Ivacaftor (Kalydeco) Tablets - Uses, Dose, MOA, Brands, Side effects

Ivacaftor (Kalydeco) tablets are used orally in the treatment of patients with cystic fibrosis. It acts by altering the absorption of salt and water via defective or mutant channels in patients with cystic fibrosis.

Ivacaftor Uses:

Cystic fibrosis:
- based on clinical and/or in vitro assay findings, used to treat cystic fibrosis (CF) in individuals older than 6 months old with a single mutation in the CF transmembrane conductance regulator (CFTR) gene that responds to ivacaftor potentiation.
- Use an FDA-cleared CF mutation test to find the presence of a CFTR mutation if the patient's genotype is unknown, followed by bidirectional sequencing for confirmation when advised by the mutation test's usage instructions.

Ivacaftor (Kalydeco) Dose in Adults:

Ivacaftor (Kalydeco) Dose in the treatment of Cystic fibrosis:

P/O: Tablet: 150 mg given every 12 hours
Dosage adjustment for ivacaftor with concomitant medications:
- CYP3A strong inhibitors (eg, ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin): 150 mg twice a week
- CYP3A moderate inhibitors (eg, erythromycin, fluconazole): 150 mg once a day
- Strong inducers of CYP3A, include St. John's wort, phenobarbital, carbamazepine, and phenytoin: Not advised for use.
Missed dose:
- If a dose is missed within six hours of the scheduled time, take it as soon as you remember; if more than xis hours passed then skip the missed dose and resume the normal dosing schedule.

Ivacaftor (Kalydeco) Dose in Children:

Ivacaftor (Kalydeco) Dose in the treatment of Cystic fibrosis: Oral:

Infants ≥6 months and Children <6 years: Oral granules:
- 5 to <7 kg: 25 mg granule packet q 12 hours.
- 7 to <14 kg: 50 mg granule packet q 12 hours.
- ≥14 kg: 75 mg granule packet q 12 hours.
Children ≥6 years and Adolescents:
- Oral tablet: 150 mg q 12 hours.

Dosage adjustment for concomitant therapy:

Coadministration with CYP3A4 strong inhibitors (eg, ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin):
- Infants ≥6 months and Children <6 years: Oral granules:
  - 5 to <7 kg: 25 mg granule packet twice a week.
  - 7 to <14 kg: 50 mg granule packet twice a week.
  - ≥14 kg: 75 mg granule packet twice a week.
- Children ≥6 years and Adolescents: Oral tablet: 150 mg twice a week.
Coadministration with CYP3A4 moderate inhibitors (eg, erythromycin, fluconazole):
- Infants ≥6 months and Children <6 years: Oral granules:
  - 5 to <7 kg: 25 mg granule packet OD.
  - 7 to <14 kg: 50 mg granule packet OD.
  - ≥14 kg: 75 mg granule packet OD.
- Children ≥6 years and Adolescents: Oral tablet: 150 mg OD.
Coadministration with CYP3A strong inducers (eg, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. John's wort):
- Not recommended.

Pregnancy Risk Category: B

Ivacaftor crosses the placenta.
A case report showed that maternal plasma and cord blood levels of ivacaftor were comparable after the mother had used ivacaftor/lumacaftor during pregnancy.
Information on ivacaftor pregnancy use is limited.

Use during breastfeeding:

Ivacaftor can be found in breast milk.
A case report found that ivacaftor was detected in infant milk and infant plasma after its mother had used it during pregnancy.
According to the manufacturer, the following are important considerations when deciding whether or not to breastfeed during therapy:
- Exposure of infants to chemicals
- Breastfeeding is good for the infant
- Mothers can reap the benefits of mother-to-child treatment.

Dose in Kidney Disease:

CrCl >30 mL/minute: Dosage adjustment not necessary (has not been studied).
CrCl ≤30 mL/minute: No dosage adjustments
End-stage renal disease (ESRD): No dosage adjustments provided

Dose in Liver disease:

Mild impairment (Child-Pugh class A): Dosage adjustment not necessary.
Moderate impairment (Child-Pugh class B): 150 mg OD.
Severe impairment (Child-Pugh class C): Use cautiously: 150 mg OD or less frequently, has not been studied.

