Dosing & Uses
Dosage Forms & Strengths
tablet
- 5mg (scored and can be divided into equal halves to provide a 2.5-mg dose)
- 7.5mg
oral solution
- 5mg/5mL
Heart Failure
Indicated to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with LVEF ≤35%, who are in sinus rhythm with resting heart rate ≥70 bpm and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use
Initial: 5 mg PO BID with meals
After 2 weeks, assess patient and adjust dose to achieve a resting heart rate of 50-60 bpm (see dose adjustment section below)
Thereafter, adjust dose as needed based on resting heart rate and tolerability; not to exceed 7.5 mg BID
Dose adjustment
- HR >60 bpm: Increase dose by 2.5 mg (given BID) up to a maximum dose of 7.5 mg BID
- HR 50-60 bpm: Maintain dose
- HR <50 bpm or signs and symptoms of bradycardia: Decrease dose by 2.5 mg (given twice daily); if current dose is 2.5 mg BID, discontinue therapy
Dosage Modifications
History of conduction defects or adults in whom bradycardia could lead to hemodynamic compromise: Decrease initial dose to 2.5 mg PO BID; may increase dose based on heart rate
Hepatic impairment
- Mild or moderate (Child-Pugh A or B): No dose adjustment required
- Severe (Child-Pugh C): Contraindicated
Renal impairment
- CrCl 15-60 mL/min: No dose adjustment required
- CrCl <15 mL/min: No data available
Heart Dysfunction (Orphan)
Designated for treatment of postcardiac transplant heart dysfunction
Orphan sponsor
- Amgen, Inc; 1 Amgen Center Drive; Thousand Oaks, CA
Dosage Forms & Strengths
tablet
- 5mg (scored and can be divided into equal halves to provide a 2.5-mg dose)
- 7.5mg
oral solution
- 5mg/5mL
Heart Failure
Indicated for treatment of stable symptomatic heart failure due to dilated cardiomyopathy (DCM) in children aged ≥6 months, who are in sinus rhythm with an elevated heart rate
<6 months: Safety and efficacy not established
≥6 months
<40 kg (oral solution)
- Initial: 0.05 mg/kg PO BID with meals
- Assess patient at 2-week intervals and adjust dose by 0.05 mg/kg to target HR reduction of at least 20%, based on tolerability
- Maximum dose aged 6 months to <1 year: Not to exceed 0.2 mg/kg BID
- Maximum dose aged ≥1 year: 0.3 mg/kg BID; not to exceed 7.5 mg BID
≥40 kg (oral tablets)
- Initial: 2.5 mg PO BID with meals
- Assess patient at 2-week intervals and adjust dose by 2.5 mg to target HR reduction of at least 20%, based on tolerability; not to exceed 7.5 mg BID
Dose reduction for bradycardia
- If bradycardia develops, reduce dose to the previous titration step
- In patients who develop bradycardia at recommended initial dosage, consider reducing dose to 0.02 mg/kg BID
Dosage Modifications
Hepatic impairment
- Mild or moderate (Child-Pugh A or B): No dose adjustment required
- Severe (Child-Pugh C): Contraindicated
Renal impairment
- CrCl 15-60 mL/min: No dose adjustment required
- CrCl <15 mL/min: No data available
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (25)
- atazanavir
atazanavir will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated
- clarithromycin
clarithromycin will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated
- cobicistat
cobicistat will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated
- conivaptan
conivaptan will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated
- darunavir
darunavir will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated
- fosamprenavir
fosamprenavir will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
- idelalisib
idelalisib will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
- imatinib
imatinib will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
- indinavir
indinavir will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
- isoniazid
isoniazid will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
- itraconazole
itraconazole will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with itraconazole is contraindicated during and 2 weeks after of itraconazole treatment.
- ketoconazole
ketoconazole will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
- levoketoconazole
levoketoconazole will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
- lopinavir
lopinavir will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
- nefazodone
nefazodone will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
- nelfinavir
nelfinavir will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
- nicardipine
nicardipine will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
- nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions. May increase risk of bradycardia or conduction disturbances associated with ivabradine.
