Update to 4.4    Special warnings and precautions for use - Rash events

Rash events typically occur during the first month of therapy. Most events were mild to moderate in severity and in rare cases, rash was associated with additional symptoms such as fever or facial swelling. In the majority of cases, administration of IVA/TEZ/ELX was continued and the rash resolved without treatment. Children have a higher incidence rate compared to adults. The incidence of rash events was also higher in females compared to males, particularly in females taking hormonal contraceptives (see section 4.8). A role for hormonal contraceptives in the occurrence of rash cannot be excluded. For patients taking hormonal contraceptives who develop rash, interrupting treatment with IVA/TEZ/ELX in combination with IVA and hormonal contraceptives should be considered. Following the resolution of rash, it should be considered if resuming IVA/TEZ/ELX in combination with IVA without hormonal contraceptives is appropriate. If rash does not recur, resumption of hormonal contraceptives can be considered (see section 4.8).

Update to 4.6    Fertility, pregnancy and lactation - Breast-feeding

Limited data show that ELX, TEZ, and IVA are excreted in human milk and have been quantified in plasma of breastfed newborns/infants of treated women. There is insufficient information on the effects of IVA/TEZ/ELX in newborns/infants. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from IVA/TEZ/ELX therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Update to 4.8    Undesirable effects Table 4 Adverse reactions

Immune system disorders - Hypersensitivity - not known

Rash events

Studies in IVA/TEZ/ELX-treated patients above 12 years of age showed an incidence of rash events (e.g., rash, rash pruritic) of 10.9% (study 445-102) compared to 6.5% in placebo‑treated patients. The paediatric population showed a higher incidence rate (see section Paediatric population for further details). The incidence of rash events by patient sex was 5.8% in males and 16.3% in females in IVA/TEZ/ELX-treated patients and 4.8% in males and 8.3% in females in placebo-treated patients. In patients treated with IVA/TEZ/ELX, the incidence of rash events was 20.5% in females taking hormonal contraceptive and 13.6% in females not taking hormonal contraceptive (see section 4.4).

Overall, rash events typically occur during the first month of therapy. Most events were mild to moderate in severity, and in rare cases, rash was associated with additional symptoms such as fever or facial swelling. In the majority of cases, administration of IVA/TEZ/ELX was continued and the rash resolved without treatment.

Rash

While studies in patients above 12 years of age showed an incidence rate of 10.9% (study 445-102), patients between 6 and 11 years of age had an incidence rate of 24.2% (study 445-106). During study 445-111 in patients aged 2 to less than 6 years, 15 (20.0%) subjects had at least 1 rash event, 4 (9.8%) females and 11 (32.4%) males.

Update to Possible side effects to add - Rash (more common in children, and in women compared to men) and Allergic reactions (hypersensitivity)