Prescribing information for TRIKAFTA^® (elexacaftor/tezacaftor/ivacaftor and ivacaftor)

Please review the full Data Sheet before prescribing. The Data Sheet and Consumer Medicine Information for TRIKAFTA^® can be accessed via https://www.medsafe.govt.nz/

TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) Mini Data Sheet

Medicine classification: Prescription Medicine

Name of Product: TRIKAFTA [co‑pack]: 100 mg of elexacaftor, 50 mg of tezacaftor and 75 mg of ivacaftor as a fixed‑dose combination tablet and 150 mg of ivacaftor as a single tablet. TRIKAFTA [co‑pack]: 50 mg of elexacaftor, 25 mg of tezacaftor and 37.5 mg of ivacaftor as a fixed‑dose combination tablet and 75 mg of ivacaftor as a single tablet. Pack size of 84 tablets (56 elexacaftor/tezacaftor/ivacaftor tablets and 28 ivacaftor tablets).

Indication: TRIKAFTA is indicated for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Contraindication:  Hypersensitivity to the active substance or to any of the excipients.    

Precautions: Please refer to Data Sheet for complete list. Patients with severe hepatic impairment (Child-Pugh Class C) should not be treated with TRIKAFTA. Treatment of patients with moderate hepatic impairment (Child-Pugh Class B) is not recommended. For patients with moderate hepatic impairment, TRIKAFTA should only be used if there is a clear medical need and the benefits are expected to outweigh the risks. Please refer to Data Sheet for Dosage Adjustment. Assessments of transaminases (ALT and AST) are recommended for all patients prior to initiating TRIKAFTA, every 3 months during the first year of treatment, and annually thereafter. Liver failure leading to transplantation has been reported in a patient with cirrhosis and portal hypertension while receiving TRIKAFTA. TRIKAFTA should be used with caution in patients with pre-existing advanced liver disease (e.g., cirrhosis, portal hypertension) and only if the benefits are expected to outweigh the risks. If used in these patients, they should be closely monitored after the initiation of treatment. Cases of non‑congenital lens opacities have been reported in paediatric patients treated with ivacaftor‑containing regimens. Baseline and follow‑up ophthalmological examinations are recommended in paediatric patients initiating treatment with TRIKAFTA.

Interactions: Please refer to Data Sheet for complete list.  Elexacaftor, tezacaftor and ivacaftor are substrates of CYP3A. Concomitant use of CYP3A inducers may result in reduced exposures and thus reduced TRIKAFTA efficacy. Therefore, co‑administration of TRIKAFTA with strong CYP3A inducers is not recommended. The dose of TRIKAFTA should be reduced when co-administered with moderate CYP3A inhibitors. When used concomitantly with digoxin or other substrates of P-gp with a narrow therapeutic index such as ciclosporin, everolimus, sirolimus, and tacrolimus, caution and appropriate monitoring should be used. When used concomitantly with substrates of OATP1B1 or OATP1B3, caution and appropriate monitoring should be used.

Pregnancy and Lactation: Pregnancy Category B3. The safe use of TRIKAFTA during breast-feeding has not been established. TRIKAFTA should only be used during breast-feeding if the potential benefit outweighs the potential risk.

Adverse Effects: Please refer to Data Sheet for complete list. The most common adverse events with an incidence of at least 10% were infective pulmonary exacerbation, sputum increase, headache, cough, diarrhoea, upper respiratory tract infection, nasopharyngitis, oropharyngeal pain, haemoptysis and fatigue.

Dosage and administration:  The recommended dose for patients aged 6 to <12 years, weighing <30 kg, is two tablets (each containing elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg) taken in the morning and one tablet (ivacaftor 75 mg) taken in the evening, approximately 12 hours apart; for patients 6 to <12 years weighing ≥30 kg or aged >12 years, two tablets (each containing elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) taken in the morning and one tablet (containing ivacaftor 150 mg) taken in the evening, approximately 12 hours apart. TRIKAFTA should be taken with fat‑containing food.

Sponsor: Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics, PO Box 62027, Sylvia Park, AUCKLAND 1644, New Zealand. Medical Information: 0508 553 435

Date of publication in the New Zealand Gazette of consent to distribute the medicine, Tablets: 9 December 2021

Date of most recent amendment to minimum Data Sheet: 1 December 2022

Prescribing information for KALYDECO^® (ivacaftor)

Please review the full Data Sheet before prescribing. The Data Sheet and Consumer Medicine Information for KALYDECO^® can be accessed via https://www.medsafe.govt.nz/

KALYDECO (ivacaftor) Minimum Data Sheet

Name of Product: KALYDECO (ivacaftor) 150 mg film-coated tablets and KALYDECO (ivacaftor) 25mg, 50mg or 75mg granules per sachet.

Indication: KALYDECO is indicated for the treatment of cystic fibrosis (CF) in patients aged 4 months and older who have at least one mutation in the CFTR gene that is responsive to ivacaftor potentiation based on clinical and/or in vitro assay data.

Contraindication: Hypersensitivity to the active substance or to any of the excipients.

