(eye va KAF tor)
Cystic fibrosis:
US labeling: For the treatment of cystic fibrosis (CF) in patients ≥2 years of age who have one of the following mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: G551D, G1244E, G1349D, G178R, G551S, R117H, S1251N, S1255P, S549N, or S549R.
If the patients genotype is unknown, a US Food and Drug Administration-cleared cystic fibrosis mutation test should be used to detect the presence of a CFTR mutation followed by verification with bidirectional sequencing when recommended by the mutation test instructions for use.
Canadian labeling: For the treatment of cystic fibrosis (CF) in patients ≥6 years of age who have one of the following mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or G970R; patients ≥18 years with an R117H mutation in the CFTR gene
Limitations of use: According to the manufacturer labeling, ivacaftor is not effective in patients with CF who are homozygous for the F508del mutation in the CTFR gene.
There are no contraindications listed in the manufacturers U.S. labeling.
Canadian labeling: Hypersensitivity to ivacaftor or any component of the formulation
Cystic fibrosis: Oral: Tablet: 150 mg every 12 hours
Dosage adjustment for ivacaftor with concomitant medications:
CYP3A strong inhibitors (eg, ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin): 150 mg twice weekly
CYP3A moderate inhibitors (eg, erythromycin, fluconazole): 150 mg once daily
CYP3A strong inducers (eg, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St Johns wort): Use is not recommended
Missed dose: If dose is missed within 6 hours of the usual time it is taken, take the dose as soon as possible; otherwise, skip the missed dose and resume the normal dosing schedule
Cystic fibrosis: Oral:
Granules:
Children 2 to <6 years:
<14 kg: 50 mg packet every 12 hours
≥14 kg: 75 mg packet every 12 hours
Tablet: Children ≥6 years and Adolescents: Refer to adult dosing.
Dosage adjustment for ivacaftor with concomitant medications:
CYP3A strong inhibitors (eg, clarithromycin, itraconazole, ketoconazole, posaconazole, telithromycin, voriconazole):
Children 2 to <6 years:
<14 kg: 50 mg granule packet twice weekly
≥14 kg: 75 mg granule packet twice weekly
Children ≥6 years and Adolescents: Refer to adult dosing.
CYP3A moderate inhibitors (eg, erythromycin, fluconazole):
Children 2 to <6 years:
<14 kg: 50 mg granule packet once daily
≥14 kg: 75 mg granule packet once daily
Children ≥6 years and Adolescents: Refer to adult dosing.
CYP3A strong inducers (eg, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St Johns wort): Refer to adult dosing.
Missed dose: If dose is missed within 6 hours of the usual time it is taken, take the dose as soon as possible; otherwise, skip the missed dose and resume the normal dosing schedule
Mild to moderate impairment (CrCl >30 mL/minute): No dosage adjustment necessary (has not been studied).
Severe impairment (CrCl ≤30 mL/minute): There are no dosage adjustments provided in the manufacturers labeling (has not been studied); use with caution.
End-stage renal disease (ESRD): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B):
Children ≥6 years, Adolescents, and Adults: 150 mg once daily
Children 2 to <6 years:
<14 kg: 50 mg granule packet once daily
≥14 kg: 75 mg granule packet once daily
Severe impairment (Child-Pugh class C): Has not been studied; use with caution
US labeling:
Children ≥6 years, Adolescents, and Adults: 150 mg once daily or less frequently.
Children 2 to <6 years:
<14 kg: 50 mg granule packet once daily or less frequently
≥14 kg: 75 mg granule packet once daily or less frequently
Canadian labeling: Initial:
Children ≥6 years, Adolescents, and Adults: 150 mg once every other day; adjust for tolerance and/or response.
Children 2 to <6 years:
<14 kg: 50 mg granule packet once every other day; adjust for tolerance and/or response.
≥14 kg: 75 mg granule packet once every other day; adjust for tolerance and/or response.
Oral:
Granules: Administer before or after high-fat-containing foods (eg, butter, cheese pizza, eggs, peanut butter, whole-milk dairy products [eg, whole milk, cheese, yogurt]). Mix entire packet of granules with 5 mL of soft food (eg, pureed fruits [excluding grapefruit or Seville oranges] or vegetables, yogurt, applesauce) or liquid (eg, water, milk, juice [excluding grapefruit juice]); food or liquid should be at or below room temperature. Granule mixture should be completely consumed within 1 hour.
Tablets: Administer with high-fat-containing foods (eg, butter, cheese pizza, eggs, peanut butter).
Take with high-fat-containing foods (eg, butter, cheese pizza, eggs, peanut butter, whole milk dairy products [eg, whole milk, cheese, yogurt]). Avoid grapefruit or Seville oranges.
