Ivabradine JensonR

1 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
  

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1. NAME OF THE MEDICINAL PRODUCT 
 
Ivabradine JensonR 5 mg film-coated tablets 
Ivabradine JensonR 7.5 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Ivabradine JensonR 5 mg film-coated tablets 
Each film-coated tablet contains 5 mg ivabradine (as hydrochloride). 
Excipient with known effect 
Each film-coated tablet contains 36.73 mg lactose (as anhydrous). 
 
Ivabradine JensonR 7.5 mg film-coated tablets 
Each film-coated tablet contains 7.5 mg ivabradine (as hydrochloride). 
Excipient with known effect 
Each film-coated tablet contains 55.09 mg lactose (as anhydrous). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
 
Ivabradine JensonR 5 mg film-coated tablets 
Pink colour, oval shape, biconvex film-coated scored tablets, approximately 7.9 mm by 4.15 mm debossed 
with “Ι 5” on one side and “M” on other side of the tablet. 
 
The tablet can be divided into equal doses. 
 
Ivabradine JensonR 7.5 mg film-coated tablets 
Pink colour, round, beveled edge, biconvex film-coated tablets, approximately 6.65 mm in diameter 
debossed with “Ι 7” on one side and “M” on other side of the tablet. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Symptomatic treatment of chronic stable angina pectoris 
Ivabradine is indicated for the symptomatic treatment of chronic stable angina pectoris in coronary artery 
disease adults with normal sinus rhythm and heart rate ≥70 bpm. Ivabradine is indicated: 
- in adults unable to tolerate or with a contraindication to the use of beta-blockers 
- or in combination with beta-blockers in patients inadequately controlled with an optimal beta-blocker 

dose. 
 
Treatment of chronic heart failure 
Ivabradine is indicated in chronic heart failure NYHA II to IV class with systolic dysfunction, in patients in 
sinus rhythm and whose heart rate is ≥75 bpm, in combination with standard therapy including beta-blocker 
therapy or when beta-blocker therapy is contraindicated or not tolerated (see section 5.1). 
 

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4.2 Posology and method of administration 
 
Posology 
 
For the different doses, film-coated tablets containing 5 mg and 7.5 mg ivabradine are available. 
 
Symptomatic treatment of chronic stable angina pectoris 
It is recommended that the decision to initiate or titrate treatment takes place with the availability of serial 
heart rate measurements, ECG or ambulatory 24-hour monitoring. 
The starting dose of ivabradine should not exceed 5 mg twice daily in patients aged below 75 years. After 
three to four weeks of treatment, if the patient is still symptomatic, if the initial dose is well tolerated and if 
resting heart rate remains above 60 bpm, the dose may be increased to the next higher dose in patients 
receiving 2.5 mg twice daily or 5 mg twice daily. The maintenance dose should not exceed 7.5 mg twice 
daily. 
 
If there is no improvement in symptoms of angina within 3 months after start of treatment, treatment of 
ivabradine should be discontinued. 
In addition, discontinuation of treatment should be considered if there is only limited symptomatic response 
and when there is no clinically relevant reduction in resting heart rate within three months. 
If, during treatment, heart rate decreases below 50 beats per minute (bpm) at rest or the patient experiences 
symptoms related to bradycardia such as dizziness, fatigue or hypotension, the dose must be titrated 
downward including the lowest dose of 2.5 mg twice daily (one half 5 mg tablet twice daily). After dose 
reduction, heart rate should be monitored (see section 4.4). Treatment must be discontinued if heart rate 
remains below 50 bpm or symptoms of bradycardia persist despite dose reduction. 
 
Treatment of chronic heart failure 
The treatment has to be initiated only in patient with stable heart failure. It is recommended that the treating 
physician should be experienced in the management of chronic heart failure. 
The usual recommended starting dose of ivabradine is 5 mg twice daily. After two weeks of treatment, the 
dose can be increased to 7.5 mg twice daily if resting heart rate is persistently above 60 bpm or decreased to 
2.5 mg twice daily (one half 5 mg tablet twice daily) if resting heart rate is persistently below 50 bpm or in 
case of symptoms related to bradycardia such as dizziness, fatigue or hypotension. If heart rate is between 50 
and 60 bpm, the dose of 5 mg twice daily should be maintained. 
If during treatment, heart rate decreases persistently below 50 beats per minute (bpm) at rest or the patient 
experiences symptoms related to bradycardia, the dose must be titrated downward to the next lower dose in 
patients receiving 7.5 mg twice daily or 5 mg twice daily. If heart rate increases persistently above 60 beats 
per minute at rest, the dose can be up titrated to the next upper dose in patients receiving 2.5 mg twice daily 
or 5 mg twice daily. 
Treatment must be discontinued if heart rate remains below 50 bpm or symptoms of bradycardia persist (see 
section 4.4). 
 
