General MedicationsORALHigh Alert

ORKAMBI

LUMACAFTOR AND IVACAFTOR

Standard Dose

2 DOSAGE AND ADMINISTRATION Age Group Weight Dose Administration 1 through 2 years 7 kg to <9 kg 1 packet of lumacaftor 75 mg/ivacaftor 94 mg granules Mixed with one teaspoon (5 mL) of soft food or liquid and administered orally every 12 hours with fat-containing food 9 kg to <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg granules 2 through 5 years <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg granules 6 through 11 years - 2 tablets of lumacaftor 100 mg/ivacaftor 125 mg (lumacaftor 200 mg/ivacaftor 250 mg per dose) Taken orally every 12 hours with fat-containing food 12 years and older - 2 tablets of lumacaftor 200 mg/ivacaftor 125 mg (lumacaftor 400 mg/ivacaftor 250 mg per dose) Reduce dosage in patients with moderate or severe hepatic impairment. ( 2.2 , 8.6 , 12.3 ) When initiating ORKAMBI in patients taking strong CYP3A inhibitors, reduce ORKAMBI dosage for the first week of treatment. ( 2.3 , 7.1 , 12.3 ) 2.1 Recommended Dosage in Adults and Pediatric Patients Aged 1 Year and Older The recommended dosage of ORKAMBI in adults and pediatric patients aged one year and older is based on patient's age and weight as described in Table 1. Table 1: Recommended Oral Dosage of ORKAMBI in Patients Aged 1 Year and Older Age Group Weight ORKAMBI Daily Dose (every 12 hours) Morning Dose Evening Dose 1 through 2 years 7 kg to <9 kg 1 packet of lumacaftor 75 mg/ivacaftor 94 mg oral granules 1 packet of lumacaftor 75 mg/ivacaftor 94 mg oral granules 9 kg to <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 2 through 5 years <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 6 through 11 years - 2 tablets of lumacaftor 100 mg/ivacaftor 125 mg (lumacaftor 200 mg/ivacaftor 250 mg per dose) 2 tablets of lumacaftor 100 mg/ivacaftor 125 mg (lumacaftor 200 mg/ivacaftor 250 mg per dose) 12 years and older - 2 tablets of lumacaftor 200 mg/ivacaftor 125 mg (lumacaftor 400 mg/ivacaftor 250 mg per dose) 2 tablets of lumacaftor 200 mg/ivacaftor 125 mg (lumacaftor 400 mg/ivacaftor 250 mg per dose) Administration Instructions for ORKAMBI Oral Granules The entire content of each packet of oral granules should be mixed with one teaspoon (5 mL) of age-appropriate soft food or liquid and the mixture completely consumed. Some examples of soft foods or liquids include puréed fruits or vegetables, flavored yogurt or pudding, applesauce, water, milk, breast milk, infant formula or juice. Food should be at room temperature or below. Each packet is for single use only. Once mixed, the product has been shown to be stable for one hour, and therefore should be ingested during this period. Administration with Fat-Containing Food for ORKAMBI Tablets and Oral Granules A fat-containing meal or snack should be consumed just before or just after dosing for all formulations. Examples of appropriate fat-containing foods include eggs, avocados, nuts, butter, peanut butter, cheese pizza, breast milk, infant formula, whole-milk dairy products (such as whole milk, cheese, and yogurt), etc. Missed Dose If a patient misses a dose and remembers the missed dose within 6 hours, the patient should take the dose with fat-containing food. If more than 6 hours elapsed after the recommended dosing time, the patient should skip that dose and resume the normal schedule for the following dose. A double dose should not be taken to make up for the forgotten dose [see Clinical Pharmacology (12.3) and Patient Counseling Information (17) ] . 