Corlanor

Other Cardiovascular Agents

Hazardous Drugs Classification
NIOSH (Draft) 2020 List: Table 2
Approved by FDA after NIOSH 2016 list published.
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown; Eye/face and respiratory protection may be needed during preparation and administration.

Administer with food. Avoid ingestion of grapefruit juice.
If a dose is missed or spit out, do not give another dose to make up for the missed or spit out dose. Give the next dose at the usual time.[59430]

Oral solution
Empty the entire contents of the ampule(s) into a medication cup.
Measure the prescribed dose with a calibrated oral syringe.
Storage: Discard unused oral solution. Do not store or reuse any oral solution left in the medication cup or ampule.[59430]

bradycardia / Rapid / 6.0-10.0
atrial fibrillation / Early / 8.3-8.3
torsade de pointes / Rapid / Incidence not known
ventricular fibrillation / Early / Incidence not known
ventricular tachycardia / Early / Incidence not known
visual impairment / Early / Incidence not known
angioedema / Rapid / Incidence not known

hypertension / Early / 8.9-8.9
hypotension / Rapid / Incidence not known
erythema / Early / Incidence not known

syncope / Early / Incidence not known
diplopia / Early / Incidence not known
rash / Early / Incidence not known
pruritus / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
vertigo / Early / Incidence not known

Corlanor

Rx

Hyperpolarization-activated cyclic nucleotide-gated channel blocker
Used for the treatment of stable symptomatic heart failure
Contraindicated when used in combination with strong CYP3A4 inhibitors

5 mg PO twice daily, initially. Adjust the dose after 2 weeks and thereafter as needed based on heart rate and tolerability. Max: 7.5 mg PO twice daily.[59430] Ivabradine is indicated to reduce the risk of hospitalization for worsening heart failure in adult patients with symptomatic (NYHA class II or III) stable chronic reduced ejection fraction (35% or less) heart failure (HFrEF) who are either receiving a beta blocker at the maximum tolerated dose or have a contraindication to beta-blocker use, and who are in sinus rhythm with a resting heart rate of 70 bpm or more.[59430] [62661]

2.5 mg PO twice daily, initially. Adjust the dose every 2 weeks as needed based on heart rate and tolerability by 2.5 mg/dose to a target heart rate reduction of at least 20%. Max: 7.5 mg PO twice daily. Ivabradine is indicated for the treatment of heart failure due to dilated cardiomyopathy (DCM) in pediatric patients in sinus rhythm with an elevated heart rate.[59430]

0.05 mg/kg/dose PO twice daily, initially. Adjust the dose every 2 weeks as needed based on heart rate and tolerability by 0.05 mg/kg/dose to a target heart rate reduction of at least 20% based on tolerability. Max: 0.3 mg/kg/dose PO twice daily or 7.5 mg PO twice daily, whichever is less. Ivabradine is indicated for the treatment of heart failure due to dilated cardiomyopathy (DCM) in pediatric patients in sinus rhythm with an elevated heart rate.[59430]

0.05 mg/kg/dose PO twice daily, initially. Adjust the dose every 2 weeks as needed based on heart rate and tolerability by 0.05 mg/kg/dose to a target heart rate reduction of at least 20% based on tolerability. Max: 0.2 mg/kg/dose PO twice daily. Ivabradine is indicated for the treatment of heart failure due to dilated cardiomyopathy (DCM) in pediatric patients in sinus rhythm with an elevated heart rate.[59430]

2.5 mg PO twice daily, initially. Adjust the dose after 3 to 4 weeks and thereafter as needed based on heart rate and tolerability. Max: 7.5 mg PO twice daily. Discontinue therapy if no improvement in angina symptoms within 3 months and consider discontinuing therapy if there is only limited symptomatic response and no clinically relevant decrease in resting heart rate within 3 months.

5 mg PO twice daily, initially. Adjust the dose after 3 to 4 weeks and thereafter as needed based on heart rate and tolerability. Max: 7.5 mg PO twice daily. Discontinue therapy if no improvement in angina symptoms within 3 months and consider discontinuing therapy if there is only limited symptomatic response and no clinically relevant decrease in resting heart rate within 3 months.

