Additional drug-drug interaction studies were performed with the following medical products and showed no clinically significant interactions with Maviret: abacavir, amlodipine, buprenorphine, caffeine, dextromethorphan, dolutegravir, emtricitabine, felodipine, lamivudine, lamotrigine, methadone, midazolam, naloxone, norethindrone or other progestin-only contraceptives, rilpivirine, tenofovir alafenamide and tolbutamide.
4.6 Fertility, pregnancy and lactation
Pregnancy
There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of glecaprevir or pibrentasvir in pregnant women.
Studies in rats/mice with glecaprevir or pibrentasvir do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Maternal toxicity associated with embryo-foetal loss has been observed in the rabbit with glecaprevir which precluded eva luation of glecaprevir at clinical exposures in this species (see section 5.3). As a precautionary measure, Maviret use is not recommended in pregnancy.
Breast-feeding
It is unknown whether glecaprevir or pibrentasvir are excreted in human milk. Available pharmacokinetic data in animals have shown excretion of glecaprevir and pibrentasvir in milk (for details see section 5.3). A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Maviret therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility
No human data on the effect of glecaprevir and/or pibrentasvir on fertility are available. Animal studies do not indicate harmful effects of glecaprevir or pibrentasvir on fertility at exposures higher than the exposures in humans at the recommended dose (see Section 5.3).
4.7 Effects on ability to drive and use machines
Maviret has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
Summary of the safety profile
The safety assessment of Maviret in subjects treated for 8, 12 or 16 weeks with compensated liver disease (with or without cirrhosis) was based on Phase 2 and 3 studies which eva luated approximately 2,300 subjects. The most commonly reported adverse reactions (incidence ≥ 10%) were headache and fatigue. Less than 0.1% of subjects treated with Maviret had serious adverse reactions (transient ischaemic attack). The proportion of subjects treated with Maviret who permanently discontinued treatment due to adverse reactions was 0.1%. The type and severity of adverse reactions in subjects with cirrhosis were overall comparable to those seen in subjects without cirrhosis.
Tabulated summary of adverse reactions
The following adverse reactions were identified in patients treated with Maviret. The adverse reactions are listed below by body 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).
Table 4: Adverse reactions identified with Maviret
Description of selected adverse reactions
Adverse reactions in subjects with severe renal impairment including subjects on dialysis
The safety of Maviret in subjects with chronic kidney disease (Stage 4 or Stage 5 including subjects on dialysis) and genotypes 1, 2, 3, 4, 5 or 6 chronic HCV infection with compensated liver disease (with or wit |