Precautions: Please refer to Data Sheet for complete list. KALYDECO is not recommended in patients with severe hepatic impairment (Child–Pugh Class C) unless the benefits outweigh the risks. Liver function tests recommended prior to initiating KALYDECO, every 3 months during the first year of treatment, and annually thereafter. Patients with a history of transaminase elevations, more frequent monitoring of liver function tests is recommended. Patients who develop unexplained increased transaminase levels during treatment should be closely monitored until abnormalities resolve. Dosing should be interrupted in patients with ALT or AST of greater than 5 times the upper limit of normal (ULN). Following resolution of transaminase elevations, consideration should be given to the continuation of treatment after assessment of the individual benefits and risks. Caution recommended while using KALYDECO in patients with severe renal impairment or end-stage renal disease.  Cases of non-congenital lens opacities without impact on vision have been reported in paediatric patients. Baseline and follow-up ophthalmological examinations are recommended in paediatric patients initiating KALYDECO treatment. Use in transplanted patients is not recommended. KALYDECO contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Pregnancy and Lactation: Pregnancy Category B3. The safe use of KALYDECO during breast-feeding has not been established. KALYDECO should only be used during breast-feeding if the potential benefit outweighs the potential risk.

Interactions: Please refer to Data Sheet for complete list. Reduction of KALYDECO dose is recommended when co-administered with strong CYP3A inhibitors (ketoconazole, itraconazole, posaconazole, voriconazole, fluconazole), or moderate CYP3A inhibitors (fluconazole and erythromycin).   Food containing grapefruit should be avoided during treatment with KALYDECO. Co-administration of ciprofloxacin did not affect exposure of ivacaftor. Co-administration with strong CYP3A inducers (rifampicin, rifabutin, phenobarbital, carbamazepine, phenytoin and St. John’s Wort (Hypericum perforatum) is not recommended. Concomitant use of weak to moderate inducers of CYP3A (e.g., dexamethasone, high-dose prednisone) may decrease the exposure of ivacaftor and thus may reduce KALYDECO efficacy. Administration of KALYDECO may increase systemic exposure of medicines which are substrates of CYP3A and/or P-gp, which may increase or prolong their therapeutic effect and adverse reactions. Use with caution and monitor for benzodiazepine-related side effects when using concomitant midazolam, alprazolam, diazepam or triazolam. Use with caution and appropriate monitoring when using concomitant digoxin, cyclosporine, or tacrolimus. Ivacaftor may inhibit CYP2C9. Monitoring of INR during co-administration with warfarin is recommended.

Adverse Effects: Please refer to Data Sheet for complete list. Very common: nasopharyngitis, upper respiratory tract infection, headache, nasal congestion, oropharyngeal pain, abdominal pain, diarrhoea and rash. Common: rhinitis, dizziness, ear discomfort, ear pain, tinnitus, tympanic membrane hyperaemia, pharyngeal erythema, sinus congestion and bacteria in sputum. The safety profile is generally consistent among children and adolescents and is also consistent with adult patients.

Dosage and Method of Administration:

KALYDECO 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 in at least one allele of the CFTR gene before starting treatment. In patients with R117H mutation, analysis of the poly-T variants should be performed. In asymptomatic patients with R117H-7T a sweat test should be conducted and a diagnosis of CF confirmed prior to treatment.

The recommended dose for patients aged 4 months to less than 6 months weighing ≥5kg is 25 mg granules (one sachet) every 12 hours (50 mg total daily dose (two sachets)).

For patients 6 months and older weighing ≥5kg to <7 kg is 25 mg granules (one sachet) every 12 hours (50 mg total daily dose (two sachets)); for patients weighing ≥7kg to <14 kg is 50mg granules (one sachet) every 12 hours (100mg total daily dose (two sachets)); for patients weighing ≥14kg to < 25kg is 75mg granules (one sachet) every 12 hours (150mg total daily dose (two sachets)) and for patients weighing ≥ 25kg is 150 mg tablet every 12 hours (300 mg total daily dose (two tablets)). KALYDECO should be taken with a fat-containing meal or snack. Meals and snacks recommended in CF guidelines or meals recommended in standard nutritional guidelines contain adequate amounts of fat.

Sponsor: Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics, PO Box 62027, Sylvia Park, AUCKLAND 1644, New Zealand. Medical Information: 0508 553 435, www.kalydeco.co.nz.

Date of publication in the New Zealand Gazette of consent to distribute the medicine, Tablets (150 mg) & Granules (50 mg and 75 mg): 17 December 2020; Granules (25 mg): 9 March 2023

Date of most recent amendment to minimum data sheet: 1 March 2024   

Consent to distribute has been granted for SYMDEKO ^® (tezacaftor/ivacaftor and ivacaftor) and ORKAMBI^® (lumacaftor and ivacaftor).

These products are not currently marketed in New Zealand.

Please contact the sponsor for more information: Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics, PO Box 62027, Sylvia Park, AUCKLAND 1644, New Zealand. Medical Information: 0508 553 435.

TRIKAFTA^®, KALYDECO^®, SYMDEKO^® and ORKAMBI^® are manufactured for Vertex Pharmaceuticals Incorporated. TRIKAFTA^®, KALYDECO^®, SYMDEKO^®, ORKAMBI^®, Vertex^® and the Vertex triangle logo are trademarks of Vertex Pharmaceuticals. Vertex Pharmaceuticals (Australia) Pty Limited ABN 34 160 157 157. Australia: Vertex Pharmaceuticals (Australia) Pty Ltd. Level 3, 601 Pacific Highway, St Leonards, NSW 2065 Australia. ABN 34 160 157 157. Vertex Medical Information contact: 1800 179 987 (AU). In New Zealand: Pharmacy Retailing (NZ) t/a Healthcare Logistics, P.O. Box 62027 Sylvia Park, Auckland 1644. Telephone: 0508 553 435 or email vertexmedicalinfo@vrtx.com. © 2024 Vertex Pharmaceuticals Incorporated. August 2024. TAPS 19160.