 62 cells / mm3, respectively; indices returned to baseline in most cases after completion of therapy.

2 patients during the course of therapy reported reduction of CD4 + T cells to a concentration of less than 200 cells / mm3 without reducing CD4 +.

The incidence of AIDS-related has not been registered for opportunistic infections.

Application Vikeyra Pak drug in liver transplant recipients

Use of the drug Vikeyra Pak in combination with ribavirin was evaluated in 34 patients who underwent liver transplantation, HCV relapse. Adverse events were recorded for more than 20% of patients: weakness (50%). headache (44%), cough (32%), diarrhea (26%), insomnia (26%), asthenia (24%), nausea (24%), muscle cramps (21%), rash (21%). In 10 patients (29%) had at least one case to reduce the concentration of hemoglobin to a concentration of less than 10 g / dl. In 10 patients was conducted ribavirin dose adjustment due to a decrease in hemoglobin concentration; 3% (1/34) of patients with ribavirin therapy was interrupted. 5 patients had received erythropoietin; all of these patients the initial dose of ribavirin was 1000-1200 mg per day. Blood transfusions were not carried out.

How to accept, acceptance rate and dosage

Inside. The drug Vikeyra Pak should be taken at meal time, no fat or caloric intake.

The recommended dose of the drug Vikeyra Pak includes:

• 2 tab. ombitasvira / paritaprevira / ritonavir, 12.5 / 75/50 mg 1 time / day (in the morning), and
• 1 tab. dasabuvir 250 mg 2 times / day (morning and evening).

In some groups of patients Vikeyra Pak drug is used in combination with ribavirin (see. Table 1).

Table 1 shows the recommended treatment regimen, and duration of therapy depending on the patient group.

Table 1. The treatment regimen and duration for different groups of patients (for the first time or after starting treatment with interferon therapy.
 

Group patsientovLekarstvennye drugs * ProdolzhitelnostGenotip Ia without tsirrozaVikeyra Pak + ribavirin12 nedelGenotip Ia with tsirrozomVikeyra Pak + ribavirin24 weeks ** Genotype Ib without tsirrozaVikeyra Pak12 nedelGenotip Ib, with tsirrozomVikeyra Pak + ribavirin12 nedelPrimechaniya:
* P Bolney with an unknown subtype of genotype I and genotype I mixed type is recommended to follow the dosing regimen for genotype Ia.
** Regimen Vikeyra Pak plus ribavirin for 12 weeks may be considered for some patients on the basis of previous therapy.

When applying a preparation Vikeyra Pak recommended dosage of ribavirin is based on patient body weight: 1000 mg / day for patients with tela75 kg weight, divided into 2 doses per day with food. If necessary, dose adjustment of ribavirin is recommended to familiarize yourself with the instructions for use.

The drug Vikeyra Pak should be taken in accordance with the duration and the recommended instructions for its use, without interruption. If the drug Vikeyra Pak is used in conjunction with ribavirin, the ribavirin should be appointed for the same term as the drug Vikeyra Park.

The patients after liver transplantation

The recommended duration of treatment (using a preparation Vikeyra Pak in combination with ribavirin) of patients with normal liver function and fibrosis scale Metavir ≤ 2 is 24 weeks, regardless of the subtype-1 genotype of HCV.

Using the drug Vikeyra Pak with calcineurin inhibitors required dose correction calcineurin inhibitors. In clinical studies in patients after liver transplantation have been individually selected dose of ribavirin, which ranged from 600 mg to 800 mg per day.

In patients co-infected with HCV / HIV-1

It should follow the recommendations given in Table 1. Guidelines for concomitant antiviral therapy of HIV-1 are presented in “The interaction with other drugs”.

Liver failure

In patients with mild hepatic insufficiency (class A of Child-Pugh) correction of a dose of the drug Vikeyra Pak is required. Safety and efficacy Vikeyra Park in patients infected with hepatitis C, with a mean hepatic insufficiency (class of Child-Pugh) has not been established; drug application Vikeyra Pakne recommended in patients with moderate hepatic impairment. Vikeyra Pakprotivopokazan drug in patients with severe hepatic insufficiency (class C by Child-Pyo).

Prior to the initiation of therapy and during treatment should be carried out monitoring of liver function.

Active substance

Dasabuvir; Ombitasvir+Paritaprevir+Ritonavir…

Interaction

Paritaprevir, ombitasvir, ritonavir and dasabuvir in vivo without inhibiting the conveyor organic anions (OAT1) also unlikely that they inhibit transporters organic cations (OST1 and OST2), transporters of organic anions (OAT3) or proteins of multiple resistance and detoxifying {MATE1 and MATE2K) at clinically relevant concentrations; Thus, the preparation Vikeyra Pak does not affect the data path excretion through the kidneys.

