Version July 2025
Cystic fibrosis: Note: Ivacaftor is generally used as monotherapy in the pediatric population. Ivacaftor may be considered in adult patients with a gene mutation responsive to ivacaftor AND an intolerance to dual or triple CFTR modulator therapy (eg, cystic fibrosis transmembrane conductance regulator corrector and cystic fibrosis transmembrane conductance regulator potentiator) (Ref).
Oral: Tablet: 150 mg every 12 hours.
Missed dose: If dose is missed <6 hours of the usual time it is taken, take the dose as soon as possible; if >6 hours has passed since the scheduled dose, skip the missed dose and resume the normal dosing schedule.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl >30 mL/minute: No dosage adjustment necessary (has not been studied).
CrCl ≤30 mL/minute: There are no dosage adjustments provided in the manufacturer's 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.
Hepatic impairment prior to treatment initiation :
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): 150 mg once daily
Severe impairment (Child-Pugh class C): Has not been studied; use with caution: 150 mg once daily or less frequently
Hepatotoxicity during treatment:
ALT or AST >5 times ULN: Hold ivacaftor; may resume if elevated transaminases resolve and after assessing benefits versus risks of continued treatment.
ALT or AST >5 times ULN: Hold ivacaftor; may resume if elevated transaminases resolved and after assessing benefits vs risks of continued treatment.
(For additional information see "Ivacaftor: Pediatric drug information")
Cystic fibrosis: Note: Use in infants <6 months of age born at GA <37 weeks has not been evaluated.
Infants <2 months weighing ≥3 kg: Oral granules: Oral: 5.8 mg granule packet every 12 hours.
Infants ≥2 to <4 months weighing ≥3 kg: Oral granules: Oral: 13.4 mg granule packet every 12 hours.
Infants 4 to <6 months weighing ≥5 kg: Oral granules: Oral: 25 mg granule packet every 12 hours.
Infants ≥6 months and Children <6 years: Oral granules:
5 to <7 kg: Oral: 25 mg granule packet every 12 hours.
7 to <14 kg: Oral: 50 mg granule packet every 12 hours.
≥14 kg: Oral: 75 mg granule packet every 12 hours.
Children ≥6 years and Adolescents: Oral tablet: Oral: 150 mg every 12 hours.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function:
Infants, Children, and Adolescents: Oral:
CrCl >30 mL/minute: No dosage adjustment necessary.
CrCl ≤30 mL/minute: There are no dosage adjustments provided in manufacturer's labeling (not studied); use with caution.
End-stage renal disease (ESRD): There are no dosage adjustments provided in manufacturer's labeling (not studied); use with caution.
Baseline hepatic impairment: Oral:
Infants <6 months: Any degree of hepatic impairment: Use is not recommended.
Infants ≥6 months, Children, and Adolescents:
Mild impairment: No dosage adjustment necessary.
Moderate impairment: Oral: Administer usual dose once daily.
Severe impairment: Oral: Administer usual dose once daily or less frequently; use with caution.
Hepatotoxicity during therapy: Oral:
Infants, Children, and Adolescents: If ALT or AST >5 times ULN: Hold ivacaftor; may resume if elevated transaminases resolved and after assessing benefits vs risks of continued treatment.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children, adolescents, and adults.
>10%:
Dermatologic: Skin rash (13%)
Gastrointestinal: Abdominal pain (16%), diarrhea (13%), nausea (12%)
Nervous system: Headache (24%)
Respiratory: Nasal congestion (20%), nasopharyngitis (15%), oropharyngeal pain (22%), upper respiratory tract infection (22%)
1% to 10%:
Dermatologic: Acne vulgaris (4% to 7%)
Endocrine & metabolic: Increased serum glucose (4% to 7%)
Hepatic: Increased liver enzymes (4% to 7%; including increased serum alanine aminotransferase, increased serum aspartate aminotransferase)
Infection: Bacterial infection (sputum: 4% to 7%)
Nervous system: Dizziness (9%)
Neuromuscular & skeletal: Arthralgia (4% to 7%), musculoskeletal chest pain (4% to 7%), myalgia (4% to 7%)
Respiratory: Paranasal sinus congestion (4% to 7%), pharyngeal erythema (4% to 7%), pleuritic chest pain (4% to 7%), rhinitis (4% to 7%), sinus headache (4% to 7%), wheezing (4% to 7%)
Frequency not defined: Endocrine & metabolic: Hypoglycemia
Postmarketing:
Hypersensitivity: Anaphylaxis
Ophthalmic: Cataract (children)
There are no contraindications listed in the manufacturer's labeling.