- posaconazole
posaconazole will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
- quinidine
quinidine will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
- ritonavir
ritonavir will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
- saquinavir
saquinavir will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
- tipranavir
tipranavir will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
- voriconazole
voriconazole will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated.
Serious - Use Alternative (55)
- amiodarone
amiodarone will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- aprepitant
aprepitant will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- armodafinil
armodafinil will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- bicalutamide
bicalutamide will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- bosentan
bosentan will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- carbamazepine
carbamazepine will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- ceritinib
ceritinib will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- cimetidine
cimetidine will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- clobazam
clobazam will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- crizotinib
crizotinib will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- cyclosporine
cyclosporine will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- dabrafenib
dabrafenib will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- dexamethasone
dexamethasone will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- diltiazem
diltiazem will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
diltiazem, ivabradine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes. - doxycycline
doxycycline will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- dronedarone
dronedarone will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- efavirenz
efavirenz will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- enzalutamide
enzalutamide will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- erythromycin base
erythromycin base will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- erythromycin stearate
erythromycin stearate will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- etravirine
etravirine will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- fexinidazole
fexinidazole will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
- fluconazole
fluconazole will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- fosaprepitant
fosaprepitant will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- fosphenytoin
fosphenytoin will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- grapefruit
grapefruit will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- haloperidol
haloperidol will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- iloperidone
iloperidone will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- lapatinib
lapatinib will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- lidocaine
lidocaine will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- metronidazole
metronidazole will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- mitotane
mitotane will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- nafcillin
nafcillin will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- netupitant/palonosetron
netupitant/palonosetron will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- nevirapine
nevirapine will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- oxcarbazepine
oxcarbazepine will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- pentobarbital
pentobarbital will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- phenobarbital
phenobarbital will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- phenytoin
phenytoin will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- primidone
primidone will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- rifabutin
rifabutin will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- rifampin
rifampin will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- rifapentine
rifapentine will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- schisandra
schisandra will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- sertraline
sertraline will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- siponimod
siponimod, ivabradine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Because of the potential additive effects on heart rate, siponimod should generally not be initiated in patients taking QT prolonging drugs with known arrhythmogenic properties, heart rate lowering calcium channel blockers, or other drugs that may decrease heart rate. If treatment considered, obtain cardiology consult regarding switching to non-heart-rate lowering drugs or appropriate monitoring for treatment initiation.
- St John's Wort
St John's Wort will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.
- tetracycline
tetracycline will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- ticagrelor
ticagrelor will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- verapamil
verapamil will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
- voxelotor
voxelotor will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.
- zileuton
zileuton will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.
Monitor Closely (25)
- acebutolol
ivabradine, acebutolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- acetylcholine
ivabradine, acetylcholine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- amiodarone
ivabradine, amiodarone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- atenolol
ivabradine, atenolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- betaxolol
ivabradine, betaxolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- bisoprolol
ivabradine, bisoprolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- carvedilol
ivabradine, carvedilol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- clonidine
ivabradine, clonidine. Either decreases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- digoxin
ivabradine, digoxin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- dronedarone
ivabradine, dronedarone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- elagolix
elagolix decreases levels of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.
- esmolol
ivabradine, esmolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- istradefylline
istradefylline will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
- labetalol
ivabradine, labetalol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- lenacapavir
lenacapavir will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- metoprolol
ivabradine, metoprolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- nadolol
ivabradine, nadolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- nebivolol
ivabradine, nebivolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- penbutolol
ivabradine, penbutolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- pindolol
ivabradine, pindolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- propranolol
ivabradine, propranolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- sotalol
ivabradine, sotalol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- tecovirimat
tecovirimat will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
- timolol
ivabradine, timolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
- verapamil
verapamil, ivabradine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.
