Delpino5 mg

Established / Approved Indications

• Chronic heart failure (reduced ejection fraction): Delpino is indicated to reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction ≤35%, who are in sinus rhythm with a resting heart rate ≥70 beats per minute, and who are either on a maximally tolerated dose of a beta-blocker or have a contraindication to beta-blocker use. Delpino is used as an add-on to standard heart failure therapy, not as a substitute for it.
• Pediatric heart failure due to dilated cardiomyopathy: Delpino is indicated to treat stable symptomatic heart failure due to dilated cardiomyopathy in pediatric patients 6 months of age and older who are in sinus rhythm with an elevated heart rate.

Guideline-Supported / Adjunct Use (Market-Dependent)

• Chronic stable angina pectoris: in several markets, Delpino is also approved as an adjunct for symptomatic treatment of chronic stable angina in adults with normal sinus rhythm who cannot tolerate or have contraindications to beta-blockers, or in combination with beta-blockers when heart rate remains inadequately controlled and dose up-titration of the beta-blocker is not possible. This use is not part of the core FDA label but is supported by clinical trial data and included in several international labels.

Note: Delpino must always be used as an adjunct to, not a replacement for, guideline-directed therapy such as beta-blockers, ACE inhibitors/ARBs/ARNI, mineralocorticoid receptor antagonists, and SGLT2 inhibitors in heart failure.

Each film-coated tablet of Ivabradine contains Ivabradine (as hydrochloride) equivalent to 5 mg or 7.5 mg of Ivabradine base. In some markets, Ivabradine is also available as an oral solution containing 5 mg/5 mL of Ivabradine, intended primarily for pediatric dosing where precise weight-based titration is required.

Delpino is a selective and specific sinoatrial (SA) node If (funny current) channel inhibitor. It is a heart-rate–lowering agent that acts purely on cardiac pacemaker activity, without affecting myocardial contractility, blood pressure, or intracardiac conduction to any clinically relevant extent at therapeutic doses. Delpino is used long-term in selected patients with chronic heart failure with reduced ejection fraction and, in some markets, as adjunctive therapy for chronic stable angina.

Cardiac Selective Sinoatrial (SA) Node If-Channel Inhibitor (Heart-Rate Lowering Agent); Antianginal / Anti-ischemic Agent

Mechanism of Action

Ivabradine selectively and specifically inhibits the cardiac pacemaker If current that controls the spontaneous diastolic depolarization in the sinoatrial node, thereby regulating heart rate. The If current is a mixed Na+/K+ inward current activated by hyperpolarization at the end of an action potential and modulated by the autonomic nervous system. By blocking this current in a dose-dependent manner, Ivabradine slows the pacemaker activity of the SA node and reduces heart rate, without affecting intracardiac conduction, myocardial contractility, or ventricular repolarization at recommended doses.

Pharmacokinetics

• Absorption: Rapidly absorbed after oral administration; absolute bioavailability is approximately 40% due to first-pass metabolism.
• Metabolism: Extensively metabolized in the liver and intestine by oxidation via the cytochrome P450 3A4 (CYP3A4) enzyme system, making it highly susceptible to interaction with CYP3A4 inhibitors and inducers.
• Elimination half-life: Approximately 2 hours (main plasma half-life); effective half-life is about 11 hours.
• Excretion: Metabolites are excreted approximately equally in urine and feces; very little unchanged drug is excreted.

Delpino should be taken orally, twice daily, with food (morning and evening meals), as food increases bioavailability and reduces variability in absorption. Tablets should be swallowed whole with water. The oral solution formulation (where available) should be measured precisely using the provided dosing device, especially for pediatric weight-based dosing. Grapefruit juice should be avoided as it can increase Delpino blood levels.

Contraindicated Combinations

• Strong CYP3A4 inhibitors (e.g., azole antifungals such as ketoconazole/itraconazole, macrolide antibiotics such as clarithromycin/erythromycin, HIV protease inhibitors, nefazodone): significantly increase Delpino plasma levels and risk of excessive bradycardia; concomitant use is contraindicated.

Combinations to Avoid

• Moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil): increase Delpino exposure and additively lower heart rate; combination should generally be avoided.
• CYP3A4 inducers (e.g., rifampicin, barbiturates, phenytoin, St. John's Wort): may reduce Delpino plasma levels and efficacy; concomitant use should be avoided or dose adjusted with caution.
• Grapefruit juice: increases Delpino exposure; avoid concomitant intake.

Interactions Requiring Monitoring

• Other heart-rate-lowering agents (beta-blockers, digoxin, amiodarone, and other negative chronotropes): additive heart-rate-lowering effect; heart rate should be monitored closely when combined with Delpino.
• QT-interval-prolonging drugs (both cardiac, e.g. quinidine, sotalol, amiodarone, and non-cardiac, e.g. certain antipsychotics, some macrolides): bradycardia caused by Delpino can potentiate the QT-prolonging effect of these drugs, increasing arrhythmia risk; combination requires careful ECG monitoring.

Very Common / Common

• Bradycardia (excessively slow heart rate) — the most frequent and dose-related adverse effect of Delpino; usually occurs within the first months of treatment.
• Luminous phenomena (phosphenes) — a transient enhanced brightness in a limited area of the visual field, halos, or image decomposition; a distinctive and well-recognized effect of Delpino, usually triggered by sudden changes in light intensity and resolving within the first months of treatment.
• Atrial fibrillation (increased incidence reported with Delpino versus placebo).
• Hypertension or elevation in blood pressure (reported paradoxically in some patients).
• Headache, dizziness (usually mild and occurring early in treatment).
• Blurred vision, diplopia (double vision).