Canadian labeling: Hypersensitivity to ivacaftor or any component of the formulation.
Concerns related to adverse effects:
• 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.
• 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).
• Hepatic effects: May increase hepatic transaminases. Monitor liver function; increased monitoring may be necessary in patients with a history of elevated hepatic transaminases. Discontinue treatment if ALT or AST >5 times ULN. Following resolution of transaminase elevations, may resume if elevated transaminases resolve and after assessing benefits versus risks of continued treatment.
• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, have been reported with ivacaftor use. If signs and symptoms of severe hypersensitivity occur, discontinue use and treat appropriately; consider risk versus benefit prior to resuming therapy.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; 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 (CrCl ≤30 mL/minute) or ESRD.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Packet, Oral:
Kalydeco: 5.8 mg (56 ea); 13.4 mg (56 ea); 25 mg (56 ea); 50 mg (56 ea); 75 mg (56 ea)
Tablet, Oral:
Kalydeco: 150 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
No
Pack (Kalydeco Oral)
5.8 mg (per each): $568.84
13.4 mg (per each): $568.84
25 mg (per each): $568.84
50 mg (per each): $568.84
75 mg (per each): $568.84
Tablets (Kalydeco Oral)
150 mg (per each): $568.84
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Packet, Oral:
Kalydeco: 13.4 mg (56 ea); 25 mg (56 ea); 50 mg (56 ea); 75 mg (56 ea)
Tablet, Oral:
Kalydeco: 150 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Product is only available via authorized pharmacies and distributors. Further information is available at https://www.vrtx.com/authorized-distributors.
Oral: Swallow tablet whole. Administer before or after high-fat-containing foods (eg, butter, eggs, peanut butter, whole-milk dairy products [eg, whole milk, cheese, yogurt]). Avoid food or drink containing grapefruit.
Granules: Mix entire packet of granules with 5 mL of soft food (eg, pureed fruits [excluding grapefruit] 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.
Oral:
Tablets: Swallow tablets whole. Administer before or after high-fat-containing foods (eg, butter, cheese pizza, eggs, peanut butter, whole milk dairy products [eg, whole milk, cheese, yogurt]).
Granules: Mix entire packet of granules with a teaspoon of soft food (eg, pureed fruits [excluding grapefruit or Seville oranges] or vegetables, yogurt, applesauce) or 5 mL of liquid (eg, water, milk, breast milk, infant formula, juice [excluding grapefruit or Seville oranges]); food or liquid should be at or below room temperature. Granule mixture should be completely consumed within 1 hour.
Missed dose: If dose is missed within 6 hours of the usual administration time, administer the dose as soon as possible and resume normal schedule; if >6 hours since missed dose, skip the missed dose and return to the normal dosing schedule.
Cystic fibrosis: Treatment of cystic fibrosis (CF) in patients ≥1 month of age who have at least one mutation in the CF transmembrane conductance regulator (CFTR) gene that is responsive to ivacaftor potentiation based on clinical and/or in vitro assay data.
If the patient's genotype is unknown, an FDA-cleared CF 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.
Note: List of CFTR gene mutations that produce CFTR protein and are responsive to ivacaftor include (this is not an all-inclusive list): A455E, D579G, D1152H, E831X, F508C / S1251N, G178R, G551D, G551S, G1244E, G1349D, L206W, P67L, R1070W, R117C, R117H, R347H, R352Q, S549N, S549R, S945L, S977F, S1251N, S1255P, 711+3A→G, 2789+5G→A, 3272-26A→G, 3849+10kbC→T.