Minor (0)
Adverse Effects
1-10%
Bradycardia (10%)
Hypertension or increased blood pressure (8.9%)
Atrial fibrillation (8.3%)
Luminous phenomena (phosphenes) or visual brightness (2.8%)
Postmarketing Reports
Syncope, hypotension
Angioedema, erythema, rash, pruritus, urticaria
Vertigo, diplopia, visual impairment
Torsade de pointes, ventricular fibrillation, ventricular tachycardia
Warnings
Contraindications
Acute decompensated heart failure
Clinically significant hypotension
Sick sinus syndrome, sinoatrial block, or third-degree AV block (unless a functioning demand pacemaker is present)
Clinically significant bradycardia
Severe hepatic impairment
Pacemaker dependence (heart rate maintained exclusively by the pacemaker)
Concomitant use of strong CYP3A4 inhibitors
Cautions
Increases the risk of atrial fibrillation; regularly monitor cardiac rhythm and discontinue drug if atrial fibrillation develops
May cause fetal toxicity when administered to a pregnant woman; inform women of childbearing potential to use effective contraception
Bradycardia and conduction disturbances
- Bradycardia, sinus arrest, and heart block reported
- Bradycardia may increase risk of QT prolongation which may lead to severe ventricular arrhythmias, including torsade de pointes, especially in patients with risk factors
- Risk factors for bradycardia include sinus node dysfunction, conduction defects (eg, first or second degree AV block, bundle-branch block), ventricular dyssynchrony, and use of other negative chronotropes (eg, beta-blockers, clonidine, digoxin, diltiazem, verapamil, amiodarone)
- Bradycardia and first-degree heart block were observed in pediatric patients; bradycardia was managed through dose titration, but did not result in study drug discontinuation
- Avoid use in patients with second-degree AV block unless a functioning demand pacemaker is present
Pacemakers
- Dosing is based on heart rate reduction, targeting a heart rate of 50-60 bpm
- Patients with demand pacemakers set to a rate ≥60 bpm cannot achieve a target heart rate <60 bpm, and these patients were excluded from clinical trials
- Not recommended in patients with demand pacemakers set to rates ≥60 bpm
Drug interactions overview
- Coadministration of verapamil or diltiazem with ivabradine increases ivabradine systemic exposure and should be avoided
- Concomitant use with negative chronotropes (eg, digoxin, amiodarone, beta-blockers) may increase the risk of bradycardia; monitor heart rate in patients taking ivabradine with other negative chronotropes
Coadministration with CYP3A4 inhibitors and inducers
- Primarily metabolized by CYP3A4
- Coadministration of CYP3A4 inhibitors increases ivabradine plasma concentrations
- Increased plasma concentrations may exacerbate bradycardia and conduction disturbances
- Contraindicated with strong CYP3A4 inhibitors
- Avoid use with moderate CYP3A4 inhibitors
- Avoid use with CYP3A4 inducers; coadministration may decrease ivabradine plasma concentrations
Pregnancy & Lactation
Pregnancy
May cause fetal toxicity when administered to a pregnant woman, based on findings in animal studies
There are no adequate and well-controlled studies in pregnant women to inform any drug-associated risks
Advise females of childbearing potential to use effective contraception
Animal data
- In animal reproduction studies, embryo-fetal toxicity and teratogenic effects (eg, abnormal shape of the heart, interventricular septal defect, complex anomalies of primary arteries) were observed
- Increased postnatal mortality was associated with these teratogenic effects in rats
- In pregnant rabbits, increased postimplantation loss was noted at an exposure 5 times the human exposure at the MRHD; lower doses were not tested in rabbits
Clinical considerations
- Stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester
- Pregnant patients with LVEF <35% on maximally tolerated doses of beta-blockers may be particularly heart rate dependent for augmenting cardiac output
- Therefore, closely follow pregnant patients starting treatment, especially during the first trimester, for destabilization of their congestive heart failure; monitor pregnant women with chronic heart failure in 3rd trimester of pregnancy for preterm birth
Lactation
Unknown if distributed in human breast milk
Animal studies have shown, however, that ivabradine is present in rat milk
Because of potential risk to breastfed infants, breastfeeding is not recommended
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker I(f) ‘funny’ current, which regulates heart rate
In clinical electrophysiology studies, the cardiac effects were most pronounced in the sinoatrial (SA) node, but prolongation of the AH interval has occurred on the surface ECG, as has PR interval prolongation
There was no effect on ventricular repolarization and no effects on myocardial contractility
Absorption
Bioavailability: ~40% (because of first-pass elimination in the gut and liver)
Peak plasma time: 1 hr (fasting)
Food delays absorption by ~1 hr and increases plasma exposure by 20-40%
Ivabradine should be taken with meals
Distribution
Protein bound: 70%
Vd: 100 L
Metabolism
Extensively metabolized in the liver and intestines by CYP3A4-mediated oxidation
Major metabolite: N-desmethylated derivative (S 18982), which is equipotent to ivabradine and circulates at concentrations ~40% that of ivabradine