2.2 Dosage Adjustment for Patients with Hepatic Impairment For dosage 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 is expected to be higher than in patients with moderate hepatic impairment. Therefore, use with caution at a maximum dose of 1 tablet in the morning and 1 tablet in the evening or less frequently, or 1 packet of oral granules once daily or less frequently in patients with severe hepatic impairment after weighing the risks and benefits of treatment [see Dosage and Administration (2.1) , Use in Specific Populations (8.6) , Clinical Pharmacology (12.3) , and Patient Counseling Information (17) ] . Table 2: Recommended Dosage for Patients with Hepatic Impairment Age Group Weight Morning Dose Evening Dose Mild (Child-Pugh Class A) 1 through 2 years 7 kg to <9 kg 1 packet of lumacaftor 75 mg/ivacaftor 94 mg oral granules 1 packet of lumacaftor 75 mg/ivacaftor 94 mg oral granules 9 kg to <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 2 through 5 years <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 6 through 11 years - 2 tablets of lumacaftor 100 mg/ivacaftor 125 mg (lumacaftor 200 mg/ivacaftor 250 mg per dose) 2 tablets of lumacaftor 100 mg/ivacaftor 125 mg (lumacaftor 200 mg/ivacaftor 250 mg per dose) 12 years and older - 2 tablets of lumacaftor 200 mg/ivacaftor 125 mg (lumacaftor 400 mg/ivacaftor 250 mg per dose) 2 tablets of lumacaftor 200 mg/ivacaftor 125 mg (lumacaftor 400 mg/ivacaftor 250 mg per dose) Moderate (Child-Pugh Class B) 1 through 2 years 7 kg to <9 kg 1 packet of lumacaftor 75 mg/ivacaftor 94 mg oral granules 1 packet of lumacaftor 75 mg/ivacaftor 94 mg oral granules every other day 9 kg to <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules every other day ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules every other day 2 through 5 years <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules every other day ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules every other day 6 through 11 years - 2 tablets of lumacaftor 100 mg/ivacaftor 125 mg (lumacaftor 200 mg/ivacaftor 250 mg per dose) 1 tablet of lumacaftor 100 mg/ivacaftor 125 mg 12 years and older - 2 tablets of lumacaftor 200 mg/ivacaftor 125 mg (lumacaftor 400 mg/ivacaftor 250 mg per dose) 1 tablet of lumacaftor 200 mg/ivacaftor 125 mg Severe (Child-Pugh Class C) 1 through 2 years 7 kg to <9 kg 1 packet of lumacaftor 75 mg/ivacaftor 94 mg oral granules or less frequently. N/A 9 kg to <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 2 through 5 years <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 6 through 11 years - 1 tablet of lumacaftor 100 mg/ivacaftor 125 mg 1 tablet of lumacaftor 100 mg/ivacaftor 125 mg 12 years and older - 1 tablet of lumacaftor 200 mg/ivacaftor 125 mg 1 tablet of lumacaftor 200 mg/ivacaftor 125 mg 2.3 Dosage Adjustment for Patients Taking CYP3A Inhibitors No dosage adjustment is necessary when CYP3A inhibitors are initiated in patients already taking ORKAMBI. However, when initiating ORKAMBI in patients currently taking strong CYP3A inhibitors, reduce the ORKAMBI dosage for the first week of treatment based on age as follows [see Dosage and Administration (2.1) and Drug Interactions (7.1) ]: 1 through 5 years of age: 1 packet of granules every other day 6 years of age and older: 1 tablet daily Following this one-week period, resume the recommended daily dosage. If ORKAMBI is interrupted for more than one-week and then re-initiated while taking strong CYP3A inhibitors, reduce the ORKAMBI dosage for the first week of treatment re-initiation based on age as follows: 1 through 5 years of age: 1 packet of granules every other day 6 years of age and older: 1 tablet daily Following this one-week period, resume the recommended daily dosage.