Substrate of CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (Weak), P-glycoprotein;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider Therapy Modification
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Aliskiren. Risk C: Monitor
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of ALPRAZolam. Risk C: Monitor
Beta-Acetyldigoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Beta-Acetyldigoxin. Risk C: Monitor
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Bilastine. Risk X: Avoid
Bitter Orange: May increase serum concentration of Ivacaftor. Risk X: Avoid
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Celiprolol. Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider Therapy Modification
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Ivacaftor. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Ivacaftor. Risk X: Avoid
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Ivacaftor. Management: Ivacaftor dose reductions may be required; consult full drug interaction monograph content for age- and weight-specific dosage recommendations. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Strong): May increase serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult full drug interaction monograph content for age- and weight-specific recommendations. Risk D: Consider Therapy Modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase active metabolite exposure of Dabigatran Etexilate. Risk C: Monitor
Digitoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Digitoxin. Risk C: Monitor
Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider Therapy Modification
Dofetilide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Dofetilide. Risk C: Monitor
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Edoxaban. Risk C: Monitor
Ensartinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ensartinib. Risk X: Avoid
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide Phosphate. Risk C: Monitor
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide. Risk C: Monitor
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Everolimus. Risk C: Monitor
Finerenone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Finerenone. Risk C: Monitor
Flibanserin: CYP3A4 Inhibitors (Weak) may increase serum concentration of Flibanserin. Risk C: Monitor
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor
Grapefruit Juice: May increase serum concentration of Ivacaftor. Risk X: Avoid
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ixabepilone. Risk C: Monitor
Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Lapatinib. Risk C: Monitor
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Larotrectinib. Risk C: Monitor
Lefamulin: May increase serum concentration of Ivacaftor. Ivacaftor may increase serum concentration of Lefamulin. Management: Consider alternatives to this combination when possible. If combined, monitor for increased lefamulin toxicities and decrease the ivacaftor dose. See full monograph for details. Risk D: Consider Therapy Modification
Lemborexant: CYP3A4 Inhibitors (Weak) may increase serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Lomitapide: CYP3A4 Inhibitors (Weak) may increase 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. Risk D: Consider Therapy Modification
Mavorixafor: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Mavorixafor. Risk C: Monitor
Midazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Midazolam. Risk C: Monitor
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Morphine (Systemic). Risk C: Monitor
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Nadolol. Risk C: Monitor
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Naldemedine. Risk C: Monitor
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Naloxegol. Risk C: Monitor
NiMODipine: CYP3A4 Inhibitors (Weak) may increase serum concentration of NiMODipine. Risk C: Monitor
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of PAZOPanib. Risk X: Avoid
Phenobarbital-Primidone: May decrease serum concentration of Ivacaftor. Risk C: Monitor
Pimozide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Pimozide. Risk X: Avoid
Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider Therapy Modification
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ranolazine. Risk C: Monitor
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider Therapy Modification
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider Therapy Modification
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Repotrectinib. Risk X: Avoid
Rifabutin: May decrease serum concentration of Ivacaftor. Risk C: Monitor
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RifAXIMin. Risk C: Monitor
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider Therapy Modification
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RisperiDONE. Risk C: Monitor
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RomiDEPsin. Risk C: Monitor
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Silodosin. Risk C: Monitor
Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentration of Simvastatin. CYP3A4 Inhibitors (Weak) may increase active metabolite exposure of Simvastatin. Risk C: Monitor
Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider Therapy Modification
Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
St John's Wort: May decrease serum concentration of Ivacaftor. Risk X: Avoid
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Teniposide. Risk C: Monitor
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid
Triazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Triazolam. Risk C: Monitor
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider Therapy Modification
Ubrogepant: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a P-gp inhibitor. Risk D: Consider Therapy Modification
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Risk D: Consider Therapy Modification
VinCRIStine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of VinCRIStine. Risk X: Avoid
Ivacaftor serum concentrations may be increased when taken with grapefruit. Management: Avoid concurrent use.