Common Side Effects of Ivacaftor (Kalydeco):

Central Nervous System:
- Headache
Dermatologic:
- Skin Rash
Gastrointestinal:
- Abdominal Pain
- Diarrhea
- Nausea
Respiratory:
- Oropharyngeal Pain
- Upper Respiratory Tract Infection
- Nasal Congestion
- Nasopharyngitis

Less Common Side Effects Of Ivacaftor (Kalydeco):

Central Nervous System:
- Dizziness
Dermatologic:
- Acne Vulgaris
Endocrine & Metabolic:
- Increased Serum Glucose
Hepatic:
- Increased Liver Enzymes
- Increased Serum Aspartate Aminotransferase
Infection:
- Bacterial Infection
Neuromuscular & Skeletal:
- Arthralgia
- Musculoskeletal Chest Pain
- Myalgia
Respiratory:
- Paranasal Sinus Congestion
- Pharyngeal Erythema
- Pleuritic Chest Pain
- Rhinitis
- Sinus Headache
- Wheezing

Frequency of side effects not defined:

Endocrine & Metabolic:
- Hypoglycemia

Contraindications to Ivacaftor (Kalydeco):

The manufacturer's label does not contain any contraindications.

Canadian labeling:

Ivacaftor and any formulation component hypersensitivity

Warnings and precautions

Cataracts
- Reports have indicated that ivacaftor has been effective in treating pediatric patients.
- However, there are other risk factors such as radiation exposure and corticosteroid use.
- Pediatric patients should have a baseline and follow-up eye exam.
CNS effects
- Dizziness can cause impairment of mental or physical abilities.
- Patients should be warned about driving or operating machinery that requires mental alertness.
Hepatic effects
- It is possible that liver transaminases could be elevated.
- Monitoring liver function is important; patients who have had a history of high hepatic transaminases in the past may need to be more vigilant.
- Treatment should be stopped temporarily if ALT or AS exceeds 5 times the upper limit for normal.
- Once transaminase elevations have been resolved, It is crucial to weigh the advantages and disadvantages of starting treatment again.
Hepatic impairment
- Take caution if you have hepatic impairment.
- It is recommended that you adjust the dosage for patients with moderate or severe (Childugh class B, C) impairment.
Renal impairment
- If you have end-stage renal disease and severe renal impairment (CrCl = 30 mL/min), use caution.