The in vitro studies indicated that Ritonavir inhibits some isozymes of cytochrome P450, but drug Vikeyra Pak at clinically relevant concentrations did not significantly affect the isozymes CYP2C9 and CYP2C19.

Paritaprevir, ritonavir and dasabuvir are inhibitors of P-gpikoproteina in vilro, but significant changes in the interaction of the drug with Vikeyra Pak digoxin – sensitive substrate of P-glycoprotein – not observed

.

Paritaprevir polypeptide is an inhibitor of the transport of organic anions and 1B1 1V3 (OATR1V1 and OATR1V3). Paritaprevir, ritonavir and dasabuvir are inhibitors of protein resistant breast cancer (Breast Cancer Resistance Protein, BCRP).

Paritaprevir, ombitasvir dasabuvir and are inhibitors of isoforms 1A1 (UGT1A1) uridindifosfatglyukuroniltransferazy, and ritonavir is an inhibitor of the isoenzyme cytochrome CYP3A4. The combined use of the drug Vikeyra Pak with drugs that are primarily metabolized by CYP3A isoenzyme or are substrates for UGT1A1, BCRP, OATP1B1 or OATP1B3, can lead to increased plasma concentrations of such drugs.

Special conditions

The increase in ALT activity observed much more frequently in women taking etipilestradiola preparations based on, for example, combined oral contraceptives, contraceptive patches, and vaginal contraceptive ring (see. The section “Contraindications”).

In the clinical trials of the drug Vikeyra Pak with ribavirin or without ribavirin, about 1% of the observed transient, asymptomatic increase in ALT activity by more than 5 times the upper limit of normal occurred (see. The section “Side effect”). < / p>

Increased ALT activity is typically observed during the 4 weeks of treatment and decreased within 2-8 weeks from the start of increase of ALT activity with continued therapy with Vikeyra Pak ribaviripom with or without ribavirin.

must stop taking preparations containing ethinylestradiol before the application Vikeyra Pak preparation. During the course of therapy with Vikeyra Pack it is recommended to use alternative methods of contraception (eg, peroralpye contraceptives Progestin-based agents, or hormonal contraceptives).

The resumption of the reception preparations containing ethinylestradiol is recommended to start after about 2 weeks after completion of therapy with Vikeyra Park.

In women who received no ethinyl estradiol and other estrogens (such as estradiol and estrogen conjugation) as hormone replacement therapy, indicators of ALT activity corresponded to the figure recorded in the patients who did not receive estrogen. However, since the number of patients treated with other estrogens, is limited, use them in combination with the drug Vikeyra Pak with caution.

The biochemical liver values ​​should be measured within the first 4 weeks of treatment and if indicators of ALT activity in serum exceed the upper limit of normal, you need to re-conduct research and continue to monitor the activity of ALT in these patients, as well as:

• , patients should be informed of the need to immediately consult with your doctor, if they have been fatigue, weakness, loss of appetite, nausea and vomiting, jaundice, or discoloration of the feces;
• consider discontinuing use of the drug Vikeyra Pak if indicators of ALT activity in serum exceed the upper limit of normal in 10 times.

Risks associated with the concurrent use of ribavirin

In the case of combined use drug Vikeyra Pak with ribavirin should consider warnings and precautions that apply to ribavirin, in relative frequency, unwanted pregnancy. A complete list of warnings and precautions during treatment with ribavirin represented in the instructions for its use.

Risks associated with side effects, or decrease the effect of the therapy due to concomitant administration of other drugs

The combined use of a number of drugs can lead to the known, or potentially significant drug interactions, resulting in possible:

• The loss of therapeutic efficacy, perhaps – with the development of resistance

.


• Clinically significant adverse reactions associated with an increase in the exposure of drugs that are used in conjunction with the preparation Vikeyra Pak, or with auxiliaries preparation.

Table 4 (section “Interaction with other drugs”) are measures to correct possible and known significant drug interactions, including – recommendations for dosage adjustment. It should evaluate the possibility of drug interactions of the drug prior Vikeyra Pak and during the course of therapy; recommended monitoring of adverse reactions associated with taking drugs used together with active compounds and auxiliaries Vikeyra Pak preparation.

Use with fluticasone

Fluticasone – glucocorticosteroid metabolized by isozyme CYP3A

.