Special populations 
 
Elderly 
In patients aged 75 years or more, a lower starting dose should be considered (2.5 mg twice daily i.e. one 
half 5 mg tablet twice daily) before up-titration if necessary. 
 
Renal impairment 
No dose adjustment is required in patients with renal insufficiency and creatinine clearance above 15 ml/min 
(see section 5.2). 
No data are available in patients with creatinine clearance below 15 ml/min. Ivabradine should therefore be 
used with precaution in this population. 
 

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Hepatic impairment   
No dose adjustment is required in patients with mild hepatic impairment. Caution should be exercised when 
using ivabradine in patients with moderate hepatic impairment. Ivabradine is contraindicated for use in 
patients with severe hepatic insufficiency, since it has not been studied in this population and a large increase 
in systemic exposure is anticipated (see sections 4.3 and 5.2). 
 
Paediatric population  
The safety and efficacy of ivabradine in the treatment of chronic heart failure in children aged below 
18 years have not been established. 
Available data are described in sections 5.1 and 5.2 but no recommendation on a posology can be made. 
 
Method of administration 
 
Tablets must be taken orally twice daily, i.e. once in the morning and once in the evening during meals (see 
section 5.2).  
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 
- Resting heart rate below 70 beats per minute prior to 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 (heart rate imposed exclusively by the pacemaker) 
- Unstable angina 
- AV-block of 3rd degree 
- 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 (see sections 4.5 and 5.2) 

- Combination with verapamil or diltiazem which are moderate CYP3A4 inhibitors with heart rate 
reducing properties (see section 4.5) 

- Pregnancy, lactation and women of child-bearing potential not using appropriate contraceptive 
measures (see section 4.6) 

 
4.4 Special warnings and precautions for use 
 
Special warnings  
 
Lack of benefit on clinical outcomes in patients with symptomatic chronic stable angina pectoris 
Ivabradine is indicated only for symptomatic treatment of chronic stable angina pectoris because ivabradine 
has no benefits on cardiovascular outcomes (e.g. myocardial infarction or cardiovascular death) (see 
section 5.1). 
 
Measurement of heart rate 
Given that the heart rate may fluctuate considerably over time, serial heart rate measurements, ECG or 
ambulatory 24-hour monitoring should be considered when determining resting heart rate before initiation of 
ivabradine treatment and in patients on treatment with ivabradine when titration is considered. This also 
applies to patients with a low heart rate, in particular when heart rate decreases below 50 bpm, or after dose 
reduction (see section 4.2). 
 

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Cardiac arrhythmias 
Ivabradine is not effective in the treatment or prevention of cardiac arrhythmias and likely loses its efficacy 
when a tachyarrhythmia occurs (e.g. ventricular or supraventricular tachycardia). Ivabradine is therefore not 
recommended in patients with atrial fibrillation or other cardiac arrhythmias that interfere with sinus node 
function. 
In patients treated with ivabradine the risk of developing atrial fibrillation is increased (see section 4.8). 
Atrial fibrillation has been more common in patients using concomitantly amiodarone or potent class I 
anti-arrhythmics. It is recommended to regularly clinically monitor ivabradine treated patients for the 
occurrence of atrial fibrillation (sustained or paroxysmal), which should also include ECG monitoring if 
clinically indicated (e.g. in case of exacerbated angina, palpitations, irregular pulse). 
Patients should be informed of signs and symptoms of atrial fibrillation and be advised to contact their 
physician if these occur. 
If atrial fibrillation develops during treatment, the balance of benefits and risks of continued ivabradine 
treatment should be carefully reconsidered. 
 
Chronic heart failure patients with intraventricular conduction defects (bundle branch block left, bundle 
branch block right) and ventricular dyssynchrony should be monitored closely. 
 
Use in patients with AV-block of 2nd degree 
Ivabradine is not recommended in patients with AV-block of 2nd degree. 
 