†Indicates off-label use

Ivabradine is contraindicated in patients with severe hepatic impairment (Child-Pugh C). No dose adjustment is required in patients with mild to moderate hepatic impairment.[59430]

No dosage adjustment is needed in patients with a CrCl 15 to 60 mL/minute. Data is not available for patients with a CrCl less than 15 mL/minute.[59430]

Acebutolol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Adagrasib: (Contraindicated) Coadministration of adagrasib with ivabradine is contraindicated due to an increase in plasma concentrations of ivabradine, which may exacerbate bradycardia and conduction disturbances. Ivabradine is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivabradine exposure by 7.7-fold.
Amiodarone: (Major) Avoid coadministration of ivarbadine and amiodarone as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; amiodarone is a moderate CYP3A4 inhibitor. In addition, coadministration of ivabradine with other negative chronotropes like amiodarone increases the risk for bradycardia. Increased ivabradine concentrations may further increase the risk of bradycardia exacerbation and conduction disturbances.
Amobarbital: (Major) Avoid coadministration of ivabradine and barbiturates including primidone. Ivabradine is primarily metabolized by CYP3A4; barbiturates induce CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) Coadministration of ivabradine and clarithromycin is contraindicated. Ivabradine is primarily metabolized by CYP3A4; clarithromycin is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Apalutamide: (Major) Avoid coadministration of ivabradine and apalutamide due to decreased plasma concentrations of ivabradine. Ivabradine is a CYP3A4 substrate and apalutamide is a CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ivabradine exposure by approximately half.
Aprepitant, Fosaprepitant: (Major) Use caution if ivabradine and aprepitant, fosaprepitant are used concurrently and monitor for an increase in ivabradine-related adverse effects, including bradycardia exacerbation and conduction disturbances, for several days after administration of a multi-day aprepitant regimen. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of ivabradine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid coadministration of ivabradine and barbiturates including primidone. Ivabradine is primarily metabolized by CYP3A4; barbiturates induce CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Atazanavir: (Contraindicated) Coadministration of ivabradine and atazanvir is contraindicated. Ivabradine is primarily metabolized by CYP3A4; atazanavir is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Atazanavir; Cobicistat: (Contraindicated) Coadministration of cobicistat with ivabradine is contraindicated due to an increase in plasma concentrations of ivabradine, which may exacerbate bradycardia and conduction disturbances. Ivabradine is primarily metabolized by CYP3A4; cobicistat is a strong inhibitor of CYP3A4. Coadministration with another strong CYP3A4 inhibitor increased ivabradine exposure by 7.7-fold. (Contraindicated) Coadministration of ivabradine and atazanvir is contraindicated. Ivabradine is primarily metabolized by CYP3A4; atazanavir is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Atenolol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Atenolol; Chlorthalidone: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Barbiturates: (Major) Avoid coadministration of ivabradine and barbiturates including primidone. Ivabradine is primarily metabolized by CYP3A4; barbiturates induce CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Berotralstat: (Major) Avoid coadministration of ivabradine and berotralstat as increased concentrations of ivabradine are possible, which may result in bradycardia exacerbation and conduction disturbances. Ivabradine is primarily metabolized by CYP3A4 and berotralstat is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors increased the AUC of ivabradine by 2- to 3-fold.
Beta-blockers: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Betaxolol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Bisoprolol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Brimonidine; Timolol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Butabarbital: (Major) Avoid coadministration of ivabradine and barbiturates including primidone. Ivabradine is primarily metabolized by CYP3A4; barbiturates induce CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Butalbital; Acetaminophen: (Major) Avoid coadministration of ivabradine and barbiturates including primidone. Ivabradine is primarily metabolized by CYP3A4; barbiturates induce CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid coadministration of ivabradine and barbiturates including primidone. Ivabradine is primarily metabolized by CYP3A4; barbiturates induce CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid coadministration of ivabradine and barbiturates including primidone. Ivabradine is primarily metabolized by CYP3A4; barbiturates induce CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid coadministration of ivabradine and barbiturates including primidone. Ivabradine is primarily metabolized by CYP3A4; barbiturates induce CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Carbamazepine: (Major) Avoid coadministration of ivabradine and carbamazepine. Ivabradine is primarily metabolized by CYP3A4; carbamazepine induces CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Carteolol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Carvedilol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Ceritinib: (Contraindicated) Coadministration of ceritinib with ivabradine is contraindicated due to an increase in plasma concentrations of ivabradine, which may exacerbate bradycardia and conduction disturbances. Ivabradine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ivabradine exposure by 7.7-fold.