Ivacaftor: Drug Interaction

Risk Factor C (Monitor therapy)
ARIPiprazole	ARIPiprazole's serum levels may rise in response to CYP3A4 Inhibitors (Weak). Management: Keep an eye out for enhanced pharmacologic effects of aripiprazole. Depending on the concurrent therapy and/or the indication, aripiprazole dosage modifications may or may not be necessary. For detailed advice, refer to the complete interaction monograph.
Bosentan	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
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.
Celiprolol	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol.
Clofazimine:	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CYP3A4 Inducers (Moderate)	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Dofetilide	CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide.
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Everolimus	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus.
Flibanserin	CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin.
Fosaprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Glimepiride	Ivacaftor may increase the serum concentration of Glimepiride.
GlipiZIDE	Ivacaftor may increase the serum concentration of GlipiZIDE.
Ivosidenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Larotrectinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Larotrectinib	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib.
Naldemedine	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine.
Naloxegol	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol.
NiMODipine	CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine.
Palbociclib	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
P-glycoprotein/ABCB1 Substrates	The serum concentration of P-glycoprotein/ABCB1 Substrates may rise in response to P-glycoprotein/ABCB1 Inhibitors. P-glycoprotein inhibitors may also make it easier for p-glycoprotein substrates to reach particular cells, tissues, and organs where p-glycoprotein is abundant (e.g., brain, T-lymphocytes, testes, etc.). Loperamide is an exception.
Prucalopride	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride.
Ranolazine	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine.
Rifabutin	May decrease the serum concentration of Ivacaftor.
RifAXIMin	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin.
Sarilumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Silodosin	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin.
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Simeprevir	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Talazoparib	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Management: These listed exceptions are discussed in detail in separate interaction monographs.
Tegaserod	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod.
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Warfarin	Ivacaftor may increase the serum concentration of Warfarin.
Risk Factor D (Consider therapy modification)
Afatinib	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Reduce afatinib by 10 mg if not tolerated. Some non-US labeling recommends avoiding combination if possible. If used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib.
Betrixaban	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease the adult betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-glycoprotein inhibitor.
Bilastine	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in patients with moderate to severe renal insufficiency who are receiving p-glycoprotein inhibitors.
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. See full monograph for details.
CYP3A4 Inhibitors (Moderate)	Ivacaftor serum concentration might rise. Management: For product-specific advice, read the full monograph. Ivacaftor dose reductions may be necessary. When taking ivacaftor/lumacaftor with a mild CYP3A4 inhibitor, there is no need to change the dosage. Exceptions: Citrus Juice.
CYP3A4 Inhibitors (Strong)	Ivacaftor serum concentration might rise. Management: Ivacaftor dosage reductions are necessary; for product-specific advice, refer to the complete monograph content.
Dabigatran Etexilate	P-glycoprotein/ABCB1 The serum levels of Dabigatran Etexilate's active metabolite(s) may rise in response to inhibitors. Reducing the dose of dabigatran may be necessary for treatment. According to US vs. Canadian labelling, a particular P-gp inhibitor, renal function, and a therapy indication for dabigatran, specific advice varies greatly. Refer to the dabigatran labelling or the complete monograph.
Dabrafenib	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate wherever possible. If concurrent therapy cannot be avoided, pay special attention to the substrate's clinical consequences (particularly therapeutic effects).
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.
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 P-gp inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation.
Lefamulin	Lefamulin's levels in the serum may rise in response to P-glycoprotein/ABCB1 inhibitors. Avoid taking lefamulin tablets at the same time as P-glycoprotein/ABCB1 inhibitors. Watch for any negative effects of lefamulin if concurrent use is necessary.
Lemborexant	Lemborexant's serum levels may rise in the presence of CYP3A4 Inhibitors (Weak). Management: When used in conjunction with weak CYP3A4 inhibitors, a maximum daily dose of 5 mg of lemborexant is advised.
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.
Lorlatinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.
MiFEPRIStone	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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.
Stiripentol	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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.
Triazolam	Triazolam's serum levels may rise in the presence of CYP3A4 Inhibitors (Weak). Management: If a patient is using a concurrent mild CYP3A4 inhibitor, consider reducing the dose of triazolam.
Ubrogepant	It's possible that CYP3A4 Inhibitors (Weak) will raise the level of ubrogepant in the blood. Treatment: The initial and second doses of ubrogepant in patients using mild CYP3A4 inhibitors should be no more than 50 mg each.
Venetoclax	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Consider a venetoclax dose reduction by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors.
Risk Factor X (Avoid combination)
Bitter Orange	Ivacaftor serum concentration might rise.
Conivaptan	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CYP3A4 Inducers (Strong)	May decrease the serum concentration of Ivacaftor.
Fusidic Acid (Systemic)	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Grapefruit Juice	May increase the serum concentration of Ivacaftor.
Idelalisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
PAZOPanib	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib.
Pimozide	CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide.
St John's Wort	May decrease the serum concentration of Ivacaftor.
Topotecan	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan.
VinCRIStine (Liposomal)	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal).