Use in patients with a low heart rate 
Ivabradine must not be initiated in patients with a pre-treatment resting heart rate below 70 beats per minute 
(see section 4.3). 
If, during treatment, resting heart rate decreases persistently below 50 bpm or the patient experiences 
symptoms related to bradycardia such as dizziness, fatigue or hypotension, the dose must be titrated 
downward or treatment discontinued if heart rate below 50 bpm or symptoms of bradycardia persist (see 
section 4.2). 
 
Combination with calcium channel blockers 
Concomitant use of ivabradine with heart rate reducing calcium channel blockers such as verapamil or 
diltiazem is contraindicated (see sections 4.3 and 4.5). No safety issue has been raised on the combination of 
ivabradine with nitrates and dihydropyridine calcium channel blockers such as amlodipine. Additional 
efficacy of ivabradine in combination with dihydropyridine calcium channel blockers has not been 
established (see section 5.1). 
 
Chronic heart failure 
Heart failure must be stable before considering ivabradine treatment. Ivabradine should be used with caution 
in heart failure patients with NYHA functional classification IV due to limited amount of data in this 
population. 
 
Stroke 
The use of ivabradine is not recommended immediately after a stroke since no data is available in these 
situations. 
 
Visual function 
Ivabradine influences on retinal function (see section 5.1). To date, there is no evidence of a toxic effect of 
ivabradine on the retina, but the effects of long-term ivabradine treatment beyond one year on retinal 
function are currently not known. Cessation of treatment should be considered if any unexpected 
deterioration in visual function occurs. Caution should be exercised in patients with retinitis pigmentosa. 
 

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Precautions for use 
 
Patients with hypotension 
Limited data are available in patients with mild to moderate hypotension, and ivabradine should therefore be 
used with caution in these patients. Ivabradine is contraindicated in patients with severe hypotension (blood 
pressure < 90/50 mmHg) (see section 4.3). 
 
Atrial fibrillation - Cardiac arrhythmias 
There is no evidence of risk of (excessive) bradycardia on return to sinus rhythm when pharmacological 
cardioversion is initiated in patients treated with ivabradine. However, in the absence of extensive data, non 
urgent DC-cardioversion should be considered 24 hours after the last dose of ivabradine. 
 
Use in patients with congenital QT syndrome or treated with QT prolonging medicinal products 
The use of ivabradine in patients with congenital QT syndrome or treated with QT prolonging medicinal 
products should be avoided (see section 4.5). If the combination appears necessary, close cardiac monitoring 
is needed. 
Heart rate reduction, as caused by ivabradine, may exacerbate QT prolongation, which may give rise to 
severe arrhythmias, in particular Torsade de pointes. 
 
Hypertensive patients requiring blood pressure treatment modifications. 
In the SHIFT trial more patients experienced episodes of increased blood pressure while treated with 
ivabradine (7.1%) compared to patients treated with placebo (6.1%). These episodes occurred most 
frequently shortly after blood pressure treatment was modified, were transient, and did not affect the 
treatment effect of ivabradine. When treatment modifications are made in chronic heart failure patients 
treated with ivabradine blood pressure should be monitored at an appropriate interval (see section 4.8). 
 
Excipients 
Since tablets contain lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase 
deficiency or glucose-galactose malabsorption should not take this medicinal product. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Pharmacodynamic interactions 
  
Concomitant use not recommended 
QT prolonging medicinal products 
- Cardiovascular QT prolonging medicinal products (e.g. quinidine, disopyramide, bepridil, sotalol, 

ibutilide, amiodarone). 
- Non cardiovascular QT prolonging medicinal products (e.g. pimozide, ziprasidone, sertindole, 

mefloquine, halofantrine, pentamidine, cisapride, intravenous erythromycin). 
 
The concomitant use of cardiovascular and non cardiovascular QT prolonging medicinal products with 
ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction. If the 
combination appears necessary, close cardiac monitoring is needed (see section 4.4). 
 
Concomitant use with precaution 
Potassium-depleting diuretics (thiazide diuretics and loop diuretics): hypokalaemia can increase the risk of 
arrhythmia. As ivabradine may cause bradycardia, the resulting combination of hypokalaemia and 
bradycardia is a predisposing factor to the onset of severe arrhythmias, especially in patients with long QT 
syndrome, whether congenital or substance-induced. 
 