Chloramphenicol: (Contraindicated) Coadministration of ivabradine and chloramphenicol is contraindicated. Ivabradine is primarily metabolized by CYP3A4; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Ciprofloxacin: (Major) Avoid coadministration of ivabradine and ciprofloxacin as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; ciprofloxacin inhibits CYP3A4. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Clarithromycin: (Contraindicated) Coadministration of ivabradine and clarithromycin is contraindicated. Ivabradine is primarily metabolized by CYP3A4; clarithromycin is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Cobicistat: (Contraindicated) Coadministration of cobicistat with ivabradine is contraindicated due to an increase in plasma concentrations of ivabradine, which may exacerbate bradycardia and conduction disturbances. Ivabradine is primarily metabolized by CYP3A4; cobicistat is a strong inhibitor of CYP3A4. Coadministration with another strong CYP3A4 inhibitor increased ivabradine exposure by 7.7-fold.
Conivaptan: (Major) Avoid coadministration of ivabradine and conivaptan as increased concentrations of ivabradine are possible, which may result in bradycardia exacerbation and conduction disturbances. Ivabradine is primarily metabolized by CYP3A and conivaptan is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors increased the AUC of ivabradine by 2- to 3-fold.
Crizotinib: (Major) Avoid coadministration of ivabradine and crizotinib as increased concentrations of ivabradine are possible, which may result in bradycardia exacerbation and conduction disturbances. Ivabradine is primarily metabolized by CYP3A4 and crizotinib is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A4 inhibitors increased the AUC of ivabradine by 2- to 3-fold.
Cyclosporine: (Major) Avoid coadministration of ivabradine and cyclosporine as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; cyclosporine inhibits CYP3A4. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Danazol: (Major) Avoid coadminsitration of ivabradine and danazol as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; danazol inhibits CYP3A4. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Darunavir: (Contraindicated) Coadministration of ivabradine and darunavir is contraindicated. Ivabradine is primarily metabolized by CYP3A4; darunavir is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Darunavir; Cobicistat: (Contraindicated) Coadministration of cobicistat with ivabradine is contraindicated due to an increase in plasma concentrations of ivabradine, which may exacerbate bradycardia and conduction disturbances. Ivabradine is primarily metabolized by CYP3A4; cobicistat is a strong inhibitor of CYP3A4. Coadministration with another strong CYP3A4 inhibitor increased ivabradine exposure by 7.7-fold. (Contraindicated) Coadministration of ivabradine and darunavir is contraindicated. Ivabradine is primarily metabolized by CYP3A4; darunavir is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Coadministration of cobicistat with ivabradine is contraindicated due to an increase in plasma concentrations of ivabradine, which may exacerbate bradycardia and conduction disturbances. Ivabradine is primarily metabolized by CYP3A4; cobicistat is a strong inhibitor of CYP3A4. Coadministration with another strong CYP3A4 inhibitor increased ivabradine exposure by 7.7-fold. (Contraindicated) Coadministration of ivabradine and darunavir is contraindicated. Ivabradine is primarily metabolized by CYP3A4; darunavir is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Delavirdine: (Contraindicated) Coadministration of ivabradine and delavirdine is contraindicated. Ivabradine is primarily metabolized by CYP3A4; delavirdine is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Digoxin: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like digoxin. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Diltiazem: (Major) Avoid coadministration of ivabradine and diltiazem. Both ivabradine and diltiazem may cause bradycardia. In addition, ivabradine is primarily metabolized by CYP3A4; diltiazem inhibits CYP3A4. Coadministration may increase the plasma concentrations of ivabradine further increasing the risk for bradycardia exacerbation and conduction disturbances.
Dorzolamide; Timolol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Dronedarone: (Major) Avoid coadministration of ivabradine and dronedarone as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; dronedarone inhibits CYP3A4. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Coadministration of cobicistat with ivabradine is contraindicated due to an increase in plasma concentrations of ivabradine, which may exacerbate bradycardia and conduction disturbances. Ivabradine is primarily metabolized by CYP3A4; cobicistat is a strong inhibitor of CYP3A4. Coadministration with another strong CYP3A4 inhibitor increased ivabradine exposure by 7.7-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Coadministration of cobicistat with ivabradine is contraindicated due to an increase in plasma concentrations of ivabradine, which may exacerbate bradycardia and conduction disturbances. Ivabradine is primarily metabolized by CYP3A4; cobicistat is a strong inhibitor of CYP3A4. Coadministration with another strong CYP3A4 inhibitor increased ivabradine exposure by 7.7-fold.