Caution should be exercised when co-use of the drug Vikeyra Pak and fluticasone or other glucocorticoids that are metabolized by the isoenzyme CYP3A4. The combined use of inhaled corticosteroids, izofermepta metabolized by CYP3A, may increase systemic effects of glucocorticoids; It has been reported cases of Cushing’s syndrome and the subsequent suppression of adrenal function drugs containing ritonavir. The combined use of the drug Vikeyra Pak and corticosteroids, in particular for long-term therapy should be initiated only if the potential benefit of treatment outweighs the risk of systemic effects of glucocorticoids.

Liver failure

In patients with mild hepatic insufficiency (class A for Chapld-Pugh) correction dose drug Vikeyra Pak is required. Safety and efficacy Vikeyra Pak patients infected with hepatitis C, with moderate hepatic failure (class B Child-Pugh) has not been established; It is not recommended to apply the preparation Vikeyra Pak with moderate hepatic insufficiency. The drug Vikeyra Pak is contraindicated in patients with severe hepatic insufficiency (class C by Child-Pyo). The drug Vikeyra Pak is not recommended for use in patients with decompensated liver disease.

The risk of development of resistance to protease inhibitors of HIV-1 in patients co-infected with HCV / HIV-1

Ritonavir, which is included in the drug Vikeyra Pak, relates to protease inhibitors of HIV-1 and can facilitate selection of the amino acid substitutions associated with resistance to inhibitors of HIV-1 protease. In patients co-infected with HCV / HIV-1 who receive a course of therapy with Vikeyra Pak should also carry out anti-retroviral therapy to reduce the risk of development of resistance to protease inhibitors of HIV-1.

Patients nocle liver transplantation

The safety and efficacy of the drug Vikeyra Pak in combination with ribavirin has been studied in 34 patients with genotype 1 HCV after liver transplant (at least 12 months after transplantation, the liver). The main objectives of this study was to evaluate the safety and determine the proportion of patients achieving a sustained virological response 12 weeks after the end of treatment (SVR12) and after 24 weeks of treatment Vikeyra Pak in combination with ribavirin. The initial dose of ribavirin is from 600 mg to 800 mg per day as the most frequently used at the beginning and end of drug treatment Vikeyra Pak.

Thirty four participants who did not receive treatment for HCV after liver transplantation and had fibrosis assessment scale Metavir ≤ 2 (29 with HCV genotype 1a and HCV genotype 5 1b) have been included in clinical trials. Thirty-one of 32 patients for whom data at time point SVR12 (96.9%) reached SVR12 (96.3% in patients with genotype 1a) were obtained. One patient with HCV genotype 1a had relapsed after treatment.

The overall safety profile Vikeyra Pak preparation in combination with ribavirin in HCV-infected patients after liver transplantation was the same as that of the patients receiving the drug Vikeyra Pak in combination with ribavirin in phase 3 clinical trials, with the exception of anemia. Ten patients (29.4%) had at least one hemoglobin value (after starting) of less than 10 g / dl. At 55.9% (19/34) of patients ribavirin dose was reduced and 2.9% (1/34), the use of ribavirin has been canceled.

Changing the dose of ribavirin did not affect the frequency of the PA to achieve a sustained virologic response. Five patients required use of erythropoietin (in all five patients applied ribavirin daily in an initial dose of 1000 mg to 1200 mg. No patient required blood transfusion).

The other genotypes of HCV

For patients infected with other HCV genotypes except genotype 1, the safety and efficacy of the drug Vikeyra Pack has not been installed.

The effect on ECG

The effect of combined use ombitasvira / paritaprevira / ritonavir and dasabuvir an interval QTc was evaluated in a randomized, double-blind study with placebo and active control (moxifloxacin 400 mg), 4-way cross-hairs, careful monitoring QT in 60 healthy subjects receiving ombitasvir / paritaprevir / ritonavir and dasabuvir.

In the study to detect small effects in doses exceeding therapeutic – paritaprevir 350 mg, 150 mg ritonavir, ombitasvir 50 mg and 500 mg dasabuvir – showed no clinically significant prolongation of the interval QT

.

Overdose

The highest documented single dose appointed healthy volunteers, were 400 mg for paritaprevira (ritonavir 100 mg), 200 mg for ritonavir (100 mg paritaprevira), 350 mg to 2000 mg and ombitasvira for dasabuvir. In case of overdose it is recommended to monitor the appearance of any signs or symptoms of adverse reactions, and, if necessary, appropriate nemedlennot provedenit symptomatic therapy.