The N-desmethylated derivative is also metabolized by CYP3A4
Elimination
Distribution half-life: 2 hr
Effective half-life: ~6 hr
Total clearance: 24 L/hr
Renal clearance: 4.2 L/hr
Excretion: 4% unchanged in urine; excretion of metabolites occurs to a similar extent via feces and urine
Administration
Oral Administration
Take BID with meals
Oral solution
- Empty entire contents of the ampule(s) into a medication cup
- With a calibrated oral syringe, measure prescribed dose from the medication cup and administer
- Oral solution is sterile and preservative-free
- Discard the unused oral solution; do not store or reuse any oral solution left in either the medication cup or an ampule
Missed dose
- If patient misses a dose, do not give another dose; give next dose at scheduled time
Storage
Tablets: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)
Oral solution: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F); protect ampule from light by storing in the foil pouch until use
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Corlanor oral - | 7.5 mg tablet |  | |
| Corlanor oral - | 5 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
Patient Handout
ivabradine oral
IVABRADINE - ORAL
(eye-VAB-ra-deen)
COMMON BRAND NAME(S): Corlanor
USES: This medication is used to treat heart failure. It is used by adults to help prevent the heart failure from getting worse and needing treatment in a hospital. It is also used by children who have heart failure due to an enlarged heart (dilated cardiomyopathy). Heart failure is a condition where your heart does not pump blood as well as it should. Ivabradine works by making your heart beat more slowly.
HOW TO USE: Read the Medication Guide provided by your pharmacist before you start taking ivabradine and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with food as directed by your doctor, usually twice daily. The dosage is based on your medical condition and response to treatment. In children, the dosage is also based on the weight. To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. Other medications are usually used along with ivabradine to treat heart failure. Carefully follow your doctor's directions for taking all your medications.If you are using the liquid form of this medication, read and follow the Instructions for Use from the manufacturer. Carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine. Ask your doctor or pharmacist for more details.Tell your doctor if your condition does not improve or if it worsens.
SIDE EFFECTS: Dizziness or tiredness may occur. If either of these effects lasts or gets worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Ivabradine may rarely cause vision changes such as brief increased brightness, or seeing halos or colored bright lights. Sudden changes in light brightness may set off this effect. If vision changes happen, they usually start within the first 2 months and may go away during treatment or after stopping this medication.Tell your doctor right away if you have any serious side effects, including: slow/fast/irregular heartbeat, fainting.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before taking ivabradine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: low blood pressure, liver problems, other heart problems (such as sick sinus syndrome, heart block, slow/irregular heartbeat, pacemaker use).This drug may make you dizzy or cause vision changes. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness or clear vision until you can do it safely. Be especially careful when driving at night because sudden changes in light brightness can happen, which may set off vision changes (see also Side Effects section). Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while using ivabradine. Ivabradine may harm an unborn baby. Ask about reliable forms of birth control while using this medication. If you become pregnant, talk to your doctor right away about the risks and benefits of this medication.It is unknown if this medication passes into breast milk. Because of the possible risk to the infant, breastfeeding while using this drug is not recommended. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: See also How to Use section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Other medications can affect the removal of ivabradine from your body, which may affect how ivabradine works. Examples include azole antifungals (such as itraconazole, ketoconazole), macrolide antibiotics (such as clarithromycin, telithromycin), diltiazem, HIV protease inhibitors (such as nelfinavir), nefazodone, rifamycins (such as rifabutin, rifampin), ritonavir, St. John's wort, verapamil, drugs used to treat seizures (such as carbamazepine, phenobarbital, phenytoin), among others.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: very slow heartbeat.
NOTES: Do not share this medication with others.Lab and/or medical tests (such as pulse, blood pressure) should be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.
MISSED DOSE: If you miss a dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.
STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
Information last revised August 2023. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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