Drugs List

Therapeutic Indications

Uses

Cystic fibrosis

Lumacaftor with ivacaftor is indicated for the treatment of cystic fibrosis in patients aged 2 years and older who are homozygous for the F508 del mutation in the CFTR gene.

Contraindications

Children under 2 years
Organ transplant recipients
Breastfeeding

Precautions and Warnings

Children aged 2 to 6 years
Elderly
Percentage predicted FEV1 <40%
Cirrhosis with portal hypertension
Moderate hepatic impairment
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
Treatment to be initiated and supervised by a specialist
Tablet formulation not suitable for children under 6 years
Take with food - particularly high fat food
Children: monitor ophthalmic function prior and during treatment
Perform liver function tests before commencing therapy
Monitor blood pressure
Monitor liver function every 3 months during first year then periodically
Reduce dose in hepatic impairment where Child Pugh greater than 7
% predicted FEV1<40: consider stopping if serious respiratory events occur
May affect results of some laboratory tests
Discontinue at first signs of jaundice
Discontinue if AST/ALT > 3 x ULN and bilirubin > 2 x ULN
Discontinue treatment if AST/ALT >5 times upper limit of normal
Advise patient not to take St John's wort concurrently
Female: Effect of hormonal contraceptive may be reduced

Pregnancy and Lactation

Pregnancy

Use lumacaftor with ivacaftor with caution during pregnancy.

The manufacturer notes that it is preferable to avoid the use of this medication during pregnancy unless the clinical condition of the mother requires its treatment.

There is a limited amount of data (less than 300 pregnancy outcomes) from the use of lumacaftor with ivacaftor in pregnant women. Animal studies with lumacaftor and ivacaftor do not indicate direct or indirect harmful effects with respect to developmental and reproductive toxicity, whereas effects were noted with ivacaftor only at maternally toxic doses.

Lactation

Lumacaftor with ivacaftor is contraindicated during breastfeeding.

The manufacturer notes that a decision must be made whether to discontinue breastfeeding or to discontinue/abstain from this medication, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.

It is unknown whether lumacaftor and/or ivacaftor and metabolites are excreted in human milk. Data in animals has shown excretion of both into the milk of lactating female rats. Risks to the suckling child cannot be excluded.

Side Effects

Abdominal pain
Amenorrhoea
Bacteria sputum identified
Breast inflammation
Breast mass
Bronchospasm
Cataracts
Chest discomfort
Cholestatic hepatitis
Creatine phosphokinase increased
Diarrhoea
Dizziness
Dysmenorrhoea
Dyspnoea
Ear congestion
Ear discomfort
Ear pain
Flatulence
Gynaecomastia
Headache
Hepatic encephalopathy
Hypertension
Increase in serum transaminases
Increased blood pressure
Increased sputum
Irregular menstruation
Menorrhagia
Metrorrhagia
Nasal congestion
Naso-sinus congestion
Nasopharyngitis
Nausea
Nipple discomfort
Oligomenorrhoea
Oropharyngeal pain
Pharyngeal erythema
Polymenorrhoea
Productive cough
Rash
Respiratory symptoms
Rhinitis
Rhinorrhoea
Tinnitus
Tympanic membrane disorder
Upper abdominal pain
Upper respiratory tract infection
Vestibular disorders
Vomiting

Presentation

Oral formulations of lumacaftor with ivacaftor.

Drugs List

Therapeutic Indications

Uses

Cystic fibrosis

Lumacaftor with ivacaftor is indicated for the treatment of cystic fibrosis in patients aged 2 years and older who are homozygous for the F508 del mutation in the CFTR gene.

Dosage

Lumacaftor with ivacaftor should only be prescribed by physicians with experience in the treatment of cystic fibrosis. If the patient's genotype is unknown, an accurate and validated genotyping method should be performed to confirm the presence of the F508 del mutation on both alleles of the CFTR gene before starting treatment.

This medication should be taken with fat-containing food. A fat-containing meal or snack should be consumed just before or just after dosing.

Sachets: Mix the contents of a sachet of granules with one teaspoon (5ml) of age-appropriate soft food or liquid (for example pureed fruits, yogurt, milk, juice) ready for consumption and consume within one hour.

Adults

Children

Patients with Hepatic Impairment

Additional Dosage Information

Contraindications

Children under 2 years
Organ transplant recipients
Breastfeeding

Precautions and Warnings

Children aged 2 to 6 years
Elderly
Percentage predicted FEV1 <40%
Cirrhosis with portal hypertension
Moderate hepatic impairment
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
Treatment to be initiated and supervised by a specialist
Tablet formulation not suitable for children under 6 years
Take with food - particularly high fat food
Children: monitor ophthalmic function prior and during treatment
Perform liver function tests before commencing therapy
Monitor blood pressure
Monitor liver function every 3 months during first year then periodically
Reduce dose in hepatic impairment where Child Pugh greater than 7
% predicted FEV1<40: consider stopping if serious respiratory events occur
May affect results of some laboratory tests
Discontinue at first signs of jaundice
Discontinue if AST/ALT > 3 x ULN and bilirubin > 2 x ULN
Discontinue treatment if AST/ALT >5 times upper limit of normal
Advise patient not to take St John's wort concurrently
Female: Effect of hormonal contraceptive may be reduced

Pregnancy and Lactation

Pregnancy

Use lumacaftor with ivacaftor with caution during pregnancy.

The manufacturer notes that it is preferable to avoid the use of this medication during pregnancy unless the clinical condition of the mother requires its treatment.

There is a limited amount of data (less than 300 pregnancy outcomes) from the use of lumacaftor with ivacaftor in pregnant women. Animal studies with lumacaftor and ivacaftor do not indicate direct or indirect harmful effects with respect to developmental and reproductive toxicity, whereas effects were noted with ivacaftor only at maternally toxic doses.

Lactation

Lumacaftor with ivacaftor is contraindicated during breastfeeding.

The manufacturer notes that a decision must be made whether to discontinue breastfeeding or to discontinue/abstain from this medication, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.

It is unknown whether lumacaftor and/or ivacaftor and metabolites are excreted in human milk. Data in animals has shown excretion of both into the milk of lactating female rats. Risks to the suckling child cannot be excluded.

Side Effects

Abdominal pain
Amenorrhoea
Bacteria sputum identified
Breast inflammation
Breast mass
Bronchospasm
Cataracts
Chest discomfort
Cholestatic hepatitis
Creatine phosphokinase increased
Diarrhoea
Dizziness
Dysmenorrhoea
Dyspnoea
Ear congestion
Ear discomfort
Ear pain
Flatulence
Gynaecomastia
Headache
Hepatic encephalopathy
Hypertension
Increase in serum transaminases
Increased blood pressure
Increased sputum
Irregular menstruation
Menorrhagia
Metrorrhagia
Nasal congestion
Naso-sinus congestion
Nasopharyngitis
Nausea
Nipple discomfort
Oligomenorrhoea
Oropharyngeal pain
Pharyngeal erythema
Polymenorrhoea
Productive cough
Rash
Respiratory symptoms
Rhinitis
Rhinorrhoea
Tinnitus
Tympanic membrane disorder
Upper abdominal pain
Upper respiratory tract infection
Vestibular disorders
Vomiting

Effects on Laboratory Tests

Lumacaftor with ivacaftor may give false positive tetrahydrocannabinol (THC) urine screening test. An alternative test should be considered to confirm results.

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: January 2021

Reference Sources

Summary of Product Characteristics: Orkambi 100mg/125mg and 200mg/125mg film-coated tablets. Vertex Pharmaceuticals (Europe) Limited. Revised November 2020.

Summary of Product Characteristics: Orkambi 100mg/125mg and 150mg/188mg granules in sachet. Vertex Pharmaceuticals (Europe) Limited. Revised November 2020.