Posology : מינונים

5 DOSAGE AND ADMINISTRATION
5.1 Recommended Dosage in Adults and Pediatric Patients Aged 6 Years and Older Recommended dosage for adult and pediatric patients aged 6 years and older is provided in Table 1. The morning and the evening dose should be taken approximately 12 hours apart. Trikafta is for oral use.

Table 1: Recommended Dosage of Trikafta for Adult and Pediatric Patients Aged 6 Years and Older Age             Weight                                      Morning Dose                                                   Evening Dose Less than           Two tablets of elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg 6 to less                                                                                                 One tablet of ivacaftor 75 mg 30 kg*              (total dose of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) than
Two tablets of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg
12 years       30 kg or more*                                                                             One tablet of ivacaftor 150 mg (total dose of elexacaftor 200 mg/tezacaftor 100 mg/ivacaftor 150 mg) 12 years                            Two tablets of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg One tablet of ivacaftor 150 mg and older                           (total dose of elexacaftor 200 mg/tezacaftor 100 mg/ivacaftor 150 mg) *Clinical study in patients aged 6 to less than 12 years did not include patients weighing less than 15 kg.


TRIK-SPC-0324-V1                                              Page 1 of 16 5.2 Recommended Dosage for Patients with Hepatic Impairment
•   Mild Hepatic Impairment (Child-Pugh Class A): No dose adjustment is recommended [see Use in Specific Populations (10.6) and Clinical Pharmacology (13.3)]. See Table 1 for recommended dosage of Trikafta. Liver function tests should be closely monitored [see Warnings and Precautions (7.1) and Adverse Reactions (8)].

•       Moderate Hepatic Impairment (Child-Pugh Class B): Treatment is not recommended. Use of Trikafta in patients with moderate hepatic impairment should only be considered when there is a clear medical need, and the benefit exceeds the risk. If used, Trikafta should be used with caution at a reduced dose (see Table 2) [see Use in Specific Populations (10.6) and Clinical Pharmacology (13.3)]. Liver function tests should be closely monitored [see Warnings and Precautions (7.1) and Adverse Reactions (8)]. Recommended dosage for patients with moderate hepatic impairment (Child-Pugh Class B) is provided in Table 2.

Table 2: Recommended Dosage of Trikafta, if used, in Patients with Moderate Hepatic Impairment (Child-Pugh Class B) 
Age        Weight                                                             Morning Dose                                                         Evening Dose Alternating daily dosing schedule as follows:
Less                                                                                                                                  No evening than                •    Day 1: Two tablets of elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg (total dose of                    ivacaftor tablet 30 kg*                    elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg)                                                         dose.
6 to less                        •    Day 2: One tablet of elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg than
12 years                   Alternating daily dosing schedule as follows: No evening
30 kg or             •    Day 1: Two tablets of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg (total dose of                     ivacaftor tablet more*                     elexacaftor 200 mg/tezacaftor 100 mg/ivacaftor 150 mg)                                                       dose.
•    Day 2: One tablet of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg 
Alternating daily dosing schedule as follows:
12 years                                                                                                                                           No evening •    Day 1: Two tablets of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg (total dose of and                                                                                                                                                ivacaftor tablet elexacaftor 200 mg/tezacaftor 100 mg/ivacaftor 150 mg) older                                                                                                                                              dose.
•    Day 2: One tablet of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg 
*Clinical study in patients aged 6 to less than 12 years did not include patients weighing less than 15 kg.

•       Severe Hepatic Impairment (Child-Pugh Class C): Should not be used. Trikafta has not been studied in patients with severe hepatic impairment (Child-Pugh Class C), but the exposure is expected to be higher than in patients with moderate hepatic impairment [see Warnings and Precautions (7.1), Adverse Reactions (8), Use in Specific Populations (10.6), and Clinical Pharmacology (13.3)].

5.3     Dosage Modification for Patients Taking Drugs that are CYP3A Inhibitors Table 3 describes the recommended dosage modification for Trikafta when co-administered with strong (e.g., ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, and clarithromycin) or moderate (e.g., fluconazole, erythromycin) CYP3A inhibitors. Avoid food or drink containing grapefruit during Trikafta treatment [see Warnings and Precautions (7.4), Drug Interactions (9.2) and Clinical Pharmacology (13.3)].

Table 3: Dosage Modification for Concomitant Use of Trikafta with Moderate and Strong CYP3A Inhibitors Age               Weight       Moderate CYP3A Inhibitors                                            Strong CYP3A Inhibitors Alternating daily dosing schedule is as follows:                     Two tablets of elexacaftor 50 mg/tezacaftor 25 mg/ ivacaftor 37.5 mg (total dose of elexacaftor 100 mg/
Day 1: Two tablets of elexacaftor 50 mg/tezacaftor 25 mg/            tezacaftor 50 mg/ivacaftor 75 mg) in the morning twice a week, Less ivacaftor 37.5 mg (total dose of elexacaftor 100 mg/tezacaftor       approximately 3 to 4 days apart.
than
50 mg/ivacaftor 75 mg) in the morning
30 kg*
Day 2: One tablet of ivacaftor 75 mg in the morning                  No evening ivacaftor tablet dose.
6 to less                      No evening ivacaftor tablet dose.
than
12 years                       Alternating daily dosing schedule is as follows:                     Two tablets of elexacaftor 100 mg/tezacaftor 50 mg/ ivacaftor 75 mg (total dose of elexacaftor 200 mg/
Day 1: Two tablets of elexacaftor 100 mg/tezacaftor                  tezacaftor 100 mg/ivacaftor 150 mg) in the morning twice a week, 30 kg or     50 mg/ivacaftor 75 mg (total dose of elexacaftor 200 mg/             approximately 3 to 4 days apart.
more*        tezacaftor 100 mg/ivacaftor 150 mg) in the morning
Day 2: One tablet of ivacaftor 150 mg in the morning                 No evening ivacaftor tablet dose.

No evening ivacaftor tablet dose.
Alternating daily dosing schedule is as follows:                     Two tablets of elexacaftor 100 mg/tezacaftor 50 mg/ ivacaftor 75 mg (total dose of elexacaftor 200 mg/
Day 1: Two tablets of elexacaftor 100 mg/tezacaftor                  tezacaftor 100 mg/ivacaftor 150 mg) in the morning twice a week, 12 years                       50 mg/ivacaftor 75 mg (total dose of elexacaftor 200 mg/             approximately 3 to 4 days apart.
and older                      tezacaftor 100 mg/ivacaftor 150 mg) in the morning Day 2: One tablet of ivacaftor 150 mg in the morning                 No evening ivacaftor tablet dose.

No evening ivacaftor tablet dose.
*Clinical study in patients aged 6 to less than 12 years did not include patients weighing less than 15 kg.
TRIK-SPC-0324-V1                                                Page 2 of 16 5.4     Recommendations Regarding Missed Dose(s)
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.
•     the missed evening dose, the patient should not take the missed dose. The next scheduled morning dose should be taken at the usual time.
Morning and evening doses should not be taken at the same time.

5.5     Administration Information
Administer Trikafta tablets with fat-containing food. Examples of meals or snacks that contain fat are those prepared with butter or oils or those containing eggs, peanut butter, cheeses, nuts, whole milk, or meats [see Clinical Pharmacology (13.3)].

Trikafta tablets are for oral use. Swallow tablets whole.