Information about Stabradine
Each film coated tablet contains:
5 mg Ivabradine (equivalent to 5,390 mgivabradine HCL) or
7.5 mg Ivabradine (equivalent to 8,085 mg ivabradineHCL).
The main pharmacodynamic property of ivabradinein humans is a specific dose dependent reduction in heart rate.
At usual recommended doses, heart rate reduction is approximately 10 bpm at rest and during exercise. This leads to a reduction in cardiac work load and myocardial oxygen consumption.
Ivabradine does not influence intracardiac conduction, contractility (no negative inotropic effect) or ventricular repolarization.
The efficacy of 5 and 7.5 mg twice daily was consistent across studies on exercise test parameters and was associated with a decrease of about 70% in the rate of angina attacks. The twice-daily dosing regimen of ivabradine gave uniform efficacy over 24 hours.
It has no pharmacological tolerance (loss of efficacy) and no rebound phenomena after abrupt treatment discontinuation. The effects on blood pressure and peripheral vascular resistance of the drug are minor and not clinically significant. It has no influence on glucose or lipid metabolism.
Ivabradine is rapidly and almost completely absorbed after oral administration with a peak plasma level reached after 1hour under fasting conditions. The absolute bio availability is around 40%. Itis approximately 70% plasma protein bound. It is extensively metabolised by the liver.
It is eliminated with a main half-life of 2 hours in plasma and an effective half-life of 11 hours. Excretions of metabolites occur to a similar extent via feces and urine.
Mechanism of action:
Ivabradine is a pure heart rate lowering agent,acting by selective and specific inhibition of the cardiac pacemaker current that controls the spontaneous diastolic depolarization in the sinus node and regulates heart rate.
Symptomatic treatment of chronic stable anginapectoris and for the treatment of chronic heart failure in adults with normalsinus rhythm.
Ivabradine is indicated:
In adults unable to tolerate or with contraindication to the use of beta blockers.
Or in combination with beta-blockers inpatients inadequately controlled with an optimal beta-blocker dose and whose heart rate >60 bpm.
Hypersensitivity to ivabradine or to any of the excipients.
Resting heart rate below 60 bpm prior to treatment.
Acute myocardial infarction.
Severe hypotension (<90/50 mm Hg).
Severe hepatic insufficiency
Sick sinus syndrome
Sino atrial block.
Warnings and precautions:
Ivabradine is not recommended in patients with atrial fibrillation or other cardiac arrhythmias that interfere with sinus node function.
It is not recommended in patients with AV-block of 2nd degree.
If during treatment resting heart ratedecreases persistently below 50 bpm or the patient experiences symptoms related to bradycardia (e.g. dizziness, fatigue or hypotension) the dose must be titrated downward or treatment discontinued if heart rate below 50 bpm or symptoms of bradycardia persist.
Combination with calcium channel blockers is not recommended.
Heart failure must be appropriately controlled before considering ivabradine treatment.
ts use is not recommended immediately afters stroke.
Long-term ivabradine treatment effects on retinal function are currently not known. Caution should be exercised inpatients with retinitis pigmentosa.
Ivabradine should be used with caution inpatients with mild to moderate hypotension.
Non-urgent DC-cardio version should be considered 24 hours after the last dose of ivabradine.
Its use in patients with congenital QT syndrome or treated with QT prolonging medicinal products should be avoided. If the combination appears necessary, close monitoring is needed.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this product.
Concomitant use not recommended with QT prolonging medicinal products (e.g. quindine, disopyramide, bepridil, sotalol,ibutilide, ammiodarone, pimozide, ziprosidone, sertindole, mefloquine,halofantrine). If the combination appears necessary, close cardiac monitoring is needed.
CYP3A4 inhibitors increase ivabradine plasma concentrations, while inducers decrease them.
Proton pump inhibitors, sildenafil, HMG CoAreductase inhibitors, dihydropyridine CCBs, digoxin, and warfarin have no significant interactions with ivabradine.
ACEIs, ARBs, diuretics, short and long acting nitrates, HMG CoA reductase inhibitors, fibrates PPIs, oral antidiabetics,aspirin and other anti-platelet medicinal products, are not restricted and therefore are routinely combined with ivabradine with no evidence of safety concerns.
No interaction studies have been performed in pediatric population.
Pregnancy and lactation:
Ivabradine is a contraindication during pregnancy and breast feeding.
Effects on ability to drive and use machines:
Ivabradine has no influence on the ability to drive and use machines. However, ivabradine may cause transient luminous phenomena consisting mainly of phosphenes.
System Organ Class
AV 1st degree block (ECG prolonged PQ interval)
Palpitations, supraventricular extrasystoles
Nausea, constipation, diarrhea
Headache, generally during the first month of treatment, dizziness
Dizziness, vertigo, dyspnea, muscle cramps
Elevated creatinine in blood
Dosage and administration:
The usual recommended starting dose of ivabradine is 5 mg twice daily. After three to four weeks of treatment the dose may be increased to 7.5 mg twice daily depending on the therapeutic response.If, during treatment, heart rate decreases persistently below 50 bpm at rest,the dose must be titrated down ward including the possible dose of 2.5 mg twice daily. Treatment must be discontinued it heart rate below 50bpm or symptoms of bradycardia persist.
For patients aged 75 years or more, a lower starting dose should be considered: 2.5mg twice daily, before up-titration if necessary.
No dose adjustment is required in patients with renal insufficiency and creatinine clearance above 15ml/min. Ivabradine should be used with precaution in patients with creatinine clearance below 15ml/min.
Caution should be exercised when using ivabradine in patients with moderate hepatic impairment, but it is contraindicated in those severe hepatic insufficiency.
Tablets must be taken orally twice daily during meals.
Overdose may lead to severe and prolonged bradycardia which should be treated symptomatically in a specialized environment. In the event of bradycardia with poor hemodynamic tolerance, symptomatic treatment including intravenous beta-stimulating medicines such as isoprenaline may be considered. Temporary cardiac electrical racing pacing may be instituted if required.
Store at room temperature below 25˚C. Away from moisture.
Packs of 30 film coated tablets for each strength