Store at 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F); after mixing the granules, the product is stable for 1 hour.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Packet, Oral:
Kalydeco: 50 mg (56 ea); 75 mg (56 ea)
Tablet, Oral:
Kalydeco: 150 mg [contains fd&c blue #2 (indigotine)]
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification
Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
Bitter Orange: May increase the serum concentration of Ivacaftor. Avoid combination
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Bosutinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib. Avoid combination
Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Ivacaftor. Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult prescribing information for specific age- and weight-based recommendations. Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult prescribing information for specific age- and weight-based recommendations. Consider therapy modification
CYP3A4 Substrates: Ivacaftor may increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Grapefruit Juice: May increase the serum concentration of Ivacaftor. Avoid combination
HYDROcodone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of HYDROcodone. Monitor therapy
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination
P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination
Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Avoid combination
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
St Johns Wort: May decrease the serum concentration of Ivacaftor. Avoid combination
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination
CF mutation test (prior to therapy initiation if G551D mutation status unknown); ALT/AST at baseline, every 3 months for 1 year, then annually thereafter or as clinically indicated (consider more frequent monitoring in patients with a history of elevated hepatic transaminases); FEV1; baseline and follow-up ophthalmological exams in pediatric patients
Frequency not always defined.
>10%:
Central nervous system: Headache (24%)
Dermatologic: Skin rash (13%)
Gastrointestinal: Abdominal pain (16%), diarrhea (13%), nausea (12%)
Respiratory: Oropharyngeal pain (22%), upper respiratory tract infection (22%), nasal congestion (20%), nasopharyngitis (15%)
1% to 10%:
Central nervous system: Dizziness (9%)
Dermatologic: Acne vulgaris (4% to 7%)
Endocrine & metabolic: Increased serum glucose (4% to 7%), hypoglycemia
Hepatic: Increased liver enzymes (4% to 7%), increased serum ALT (4% to 7%)
Neuromuscular & skeletal: Arthralgia (4% to 7%), musculoskeletal chest pain (4% to 7%), myalgia (4% to 7%)
Ophthalmic: Cataract (children ≤12)
Respiratory: Change in bronchial secretions (4% to 7%; bacteria present), pharyngeal erythema (4% to 7%), pleuritic chest pain (4% to 7%), rhinitis (4% to 7%), sinus congestion (4% to 7%), sinus headache (4% to 7%), wheezing (4% to 7%)
Miscellaneous: Bacteria in sputum (4% to 7%)
The impact of severe hepatic impairment (Child-Pugh class C, score 10 to 15) on the pharmacokinetics of ivacaftor has not been studied; however, the magnitude of increase in exposure in these patients is expected to be substantially higher than that observed in patients with moderate hepatic impairment.
Concerns related to adverse effects:
- CNS effects: May cause dizziness, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
- Cataracts: Noncongenital lens opacities and cataracts have been reported in pediatric patients treated with ivacaftor; other risk factors were present in some cases (eg, corticosteroid use, exposure to radiation), but a possible risk related to ivacaftor cannot be excluded. Baseline and follow-up ophthalmological examinations are recommended in pediatric patients.
- Hepatic effects: May increase hepatic transaminases. Monitor liver function; increased monitoring may be necessary in patients with a history of elevated hepatic transaminases. Temporarily discontinue treatment if ALT or AST >5 times ULN.
Disease-related concerns:
- Hepatic impairment: Use with caution; dosage adjustment recommended in patients with moderate to severe (Child-Pugh class B or C) impairment.
- Renal impairment: Use with caution in patients with severe renal impairment or ESRD.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed. information
B
Adverse events have not been observed in animal reproduction studies.
Potentiates epithelial cell chloride ion transport of defective (G551D mutant) cell-surface CFTR protein thereby improving the regulation of salt and water absorption and secretion in various tissues (eg, lung, gastrointestinal tract).
Variable; increased (by two- to fourfold) with fatty foods
Vd: 353 L ‚ ± 122 L
Hepatic; extensive via CYP3A; forms 2 major metabolites (M1 [active; 1/6 potency] and M6 [inactive])
Feces (88%, 65% of administered dose as metabolites); urine (minimal, as unchanged drug)
FEV1 increased, sweat chloride decreased within ~2 weeks
~4 hours
~12 hours
~99%; primarily to alpha1 acid glycoprotein, albumin
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache, dizziness, pharyngitis, rhinitis, rhinorrhea, diarrhea, abdominal pain, nausea, acne, joint pain, or muscle pain. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), signs of high blood sugar (confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit), angina, or vision changes (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.