Drug Detail:Symdeko (Ivacaftor and tezacaftor [ eye-va-kaf-tor-and-tez-a-kaf-tor ])
Generic Name: Tezacaftor 100mg, Ivacaftor 150mg; Ivacaftor 150mg
Dosage Form: kit
Drug Class: CFTR combinations
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 (12.3)].
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.
| Age | Morning (one tablet) |
Evening (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 |
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.
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 (8.6), Clinical Pharmacology (12.3), and Patient Counseling Information (17)].
| Hepatic Impairment | Morning | Evening | |
|---|---|---|---|
| Patients Age 6 to <12 Years Weighing <30kg | Patients Age 6 to <12 Years Weighing ≥30 kg and Patients Age ≥12 Years | All Patients | |
| Mild (Child-Pugh Class A) | No dose adjustment | No dose adjustment | No dose adjustment |
| Moderate (Child-Pugh Class B) | One tablet of tezacaftor 50 mg/ivacaftor 75 mg once daily | One tablet of tezacaftor 100 mg/ivacaftor 150 mg once daily | No ivacaftor dose |
| Severe (Child-Pugh Class C) | One tablet of tezacaftor 50 mg/ivacaftor 75 mg once daily (or less frequently) |
One tablet of tezacaftor 100 mg/ivacaftor 150 mg once daily (or less frequently) |
|
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 (7.2), Clinical Pharmacology (12.3), and Patient Counseling Information (17)].
| 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 | - | - | - | - |
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 (7.2), Clinical Pharmacology (12.3), and Patient Counseling Information (17)].
| 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 | - | - | - |
Food or drink containing grapefruit should be avoided during treatment with SYMDEKO [see Drug Interactions (7.2) and Patient Counseling Information (17)].