Ivacaftor: Drug Interaction

Risk Factor C (Monitor therapy)
ARIPiprazole	ARIPiprazole's serum levels may rise in response to CYP3A4 Inhibitors (Weak). Management: Keep an eye out for enhanced pharmacologic effects of aripiprazole. Depending on the concurrent therapy and/or the indication, aripiprazole dosage modifications may or may not be necessary. For detailed advice, refer to the complete interaction monograph.
Bosentan	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
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.
Celiprolol	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol.
Clofazimine:	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CYP3A4 Inducers (Moderate)	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Dofetilide	CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide.
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Everolimus	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus.
Flibanserin	CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin.
Fosaprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Glimepiride	Ivacaftor may increase the serum concentration of Glimepiride.
GlipiZIDE	Ivacaftor may increase the serum concentration of GlipiZIDE.
Ivosidenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Larotrectinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Larotrectinib	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib.
Naldemedine	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine.
Naloxegol	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol.
NiMODipine	CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine.
Palbociclib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
P-glycoprotein/ABCB1 Substrates	The serum concentration of P-glycoprotein/ABCB1 Substrates may rise in response to P-glycoprotein/ABCB1 Inhibitors. P-glycoprotein inhibitors may also make it easier for p-glycoprotein substrates to reach particular cells, tissues, and organs where p-glycoprotein is abundant (e.g., brain, T-lymphocytes, testes, etc.). Loperamide is an exception.
Prucalopride	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride.
Ranolazine	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine.
Rifabutin	May decrease the serum concentration of Ivacaftor.
RifAXIMin	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin.
Sarilumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Silodosin	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin.
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Simeprevir	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Talazoparib	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Management: These listed exceptions are discussed in detail in separate interaction monographs.
Tegaserod	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod.
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Warfarin	Ivacaftor may increase the serum concentration of Warfarin.
Risk Factor D (Consider therapy modification)
Afatinib	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Reduce afatinib by 10 mg if not tolerated. Some non-US labeling recommends avoiding combination if possible. If used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib.
Betrixaban	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease the adult betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-glycoprotein inhibitor.
Bilastine	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in patients with moderate to severe renal insufficiency who are receiving p-glycoprotein inhibitors.
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. See full monograph for details.
CYP3A4 Inhibitors (Moderate)	Ivacaftor serum concentration might rise. Management: For product-specific advice, read the full monograph. Ivacaftor dose reductions may be necessary. When taking ivacaftor/lumacaftor with a mild CYP3A4 inhibitor, there is no need to change the dosage. Exceptions: Citrus Juice.
CYP3A4 Inhibitors (Strong)	Ivacaftor serum concentration might rise. Management: Ivacaftor dosage reductions are necessary; for product-specific advice, refer to the complete monograph content.
Dabigatran Etexilate	P-glycoprotein/ABCB1 The serum levels of Dabigatran Etexilate's active metabolite(s) may rise in response to inhibitors. Reducing the dose of dabigatran may be necessary for treatment. According to US vs. Canadian labelling, a particular P-gp inhibitor, renal function, and a therapy indication for dabigatran, specific advice varies greatly. Refer to the dabigatran labelling or the complete monograph.
Dabrafenib	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: When possible, look for substitutes for the CYP3A4 substrate. If concurrent therapy cannot be avoided, pay special attention to the substrate's clinical consequences (particularly therapeutic effects).
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.
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 P-gp inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation.
Lefamulin	Lefamulin's levels in the serum may rise in response to P-glycoprotein/ABCB1 inhibitors. Avoid taking lefamulin tablets at the same time as P-glycoprotein/ABCB1 inhibitors. Watch for any negative effects of lefamulin if concurrent use is necessary.
Lemborexant	Lemborexant's serum levels may rise in the presence of CYP3A4 Inhibitors (Weak). Management: When used in conjunction with weak CYP3A4 inhibitors, a maximum daily dose of 5 mg of lemborexant is advised.
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.
Lorlatinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.
MiFEPRIStone	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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.
Stiripentol	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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.
Triazolam	Triazolam's serum levels may rise in the presence of CYP3A4 Inhibitors (Weak). Management: If a patient is using a concurrent mild CYP3A4 inhibitor, consider reducing the dose of triazolam.
Ubrogepant	It's possible that CYP3A4 Inhibitors (Weak) will raise the level of ubrogepant in the blood. Treatment: The initial and second doses of ubrogepant in patients using mild CYP3A4 inhibitors should be no more than 50 mg each.
Venetoclax	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Consider a venetoclax dose reduction by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors.
Risk Factor X (Avoid combination)
Bitter Orange	Ivacaftor serum concentration might rise.
Conivaptan	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CYP3A4 Inducers (Strong)	May decrease the serum concentration of Ivacaftor.
Fusidic Acid (Systemic)	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Grapefruit Juice	May increase the serum concentration of Ivacaftor.
Idelalisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
PAZOPanib	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib.
Pimozide	CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide.
St John's Wort	May decrease the serum concentration of Ivacaftor.
Topotecan	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan.
VinCRIStine (Liposomal)	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal).

Monitoring parameters:

CF mutation test ( if G551D mutation status unknown should be done prior to therapy initiation).
ALT/AST should be done at baseline than every 3 monthly for 1 year, then annually thereafter or as clinically indicated (in patients with a history of elevated hepatic transaminases more frequent monitoring should be considered).
FEV
Ophthalmological exams in pediatric patients at baseline and at follow-up.

How to administer Ivacaftor (Kalydeco)?

P/O:

It should be given before or after food that contains high-fat content eg, butter, eggs, yogurt.

Granules:

A full packet of granules should be combined with 5 mL of soft food (such as yoghurt, applesauce, or pureed fruits or vegetables, avoiding grapefruit or Seville oranges) or liquid (such as water, milk, or juice, excluding grapefruit juice). Within an hour, finish the granule combination.

Mechanism of action of Ivacaftor (Kalydeco):

It increases the cell-surface protein CFTR's ability to transport chloride into epithelial cells, which improves the tissues' ability to absorb salt and water (eg lung, GI tract).

The beginning of action: Faster than a week, increased FEV-1 and decreased sweat chloride

AbsorptionVariable: Absorption is affected by fatty foods (between 2.5- and 4-fold).

Protein binding: Nearly 99% of drug is protein-bound, primarily to albumin and alpha acid glycoprotein.

MetabolismCYP3A: The liver is able to extensively metabolize the drug via CYP3A. Two major metabolites (M1 [active], 1/6 potency, and M6]) are formed.

Half-life elimination: Almost 12 hours

Time to peak: Median: Almost 4 hours (range: 3 to 6 hours) (fed state)

Excretion: 87.8%, almost 65% of the administered dose is excreted in feces as metabolites; minimal excretion in the form of unchanged drug is excreted in the urine.

International Brand Names of Ivacaftor:

Kalydeco
Ivadeco

Ivacaftor Brand Names in Pakistan:

No Brands Available in Pakistan.

Ivacaftor (Kalydeco) Tablets - Uses, Dose, MOA, Brands, Side effects

Ivacaftor Uses:

Cystic fibrosis:

Ivacaftor (Kalydeco) Dose in Adults:

Ivacaftor (Kalydeco) Dose in the treatment of Cystic fibrosis:

Dosage adjustment for ivacaftor with concomitant medications:

Missed dose:

Ivacaftor (Kalydeco) Dose in Children:

Ivacaftor (Kalydeco) Dose in the treatment of Cystic fibrosis: Oral:

Infants ≥6 months and Children <6 years: Oral granules:

Children ≥6 years and Adolescents:

Dosage adjustment for concomitant therapy:

Pregnancy Risk Category: B

Use during breastfeeding:

Dose in Kidney Disease:

Dose in Liver disease:

Common Side Effects of Ivacaftor (Kalydeco):

Central Nervous System:

Dermatologic:

Gastrointestinal:

Respiratory:

Less Common Side Effects Of Ivacaftor (Kalydeco):

Central Nervous System:

Dermatologic:

Endocrine & Metabolic:

Hepatic:

Infection:

Neuromuscular & Skeletal:

Respiratory:

Frequency of side effects not defined:

Endocrine & Metabolic:

Contraindications to Ivacaftor (Kalydeco):

Warnings and precautions

Cataracts

CNS effects

Hepatic effects

Hepatic impairment

Renal impairment

Monitoring parameters:

How to administer Ivacaftor (Kalydeco)?

Mechanism of action of Ivacaftor (Kalydeco):

International Brand Names of Ivacaftor:

Ivacaftor Brand Names in Pakistan:

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