effects have been demonstrated in all animal species exposed to ribavirin (see section 4.4). Women of childbearing potential or their male partners must use an effective form of contraception during treatment and for a period of time after the treatment has concluded as recommended in the Summary of Product Characteristics for ribavirin. Refer to the Summary of Product Characteristics for ribavirin for additional information.
Pregnancy
There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of sofosbuvir in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. No effects on foetal development have been observed in rats and rabbits at the highest doses tested. However, it has not been possible to fully estimate exposure margins achieved for sofosbuvir in the rat relative to the exposure in humans at the recommended clinical dose (see section 5.3).
As a precautionary measure, it is preferable to avoid the use of Sovaldi during pregnancy.
However, if ribavirin is co-administered with sofosbuvir, the contraindications regarding use of ribavirin during pregnancy apply (see also the Summary of Product Characteristics for ribavirin).
Breast-feeding
It is unknown whether sofosbuvir and its metabolites are excreted in human milk.
Available pharmacokinetic data in animals has shown excretion of metabolites in milk (for details see section 5.3).
A risk to newborns/infants cannot be excluded. Therefore, Sovaldi should not be used during breast-feeding.
Fertility
No human data on the effect of Sovaldi on fertility are available. Animal studies do not indicate harmful effects on fertility.
4.7 Effects on ability to drive and use machines
Sovaldi has moderate influence on the ability to drive and use machines. Patients should be informed that fatigue and disturbance in attention, dizziness and blurred vision have been reported during treatment with sofosbuvir in combination with peginterferon alfa and ribavirin (see section 4.8).
4.8 Undesirable effects
Summary of the safety profile
During treatment with sofosbuvir in combination with ribavirin or with peginterferon alfa and ribavirin, the most frequently reported adverse drug reactions were consistent with the expected safety profile of ribavirin and peginterferon alfa treatment, without increasing the frequency or severity of the expected adverse drug reactions.
Assessment of adverse reactions is based on pooled data from five Phase 3 clinical studies (both controlled and uncontrolled).
The proportion of subjects who permanently discontinued treatment due to adverse reactions was 1.4% for subjects receiving placebo, 0.5% for subjects receiving sofosbuvir + ribavirin for 12 weeks, 0% for subjects receiving sofosbuvir + ribavirin for 16 weeks, 11.1% for subjects receiving peginterferon alfa + ribavirin for 24 weeks and 2.4% for subjects receiving sofosbuvir + peginterferon alfa + ribavirin for 12 weeks.
Tabulated summary of adverse reactions
Sovaldi has mainly been studied in combination with ribavirin, with or without peginterferon alfa. In this context, no adverse drug reactions specific to sofosbuvir have been identified. The most common adverse drug reactions occurring in subjects receiving sofosbuvir and ribavirin or sofosbuvir, ribavirin and peginterferon alfa were fatigue, headache, nausea and ins
