Side Effects of Corlanor (ivabradine)

Corlanor (ivabradine) is a hyperpolarization-activated cyclic nucleotide-gated channel blocker used to treat adults who have chronic heart failure, with symptoms, to reduce their risk of hospitalization for worsening heart failure, and to treat certain children 6 months of age and older who have stable heart failure, with symptoms, that is due to an enlarged heart (dilated cardiomyopathy).

Common side effects of Corlanor include

• increased blood pressure and
• temporary brightness in part of your field of vision. 

Serious side effects of Corlanor include

• increased risk of irregular or rapid heartbeat (atrial fibrillation or heart rhythm problems) (symptoms include palpitations, chest pressure, worsened shortness of breath, and near fainting or fainting) or
• slower than normal heart rate (symptoms include dizziness, fatigue, lack of energy; in children poor feeding, difficulty breathing or turning blue). 

Drug interactions of Corlanor include grapefruit juice and St. John’s wort because these can affect the way Corlanor works and may cause serious side effects.

Corlanor is primarily metabolized by CYP3A4. Concomitant use of CYP3A4 inhibitors such as azole antifungals, macrolide antibiotics, HIV protease inhibitors, and nefazodone increases Corlanor plasma concentrations and use of CYP3A4 inducers decreases them. Increased plasma concentrations may exacerbate slow heart rate and conduction disturbances.

Avoid concomitant use of CYP3A4 inducers such as St. John’s wort, rifampicin, barbiturates, and phenytoin when using Corlanor.

The risk of slow heart rate increases with concomitant administration of drugs that slow heart rate (e.g., digoxin, amiodarone, beta-blockers). The use of Corlanor is not recommended in patients with demand pacemakers set to rates 60 or more beats per minute.

Corlanor may cause harm to a fetus. Females who are able to get pregnant must use effective birth control during treatment with Corlanor. Tell your doctor right away if you become pregnant during treatment with Corlanor. Breastfeeding is not recommended while using Corlanor.

Corlanor may cause serious side effects in adults and children, including:

• Increased risk of irregular or rapid heartbeat (atrial fibrillation or heart rhythm problems). Tell your doctor if you feel any of the following symptoms of an irregular or rapid heartbeat:
  • heart is pounding or racing (palpitations).
  • chest pressure.
  • worsened shortness of breath.
  • near fainting or fainting.
• Slower than normal heart rate (bradycardia). Tell your doctor if you have:
  • a slowing of heart rate, or
  • symptoms of a slow heart rate such as dizziness, fatigue, lack of energy.

In young children signs and symptoms of slow heart rate may include:

• poor feeding,
• difficulty breathing or
• turning blue.

The most common side effects of Corlanor are:

• increased blood pressure
• temporary brightness in part of your field of vision. This is usually caused by sudden changes in light (luminous phenomena). This brightness usually happens within the first 2 months of treatment with Corlanor and may go away during or after treatment with Corlanor. Be careful when driving or operating machinery where sudden changes in light can happen, especially when driving at night.

These are not all the side effects of Corlanor. Ask your doctor or pharmacist for more information. Call your doctor for medical advice about side effects.

Clinically significant adverse reactions that appear in other sections of the labeling include:

• Atrial Fibrillation
• Bradycardia and Conduction Disturbances

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adult Patients With Heart Failure

In the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT), safety was evaluated in 3260 patients treated with Corlanor and 3278 patients given placebo. The median duration of Corlanor exposure was 21.5 months.

The most common adverse drug reactions in the SHIFT trial are shown in Table 2.

Table 2: Adverse Drug Reactions with Rates ≥ 1.0% Higher on Ivabradine than Placebo occurring in > 1% on Ivabradine in SHIFT

Luminous Phenomena (Phosphenes)

• Phosphenes are phenomena described as a transiently enhanced brightness in a limited area of the visual field, halos, image decomposition (stroboscopic or kaleidoscopic effects), colored bright lights, or multiple images (retinal persistency).
• Phosphenes are usually triggered by sudden variations in light intensity. Corlanor can cause phosphenes, thought to be mediated through Corlanor's effects on retinal photoreceptors.
• Onset is generally within the first 2 months of treatment, after which they may occur repeatedly.
• Phosphenes were generally reported to be of mild to moderate intensity and led to treatment discontinuation in < 1% of patients; most resolved during or after treatment.

Pediatric Patients With Heart Failure

• The safety of Corlanor in pediatric patients 6 months to less than 18 years of age is based on a clinical trial in symptomatic heart failure patients with dilated cardiomyopathy and elevated heart rate.
• This trial provides experience in 73 patients treated with Corlanor for a median duration of 397 days, and 42 patients given placebo. Bradycardia (symptomatic and asymptomatic) occurred at rates similar to those in adults. Phosphenes were observed in pediatric patients treated with Corlanor.

Postmarketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or establish a causal relationship to drug exposure.

The following adverse reactions have been identified in adults during post-approval use of Corlanor:

• syncope,
• hypotension,
• torsade de pointes,
• ventricular fibrillation,
• ventricular tachycardia,
• angioedema,
• erythema,
• rash,
• pruritus,
• urticaria,
• vertigo, and diplopia, and
• visual impairment.

Cytochrome P450-Based Interactions

Corlanor is primarily metabolized by CYP3A4. Concomitant use of CYP3A4 inhibitors increases ivabradine plasma concentrations and use of CYP3A4 inducers decreases them. Increased plasma concentrations may exacerbate bradycardia and conduction disturbances.

The concomitant use of strong CYP3A4 inhibitors is contraindicated. Examples of strong CYP3A4 inhibitors include

• azole antifungals (e.g., itraconazole),
• macrolide antibiotics (e.g., clarithromycin, telithromycin),
• HIV protease inhibitors (e.g., nelfinavir), and
• nefazodone.

Avoid concomitant use of moderate CYP3A4 inhibitors when using Corlanor. Examples of moderate CYP3A4 inhibitors include

• diltiazem,
• verapamil, and
• grapefruit juice.

Avoid concomitant use of CYP3A4 inducers when using Corlanor. Examples of CYP3A4 inducers include

• St. John's wort,
• rifampicin,
• barbiturates, and
• phenytoin.

Negative Chronotropes

Most patients receiving Corlanor will also be treated with a beta-blocker. The risk of bradycardia increases with concomitant administration of drugs that slow heart rate (e.g., digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking Corlanor with other negative chronotropes.

Pacemakers In Adults

Corlanor dosing is based on heart rate reduction, targeting a heart rate of 50 to 60 beats per minute in adults. Patients with demand pacemakers set to a rate = 60 beats per minute cannot achieve a target heart rate < 60 beats per minute, and these patients were excluded from clinical trials.

The use of Corlanor is not recommended in patients with demand pacemakers set to rates ≥ 60 beats per minute.