Drugs List

Therapeutic Indications

Uses

Cystic fibrosis

Tablets
Monotherapy treatment of patients aged 6 years and above weighing more than 25kg with cystic fibrosis who have the R117H mutation.

If the patient's genotype is unknown, an accurate and validated genotyping method should be performed to confirm the presence of the G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R or R117H mutations in at least one allele of the CFTR gene before starting treatment. The phase of the poly-T variant identified with the R117H mutation should be determined in accordance with local clinical recommendations.

Combination treatment with ivacaftor and tezacaftor tablets of patients aged 6 years and above with cystic fibrosis who are homozygous for F508del mutation, or heterozygous for F508del mutation and have one of the following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A to G, S945L, S977F, R1070W, D1152H, 2789+5G to A, 3272-26A to G and 3849+10kbC to T.

Combination treatment with ivacaftor, tezacaftor and elexacaftor tablets of patients aged 6 years and older with cystic fibrosis who are homozygous for the F508del mutation in the CFTR gene or heterozygous for F508del and have minimal function mutation in the CFTR gene.

Granules
Treatment of patients aged 4 months and above weighing 5kg to less than 25kg with cystic fibrosis who have an R117H CFTR mutation.

If the patient's genotype is unknown, an accurate and validated genotyping method should be performed to confirm the presence of the G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R mutations in at least one allele of the CFTR gene before starting treatment.

Contraindications

Children under 4 months
Organ transplant recipients
Galactosaemia

Precautions and Warnings

Children aged 4 months to 18 years
Breastfeeding
Elevated serum transaminases
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
Hepatic impairment - Child-Pugh score between 7 and 9
Lactose intolerance
Portal hypertension
Pregnancy
Renal impairment - creatinine clearance below or equal to 30ml/minute

Advise patient dizziness may affect ability to drive or operate machinery
Confirm relevant CFTR gene mutation before start of treatment
Not all formulations are suitable for all age groups/body weights
Treatment to be initiated and supervised by a specialist
Contains lactose
Take with food - particularly high fat food
Children: monitor ophthalmic function prior and during treatment
Perform liver function tests before commencing therapy
Monitor liver function every 3 months during first year then periodically
Reduce dose in hepatic impairment where Child Pugh greater than 7
Interrupt treatment if ALT or AST > 5 x ULN
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level

Liver failure leading to transplantation has been reported from patients with cirrhosis and portal hypertension while receiving ivacaftor in a combination regimen with ivacaftor/tezacaftor/elexacaftor. Where transaminase and bilirubin elevations have occurred and treatment interrupted, the benefits and risks of resuming treatment should be considered upon resolution of any abnormalities.

Patients taking hormonal contraceptives who develop a rash should consider interrupting treatment with ivacaftor in a combination regimen. Following resolution it should be considered if treatment is appropriate to resume. If the rash does not re-appear treatment resumption can be considered.

Pregnancy and Lactation

Pregnancy

Use ivacaftor with caution during pregnancy.

The manufacturer suggests it is preferable to avoid ivacaftor treatment during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus. Animal toxicity studies have revealed no evidence of harm to the foetus due to ivacaftor. At the time of writing there is limited human data available. Risks are unknown.

Lactation

Use ivacaftor with caution during breastfeeding.

The manufacturer recommends discontinuing ivacaftor while breastfeeding considering the benefit of therapy for the mother and the benefit of breastfeeding for the child. It is unknown whether ivacaftor and/or its metabolites are excreted in human milk. Ivacaftor was shown to be excreted into the milk of lactating female rats. The safe use of this medication during breastfeeding has not been established.

Side Effects

Abdominal pain
Alanine aminotransferase increased
Aspartate aminotransferase increased
Bacteria sputum identified
Breast inflammation
Breast mass
Diarrhoea
Dizziness
Ear congestion
Ear discomfort
Ear pain
Gynaecomastia
Headache
Increase in serum transaminases
Lens opacities
Liver damage
Nasal congestion
Naso-sinus congestion
Nasopharyngitis
Nipple discomfort
Oropharyngeal pain
Pharyngeal erythema
Rash
Rhinitis
Serum bilirubin increased
Tinnitus
Tympanic membrane disorder
Upper respiratory tract infection
Vestibular disorders

Presentation

Oral formulations of ivacaftor.

Drugs List

Therapeutic Indications

Uses

Cystic fibrosis

Tablets
Monotherapy treatment of patients aged 6 years and above weighing more than 25kg with cystic fibrosis who have the R117H mutation.

If the patient's genotype is unknown, an accurate and validated genotyping method should be performed to confirm the presence of the G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R or R117H mutations in at least one allele of the CFTR gene before starting treatment. The phase of the poly-T variant identified with the R117H mutation should be determined in accordance with local clinical recommendations.

Combination treatment with ivacaftor and tezacaftor tablets of patients aged 6 years and above with cystic fibrosis who are homozygous for F508del mutation, or heterozygous for F508del mutation and have one of the following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A to G, S945L, S977F, R1070W, D1152H, 2789+5G to A, 3272-26A to G and 3849+10kbC to T.

Combination treatment with ivacaftor, tezacaftor and elexacaftor tablets of patients aged 6 years and older with cystic fibrosis who are homozygous for the F508del mutation in the CFTR gene or heterozygous for F508del and have minimal function mutation in the CFTR gene.

Granules
Treatment of patients aged 4 months and above weighing 5kg to less than 25kg with cystic fibrosis who have an R117H CFTR mutation.

If the patient's genotype is unknown, an accurate and validated genotyping method should be performed to confirm the presence of the G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R mutations in at least one allele of the CFTR gene before starting treatment.

Dosage

This medication should be taken with fat-containing food.

Food containing grapefruit should be avoided during treatment with this medication.

Adults

Children

Patients with Hepatic Impairment

Additional Dosage Information

Contraindications

Children under 4 months
Organ transplant recipients
Galactosaemia

Precautions and Warnings

Children aged 4 months to 18 years
Breastfeeding
Elevated serum transaminases
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
Hepatic impairment - Child-Pugh score between 7 and 9
Lactose intolerance
Portal hypertension
Pregnancy
Renal impairment - creatinine clearance below or equal to 30ml/minute

Advise patient dizziness may affect ability to drive or operate machinery
Confirm relevant CFTR gene mutation before start of treatment
Not all formulations are suitable for all age groups/body weights
Treatment to be initiated and supervised by a specialist
Contains lactose
Take with food - particularly high fat food
Children: monitor ophthalmic function prior and during treatment
Perform liver function tests before commencing therapy
Monitor liver function every 3 months during first year then periodically
Reduce dose in hepatic impairment where Child Pugh greater than 7
Interrupt treatment if ALT or AST > 5 x ULN
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level

Liver failure leading to transplantation has been reported from patients with cirrhosis and portal hypertension while receiving ivacaftor in a combination regimen with ivacaftor/tezacaftor/elexacaftor. Where transaminase and bilirubin elevations have occurred and treatment interrupted, the benefits and risks of resuming treatment should be considered upon resolution of any abnormalities.

Patients taking hormonal contraceptives who develop a rash should consider interrupting treatment with ivacaftor in a combination regimen. Following resolution it should be considered if treatment is appropriate to resume. If the rash does not re-appear treatment resumption can be considered.

Pregnancy and Lactation

Pregnancy

Use ivacaftor with caution during pregnancy.

The manufacturer suggests it is preferable to avoid ivacaftor treatment during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus. Animal toxicity studies have revealed no evidence of harm to the foetus due to ivacaftor. At the time of writing there is limited human data available. Risks are unknown.

Lactation

Use ivacaftor with caution during breastfeeding.

The manufacturer recommends discontinuing ivacaftor while breastfeeding considering the benefit of therapy for the mother and the benefit of breastfeeding for the child. It is unknown whether ivacaftor and/or its metabolites are excreted in human milk. Ivacaftor was shown to be excreted into the milk of lactating female rats. The safe use of this medication during breastfeeding has not been established.

Side Effects

Abdominal pain
Alanine aminotransferase increased
Aspartate aminotransferase increased
Bacteria sputum identified
Breast inflammation
Breast mass
Diarrhoea
Dizziness
Ear congestion
Ear discomfort
Ear pain
Gynaecomastia
Headache
Increase in serum transaminases
Lens opacities
Liver damage
Nasal congestion
Naso-sinus congestion
Nasopharyngitis
Nipple discomfort
Oropharyngeal pain
Pharyngeal erythema
Rash
Rhinitis
Serum bilirubin increased
Tinnitus
Tympanic membrane disorder
Upper respiratory tract infection
Vestibular disorders

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: February 2021

Reference Sources

Summary of Product Characteristics: Kalydeco 25mg granules sachets. Vertex Pharmaceuticals (Europe) Ltd. Revised November 2020.

Summary of Product Characteristics: Kalydeco 50mg granules sachets. Vertex Pharmaceuticals (Europe) Ltd. Revised November 2020.

Summary of Product Characteristics: Kalydeco 75mg granules sachets. Vertex Pharmaceuticals (Europe) Ltd. Revised November 2020.

Summary of Product Characteristics: Kalydeco 150mg tablets. Vertex Pharmaceuticals (Europe) Ltd. Revised April 2022.

Summary of Product Characteristics: Kalydeco 75mg tablets. Vertex Pharmaceuticals (Europe) Ltd. Revised April 2022.