Ivabradine

●  Brand Names: Corlanor (US), Lancora (Canada), Procoralan (United Kingdom)

●  Indications: Ivabradine primarily introduced as a treatment for congestive heart failure. Off-label use for inappropriate sinus tachycardia, POTS, and in patients with neurally mediated syncope linked to sinus tachycardia.

●  Contraindications: Not recommended for patients with a resting heart rate below 60 bpm. Caution is also advised when using alongside calcium channel blockers and beta-blockers.

●  Mechanism of Action: Ivabradine selectively blocks hyperpolarization-activated, cyclic-nucleotide gated channels in the sinoatrial node, which selectively inhibits the cardiac pacemaker reducing heart rate without significantly affecting blood pressure or autonomic/cardiac function

●  Side Effects: Rare and transient luminous phenomena known as phosphenes may develop in the retina (visual disturbances include halos, colored bright lights, or kaleidoscopic effects in the visual field). Fatigue, lightheadedness, headache, and nausea. Caution is advised with CYP3A4 inhibitors (i.e. itraconazole, clarithromycin, telithromycin, diltiazem, verapamil, or grapefruit juice), as they can increase ivabradine levels and lead to bradycardia. Use with caution with patients with lactose intolerance as there is an inactive ingredient of lactose monohydrate in the pill.

●  Expected Benefits: Reduces tachycardia, palpitations, syncope, and fatigue. It can help patients manage heart rate during exercise, enabling greater physical activity

●  Dosage: Available in 5 mg and 7.5 mg strengths. Advised to take with meals to aid in absorption. The initial dosing schedule involves gradual increases (i.e. 2.5 mg AM for 1-3 days, then 2.5 mg AM and PM around 4-5 pm for 4-7 days, 5mg twice a day for days 11-13 etc), ultimately aiming for a target dose based on heart rate, typically between 5 mg to 7.5 mg twice daily. The medication should not be increased if the resting heart rate is below 60 beats per minute and should be adjusted if the patient is having symptomatic bradycardia or if the rate is <50 beats per minute.

●  Reproductive and Pregnancy Considerations: Effective contraception is recommended for patients who could become pregnant. Women planning a pregnancy should transition to a safer medication before conception. Data on the use of ivabradine during pregnancy is limited but animal data does show potential teratogenic effect, embryofetal toxicity, and increased post-implantation loss, and increased intrauterine/postnatal mortality. Therefore, ivabradine is considered a Category D drug and is not recommended for pregnant patients. It is unclear whether ivabradine is excreted in breast milk. Due to limited animal data (which show ivabradine present in rat milk) and potential risks to a breastfeeding infant, the manufacturer advises against breastfeeding while using ivabradine.

Citations

Amgen Inc. Corlanor® (ivabradine) tablets prescribing information. Thousand Oaks, CA; 2015 Apr.

Gee, M. E., Watkins, A. K., Brown, J. N., et al. "Ivabradine for the Treatment of Postural Orthostatic Tachycardia Syndrome: A Systematic Review." American Journal of Cardiovascular Drugs, vol. 18, 2018, pp. 195–204. https://doi.org/10.1007/s40256-017-0252-1.

U.S. Food and Drug Administration. Highlights of Prescribing Information: Corlanor (Ivabradine). 2023, https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209964lbl.pdf

Hoeltzenbein, M., Lehmann, M. L., Beck, E., Dathe, K., & Schaefer, C. (2021). Ivabradine use in pregnant women-treatment indications and pregnancy outcome: an evaluation of the German Embryotox database. European journal of clinical pharmacology, 77(7), 1029–1037. https://doi.org/10.1007/s00228-020-03066-w

Taub, Pam R et al. “Randomized Trial of Ivabradine in Patients With Hyperadrenergic Postural Orthostatic Tachycardia Syndrome.” Journal of the American College of Cardiology vol. 77,7 (2021): 861-871 https://doi.org/10.1016/j.jacc.2020.12.029

Sheldon, Robert S et al. “2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal