Elexacaftor and ivacaftor and tezacaftor oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of elexacaftor, ivacaftor and tezacaftor.
Drugs List
Therapeutic Indications
Uses
Cystic fibrosis
Elexacaftor, ivacaftor and tezacaftor are indicated in a combination with ivacaftor 150mg and 75mg tablets to treat cystic fibrosis (CF) in patients over the age of 6 years old who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
Dosage
Elexacaftor, ivacaftor and tezacaftor should only be prescribed by the healthcare professionals experienced in treating cystic fibrosis. Genotype of the patient should be confirmed for the presence of two or at least one F508del mutations.
Adults
2 tablets of elexacaftor and ivacaftor and tezacaftor (100mg+75mg+50mg) taken in the morning.
In the evening take one ivacaftor 150mg tablet (about 12 hours apart).
Children
Children aged 12 to 18 years:
See Dosage; Adult.
Children aged 6 to 12 years weighing greater than or equal to 30kg:
See Dosage; Adult.
Children aged 6 to 12 years weighing less than 30kg:
2 tablets of elexacaftor and ivacaftor and tezacaftor (50mg+37.5mg+25mg) taken in the morning.
In the evening take one ivacaftor 75mg tablet (about 12 hours apart).
Patients with Hepatic Impairment
Mild (Child-Pugh Class A): No dose adjustment required.
Moderate (Child-Pugh Class B): Use not recommended. If used: alternate each day between two elexacaftor, ivacaftor and tezacaftor tablets and one elexacaftor, ivacaftor and tezacaftor tablets. No ivacaftor dose in the evening.
Severe (Child-Pugh Class C): Should not be used.
Additional Dosage Information
Missed dose
If 6 hours or less have passed since the missed morning or evening dose, the patient should take the missed dose as soon as possible and continue on the original schedule.
If more than 6 hours have passed since the missed morning dose, the patient should take the missed dose as soon as possible and should not take the evening dose. The next scheduled morning dose should be taken at the usual time.
If more than 6 hours have passed since the missed evening dose, the patient should not take the missed dose. The next scheduled morning dose should be taken at the usual time.
Use with moderate CYP3A inhibitors
When co-administered with moderate CYP3A inhibitors (for example fluconazole, erythromycin and verapamil), the dose should be adjusted as follows:
Day 1: Two elexacaftor/ivacaftor/tezacaftor (100mg + 75mg + 50mg) tablets taken in the morning.
Day 2: One ivacaftor (150mg) tablet taken in the morning.
Day 3: Two elexacaftor/ivacaftor/tezacaftor (100mg + 75mg + 50mg) tablets taken in the morning.
Day 4: One ivacaftor (150mg) tablet taken in the morning
Continue dosing with two elexacaftor/ivacaftor/tezacaftor (100mg + 75mg + 50mg) tablets and one ivacaftor (150mg) tablet on alternate days. No evening dose of ivacaftor should be taken.
Use with strong CYP3A inhibitors
When co-administered with strong CYP3A inhibitors (for example ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin and clarithromycin), the dose should be adjusted as follows:
Day 1: Two elexacaftor/ivacaftor/tezacaftor (100mg + 75mg + 50mg) tablets taken in the morning.
Day 2: No dose
Day 3: No dose
Day 4: Two elexacaftor/ivacaftor/tezacaftor (100mg + 75mg + 50mg) tablets taken in the morning.
Continue dosing with two elexacaftor/ivacaftor/tezacaftor (100mg + 75mg + 50mg) tablets, taken approximately 3 to 4 days apart. The evening dose of ivacaftor should not be taken.
Contraindications
Children under 6 years
Organ transplant recipients
Severe hepatic impairment
Precautions and Warnings
Children 6 to 12 years
Breastfeeding
Moderate hepatic impairment
Pregnancy
Severe renal impairment
Reduce dose in moderate hepatic impairment (Child-Pugh Class B)
Advise ability to drive/operate machinery may be affected by side effects
Confirm relevant CFTR gene mutation before start of treatment
Treatment to be initiated and supervised by a specialist
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
Concurrent hormonal contraceptives may increase incidence of rash
Discontinue if AST or ALT level > 3x ULN and bilirubin > 2x ULN
Discontinue treatment if AST/ALT >5 times upper limit of normal
Advise patient not to take St John's wort concurrently
Advise patient Seville (sour) orange products may increase plasma level
Advise patient to avoid grapefruit products
Females taking hormonal contraceptives, who develop rash, should consider the interruption of treatment with elexacaftor, ivacaftor and tezacaftor in combination with ivacaftor. The treatment may be restarted after resolution of rash and without hormonal contraceptives if it is appropriate. If no new rash event recurs, the hormonal contraceptives may be restarted.
Pregnancy and Lactation
Pregnancy
Use elexacaftor, ivacaftor and tezacaftor with caution during pregnancy.
The manufacturer does not recommend using elexacaftor, ivacaftor and tezacaftor during pregnancy.
At the time of writing, there is limited data (less than 300 pregnancy outcomes) from the use of elexacaftor, ivacaftor or tezacaftor in pregnant women.
Animal studies does not indicate an increased risk of teratogenic or developmental effects.
Lactation
Use elexacaftor, ivacaftor and tezacaftor with caution during breastfeeding.
The manufacturer advises that the patient either discontinues the use of elexacaftor, ivacaftor and tezacaftor or discontinues breastfeeding.
Animal data reports the presence of elexacaftor, ivacaftor and tezacaftor in the breast milk however the presence in human milk is unknown and the risk to newborns and infants cannot be ruled out.
Side Effects
Abdominal pain
Acne
Alanine aminotransferase increased
Aspartate aminotransferase increased
Bacteria sputum identified
Breast inflammation
Breast mass
Creatine phosphokinase increased
Diarrhoea
Dizziness
Ear congestion
Ear discomfort
Ear pain
Flatulence
Gynaecomastia
Headache
Hyperaemia
Hypertension
Hypoglycaemia
Increase of liver transaminases
Influenza
Lens opacities
Liver damage
Nasal congestion
Naso-sinus congestion
Nasopharyngitis
Nausea
Nipple disorder
Nipple pain
Oropharyngeal pain
Pharyngeal erythema
Pruritus
Rash
Rhinitis
Rhinorrhoea
Serum bilirubin increased
Tinnitus
Unusual breathing patterns
Upper respiratory tract infection
Vestibular disorders
Wheezing
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 2022
Reference Sources
Summary of Product Characteristics: Kaftrio 75mg 50mg 100mg film coated tablets. Vertex Pharmaceuticals (Europe). Revised November 2021.
Summary of Product Characteristics: Kaftrio 37.5mg 25mg 50mg film coated tablets. Vertex Pharmaceuticals (Europe). Revised January 2022.
NICE Evidence Services
Available at: www.nice.org.uk
Last accessed: 06 October 2022
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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