Enzalutamide: (Major) Avoid coadministration of ivabradine and enzalutamide due to decreased plasma concentrations of ivabradine. Ivabradine is a CYP3A4 substrate and enzalutamide is a CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ivabradine exposure by approximately half.
Erythromycin: (Major) Avoid coadministration of ivabradine and erythromycin as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; erythromycin inhibits CYP3A4. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Esmolol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Fedratinib: (Major) Avoid coadministration of ivabradine and fedratinib as increased concentrations of ivabradine are possible, which may result in bradycardia exacerbation and conduction disturbances. Ivabradine is primarily metabolized by CYP3A4 and fedratinib is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors increased the AUC of ivabradine by 2- to 3-fold.
Fluconazole: (Major) Avoid coadministration of ivabradine and fluconazole as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; fluconazole inhibits CYP3A4. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Fluvoxamine: (Moderate) Coadministration may increase the plasma concentrations of ivabradine, potentially increasing the risk for bradycardia exacerbation and conduction disturbances. Ivabradine is primarily metabolized by CYP3A4 and fluvoxamine is a moderate CYP3A4 inhibitor.
Fosamprenavir: (Major) Avoid coadministration of ivabradine and fosamprenavir as increased concentrations of ivabradine are possible, which may result in bradycardia exacerbation and conduction disturbances. Ivabradine is primarily metabolized by CYP3A and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors increased the AUC of ivabradine by 2- to 3-fold.
Fosphenytoin: (Major) Avoid coadministration of ivabradine and phenytoin or fosphenytoin. Ivabradine is primarily metabolized by CYP3A4; phenytoin induces CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Grapefruit juice: (Major) Avoid consuming grapefruit juice during ivabradine therapy. Ivabradine is primarily metabolized by CYP3A4; grapefruit juice inhibits CYP3A4. Coadministration may increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Idelalisib: (Contraindicated) Coadministration of ivabradine and idelalisib is contraindicated. Ivabradine is primarily metabolized by CYP3A4; idelalisib is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Imatinib: (Major) Avoid coadministration of ivabradine and imatinib, STI-571 as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; imatinib inhibits CYP3A4. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Indinavir: (Contraindicated) Coadministration of ivabradine and indinavir is contraindicated. Ivabradine is primarily metabolized by CYP3A4; indinavir is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Isavuconazonium: (Major) Avoid coadministration of ivabradine and isavuconazonium. Ivabradine is primarily metabolized by CYP3A4; isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration may increase the plasma concentrations of ivabradine further increasing the risk for bradycardia exacerbation and conduction disturbances.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of ivabradine and rifampin. Ivabradine is primarily metabolized by CYP3A4; rifampin induces CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of ivabradine and rifampin. Ivabradine is primarily metabolized by CYP3A4; rifampin induces CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Itraconazole: (Contraindicated) Ivabradine is contraindicated for use during and for 2 weeks after itraconazole therapy. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances. Ivabradine is primarily metabolized by CYP3A4; itraconazole is a strong CYP3A4 inhibitor.
Ketoconazole: (Contraindicated) Coadministration of ivabradine and ketoconazole is contraindicated. Ivabradine is primarily metabolized by CYP3A4; ketoconazole is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Labetalol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) Coadministration of ivabradine and clarithromycin is contraindicated. Ivabradine is primarily metabolized by CYP3A4; clarithromycin is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Lasmiditan: (Moderate) Monitor heart rate if lasmiditan is coadministered with ivabradine as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Lefamulin: (Major) Avoid coadministration of ivabradine and oral lefamulin as increased concentrations of ivabradine are possible, which may result in bradycardia exacerbation and conduction disturbances. Ivabradine is primarily metabolized by CYP3A4 and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. Coadministration with other moderate CYP3A4 inhibitors increased the AUC of ivabradine by 2- to 3-fold.