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Pharmacokinetic interactions 
 
Cytochrome P450 3A4 (CYP3A4) 
Ivabradine is metabolised by CYP3A4 only and it is a very weak inhibitor of this cytochrome. Ivabradine 
was shown not to influence the metabolism and plasma concentrations of other CYP3A4 substrates (mild, 
moderate and strong inhibitors). CYP3A4 inhibitors and inducers are liable to interact with ivabradine and 
influence its metabolism and pharmacokinetics to a clinically significant extent. Drug-drug interaction 
studies have established that CYP3A4 inhibitors increase ivabradine plasma concentrations, while inducers 
decrease them. Increased plasma concentrations of ivabradine may be associated with the risk of excessive 
bradycardia (see section 4.4). 
 
Contraindication of concomitant use 
The concomitant use of potent CYP3A4 inhibitors such as azole antifungals (ketoconazole, itraconazole), 
macrolide antibiotics (clarithromycin, erythromycin per os, josamycin, telithromycin), HIV protease 
inhibitors (nelfinavir, ritonavir) and nefazodone is contraindicated (see section 4.3). The potent CYP3A4 
inhibitors ketoconazole (200 mg once daily) and josamycin (1 g twice daily) increased ivabradine mean 
plasma exposure by 7 to 8 fold. 
 
Moderate CYP3A4 inhibitors: specific interaction studies in healthy volunteers and patients have shown that 
the combination of ivabradine with the heart rate reducing agents diltiazem or verapamil resulted in an 
increase in ivabradine exposure (2 to 3 fold increase in AUC) and an additional heart rate reduction of 
5 bpm. The concomitant use of ivabradine with these medicinal products is contraindicated (see section 4.3). 
 
Concomitant use not recommended 
Grapefruit juice: ivabradine exposure was increased by 2-fold following the co-administration with 
grapefruit juice. Therefore the intake of grapefruit juice should be avoided. 
 
Concomitant use with precautions 
- Moderate CYP3A4 inhibitors: the concomitant use of ivabradine with other moderate CYP3A4 

inhibitors (e.g. fluconazole) may be considered at the starting dose of 2.5 mg twice daily and if resting 
heart rate is above 70 bpm, with monitoring of heart rate. 

- CYP3A4 inducers: CYP3A4 inducers (e.g. rifampicin, barbiturates, phenytoin, Hypericum perforatum 
[St John’s wort]) may decrease ivabradine exposure and activity. The concomitant use of CYP3A4 
inducing medicinal products may require an adjustment of the dose of ivabradine. The combination of 
ivabradine 10 mg twice daily with St John’s wort was shown to reduce ivabradine AUC by half. The 
intake of St John’s wort should be restricted during the treatment with ivabradine. 

 
Other concomitant use 
Specific drug-drug interaction studies have shown no clinically significant effect of the following medicinal 
products on pharmacokinetics and pharmacodynamics of ivabradine: proton pump inhibitors (omeprazole, 
lansoprazole), sildenafil, HMG CoA reductase inhibitors (simvastatin), dihydropyridine calcium channel 
blockers (amlodipine, lacidipine), digoxin and warfarin. In addition there was no clinically significant effect 
of ivabradine on the pharmacokinetics of simvastatin, amlodipine, lacidipine, on the pharmacokinetics and 
pharmacodynamics of digoxin, warfarin and on the pharmacodynamics of aspirin. 
In pivotal phase III clinical trials the following medicinal products were routinely combined with ivabradine 
with no evidence of safety concerns: angiotensin converting enzyme inhibitors, angiotensin II antagonists, 
beta-blockers, diuretics, anti-aldosterone agents, short and long acting nitrates, HMG CoA reductase 
inhibitors, fibrates, proton pump inhibitors, oral antidiabetics, aspirin and other anti-platelet medicinal 
products. 
 
Paediatric population 
Interaction studies have only been performed in adults. 
 

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4.6 Fertility, pregnancy and lactation 
 
Women of child-bearing potential 
Women of child-bearing potential should use appropriate contraceptive measures during treatment (see 
section 4.3). 
 
Pregnancy 
There are no or limited amount of data from the use of ivabradine in pregnant women. 
Studies in animals have shown reproductive toxicity. These studies have shown embryotoxic and teratogenic 
effects (see section 5.3). The potential risk for humans is unknown. Therefore, ivabradine is contraindicated 
during pregnancy (see section 4.3). 
 
Breast-feeding 
Animal studies indicate that ivabradine is excreted in milk. Therefore, ivabradine is contraindicated during 
breast-feeding (see section 4.3). 
Women that need treatment with ivabradine should stop breast-feeding, and choose for another way of 
feeding their child. 
 
