Ivabradina Krka (Ivabradine)

Ivabradine acts on cardiac rhythm regulation and is indicated for the following cardiovascular conditions:

• Chronic stable angina pectoris: reduces frequency of angina attacks by lowering heart rate.
• Heart failure with reduced ejection fraction: improves symptoms and lowers risk of hospitalization by decreasing heart rate.

• Ivabradine selectively binds to the hyperpolarization‑activated cyclic nucleotide‑gated (HCN) channels that generate the funny (If) current in sino‑atrial node cells. By inhibiting this inward mixed Na⁺/K⁺ current, the drug slows spontaneous depolarisation, reducing the heart‑rate without affecting myocardial contractility, ventricular repolarisation, or blood pressure. The effect is dose‑dependent and reversible, allowing precise control of chronotropy while preserving inotropic function through selective channel modulation.

Ivabradine may be associated with several adverse reactions, which are classified by frequency and severity.

Common Side Effects

• Bradycardia: resting heart rate below 50 beats per minute.
• Visual disturbances (phosphenes): transient luminous phenomena.
• Headache: mild to moderate intensity.
• Dizziness: sensation of light‑headedness.

Serious or Rare Side Effects

• Symptomatic bradycardia requiring medical attention.
• Atrial fibrillation or other supraventricular arrhythmias.
• Severe hypotension with syncope.
• Heart block (second‑ or third‑degree) leading to conduction abnormalities.

When prescribing Ivabradine, several precautions should be observed to ensure safe use.

• Heart rate monitoring: check resting heart rate before initiation and periodically during therapy.
• Contraindication in severe hepatic impairment: avoid use in patients with Child‑Pugh class C liver disease.
• Caution in sick sinus syndrome: assess sinus node function prior to treatment.
• Avoid concomitant use with other heart‑rate lowering agents: beta‑blockers or digoxin may cause excessive bradycardia.
• Pregnancy and lactation: use only if potential benefit justifies potential risk, as safety data are limited.
• Store at room temperature: keep in the original container, protect from moisture and light.

Ivabradine can interact with other medicines, affecting its plasma concentration or combined pharmacodynamic effects.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): may increase Ivabradine levels and risk of bradycardia.
• Co‑administration with other heart‑rate lowering drugs (beta‑blockers, digoxin, calcium‑channel blockers): can cause excessive bradycardia or AV block.
• Drugs that cause AV conduction delay (e.g., amiodarone): may potentiate conduction abnormalities.

Moderate Interactions (Monitor Closely)

• Moderate CYP3A4 inhibitors (e.g., erythromycin, fluconazole): may modestly raise Ivabradine exposure.
• CYP3A4 inducers (e.g., rifampicin, carbamazepine): may reduce Ivabradine effectiveness.
• QT‑prolonging agents (e.g., sotalol, certain antipsychotics): monitor ECG for additive effects.