Lenacapavir: (Major) Avoid coadministration of ivabradine and lenacapavir as increased concentrations of ivabradine are possible, which may result in bradycardia exacerbation and conduction disturbances. Ivabradine is primarily metabolized by CYP3A and lenacapavir is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors increased the AUC of ivabradine by 2- to 3-fold.
Letermovir: (Major) Avoid concurrent use of ivabradine and letermovir as increased concentrations of ivabradine are possible, which may result in bradycardia exacerbation and conduction disturbances. Concurrent use is contraindicated if the patient is also receiving cyclosporine because the magnitude of the interaction may be amplified. Ivabradine is primarily metabolized by CYP3A4. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A4 inhibitor increased ivabradine exposure by 7.7-fold, while concomitant use of moderate CYP3A4 inhibitors increased exposure of ivabradine by 2-fold to 3-fold.
Levobunolol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Levoketoconazole: (Contraindicated) Coadministration of ivabradine and ketoconazole is contraindicated. Ivabradine is primarily metabolized by CYP3A4; ketoconazole is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Lonafarnib: (Contraindicated) Coadministration of lonafarnib with ivabradine is contraindicated due to an increase in plasma concentrations of ivabradine, which may exacerbate bradycardia and conduction disturbances. Ivabradine is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ivabradine exposure by 7.7-fold.
Lopinavir; Ritonavir: (Contraindicated) Coadministration of ivabradine and ritonavir is contraindicated. Ivabradine is primarily metabolized by CYP3A4; ritonavir is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may decrease the systemic exposure and therapeutic efficacy of ivabradine; avoid concurrent use. Ivabradine is primarily metabolized by CYP3A4. Lumacaftor is a strong CYP3A inducer.
Methohexital: (Major) Avoid coadministration of ivabradine and barbiturates including primidone. Ivabradine is primarily metabolized by CYP3A4; barbiturates induce CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Metoprolol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Mifepristone: (Major) Avoid coadministration of ivabradine and mifepristone as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; mifepristone inhibits CYP3A4. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances. Due to the slow elimination of mifepristone from the body, drug interactions may be prolonged.
Mitotane: (Major) Avoid the concomitant use of mitotane with ivabradine; if coadministration cannot be avoided, monitor for decreased efficacy of ivabradine. Mitotane is a strong CYP3A4 inducer and ivabradine is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of ivabradine.
Nadolol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Nebivolol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Nebivolol; Valsartan: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Nefazodone: (Contraindicated) Coadministration of ivabradine and nefazodone is contraindicated. Ivabradine is primarily metabolized by CYP3A4; nefazodone is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Nelfinavir: (Contraindicated) Coadministration of ivabradine and nelfinavir is contraindicated. Ivabradine is primarily metabolized by CYP3A4; nelfinavir is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Netupitant, Fosnetupitant; Palonosetron: (Major) Avoid coadministration of ivabradine and netupitant; palonosetron as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; netupitant is a moderate CYP3A4 inhibitor. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Nilotinib: (Major) Avoid coadministration of ivabradine and nilotinib as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; nilotinib inhibits CYP3A4. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Nirmatrelvir; Ritonavir: (Contraindicated) Coadministration of ivabradine and ritonavir is contraindicated. Ivabradine is primarily metabolized by CYP3A4; ritonavir is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances. (Contraindicated) Concomitant use of ritonavir-boosted nirmatrelvir and ivabradine is contraindicated due to the potential for bradycardia or conduction disturbances; consider an alternative COVID-19 therapy. Coadministration may increase ivabradine exposure resulting in increased toxicity. Ivabradine is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor.
Pentobarbital: (Major) Avoid coadministration of ivabradine and barbiturates including primidone. Ivabradine is primarily metabolized by CYP3A4; barbiturates induce CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Phenobarbital: (Major) Avoid coadministration of ivabradine and barbiturates including primidone. Ivabradine is primarily metabolized by CYP3A4; barbiturates induce CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of ivabradine and barbiturates including primidone. Ivabradine is primarily metabolized by CYP3A4; barbiturates induce CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Phenytoin: (Major) Avoid coadministration of ivabradine and phenytoin or fosphenytoin. Ivabradine is primarily metabolized by CYP3A4; phenytoin induces CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Pindolol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Ponesimod: (Major) Avoid concomitant use of ponesimod and medications that may decrease heart rate such as ivabradine due to the risk for severe bradycardia and heart block. Consider consultation from a cardiologist if concomitant use is necessary.
