Viekirax

Treatment with Viekirax should be initiated and monitored by a physician experienced in the management of chronic hepatitis C. 5 mg / 75 mg / 50 mg tablets once daily with food. Viekirax should be used in combination with other medicinal products for the treatment of HCV (see Table 1).

Medicinal product no longer authorised 3 Table 1. ) Genotype 4, without cirrhosis or with compensated cirrhosis Viekirax + ribavirin 12 weeks *Note: Follow the genotype 1a dosing recommendations in patients with an unknown genotype 1 subtype or with mixed genotype 1 infection.

** When assessing severity of liver disease using non-invasive methods, a combination of blood biomarkers or the combination of liver stiffness measurement and a blood test improves accuracy and should be undertaken prior to 8 week treatment in all patients with moderate fibrosis.

For specific dosage instructions for dasabuvir and ribavirin, including dose modification, refer to the respective Summaries of Product Characteristics. Missed doses In case a dose of Viekirax is missed, the prescribed dose can be taken within 12 hours.

If more than 12 hours have passed since Viekirax is usually taken, the missed dose should NOT be taken and the patient should take the next dose per the usual dosing schedule. Patients should be instructed not to take a double dose.

Special populations HIV-1 Co-infection The dosing recommendations in Table 1 should be followed. 5. 1 for additional information. Liver transplant recipients Viekirax and dasabuvir in combination with ribavirin is recommended for 24 weeks in liver transplant recipients with genotype 1 HCV infection.

Viekirax in combination with ribavirin is recommended in genotype 4 infection. Lower ribavirin dose at initiation may be appropriate. 1). 5. 2). 2). For patients that require ribavirin, refer to the ribavirin Summary of Product Characteristics for information regarding use in patients with renal impairment.

Hepatic impairment No dose adjustment of Viekirax is required in patients with mild hepatic impairment (Child-Pugh A). 2). Paediatric population The safety and efficacy of Viekirax in children less than 18 years of age have not been established.

No data are available. Method of administration The film-coated tablets are for oral use. e. patients should not chew, break or dissolve the tablet). 2).

Summary of the safety profile In subjects receiving Viekirax and dasabuvir with ribavirin, the most commonly reported adverse reactions (greater than 20% of subjects) were fatigue and nausea. 8% (99/2,044) of subjects had ribavirin dose reductions due to adverse reactions.

Tabulated list of adverse reactions The safety summary is based on pooled data from phase 2 and 3 clinical trials in subjects who received Viekirax and dasabuvir with or without ribavirin. The majority of adverse reactions presented in Table 3 were of grade 1 severity in Viekirax and dasabuvir-containing regimens.

The adverse reactions 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 (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000) or very rare (<1/10,000).

Medicinal product no longer authorised 39 Table 3. Adverse drug reactions identified with Viekirax in combination with dasabuvir with and without ribavirin Frequency Viekirax + dasabuvir + ribavirin* N = 2,044 Viekirax + dasabuvir N = 588 Blood and lymphatic system disorders Common Anaemia Immune system disorders Frequency unknown Anaphylactic reactions Anaphylactic reactions Metabolism and nutrition disorders Uncommon Dehydration Psychiatric disorders Very common Insomnia Gastrointestinal disorders Very common Nausea, Diarrhoea Common Vomiting Hepatobiliary disorders Frequency unknown Hepatic decompensation and hepatic failure Hepatic decompensation and hepatic failure Skin and subcutaneous tissue disorders Very common Pruritus Common Pruritus Rare Angioedema Angioedema General disorders and administration and administration site conditions Very common Asthenia Fatigue *Data set includes all genotype 1-infected subjects in Phase 2 and 3 trials including subjects with cirrhosis.

Note:

1). Risk of hepatic decompensation and hepatic failure in patients with cirrhosis Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have been reported postmarketing in patients treated with Viekirax with and without dasabuvir and with and without ribavirin.

Most patients with these severe outcomes had evidence of advanced or decompensated cirrhosis prior to initiating therapy. Although causality is difficult to establish due to background advanced liver disease, a potential risk cannot be excluded.

2). For patients with cirrhosis: • Monitoring should be performed for clinical signs and symptoms of hepatic decompensation (such as ascites, hepatic encephalopathy, variceal haemorrhage). • Hepatic laboratory testing including direct bilirubin levels should be performed at baseline, during the first 4 weeks of starting treatment and as clinically indicated thereafter.

• Treatment should be discontinued in patients who develop evidence of hepatic decompensation. Medicinal product no longer authorised 6 ALT elevations During clinical trials with Viekirax and dasabuvir with or without ribavirin, transient elevations of ALT to greater than 5 times the upper limit of normal occurred in approximately 1% of subjects (35 of 3,039).

ALT elevations were asymptomatic and generally occurred during the first 4 weeks of treatment, without concomitant elevations of bilirubin, and declined within approximately two weeks of onset with continued dosing of Viekirax and dasabuvir with or without ribavirin.

3). , oral and topical oestradiol and conjugated oestrogens) was similar to the rate observed in subjects who were not using oestrogen-containing products (approximately 1% in each group). e. 5). Although ALT elevations associated with Viekirax and dasabuvir have been asymptomatic, patients should be instructed to watch for early warning signs of liver inflammation, such as fatigue, weakness, lack of appetite, nausea and vomiting, as well as later signs such as jaundice and discoloured faeces, and to consult a doctor without delay if such symptoms occur.

1. 2). 5). 5). Examples are provided below. 5). Examples of contraindicated strong or moderate enzyme inducers are provided below. Enzyme inducers:  carbamazepine, phenytoin, phenobarbital  efavirenz, nevirapine, etravirine  apalutamide,enzalutamide  mitotane  rifampicin  St.

5). Examples of contraindicated strong CYP3A4 inhibitors are provided below. CYP3A4 inhibitors:  cobicistat  indinavir, lopinavir/ritonavir, saquinavir, tipranavir,  itraconazole, ketoconazole, posaconazole, voriconazole  clarithromycin, telithromycin  conivaptan