Medicinal Products

Dasabuvir Abbvie 250 mg

Generic drug of the therapeutic class: Infectiology - Parasitology
Active ingredients: Dasabuvir
laboratory: Abb Vie

Coated tablet
bottle of 64
All forms

Indication

Dasabuvir Abbvie in combination with ombitasvir / paritaprevir / ritonavir with or without ribavirin, used in the cohort ATU, is indicated for the treatment of chronic hepatitis C due to HCV genotype 1 in adult patients with advanced disease (with F3 liver fibrosis or compensated cirrhosis or with extrahepatic HCV mani- festations).

Dosage Dasabuvir Abbvie 250 mg film-coated tablet vial of 64

Dasabuvir Abbvie in combination with ombitasvir / paritaprevir / ritonavir with or without ribavirin, used in the cohort ATU, is indicated for the treatment of chronic hepatitis C due to HCV genotype 1 in adult patients with advanced disease (with F3 liver fibrosis or compensated cirrhosis or with extrahepatic HCV mani- festations).

Against indications

Hypersensitivity to the active substances or to any of the excipients listed under Composition .

Use of drugs containing ethinyl estradiol such as most combination oral contraceptives or vaginal contraceptive rings (see Warnings and Precautions for Use and Interactions with Other Drugs and Other Interactions ) sections.

Concomitant administration of Dasabuvir AbbVie with drugs that are potent or moderate enzyme inducers may decrease the plasma concentrations of dasabuvir and reduce its therapeutic effect (see section 4.5. Interactions with other medicinal products and other forms of interaction ). Examples of contraindicated inducers are shown below.

Enzyme inducers:

• carbamazepine, phenytoin, phenobarbital

• efavirenz, nevirapine, etravirine

• enzalutamide

• mitotane

• rifampicin

• St. John's wort (Hypericum perforatum)

Drugs that are potent inhibitors of CYP2C8 may increase plasma concentrations of dasabuvir and should not be co-administered with Dasabuvir AbbVie (see section 4.5 Interaction with other medicinal products and other forms of interaction ). Examples of contraindicated CYP2C8 inhibitors are shown below.

Inhibitors of CYP2C8:

• gemfibrozil

Dasabuvir AbbVie is given with ombitasvir / paritaprevir / ritonavir. For contraindications with ombitasvir / paritaprevir / ritonavir refer to the Summary of Product Characteristics of ombitasvir / paritaprevir / ritonavir.

Adverse effects Dasabuvir Abbvie

Summary of the job security profile

The safety profile is based on cumulative data from phase 2 and 3 clinical studies in more than 2, 600 patients who received Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir with or without ribavirin.

Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir with ribavirin (including patients with compensated cirrhosis)

In patients treated with Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir with ribavirin, the most commonly reported adverse events (in more than 20% of patients) were fatigue and nausea. The proportion of patients who permanently discontinued treatment due to adverse events was 0.2% (5/2, 044). 0.2% (5/2, 044) of patients discontinued treatment due to adverse events. 4.8% (99/2 044) of patients had a reduction in ribavirin dose due to adverse effects.

With the exception of increased transient hyperbilirubinemia, the safety profile of Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir with ribavirin in patients with compensated cirrhosis was comparable to that observed in patients without cirrhosis.

Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir without ribavirin

No patient has permanently stopped or discontinued treatment due to undesirable effects.

Tabulated list of adverse effects

Table 3 lists adverse events for which a causal relationship between dasabuvir, in combination with ombitasvir / paritaprevir / ritonavir, with or without ribavirin, and the adverse event is possible. Most of the adverse events presented in Table 3 were of grade 1 severity with Dasabuvir AbbVie and regimens containing ombitasvir / paritaprevir / ritonavir.

The undesirable effects are listed below by system organ class and frequency. Frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1000 to <1/100), rare (≥ 1 / 10, 000 to <1/1000) or very rare (<1 / 10, 000).

Table 3. Undesirable effects identified with Dasabuvir AbbVie in combination with ombitasvir / paritaprevir / ritonavir or ombitasvir / paritaprevir / ritonavir and ribavirin

Frequency

Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir + ribavirin *

N = 2, 044

Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir

N = 588

Blood and lymphatic system disorders

Frequent

Anemia

Psychiatric disorders

Very common

Insomnia

Gastrointestinal disorders

Very common

nausea

Skin and subcutaneous tissue disorders

Very common

itching

Frequent

itching

General disorders and administration site conditions

Very common

Asthenia

Tired

* The dataset includes all patients infected with HCV genotype 1 phase 2 and 3 trials, including cirrhotic patients. Note: For biological abnormalities, refer to Table 4.

