Posology : מינונים

5    DOSAGE AND ADMINISTRATION
5.1 General Dosing Information
Swallow the tablets whole.
SYMDEKO should be taken with fat-containing food, such as food recommended in standard nutritional guidelines. Examples of meals or snacks that contain fat are those prepared with butter or oils or those containing eggs, cheeses, nuts, whole milk, or meats, etc. [see Clinical Pharmacology (13.3)].

5.2 Recommended Dosage in Adults, Adolescents, and Children Age 6 Years and Older Adults, adolescents, and children age 6 years and older should be dosed according to Table 1. The morning and the evening dose should be taken approximately 12 hours apart.

Table 1: Recommended Dosage for Patients Age 6 Years and Older
Age                                   Morning                                          Evening (one tablet)                                    (one tablet)
6 to <12 years weighing <30 kg    tezacaftor 50 mg/ivacaftor 75 mg                            ivacaftor 75 mg 6 to <12 years weighing ≥30 kg    tezacaftor 100 mg/ivacaftor 150 mg                          ivacaftor 150 mg ≥12 years                         tezacaftor 100 mg/ivacaftor 150 mg                          ivacaftor 150 mg 

SYMD-SPC-0923-V1                                                            Page 1 of 15 Information for Missed Doses:
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 or evening dose, the patient should not take the missed dose. The next scheduled dose can be taken at the usual time. More than one dose should not be taken at the same time.

5.3 Recommended Dosage for Patients with Hepatic Impairment
For dose adjustment for patients with hepatic impairment, refer to Table 2.
Studies have not been conducted in patients with severe hepatic impairment (Child-Pugh Class C), but exposure of tezacaftor and ivacaftor is expected to be higher than in patients with moderate hepatic impairment. Therefore, SYMDEKO should be used with caution at an adjusted dose after weighing the risks and benefits of treatment in these patients [see Use in Specific Populations (10.5) and Clinical Pharmacology (13.3)].

Table 2: Recommended Dosage for Patients with Hepatic Impairment
Morning                                                          Evening Patients Age 6 to <12 Years
Hepatic Impairment                  Patients Age 6 to <12 Years                    Weighing ≥30 kg All Patients
Weighing <30kg                                   and
Patients Age ≥12 Years
Mild (Child-Pugh Class A)                      No dose adjustment                         No dose adjustment              No dose adjustment One tablet of tezacaftor                  One tablet of tezacaftor
Moderate (Child-Pugh Class B)
50 mg/ivacaftor 75 mg once daily         100 mg/ivacaftor 150 mg once daily No ivacaftor dose
One tablet of tezacaftor                  One tablet of tezacaftor
Severe (Child-Pugh Class C)             50 mg/ivacaftor 75 mg once daily         100 mg/ivacaftor 150 mg once daily (or less frequently)                      (or less frequently)

5.4 Dosage Adjustment for Patients Taking Drugs that are CYP3A Inhibitors The dosing regimen of SYMDEKO should be adjusted when co-administered with moderate and strong CYP3A inhibitors.

Moderate CYP3A inhibitors:
When co-administered with moderate CYP3A inhibitors (e.g., fluconazole, erythromycin), the dosing regimen should be adjusted as in Table 3 [see Drug Interactions (9.2) and Clinical Pharmacology (13.3).

Table 3: Dosing Schedule for Concomitant Use of SYMDEKO with Moderate CYP3A Inhibitors Day 1                Day 2       Day 3                   Day 4*
Patients Age 6 to <12 Years Weighing <30 kg
Morning
Tezacaftor 50 mg/ivacaftor 75 mg tablet           ✓                    -          ✓                             - Ivacaftor 75 mg tablet            -                   ✓           -                            ✓ Evening
Ivacaftor 75 mg tablet            -                   -           -                            - Patients Age 6 to <12 Years Weighing ≥30 kg and
Patients Age ≥12 Years
Morning
Tezacaftor 100 mg/ivacaftor 150 mg tablet            ✓                    -          ✓                             - Ivacaftor 150 mg tablet             -                   ✓           -                            ✓ Evening
Ivacaftor 150 mg tablet             -                   -           -                            - * Continue dosing with tezacaftor/ivacaftor or ivacaftor tablets on alternate days.

Strong CYP3A inhibitors:
When co-administered with strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, and clarithromycin), the dosing regimen should be adjusted as in Table 4 [see Drug Interactions (9.2) and Clinical Pharmacology (13.3)].

Table 4: Dosing Schedule for Concomitant Use of SYMDEKO with Strong CYP3A Inhibitors Day 1                Day 2 and Day 3                Day 4*
Patients Age 6 to <12 Years Weighing <30 kg
Morning
Tezacaftor 50 mg/ivacaftor 75 mg tablet                 ✓                        -                        ✓ Evening†
Ivacaftor 75 mg tablet                -                        -                           - Patients Age 6 to <12 Years Weighing ≥30 kg and
Patients Age ≥12 Years
Morning
Tezacaftor 100 mg/ivacaftor 150 mg tablet                 ✓                        -                        ✓ Evening†
Ivacaftor 150 mg tablet                 -                        -                           - * Continue dosing with tezacaftor/ivacaftor tablets twice a week, taken approximately 3 to 4 days apart.
† The evening dose of ivacaftor should not be taken on any day.

SYMD-SPC-0923-V1                                                             Page 2 of 15 Food or drink containing grapefruit should be avoided during treatment with SYMDEKO [see Drug Interactions (9.2)].