ALYFTREK

Alyftrek should only be prescribed by healthcare professionals with experience in the treatment of CF. 1). Monitoring of transaminases (ALT and AST) and total bilirubin is recommended for all patients prior to initiating treatment, every 3 months during the first year of treatment and annually thereafter.

4). Posology Adults and paediatrics aged 6 years and older should be dosed according to Table 1.

Table 1:

Dosing recommendation for people with CF aged 6 years and older Age Weight Daily Dose (once daily) 6 to < 12 years < 40 kg Three tablets of deutivacaftor 50 mg/tezacaftor 20 mg/vanzacaftor 4 mg (total dose of deutivacaftor 150 mg/tezacaftor 60 mg/vanzacaftor 12 mg) 6 to < 12 years ≥ 40 kg ≥ 12 years Any weight Two tablets of deutivacaftor 125 mg/ tezacaftor 50 mg/ vanzacaftor 10 mg (total dose of deutivacaftor 250 mg/tezacaftor 100 mg/vanzacaftor 20 mg) Each dose should be taken in its entirety with fat-containing food once daily at approximately the same time each day (see Method of administration).

Missed dose If 6 hours or less have passed since the missed dose, the missed dose should be taken as soon as possible, and the original schedule should be continued the next day. If more than 6 hours have passed since the missed dose, the missed dose should be skipped, and the original schedule should be continued the next day.

5). 5).

Table 2:

Dosing schedule for concomitant use of Alyftrek with moderate or strong CYP3A inhibitors Age Weight Moderate CYP3A Inhibitors Strong CYP3A Inhibitors 6 to < 12 years < 40 kg Two tablets of deutivacaftor 50 mg/ tezacaftor 20 mg/vanzacaftor 4 mg every other day (total dose of deutivacaftor 100 mg/tezacaftor 40 mg/vanzacaftor 8 mg) Two tablets of deutivacaftor 50 mg/ tezacaftor 20 mg/ vanzacaftor 4 mg once a week (total dose of deutivacaftor 100 mg/tezacaftor 40 mg/vanzacaftor 8 mg) 6 to < 12 years ≥ 40 kg ≥ 12 years Any weight One tablet of deutivacaftor 125 mg/ tezacaftor 50 mg/ vanzacaftor 10 mg every other day One tablet of deutivacaftor 125 mg/ tezacaftor 50 mg/vanzacaftor 10 mg once a week Special populations Elderly population Clinical studies of Alyftrek did not include a sufficient number of people with CF aged 65 years and older to determine whether they respond differently from younger people with CF.

Summary of the safety profile The safety profile of Alyftrek is based on data from 480 participants aged 12 years and older in two randomized, ivacaftor/tezacaftor/elexacaftor (IVA/TEZ/ELX)- controlled phase 3 studies (studies 121-102 and 121-103) with 52 weeks of treatment duration.

In both studies, all subjects participated in a 4-week run-in period with IVA/TEZ/ELX. 8%. 4%). 1%). Tabulated list of adverse reactions Table 3 shows overall incidence of adverse drug reactions of people with CF treated with Alyftrek.

Adverse drug reactions for Alyftrek are ranked under the MedDRA frequency classification: 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); very rare (< 1/10,000); not known (cannot be estimated from the available data).

Table 3:

Adverse reactions by preferred term, frequency System Organ Class (SOC) Adverse Drug Reactions (Preferred Term) Frequency for Alyftrek Nervous system disorders Headache very common Gastrointestinal disorders Diarrhoea very common Alanine aminotransferase increased common Hepatobiliary disorders Aspartate aminotransferase increased common Skin and subcutaneous tissue disorders Rash common Investigations Blood creatine phosphokinase increased common Safety data from the following studies were generally consistent with the safety data observed in studies 121-102 and 121-103: • A 24-week, open-label study (study 121-105, Cohort B1) in 78 people with CF aged 6 to less than 12 years.

0% with Alyftrek. 0% with Alyftrek. 5% discontinued treatment for elevated transaminases. 8%, respectively. 0% with Alyftrek. The rash events were generally mild to moderate in severity. 0% in females. A role for hormonal contraceptives in the occurrence of rash cannot be excluded.

For people with CF taking hormonal contraceptives who develop rash, consider interrupting Alyftrek and hormonal contraceptives. Following the resolution of rash, consider resuming Alyftrek without the hormonal contraceptives. If rash does not recur, resumption of hormonal contraceptives can be considered.

Elevated transaminases and hepatic injury Elevated transaminases are common in people with CF and have been observed in some people with CF treated with Alyftrek. Assessments of transaminases (ALT and AST) and total bilirubin are recommended for all people with CF prior to initiating Alyftrek, every 3 months during the first year of treatment, and annually thereafter.

For people with CF with a history of liver disease or transaminase elevations, more frequent monitoring should be considered. In the event of ALT or AST > 5 × the upper limit of normal (ULN), or ALT or AST > 3 × ULN with bilirubin > 2 × ULN, dosing should be interrupted and laboratory tests closely followed until the abnormalities resolve.

2). , cirrhosis, portal hypertension) and only if the benefits are expected to outweigh the risks. 2). 5). CYP3A inhibitors Exposures to VNZ, TEZ and D-IVA are increased when co-administered with moderate or strong CYP3A inhibitors. 5).

Cataracts Cases of non-congenital lens opacities without impact on vision have been reported in people with CF aged less than 18 years treated with ivacaftor (IVA)-containing regimens. Although other risk factors were present in some cases (such as corticosteroid use, exposure to radiation) a possible risk attributable to treatment with IVA cannot be excluded.

3). Excipients with known effect Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

1.