Description of some adverse effects

Biological abnormalities

The variations of some biological parameters are described in Table 4. A parallel entry table simplifies the presentation, a direct comparison between the trials being not possible in view of the different study designs.

Table 4. Selection of treatment-related biological abnormalities

Biological parameters

SAPPHIRE I and II

PEARL II, III and IV

TURQUOISE II (cirrhotic patients)

Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir + ribavirin

12 weeks

N = 770

not ( % )

Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir

12 weeks

N = 509

not ( % )

Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir + ribavirin

12 or 24 weeks

N = 380

not (%)

ALT

> 5 to 20 x L SN *

(Grade 3)

6/765 (0.8%)

1/509 (0.2%)

4/380 (1.1%)

> 20 x lsn (Grade 4)

3/765 (0 4%)

0

2/380 (0 5%)

Hemoglobin

<100 to 80 g / l (grade 2)

41/765 (5.4%)

0

30/380 (7.9%)

<80 to 65 g / l (grade 3)

1/765 (0.1%)

0

3/380 (0.8%)

<65 g / l (grade 4)

0

0

1/380 (0.3%)

Total bilirubin

> 3 to 10 x ULN (Grade 3)

19/765 (2.5%)

2/509 (0.4%)

37/380 (9.7%)

> 10 x ULN (Grade 4)

1/765 (0.1%)

0

0

* LSN: Upper limit of normal

Elevations of serum ALT levels

In a combined analysis of clinical studies of Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir with and without ribavirin, 1% of patients experienced serum ALT levels greater than 5 times the upper limit of normal (ULN) after the beginning of the treatment. The incidence of these elevations was 26% in women taking concomitant medications containing ethinyl estradiol, these drugs are contraindicated with Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir. No increase in the incidence of ALT elevations has been observed with other types of systemic estrogens commonly used in hormone replacement therapy (eg, estradiol and conjugated estrogens). In general, elevations of ALT were asymptomatic, occurred during the first 4 weeks of treatment (mean delay 20 days, range 8-57 days) and resolved in most cases with continued treatment. Two patients discontinued treatment with Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir due to elevated ALT levels, including one patient taking ethinyl estradiol. Three patients discontinued Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir for one to seven days, one of whom was taking ethinyl estradiol. In the majority of cases, these elevations of ALT were transient and assessed as being related to Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir. ALT elevations were generally not associated with elevations of bilirubin. Cirrhosis was not a risk factor for elevation of ALT (see Warnings and Precautions section ).

Elevations of serum bilirubin

Transient increases in serum bilirubin levels (predominantly indirect) have been observed in patients treated with Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir with ribavirin, related to the inhibition of bilirubin OATP1B1 / 1B3 transporters by paritaprevir and with ribavirin-induced hemolysis. Elevations of bilirubin occurred after initiation of treatment, with peak values ​​at Week 1 of the study, and usually disappeared during treatment. Elevations of bilirubin were not associated with elevations of aminotransferase. The incidence of indirect bilirubin elevations was lower in patients who did not receive ribavirin.

Hepatic transplant patients

The overall safety profile for HCV-infected patients who received liver transplantation and received Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir and ribavirin (in addition to their immunosuppressive drugs) was similar to that patients treated with Dasabuvir AbbVie and ombitasvir / paritaprevir / ritonavir and ribavirin in phase 3 clinical studies, although the frequency of some adverse events was increased. 10 patients (29.4%) had at least a hemoglobin value of less than 10 g / dl after inclusion. Ten of 34 patients (29.4%) had a change in ribavirin dose due to a decrease in hemoglobin and 2.9% (1/34) discontinued ribavirin. Ribavirin dose modification had no impact on SVR rates. 5 required erythropoietin, all received a daily dose of 1000 to 1200 mg at initiation. No patient received a blood transfusion.

HIV / HCV coinfected patients

The overall safety profile for patients co-infected with HCV and HIV-1 was similar to that observed in mono-infected patients. Transient elevations of total bilirubin> 3 x ULN (predominantly indirect) occurred in 17 patients (27.0%); 15 of these patients were receiving atazanavir. None of the patients with hyperbilirubinemia had concomitant elevations of aminotransferases.

Pediatric population

The safety of Dasabuvir AbbVie in children and adolescents under the age of 18 has not been established. No data available.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions is important. It allows continuous monitoring of the benefit / risk ratio of the drug. Healthcare professionals should report any suspected adverse reactions using the corresponding sheet (see Annex D) of the Therapeutic Use and Collection Protocol.

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