Posaconazole: (Contraindicated) Coadministration of ivabradine and posaconazole is contraindicated. Ivabradine is primarily metabolized by CYP3A4; posaconazole is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Primidone: (Major) Avoid coadministration of ivabradine and barbiturates including primidone. Ivabradine is primarily metabolized by CYP3A4; barbiturates induce CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Propranolol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Ribociclib: (Contraindicated) Coadministration of ribociclib with ivabradine is contraindicated due to an increase in plasma concentrations of ivabradine, which may exacerbate bradycardia and conduction disturbances. Ivabradine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ivabradine exposure by 7.7-fold.
Ribociclib; Letrozole: (Contraindicated) Coadministration of ribociclib with ivabradine is contraindicated due to an increase in plasma concentrations of ivabradine, which may exacerbate bradycardia and conduction disturbances. Ivabradine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ivabradine exposure by 7.7-fold.
Rifampin: (Major) Avoid coadministration of ivabradine and rifampin. Ivabradine is primarily metabolized by CYP3A4; rifampin induces CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Rifapentine: (Major) Avoid coadministration of ivabradine and rifapentine due to decreased plasma concentrations of ivabradine. Ivabradine is a CYP3A4 substrate and rifapentine is a CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ivabradine exposure by approximately half.
Ritlecitinib: (Major) Avoid coadministration of ivabradine and ritlecitinib as increased concentrations of ivabradine are possible, which may result in bradycardia exacerbation and conduction disturbances. Ivabradine is primarily metabolized by CYP3A and ritlecitinib is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors increased the AUC of ivabradine by 2- to 3-fold.
Ritonavir: (Contraindicated) Coadministration of ivabradine and ritonavir is contraindicated. Ivabradine is primarily metabolized by CYP3A4; ritonavir is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Saquinavir: (Contraindicated) Coadministration of ivabradine and saquinavir is contraindicated. Ivabradine is primarily metabolized by CYP3A4; saquinavir is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Secobarbital: (Major) Avoid coadministration of ivabradine and barbiturates including primidone. Ivabradine is primarily metabolized by CYP3A4; barbiturates induce CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving ivabradine due to the potential for additive effects on heart rate. Consult a cardiologist regarding appropriate monitoring if siponimod use is required.
Sotalol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of ivabradine and St. John's wort. Ivabradine is primarily metabolized by CYP3A4; St. John's wort induces CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for reduced efficacy of ivabradine.
Timolol: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Tipranavir: (Contraindicated) Coadministration of ivabradine and tipranavir is contraindicated. Ivabradine is primarily metabolized by CYP3A4; tipranavir is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Trandolapril; Verapamil: (Major) Avoid coadministration of ivabradine and verapamil. Both ivabradine and verapamil may cause bradycardia. In addition, ivabradine is primarily metabolized by CYP3A4; verapamil inhibits CYP3A4. Coadministration may increase the plasma concentrations of ivabradine further increasing the risk for bradycardia exacerbation and conduction disturbances.
Tucatinib: (Contraindicated) Coadministration of tucatinib with ivabradine is contraindicated due to an increase in plasma concentrations of ivabradine, which may exacerbate bradycardia and conduction disturbances. Ivabradine is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ivabradine exposure by 7.7-fold.
Verapamil: (Major) Avoid coadministration of ivabradine and verapamil. Both ivabradine and verapamil may cause bradycardia. In addition, ivabradine is primarily metabolized by CYP3A4; verapamil inhibits CYP3A4. Coadministration may increase the plasma concentrations of ivabradine further increasing the risk for bradycardia exacerbation and conduction disturbances.
Vonoprazan; Amoxicillin; Clarithromycin: (Contraindicated) Coadministration of ivabradine and clarithromycin is contraindicated. Ivabradine is primarily metabolized by CYP3A4; clarithromycin is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Voriconazole: (Contraindicated) Coadministration of voriconazole with ivabradine is contraindicated due to an increase in plasma concentrations of ivabradine, which may exacerbate bradycardia and conduction disturbances. Ivabradine is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ivabradine exposure by 7.7-fold.
Voxelotor: (Major) Avoid coadministration of ivabradine and voxelotor as increased concentrations of ivabradine are possible, which may result in bradycardia exacerbation and conduction disturbances. Ivabradine is primarily metabolized by CYP3A and voxelotor is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors increased the AUC of ivabradine by 2- to 3-fold.

