potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Potentiates the cystic fibrosis transmembrane conductance regulator (CFTR) The CFTR protein is a chloride channel present at the surface of epithelial cells in multiple organs; ivacaftor facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the G551D-CFTR protein CFTR gene mutations that produce CFTR protein and are responsive to ivacaftor 711+3A→G, 2789+5G→A, 3272-26A→G, 3849+10κβC→T A120T, A234D, A349V, A455E, A1067T D110E, D110H, D192G, D579G, D924N, D1152H, D1270N E56K, E193K, E822K, E831X F311del, F311L, F508C, F508C;S1251N, F1052V, F1074L G178E, G178R, G194R, G314E, G551D, G551S, G576A, G970D, G1069R, G1244E, G1249R, G1349D H939R, H1375P I148T, I175V, I807M, I1027T, I1139V K1060T L206W, L320V, L967S, L997F, L1480P M152V, M952I, M952T P67L Q237E, Q237H, Q359R, Q1291R R74W, R75Q, R117C, R117G, R117H, R117L, R117P, R170H, R347H, R347L, R352Q, R553Q, R668C, R792G, R933G, R1070Q, R1070W, R1162L, R1283M S549N, S549R, S589N, S737F, S945L, S977F, S1159F, S1159P, S1251N, S1255P T338I, T1053I V232D, V562I, V754M, V1293G W1282R Y1014C, Y1032C Absorption Peak Plasma Time: 4 hr (with high fat food) Peak Plasma Concentration: 768 ng/mL AUC 6 to <12 months, 5 to <7 kg (25 mg PO q12hr): 5790 ng•hr/mL 6 to <12 months, 7 to <14 kg (50 mg PO q12hr): 9250 ng•hr/mL 12 to <24 months, 7 to <14 kg (50 mg PO q12hr): 9050 ng•hr/mL 12 to <24 months, ≥14 to <25 kg (75 mg PO q12hr): 9600 ng•hr/mL 2 to <6 years, <14 kg (50 mg PO q12hr): 10,500 ng•hr/mL 2 to <6 years, ≥14 to <25 kg (75 mg PO q12hr): 11,300 ng•hr/mL 6 to <12 years (150 mg PO q12hr): 20,000 ng•hr/mL 12 to <18 years (150 mg PO q12hr): 9240 ng•hr/mL ≥18 years (150 mg PO q12hr): 10,700 ng•hr/mL Distribution Protein Bound: 99% (primarily albumin and alpha 1-acid glycoprotein) Does not bind to red blood cells Vd: 353 L Metabolism Metabolized by CYP3A Metabolites: M1 and M6 are the 2 major metabolites; M1 has 1/6 the potency of ivacaftor and is considered pharmacologically active; whereas, M6 has <1/50 the potency of ivacaftor and is not considered pharmacologically active Ivacaftor and its M1 metabolite may inhibit CYP3A and P-gp Elimination Half-life: 12 hr Total body clearance: 17.3 L/hr Excretion: feces 87.8% (M1 and M6 accounted for approximately 65% of the total dose eliminated with 22% as M1 and 43% as M6); urine (negligible) Pharmacogenomics G551D mutation in the CFTR gene In 2 studies of patients with the G551D mutation, treatment with ivacaftor resulted in a significant improvement in FEV1 The treatment difference between ivacaftor and placebo for the mean absolute change in percent predicted FEV1 from baseline through Week 24 was 10.6 percentage points (P < 0.0001) in Trial 1 and 12.5 percentage points (P < 0.0001) in Trial 2 These changes persisted through 48 weeks G1244E, G1349D, G178R, G551S, G970R, S1251N, S1255P, S549N, or S549R Mutation in the CFTR gene Efficacy and safety in patients with CF who have a G1244E, G1349D, G178R, G551S, G970R, S1251N, S1255P, S549N, or S549R mutation in the CFTR gene were evaluated in a double-blind, placebo-controlled, crossover design clinical trial For the 9 mutations studied, ivacaftor compared to placebo resulted in significant improvement in percent predicted FEV1 through Week 8 High degree of variability of efficacy responses among the 9 mutations R117H mutation in the CFTR gene CF patients who have an R117H mutation in the CFTR gene were evaluated in a clinical trial Primary efficacy endpoint was improvement in lung function by percent predicted FEV1 baseline through 24 weeks of treatment: did not reach statistical significance Heterozygous for the F508del mutation and a second mutation Ivacaftor compared to placebo resulted in significant improvement in ppFEV1 [4.7 percent points from study baseline to average of Week 4 and Week 8 and CFQ-R respiratory domain score (9.7 points from study baseline to average of Week 4 and Week 8) Statistically significant improvements compared to placebo were also observed in the subgroup of patients with splice mutations and missense mutation Homozygous for the F508del mutation in the CFTR gene Should not be used in patients homozygous for the F508del mutation in the CFTR gene Efficacy results from a double-blind, placebo-controlled trial in patients with CF who are homozygous for the F508del mutation in the CFTR gene showed no statistically significant difference in forced expiratory volume exhaled in one second (FEV1) over 16 weeks of ivacaftor treatment compared to placebo Oral Administration Administer tablets or oral granules