For: Cystic Fibrosis
Orkambi (ivacaftor and lumacaftor) is a CFTR potentiator and CFTR corrector combination for the treatment of the underlying cause of cystic fibrosis in patients 2 years and older with two copies of the F508del mutation in their CFTR gene. These highlights do not include all the information needed to use ORKAMBI safely and effectively. See full prescribing information for ORKAMBI.
ORKAMBI� (lumacaftor/ivacaftor) tablets, for oral use
ORKAMBI� (lumacaftor/ivacaftor) oral granules
Initial U.S. Approval: 2015
RECENT MAJOR CHANGES
Indications and Usage (1) 8/2018
Dosage and Administration (2) 8/2018
INDICATIONS AND USAGE
ORKAMBI is a combination of lumacaftor and ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, indicated for the treatment of cystic fibrosis (CF) in patients age 2 years 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)
DOSAGE AND ADMINISTRATION
Pediatric patients age 2 through 5 years and weighing less than 14 kg: one packet of granules (each containing lumacaftor 100 mg/ivacaftor 125 mg) mixed with 1 teaspoon (5 mL) of soft food or liquid and administered orally every 12 hours with fat-containing food. (2.1, 12.3)
Pediatric patients age 2 through 5 years and weighing 14 kg or greater: one packet of granules (each containing lumacaftor 150 mg/ivacaftor 188 mg) mixed with 1 teaspoon (5 mL) of soft food or liquid and administered orally every 12 hours with fat-containing food. (2.1, 12.3)
Pediatric patients age 6 through 11 years: two tablets (each containing lumacaftor 100 mg/ivacaftor 125 mg) taken orally every 12 hours with fat-containing food. (2.1, 12.3)
Adults and pediatric patients age 12 years and older: two tablets (each containing lumacaftor 200 mg/ivacaftor 125 mg) taken orally every 12 hours with fat-containing food. (2.1, 12.3)
Reduce dose 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 dose for the first week of treatment. (2.3, 7.1, 12.3)
DOSAGE FORMS AND STRENGTHS
Tablets: lumacaftor 100 mg and ivacaftor 125 mg; lumacaftor 200 mg and ivacaftor 125 mg. (3)
Oral granules: Unit-dose packets of lumacaftor 100 mg and ivacaftor 125 mg; lumacaftor 150 mg and ivacaftor 188 mg. (3)
CONTRAINDICATIONS
None. (4)
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 dose 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. Measure serum transaminases and bilirubin before initiating ORKAMBI, every 3 months during the first year of treatment, and annually thereafter. For patients with a history of ALT, AST, or bilirubin elevations, more frequent monitoring should be considered. Interrupt dosing in patients with ALT or AST >5 � upper limit of normal (ULN), or ALT or AST >3 � ULN with bilirubin >2 � ULN. Following resolution, consider the benefits and risks of resuming dosing. (5.2, 6.1)
Respiratory events: Chest discomfort, dyspnea, and respiration abnormal were observed more commonly during initiation of ORKAMBI. Clinical experience in patients with percent predicted FEV1 (ppFEV1) <40 is limited, and additional monitoring of these patients is recommended during initiation of therapy. (5.3, 6.1)
Blood pressure: Increased blood pressure has been observed in some patients. Periodically monitor blood pressure in all patients. (5.4, 6.1)
Drug interactions: Use with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index may decrease systemic exposure of the medicinal products and co-administration is not recommended. Hormonal contraceptives should not be relied upon as an effective method of contraception and their use is associated with increased menstruation-related adverse reactions. Use with strong CYP3A inducers may diminish exposure of ivacaftor, which may diminish its effectiveness; therefore, co-administration is not recommended. (5.5, 6.1, 7, 12.3)
Cataracts: Non-congenital lens opacities/cataracts have been reported in pediatric patients treated with ORKAMBI and ivacaftor, a component of ORKAMBI. Baseline and follow-up examinations are recommended in pediatric patients initiating ORKAMBI. (5.6)
ADVERSE REACTIONS
The most common adverse reactions to ORKAMBI (occurring in ?5% of patients with CF homozygous for the F508del mutation in the CFTR gene) were dyspnea, nasopharyngitis, nausea, diarrhea, upper respiratory tract infection, fatigue, respiration abnormal, blood creatine phosphokinase increased, rash, flatulence, rhinorrhea, influenza. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Vertex Pharmaceuticals Incorporated at 1-877-634-8789 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
See Full Prescribing Information for a complete list. (2.3, 7, 12.3)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 7/2019