Lancora (ivabradine)

How does Lancora work?

Lancora lowers heart rate by selective and specific inhibition of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (f-channels) within the sinoatrial (SA) node. Inhibition of the f-channels disrupts the I_f ion current flow and prolongs diastolic depolarization, slowing firing in the SA node.

Lancora can also inhibit the retinal current I_h, which is involved in retinal responses to bright lights. This is the postulated mechanism that results in the visual side effects of the medication.

Dosage and How to Use

Lancora is available in the following dosage forms:

• 5 mg film-coated tablet
• 7.5 mg film-coated tablet

Lancora should be taken twice daily, once with the morning meal and once with the evening meal. It must be taken with food.

Storage

Store at room temperature (25ºC or 77ºF). Temperature excursions are permitted between 15ºC and 30ºC (59ºF and 86ºF).

Overdosage

If overdosage amounts of Lancora are ingested, seek medical attention immediately. Lancora overdose may lead to severe and prolonged bradycardia. Cardiac pacing may be required if there is poor hemodynamic tolerance. Intravenous (IV) fluids, atropine, IV beta-stimulating agents, and other supportive treatments may be considered.

Side Effects

The most common side effects of Lancora are:

• Temporary brightness in parts of the field of vision, also known as phosphenes
  • Use caution while driving or operating machinery where sudden changes in light can happen, especially at night.
• Increased blood pressure

Rare but more severe side effects are:

• Bradycardia (slowed heart rate)
  • Tell your doctor if you have the following:
    • Slowing heart rate
    • Dizziness
    • Fatigue, lack of energy

• Irregular or rapid heartbeat (atrial fibrillation or heart rhythm problems)
  • Tell your doctor if you have any of the following symptoms of an irregular or fast heartbeat:
    • Heart is pounding (palpitations)
    • Chest pressure
    • Worsening shortness of breath
    • Fainting or near fainting

• Signs of an allergic reaction
  • Rash
  • Hives
  • Itching
  • Redness
  • Swollen
  • Trouble breathing or swallowing

This is not a comprehensive list of all the possible side effects. Please reach out to your doctor or pharmacist for more information. Contact your doctor or seek medical attention immediately if you are experiencing a severe side effect.

Warnings & Precautions

Atrial fibrillation

• Lancora can increase the risk of atrial fibrillation. Cardiac rhythm should be monitored, and discontinue treatment if atrial fibrillation develops.

Bradycardia and conduction disturbances

• Bradycardia, sinus arrest, and heart block have occurred in patients taking Lancora. Heart rate should be monitored during initiation and any dosage increase. Bradycardia may increase the risk of QT prolongation and torsade de pointes.

Visual disturbances

• Lancora affects retinal function, although there is no evidence of long-lasting effects. Lancora should be discontinued if an unexpected deterioration in visual function occurs. Use caution in patients with retinitis pigmentosa.

Fetal toxicity

• Lancora may cause fetal toxicity when given to pregnant women. Embryo-fetal toxicity and cardiac teratogenicity have been observed in animal studies. Women of reproductive potential must use effective contraception during treatment with Lancora.

Combination with calcium channel blockers

• Concomitant use of Lancora with verapamil or diltiazem is contraindicated. Verapamil and diltiazem increase exposure to Lancora and have additive heart rate-lowering properties.

 Drug Interactions and Other Interactions

Cytochrome P450-based interactions

• Concomitant use of CYP3A4 inhibitors increases Lancora plasma concentrations and may exacerbate bradycardia and conduction disturbances. CYP3A4 inducers decrease plasma concentrations and may lead to reduced efficacy of Lancora.

• Concomitant use with strong CYP3A4 inhibitors is contraindicated. A list of some examples of strong CYP3A4 inhibitors is below:
  • Azole antifungals (e.g., itraconazole)
  • Macrolide antibiotics (e.g., clarithromycin, telithromycin)
  • HIV protease inhibitors (e.g., nelfinavir)
  • Nefazodone

• Concomitant use with moderate CYP3A4 inhibitors should be avoided. See list of some examples below:
  • Diltiazem and verapamil
  • Grapefruit juice

• Concomitant use with CYP3A4 inducers should be avoided. See list of some examples below:
  • St. John’s wort
  • Rifampicin
  • Barbiturates
  • Phenytoin

Negative chronotropes

• The risk of bradycardia increases with coadministration of Lancora with other medications that slow heart rate (e.g., digoxin, amiodarone, beta-blockers).

Pacemakers in adults

• Lancora dosing is determined by heart rate reduction (target of 50 – 60 beats per minute in adults). Lancora is not recommended in patients with demand pacemakers set to rates ? 60 beats per minute.

Contraindications

Lancora is contraindicated in patients with any of the following:

• Hypersensitivity to the active substance or any of the excipients
• Resting heart rate below 70 beats per minute before treatment
• Cardiogenic shock
• Acute myocardial infarction
• Severe hypotension (< 90/50 mmHg)
• Severe hepatic insufficiency
• Sick sinus syndrome
• Sino-atrial block
• Unstable or acute heart failure
• Pacemaker dependent
• Unstable angina
• 3rd-degree AV-block
• Combination with strong cytochrome P450 3A4 inhibitors such as azole antifungals (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, erythromycin per os, josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone
• Combination with verapamil or diltiazem, which are moderate CYP3A4 inhibitors with heart rate-reducing properties
• Pregnancy, lactation, and women of childbearing potential not using appropriate contraceptive measures