Tezacaftor with ivacaftor oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulation of tezacaftor with ivacaftor.
Drugs List
Therapeutic Indications
Uses
Cystic fibrosis
Tezacaftor with ivacaftor is indicated in a combination regimen with ivacaftor 150mg tablets for the treatment of cystic fibrosis in patients aged 6 years and older who are homozygous for the F508 del mutation or who are heterozygous for the F508 del 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
3849+10kbC to T
Tezacaftor with ivacaftor should not be prescribed in patients with cystic fibrosis who are heterozygous for the F508del mutation and have a second CFTR mutation not listed above.
Dosage
Tezacaftor 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 an indicated mutation using a genotyping assay.
This medication should be taken with fat-containing food.
Adults
One tezacaftor with ivacaftor (100mg + 150mg) tablet taken in the morning and one ivacaftor (150mg) tablet taken in the evening, approximately 12 hours apart.
Children
Children over 12 years
One tezacaftor with ivacaftor (100mg + 150mg) tablet taken in the morning and one ivacaftor (150mg) tablet taken in the evening, approximately 12 hours apart.
Children aged 6 to 12 years weighing 30kg or more
One tezacaftor with ivacaftor (100mg + 150mg) tablet taken in the morning and one ivacaftor (150mg) tablet taken in the evening, approximately 12 hours apart.
Children aged 6 to 12 years weighing less than 30kg
One tezacaftor with ivacaftor (50mg + 75mg) tablet taken in the morning and one ivacaftor (75mg) tablet taken in the evening, approximately 12 hours apart.
Patients with Hepatic Impairment
Adults and children over 6 years old and weighing 30kg or more
Mild (Child-Pugh Class A): No dose adjustment required.
Moderate (Child-Pugh Class B): One tezacaftor with ivacaftor (100mg + 150mg) tablet taken in the morning. No ivacaftor 150mg dose in the evening.
Severe (Child-Pugh Class C): Use of tezacaftor with ivacaftor not recommended unless the benefits outweigh the risks. Starting dose of one tezacaftor with ivacaftor (100mg + 150mg) tablet taken in the morning and dosing intervals modified according to clinical response and tolerability. No ivacaftor 150mg dose in the evening.
Children aged 6 to 12 years and weighing less than 30kg
Mild (Child-Pugh Class A): No dose adjustment required.
Moderate (Child-Pugh Class B): One tezacaftor with ivacaftor (50mg + 75mg) tablet taken in the morning. No ivacaftor dose in the evening.
Severe (Child-Pugh Class C): Use of tezacaftor with ivacaftor not recommended unless the benefits outweigh the risks. Starting dose of one tezacaftor with ivacaftor (50mg + 75mg) tablet taken in the morning and dosing intervals modified according to clinical response and tolerability. No ivacaftor dose in the evening.
Additional Dosage Information
Missed Dose
If less than 6 hours have passed since the missed morning or evening dose, the patient should take the missed dose as soon as possible and then continue with the original schedule.
If more than 6 hours have passed since the missed morning or evening dose, the patient should not take the missed dose. The next scheduled dose can be taken at the usual time.
Use with moderate CYP3A inhibitors
Adults and children over 6 years old and weighing 30kg or more
When co-administered with moderate CYP3A inhibitors (for example fluconazole and erythromycin), the dose should be adjusted as follows:
Day 1: One tezacaftor with ivacaftor (100mg + 150mg) tablet taken in the morning
Day 2: One ivacaftor (150mg) tablet taken in the morning
Day 3: One tezacaftor with ivacaftor (100mg + 150mg) tablet taken in the morning
Day 4: One ivacaftor (150mg) tablet taken in the morning
Continue dosing with one tezacaftor with ivacaftor (100mg + 150mg) tablet or one ivacaftor (150mg) tablet on alternate days. No evening dose of ivacaftor should be taken.
Children aged 6 to 12 years and weighing less than 30kg
Day 1: One tezacaftor with ivacaftor (50mg + 75mg) tablet taken in the morning
Day 2: One ivacaftor (75mg) tablet taken in the morning
Day 3: One tezacaftor with ivacaftor (50mg + 75mg) tablet taken in the morning
Day 4: One ivacaftor (75mg) tablet taken in the morning
Continue dosing with one tezacaftor with ivacaftor (50mg + 75mg) tablet or one ivacaftor (75mg) tablet on alternate days. No evening dose of ivacaftor should be taken.
Use with strong CYP3A inhibitors
Adults and children over 6 years old and weighing 30kg or more
When co-administered with strong CYP3A inhibitors (for example ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin and clarithromycin), the dose should be adjusted to one tezacaftor with ivacaftor tablet (100mg + 150mg) twice a week, taken approximately 3 to 4 days apart. The evening dose of ivacaftor should not be taken.
Children aged 6 to 12 years and weighing less than 30kg
When co-administered with strong CYP3A inhibitors (for example ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin and clarithromycin), the dose should be adjusted to one tezacaftor with ivacaftor tablet (50mg + 75mg) twice a week, taken approximately 3 to 4 days apart. The evening dose of ivacaftor should not be taken.
Contraindications
Children under 6 years
Organ transplant recipients
Breastfeeding
Precautions and Warnings
Pregnancy
Severe hepatic impairment
Severe renal impairment
Reduce dose in moderate hepatic impairment (Child-Pugh Class B)
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
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
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 grapefruit products may increase plasma level
Advise patient to avoid grapefruit products
Pregnancy and Lactation
Pregnancy
Use the combination of tezacaftor and ivacaftor with caution during pregnancy.
The manufacturer notes that it is preferable to avoid the use of this medication during pregnancy. There is little data on the use of the combination of tezacaftor and ivacaftor in pregnant women (less that 300 pregnancy outcomes). Animal studies neither indicate direct or indirect harmful effects in respect to reproductive toxicity.
Lactation
The combination of tezacaftor and ivacaftor is contraindicated during breastfeeding.
The manufacturer notes a decision should be made whether to cease breastfeeding or stop taking the medication.
It is unknown whether tezacaftor, ivacaftor or their metabolites are excreted in human milk. Animal data has shown excretion of this medication into the milk of lactating female rats. Hence, a risk to the newborn/infant cannot be excluded.
Side Effects
Abdominal pain
Bacteria sputum identified
Breast inflammation
Breast mass
Diarrhoea
Dizziness
Ear congestion
Ear discomfort
Ear pain
Gynaecomastia
Headache
Increase in serum transaminases
Lens opacities
Naso-sinus congestion
Nasopharyngitis
Nausea
Nipple discomfort
Oropharyngeal pain
Pharyngeal erythema
Rash
Rhinitis
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: Symkevi 100mg/150mg film coated tablets. Vertex Pharmaceuticals (Europe) Limited. Revised November 2020.
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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