effects have been demonstrated in all animal species exposed to ribavirin; therefore, ribavirin is contraindicated in women who are pregnant and in the male partners of women who are pregnant. Women of childbearing potential and their male partners should not receive ribavirin unless they are using an effective form of contraception during treatment with ribavirin and for 6 months after treatment. Ethinylestradiol is contraindicated in combination with Exviera (see section 4.3). See additional information on specific hormonal contraceptives in sections 4.3 and 4.4.
Pregnancy
There are very limited data from the use of Exviera in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Exviera during pregnancy.
If ribavirin is co-administered with Exviera and ombitasvir/paritaprevir/ritonavir, the contraindications regarding use of ribavirin during pregnancy apply (see also the Summary of Product Characteristics of ribavirin).
Breast-feeding
It is not known whether dasabuvir and metabolites are excreted in human breast milk. Available pharmacokinetic data in animals have shown excretion of dasabuvir and metabolites in milk (see section 5.3). Because of the potential for adverse reactions from the medicinal product in breastfed infants, a decision must be made whether to discontinue breastfeeding or discontinue treatment with Exviera, taking into account the importance of the therapy to the mother. Patients receiving ribavirin should also refer to the Summary of Product Characteristics of ribavirin.
Fertility
No human data on the effect of dasabuvir on fertility are available. Animal studies do not indicate harmful effects on fertility (see section 5.3).
4.7 Effects on ability to drive and use machines
Patients should be informed that fatigue has been reported during treatment with Exviera in combination with ombitasvir/paritaprevir/ritonavir and ribavirin (see section 4.8).
4.8 Undesirable effects
Summary of the safety profile
The safety summary is based on pooled data from phase 2 and 3 clinical trials in more than 2,600 subjects who received Exviera and ombitasvir/paritaprevir/ritonavir with or without ribavirin.
Exviera and ombitasvir/paritaprevir/ritonavir with ribavirin (including subjects with compensated cirrhosis)
In subjects receiving Exviera and ombitasvir/paritaprevir/ritonavir with ribavirin, the most commonly reported adverse reactions (greater than 20% of subjects) were fatigue and nausea. The proportion of subjects who permanently discontinued treatment due to adverse reactions was 0.2% (5/2,044). 0.2% (5/2,044) of subjects interrupted treatment due to adverse reactions. 4.8% (99/2,044) of subjects had ribavirin dose reductions due to adverse reactions.
With the exception of increased rates of transient hyperbilirubinemia, the safety profile of Exviera and ombitasvir/paritaprevir/ritonavir with ribavirin in subjects with compensated cirrhosis was similar to that of subjects without cirrhosis.
Exviera and ombitasvir/paritaprevir/ritonavir without ribavirin:
No subjects permanently discontinued treatment or had treatment interruptions due to adverse reactions.
Tabulated list of adverse reactions
Table 3 lists adverse reactions for which a causal relationship between dasabuvir, in combination with ombitasvir/paritapre |