Fertility and contraception should be reassessed prior to starting variant-specific cystic fibrosis transmembrane conductance regulator (CFTR) therapy (Southern 2023). Fertility may improve with use of CFTR therapy and an increase in unintentional pregnancies has been observed. Contraception advice is recommended for patients who do not wish to become pregnant (Gramegna 2024; Southern 2023).
Ivacaftor crosses the placenta (Trimble 2018).
In one case report, cord blood concentrations of ivacaftor at delivery were similar to maternal plasma concentrations following maternal use of ivacaftor/lumacaftor during pregnancy (Trimble 2018).
Data related to the safety of variant-specific cystic fibrosis transmembrane conductance regulator (CFTR) therapy during pregnancy are limited (Southern 2023). Outcome data specific to ivacaftor monotherapy use in pregnancy are limited (Kaminski 2016; Ladores 2017; Marco 2015; Nash 2020; Vekaria 2020). Refer to combination monographs for additional information.
Monitoring of newborns exposed to CFTR therapy during pregnancy should include genetic testing, LFTs, and ophthalmic exams (Gramegna 2024). In addition, exposed infants may have a false-negative immunoreactive trypsinogen test for cystic fibrosis during the newborn baby screen (Castellani 2023; Southern 2023).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of CFTR therapy may be altered (Qiu 2020). Available data are limited (based on a study conducted with ivacaftor in combination with elexacaftor and tezacaftor) and show high interpatient variability. Dose adjustments based on routine clinical monitoring and therapeutic drug monitoring may be needed (Christina 2025). Increased monitoring during pregnancy is recommended (Gramegna 2024).
Patients taking variant-specific CFTR therapy prior to pregnancy may have an acute deterioration of health if treatment is discontinued once pregnant. Continuing or discontinuing therapy during pregnancy should be based on a shared decision-making process (Gramegna 2024).
Ivacaftor is present in breast milk (Trimble 2018).
Refer to combination monographs for additional information.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Safety data related to the use of variant-specific cystic fibrosis transmembrane conductance regulator (CFTR) therapy while breastfeeding are limited (Southern 2023). Monitoring of liver function and ophthalmic exams are recommended in infants exposed to CFTR therapy via breast milk (Southern 2023).
Avoid grapefruit.
CF mutation test (prior to therapy initiation if mutation status unknown); ALT/AST (baseline, every 3 months for 1 year, then annually thereafter or as clinically indicated; increased monitoring may be necessary in patients with a history of elevated hepatic transaminases); FEV1; ophthalmological exams (baseline and follow-up in pediatric patients).
Potentiates epithelial cell chloride ion transport of defective cell-surface CFTR protein thereby improving the regulation of salt and water absorption and secretion in various tissues (eg, lung, GI tract).
Onset of action: FEV1 increased, sweat chloride decreased within ~2 weeks (Ramsey 2011)
Absorption: Variable; increased (by 2.5- to 4-fold) with fatty foods
Distribution: Vd: 353 L ± 122 L (fed state)
Protein binding: ~99%; primarily to alpha1 acid glycoprotein, albumin
Metabolism: Hepatic; extensive via CYP3A; forms 2 major metabolites (M1 [active; 1/6 potency] and M6 [inactive])
Half-life elimination: ~12 hours
Time to peak: Median: ~4 hours (range: 3 to 6 hours) (fed state)
Excretion: Feces (87.8%, ~65% of administered dose as metabolites); urine (minimal, as unchanged drug)
Hepatic function impairment: Adults with moderate hepatic impairment (Child-Pugh class B) had an ~2-fold increase in ivacaftor AUC0-∞; in adults with mild hepatic impairment (Child-Pugh class A), increase is expected to be <2-fold. The magnitude of increase in exposure in patients with severe hepatic impairment (Child-Pugh class C) is expected to be substantially higher than that observed in patients with moderate hepatic impairment.