Corlanor Oral Sol: 5mg, 5mL
Corlanor Oral Tab: 5mg, 7.5mg

7.5 mg PO twice daily.

7.5 mg PO twice daily.

Weighing 40 kg or more: 7.5 mg PO twice daily.
Weighing less than 40 kg: 0.3 mg/kg/dose PO twice daily (Max: 7.5 mg/dose).

Weighing 40 kg or more: 7.5 mg PO twice daily.
Weighing less than 40 kg: 0.3 mg/kg/dose PO twice daily (Max: 7.5 mg/dose).

6 to 11 months: 0.2 mg/kg/dose PO twice daily.
1 to 5 months: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Ivabradine is a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker. Ivabradine selectively and specifically inhibits the cardiac pacemaker If current in the sinoatrial node resulting in a dose-dependent reduction in heart rate. Studies in healthy hearts suggest ivabradine does not affect other channels in the heart or vascular system. Unlike beta-blockers, ivabradine does not affect myocardial contractility and intracardiac conduction, even in patients with impaired systolic function. The magnitude of heart rate reduction is proportional to the baseline heart rate with a plateau effect at doses more than 20 mg twice daily. Because ivabradine also inhibits h-channels, which carry the Ih current in the retina, some patients have experienced luminous phenomena (phosphenes).[50184] [59430]
 
In clinical studies, ivabradine was associated with a dose-dependent increase of 18 to 30 msec in the uncorrected QT interval with heart rate reduction. However, the rate-corrected increase in QT interval did not exceed 2 msec which is below the limit of 5 msec for torsadogenicity.[59466]

Ivabradine is administered orally. Plasma protein binding is approximately 70% with a steady-state volume of distribution of about 100 L. Ivabradine undergoes extensive metabolism in the liver and intestines via CYP3A4-mediated oxidation. The N-desmethylated derivative (S 18982) is the major metabolite and is equipotent to ivabradine. S 18982 circulates at concentrations approximately 40% that of ivabradine and is also metabolized by CYP3A4. The effective half-life of ivabradine is approximately 6 hours. The total clearance of ivabradine is 24 L/hour, and renal clearance is approximately 4.2 L/hour with approximately 4% of an oral dose excreted unchanged in the urine. Metabolites are excreted to a similar extent in the feces and urine.[59430]
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
Ivabradine is primarily metabolized by CYP3A4. The plasma concentrations of ivabradine are altered by coadministration of CYP3A4 inhibitors and inducers.[59430]

The absolute oral bioavailability of ivabradine is 40%. Ivabradine undergoes extensive first-pass elimination in the gut and liver. Cmax occurs 1 hour after administration in the fasted state. Food delays absorption by approximately 1 hour and increases plasma exposure by 20% to 40%. Cmax and AUC are similar for ivabradine and its major active metabolite (S 18982) between oral solution and tablets for the same dose.[59430]

There are no adequate and well-controlled studies of ivabradine in pregnant women to inform any drug-associated risks. Based on animal studies, ivabradine may cause fetal harm if administered during human pregnancy. Doses providing 1 to 3 times the human exposure at the maximum recommended human dose (MRHD) resulted in embryo-fetal toxicity and teratogenicity manifested as abnormal shape of the heart, interventricular septal defect, and complex anomalies of primary arteries with associated postnatal mortality in animal reproduction studies. At doses 5 times the human exposure at the MRHD, there was an increased rate of post-implantation loss. During pregnancy, stroke volume and heart rate increase, resulting in increased cardiac output, particularly during the first trimester. Pregnant patients with left ventricular ejection fraction less than 35% on maximally tolerated doses of beta-blockers may be particularly heart-rate dependent for augmenting cardiac output. Closely follow pregnant patients started on ivabradine, especially in the first trimester, for destabilization of congestive heart failure that could result in slowing of the heart rate. Pregnant women with chronic heart failure should be monitored for pre-term birth in the third trimester.

There is no information about the presence of ivabradine in human milk or the effects of ivabradine on the breast-fed infant or milk production. Animal studies found ivabradine was present in rat milk. Because of the potential risk to breast-fed infants from exposure to ivabradine, breast-feeding is not recommended.