with fat-containing food; examples include eggs, butter, peanut butter, cheese pizza, whole-milk dairy products (eg, whole milk, cheese, yogurt, breast milk, or infant formula) Tablets Swallow tablets whole Oral granules Mix entire contents of each packet of oral granules with 1 teaspoon (5 mL) of age-appropriate soft food or liquid and completely consumed; food or liquid should be at or below room temperature Once mixed, administer within 1 hr Some examples of soft foods or liquids may include puréed fruits or vegetables, yogurt, applesauce, water, milk, or juice Storage Capsules or granules: Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF) Mixed granules: Stable for 1 hr after mixed with soft foods or liquid BRAND FORM. UNIT PRICE PILL IMAGE Kalydeco oral- 13.4 mg packageKalydeco oral- 25 mg packageKalydeco oral- 150 mg tabletCopyright © 2010 First DataBank, Inc.Print Patient Educationivacaftor oral IVACAFTOR - ORAL (EYE-va-KAF-tor) COMMON BRAND NAME(S): Kalydeco USES: This medication is used to treat cystic fibrosis in certain people (those with an abnormal "CFTR" gene). It may help to improve breathing, reduce the risk of lung infections, and improve weight gain. HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start taking ivacaftor and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth as directed by your doctor, usually twice daily (every 12 hours).If you are taking the tablet form of this medication, take this medication with fat-containing foods (such as eggs, butter, peanut butter, cheese). The manufacturer directs to swallow this medication whole. However, many similar drugs (immediate-release tablets) can be split/crushed. Follow your doctor's directions on how to take this medication.If you are taking the granules form of this medication, gently shake the packet before use. Empty the packet into a small cup with 1 teaspoonful (5 milliliters) of soft food (such as yogurt, applesauce) or liquid (such as water, milk, infant formula). The soft food or liquid should be at or below room temperature. Mix the granules with the soft food or liquid and take the entire mixture within 1 hour of mixing. Eat a fat-containing food either right before or just after taking the mixture.The dosage is based on your medical condition, age, weight, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time(s) each day.Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine. Ask your doctor or pharmacist for more details.Tell your doctor if your condition does not improve or if it worsens. SIDE EFFECTS: Dizziness, headache, or nausea may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: vision changes.Ivacaftor may rarely cause serious liver disease. Get medical help right away if you have any symptoms of liver damage, including: nausea/vomiting that doesn't stop, loss of appetite, dark urine, stomach/abdominal pain, yellowing eyes/skin.Ivacaftor can commonly cause a rash that is usually not serious. However, you may not be able to tell it apart from a rare rash that could be a sign of a severe reaction. Tell your doctor right away if you develop any rash.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345. PRECAUTIONS: Before taking ivacaftor, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease.This drug may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.This medication passes into breast milk. Consult your doctor before breast-feeding. DRUG INTERACTIONS: See also How To Use section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Other medications can affect the removal of ivacaftor from your body, which may affect how ivacaftor works. Examples include mifepristone, rifamycins (such as rifabutin), drugs for seizures (such as carbamazepine, phenytoin), St. John's wort, among others. OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. NOTES: Do not share this medication with others.Lab and/or medical tests (such as CFTR gene testing, liver/lung function, eye exams) will be done before you start taking this medication and while you are taking it. Keep all medical and lab appointments. Consult your doctor for more details. MISSED DOSE: If you miss a dose and it has been less than 6 hours, take it as soon as you remember. If you miss a dose and it has been more than 6 hours, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up. STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company. Information last revised May 2023. Copyright(c) 2023 First Databank, Inc. IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs. FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and