KALYDECO

Kalydeco should only be prescribed by physicians with experience in the treatment of cystic fibrosis. 1). The phase of the poly-T variant identified with the R117H mutation should be determined in accordance with local clinical recommendation.

Posology Infants aged at least 1 month, toddlers, children, adolescents and adults should be dosed according to Table 1. 4 mg granules 3 months to less than 6 months ≥ 3 kg One sachet of ivacaftor 25 mg granules One sachet of ivacaftor 25 mg granules ≥ 5 kg to < 7 kg One sachet of ivacaftor 25 mg granules One sachet of ivacaftor 25 mg granules ≥ 7 kg to < 14 kg One sachet of ivacaftor 50 mg granules One sachet of ivacaftor 50 mg granules ≥ 14 kg to < 25 kg One sachet of ivacaftor 75 mg granules One sachet of ivacaftor 75 mg granules 6 months and older ≥ 25 kg See Kalydeco tablets SmPC for further details.

5 mg granules 2 years to less than 6 years ≥ 14 kg One sachet of ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg granules One sachet of ivacaftor 75 mg granules Ivacaftor is not recommended for use in children under 1 month of age.

† Use of ivacaftor in patients aged 1 to less than 6 months born at a gestational age < 37 weeks has not been evaluated. The morning and evening dose should be taken approximately 12 hours apart with fat- containing food (see Method of administration).

Missed dose If 6 hours or less have passed since the missed morning or evening dose, the patient should be advised to take it as soon as possible and then take the next dose at the regularly scheduled time. If more than 6 hours have passed since the time the dose is usually taken, the patient should be advised to wait until the next scheduled dose.

Patients receiving Kalydeco in a combination regimen should be advised not to take more than one dose of either medicinal product at the same time. Concomitant use of CYP3A inhibitors When co-administered with moderate or strong inhibitors of CYP3A, either as monotherapy or in a combination regimen with ivacaftor/tezacaftor/elexacaftor, in patients aged 6 months and older, the dosing should be reduced (see Table 2 for the recommended dosing).

Treatment with ivacaftor is not recommended when co-administered with moderate or strong inhibitors of CYP3A in patients aged 4 months to less than 6 months, unless the benefits outweigh the risks. In such cases, the dosing should be reduced (see Table 2 for dosing recommendations).

8%). 5% of placebo-treated patients. 8%). 4). Tabulated list of adverse reactions Table 4 reflects the adverse reactions observed with ivacaftor in clinical trials (placebo-controlled and uncontrolled studies) in which the length of exposure to ivacaftor ranged from 16 weeks to 144 weeks.

The frequency of adverse reactions is 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); very rare (< 1/10,000); not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 4:

Adverse reactions System organ class Adverse reactions Frequency Upper respiratory tract infection very common Nasopharyngitis very common Influenza* common Infections and infestations Rhinitis common Metabolism and nutrition disorders Hypoglycaemia* common Headache very commonNervous system disorders Dizziness very common Ear pain commonEar and labyrinth disorders Ear discomfort common System organ class Adverse reactions Frequency Tinnitus common Tympanic membrane hyperaemia common Vestibular disorder common Ear congestion uncommon Oropharyngeal pain very common Nasal congestion very common Abnormal breathing* common Rhinorrhoea* common Sinus congestion common Pharyngeal erythema common Respiratory, thoracic and mediastinal disorders Wheezing* uncommon Abdominal pain very common Diarrhoea very common Abdominal pain upper* common Gastrointestinal disorders Flatulence* common Transaminase elevations very common Alanine aminotransferase increased* common Aspartate aminotransferase increased* common Liver injury† not known Hepatobiliary disorders Total bilirubin elevations† not known Rash very common Acne* common Skin and subcutaneous tissue disorders Pruritus* common Breast mass common Breast inflammation uncommon Gynaecomastia uncommon Nipple disorder uncommon Reproductive system and breast disorders Nipple pain uncommon Bacteria in sputum very common Blood creatine phosphokinase increased* common Investigations Blood pressure increased* uncommon * Adverse reaction and frequency reported from clinical studies with ivacaftor in combination with ivacaftor/tezacaftor/elexacaftor.

1). 1). In study 5, four patients with the G970R mutation were included. In three of four patients the change in the sweat chloride test was < 5 mmol/L and this group did not demonstrate a clinically relevant improvement in FEV1 after 8 weeks of treatment.

1). 1). Therefore, use of ivacaftor as monotherapy in these patients is not recommended. Elevated transaminases and hepatic injury In a patient with cirrhosis and portal hypertension, liver failure leading to transplantation has been reported while receiving ivacaftor in a combination regimen with ivacaftor/tezacaftor/elexacaftor.

, cirrhosis, portal hypertension) and only if the benefits are expected to outweigh the risks. 2). Moderate transaminase (alanine transaminase [ALT] or aspartate transaminase [AST]) elevations are common in subjects with CF. Transaminase elevations have been observed in some patients treated with ivacaftor as monotherapy and in combination regimens with ivacaftor/tezacaftor/elexacaftor.

In patients taking ivacaftor in a combination regimen with ivacaftor/tezacaftor/elexacaftor, these elevations have sometimes been associated with concomitant elevations in total bilirubin. Therefore, assessments of transaminases (ALT and AST) and total bilirubin are recommended for all patients prior to initiating ivacaftor, every 3 months during the first year of treatment and annually thereafter.

For all patients with a history of liver disease or transaminase elevations, more frequent monitoring of liver function tests should be considered. , patients with 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). Hepatic impairment Use of ivacaftor, either as monotherapy or in a combination regimen with ivacaftor/tezacaftor/elexacaftor, is not recommended in patients with severe hepatic impairment unless the benefits are expected to outweigh the risks.

1.