Max Dose

See official label

Primary Use

1 INDICATIONS AND USAGE ORKAMBI is indicated for the treatment of cystic fibrosis (CF) in patients aged 1 year and older who are homozygous for the F508del mutation in the CFTR gene.

Summary

If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene.

Structured Monograph

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE ORKAMBI is indicated for the treatment of cystic fibrosis (CF) in patients aged 1 year and older who are homozygous for the F508del mutation in the CFTR gene. If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene. ORKAMBI is a combination of ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, and lumacaftor, indicated for the treatment of cystic fibrosis (CF) in patients aged 1 year and older who are homozygous for the F508del mutation in the CFTR gene. If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene. ( 1 ) Limitations of Use: The efficacy and safety of ORKAMBI have not been established in patients with CF other than those homozygous for the F508del mutation. ( 1 ) Limitations of Use The efficacy and safety of ORKAMBI have not been established in patients with CF other than those homozygous for the F508del mutation . Dosage and administration 2 DOSAGE AND ADMINISTRATION Age Group Weight Dose Administration 1 through 2 years 7 kg to <9 kg 1 packet of lumacaftor 75 mg/ivacaftor 94 mg granules Mixed with one teaspoon (5 mL) of soft food or liquid and administered orally every 12 hours with fat-containing food 9 kg to <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg granules 2 through 5 years <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg granules 6 through 11 years - 2 tablets of lumacaftor 100 mg/ivacaftor 125 mg (lumacaftor 200 mg/ivacaftor 250 mg per dose) Taken orally every 12 hours with fat-containing food 12 years and older - 2 tablets of lumacaftor 200 mg/ivacaftor 125 mg (lumacaftor 400 mg/ivacaftor 250 mg per dose) Reduce dosage in patients with moderate or severe hepatic impairment. ( 2.2 , 8.6 , 12.3 ) When initiating ORKAMBI in patients taking strong CYP3A inhibitors, reduce ORKAMBI dosage for the first week of treatment. ( 2.3 , 7.1 , 12.3 ) 2.1 Recommended Dosage in Adults and Pediatric Patients Aged 1 Year and Older The recommended dosage of ORKAMBI in adults and pediatric patients aged one year and older is based on patient's age and weight as described in Table 1. Table 1: Recommended Oral Dosage of ORKAMBI in Patients Aged 1 Year and Older Age Group Weight ORKAMBI Daily Dose (every 12 hours) Morning Dose Evening Dose 1 through 2 years 7 kg to <9 kg 1 packet of lumacaftor 75 mg/ivacaftor 94 mg oral granules 1 packet of lumacaftor 75 mg/ivacaftor 94 mg oral granules 9 kg to <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 2 through 5 years <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 6 through 11 years - 2 tablets of lumacaftor 100 mg/ivacaftor 125 mg (lumacaftor 200 mg/ivacaftor 250 mg per dose) 2 tablets of lumacaftor 100 mg/ivacaftor 125 mg (lumacaftor 200 mg/ivacaftor 250 mg per dose) 12 years and older - 2 tablets of lumacaftor 200 mg/ivacaftor 125 mg (lumacaftor 400 mg/ivacaftor 250 mg per dose) 2 tablets of lumacaftor 200 mg/ivacaftor 125 mg (lumacaftor 400 mg/ivacaftor 250 mg per dose) Administration Instructions for ORKAMBI Oral Granules The entire content of each packet of oral granules should be mixed with one teaspoon (5 mL) of age-appropriate soft food or liquid and the mixture completely consumed. Some examples of soft foods or liquids include puréed fruits or vegetables, flavored yogurt or pudding, applesauce, water, milk, breast milk, infant formula or juice. Food should be at room temperature or below. Each packet is for single use only. Once mixed, the product has been shown to be stable for one hour, and therefore should be ingested during this period. Administration with Fat-Containing Food for ORKAMBI Tablets and Oral Granules A fat-containing meal or snack should be consumed just before or just after dosing for all formulations. Examples of appropriate fat-containing foods include eggs, avocados, nuts, butter, peanut butter, cheese pizza, breast milk, infant formula, whole-milk dairy products (such as whole milk, cheese, and yogurt), etc. Missed Dose If a patient misses a dose and remembers the missed dose within 6 hours, the patient should take the dose with fat-containing food. If more than 6 hours elapsed after the recommended dosing time, the patient should skip that dose and resume the normal schedule for the followi

Monitoring

• 5 WARNINGS AND PRECAUTIONS Use in patients with advanced liver disease: ORKAMBI should be used with caution in these patients and only if the benefits are expected to outweigh the risks.
• If ORKAMBI is used in these patients, they should be closely monitored after the initiation of treatment and the dosage should be reduced.
• Liver function decompensation, including liver failure leading to death, has been reported in CF patients with pre-existing cirrhosis with portal hypertension.
• ( 2.2 , 5.1 , 6.1 ) Liver-related events: Elevated transaminases (ALT/AST) have been observed in some cases associated with elevated bilirubin.

Interaction Notes

• 5.8 Drug Interactions Substrates of CYP3A Lumacaftor is a strong inducer of CYP3A.
• Administration of ORKAMBI may decrease systemic exposure of medicinal products that are substrates of CYP3A, which may decrease therapeutic effect.
• Co-administration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index is not recommended.
• ORKAMBI may substantially decrease hormonal contraceptive exposure, reducing their effectiveness and increasing the incidence of menstruation-associated adverse reactions, e.g., amenorrhea, dysmenorrhea, menorrhagia, menstrual irregular (27% in women using hormonal contraceptives compared with 3% in women not using hormonal contraceptives).