Uncommon / Rare (including postmarketing reports)

• First-, second-, or third-degree AV block; ventricular extrasystoles.
• Syncope, hypotension.
• Torsades de pointes, ventricular tachycardia/fibrillation (rare, generally in predisposed patients).
• Angioedema, rash, pruritus, urticaria.
• Nausea, constipation, diarrhoea.
• Vertigo.

Pregnancy

Delpino should not be used during pregnancy unless clearly necessary, as animal studies have shown embryo-fetal toxicity and cardiac teratogenic effects at exposures close to those used therapeutically in humans, and there is limited data on use in pregnant women. Women of reproductive potential should use effective contraception during treatment with Delpino. If pregnancy occurs or is planned, Delpino should be discontinued and the physician consulted promptly to weigh potential fetal risk against maternal benefit.

Lactation

It is not known whether Delpino passes into human breast milk in clinically relevant amounts, but animal data show transfer into milk at concentrations higher than plasma. Breastfeeding is generally not recommended during treatment with Delpino; a physician should be consulted to decide between discontinuing breastfeeding or discontinuing therapy, considering the benefit of the drug to the mother.

• Fetal risk: see Pregnancy and Lactation; use effective contraception during therapy.
• Atrial fibrillation: patients on Delpino have an increased incidence of atrial fibrillation compared with placebo; periodic clinical monitoring for irregular heart rhythm is recommended, and Delpino should be discontinued if atrial fibrillation develops, per physician judgment.
• Bradycardia and conduction disturbances: risk is increased in patients with sinus node dysfunction, existing conduction defects, or when combined with other heart-rate-lowering agents; heart rate should be monitored, especially during dose titration.
• Use with pacemakers: Delpino is not recommended in patients whose demand pacemaker fires at a rate ≥60 bpm, as the intended heart-rate-lowering effect cannot be reliably achieved or assessed.
• Hepatic impairment: use with caution in mild-to-moderate impairment; contraindicated in severe impairment (see Contraindications).
• Renal impairment: use with caution in severe renal impairment (creatinine clearance below 15 mL/min), as this population has not been studied.
• Do not stop abruptly without medical advice, as heart failure or angina symptoms may worsen; dose changes should always be physician-directed.
• Driving/operating machinery: luminous phenomena (phosphenes) may transiently affect visual perception; caution is advised, particularly during sudden changes in light intensity, especially at night driving.

Overdose with Delpino may cause severe and prolonged bradycardia, along with possible hypotension, headache, or dizziness. Any suspected overdose of Delpino requires immediate medical attention — contact emergency services or a poison control center right away. In a hospital setting, severe bradycardia with poor hemodynamic tolerance may require supportive care, including intravenous fluids, and, if needed, temporary cardiac pacing or beta-agonist support under close cardiac monitoring; there is no specific antidote. Do not attempt to manage a suspected overdose of Delpino at home.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children. Do not use after the expiry date printed on the pack.

• Pediatric patients: Delpino is approved for heart failure due to dilated cardiomyopathy from age 6 months, with weight-based dosing (see Pediatric Uses and Dosage and Administration); safety and efficacy below 6 months of age have not been established.
• Elderly patients: no clinically relevant pharmacokinetic differences have been observed in patients aged 65 years and older; a lower starting dose (2.5 mg twice daily) is recommended in patients over 75 years or others at higher risk of excessive heart-rate lowering.
• Hepatic impairment: no dose adjustment is needed in mild-to-moderate impairment (Child-Pugh A/B); Delpino is contraindicated in severe hepatic impairment (Child-Pugh C).
• Renal impairment: no dose adjustment is required for creatinine clearance 15–60 mL/min; Delpino has not been studied below 15 mL/min and should be used with caution in this population.
• Pregnancy and lactation: see the dedicated Pregnancy and Lactation section above.

In chronic heart failure, Delpino is generally intended for long-term, continuous use alongside standard heart failure therapy, for as long as the underlying condition and heart-rate criteria persist and benefit is maintained, as determined by the treating physician. In chronic stable angina, treatment duration is likewise long-term and individualized based on symptom control and tolerability. Delpino should not be stopped or the dose changed without medical advice, as this can affect heart-rate control and disease management.

Selective Sinoatrial (SA) Node If-Channel Inhibitors; Heart-Rate Lowering Agents; Antianginal Agents

Ivabradine works by selectively inhibiting the If ("funny") current in the sinoatrial node — the current responsible for the spontaneous, gradual depolarization that sets the heart's natural pacing rate. By blocking this current in a dose-dependent way, Ivabradine reduces the rate of diastolic depolarization and lowers heart rate, without exerting a clinically relevant negative inotropic effect on the heart muscle, without altering blood pressure significantly, and without affecting intracardiac conduction. This heart-rate-specific action distinguishes Ivabradine from beta-blockers and calcium channel blockers, which additionally affect contractility and/or conduction.

Delpino is approved for the treatment of stable, symptomatic heart failure due to dilated cardiomyopathy in pediatric patients 6 months of age and older who are in sinus rhythm with an elevated heart rate. Dosing is weight-based and titrated gradually under close physician and, where possible, cardiology supervision (see Dosage and Administration for the full schedule). Safety and efficacy of Delpino in children younger than 6 months have not been established, and Delpino should not be used in this age group outside of specialist guidance. Pediatric patients treated with Delpino require regular monitoring of heart rate and cardiac rhythm, as bradycardia has been reported more frequently than in adults in some studies.