Fertility 
Studies in rats have shown no effect on fertility in males and females (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
A specific study to assess the possible influence of ivabradine on driving performance has been performed in 
healthy volunteers where no alteration of the driving performance was evidenced. However, in 
post-marketing experience, cases of impaired driving ability due to visual symptoms have been reported. 
Ivabradine may cause transient luminous phenomena consisting mainly of phosphenes (see section 4.8). The 
possible occurrence of such luminous phenomena should be taken into account when driving or using 
machines in situations where sudden variations in light intensity may occur, especially when driving at night. 
Ivabradine has no influence on the ability to use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
Ivabradine has been studied in clinical trials involving nearly 45,000 participants. 
The most common adverse reactions with ivabradine, luminous phenomena (phosphenes) and bradycardia, 
are dose dependent and related to the pharmacological effect of the medicinal product. 
 
Tabulated list of adverse reactions 
The following adverse reactions have been reported during clinical trials and are ranked using the following 
frequency: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare 
(≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data). 
 

System Organ Class Frequency Preferred Term 
Blood and lymphatic system 
disorders 

Uncommon Eosinophilia 

Metabolism and nutrition 
disorders 

Uncommon Hyperuricaemia 

Nervous system disorders Common Headache, generally during the 
first month of treatment 
Dizziness, possibly related to 
bradycardia 

Uncommon* Syncope, possibly related to 
bradycardia 

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Eye disorders Very common Luminous phenomena 
(phosphenes) 

Common Blurred vision 
Uncommon* Diplopia 

Visual impairment 
Ear and labyrinth disorders Uncommon Vertigo 
Cardiac disorders Common Bradycardia 

AV 1st degree block (ECG 
prolonged PQ interval) 
Ventricular extrasystoles 
Atrial fibrillation 

Uncommon Palpitations, supraventricular 
extrasystoles 

Very rare AV 2nd degree block, AV 3rd 
degree block 
Sick sinus syndrome 

Vascular disorders Common Uncontrolled blood pressure 
Uncommon* Hypotension, possibly related 

to bradycardia 
Respiratory, thoracic and 
mediastinal disorders 

Uncommon Dyspnoea 

Gastrointestinal disorders Uncommon Nausea 
Constipation 
Diarrhoea 
Abdominal pain* 

Skin and subcutaneous tissue 
disorders 

Uncommon* Angioedema 
Rash 

Rare* Erythema 
Pruritus 
Urticaria 

Musculoskeletal and 
connective tissue disorders 

Uncommon Muscle cramps 

General disorders and 
administration site conditions 

Uncommon* Asthenia, possibly related to 
bradycardia 
Fatigue, possibly related to 
bradycardia 

Rare* Malaise, possibly related to 
bradycardia 

Investigations Uncommon Elevated creatinine in blood 
ECG prolonged QT interval 

* Frequency calculated from clinical trials for adverse events detected from spontaneous report 
 
Description of selected adverse reactions 
Luminous phenomena (phosphenes) were reported by 14.5% of patients, described as a transient enhanced 
brightness in a limited area of the visual field. They are usually triggered by sudden variations in light 
intensity. Phosphenes may also be described as a halo, image decomposition (stroboscopic or kaleidoscopic 
effects), coloured bright lights, or multiple image (retinal persistency). The onset of phosphenes is generally 
within the first two months of treatment after which they may occur repeatedly. Phosphenes were generally 
reported to be of mild to moderate intensity. All phosphenes resolved during or after treatment, of which a 
majority (77.5%) resolved during treatment. Fewer than 1% of patients changed their daily routine or 
discontinued the treatment in relation with phosphenes. 
 

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Bradycardia was reported by 3.3% of patients particularly within the first 2 to 3 months of treatment 
initiation. 0.5% of patients experienced a severe bradycardia below or equal to 40 bpm. 
 
In the SIGNIFY study atrial fibrillation was observed in 5.3% of patients taking ivabradine compared to 
3.8% in the placebo group. In a pooled analysis of all the Phase II/III double blind controlled clinical trials 
with a duration of at least 3 months including more than 40,000 patients, the incidence of atrial fibrillation 
was 4.86% in ivabradine treated patients compared to 4.08% in controls, corresponding to a hazard ratio of 
1.26, 95% CI [1.15-1.39]. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 
continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked 
to report any suspected adverse reactions via the national reporting system listed in Appendix V. 
 
4.9 Overdose 
 
Symptoms  
Overdose may lead to severe and prolonged bradycardia (see section 4.8). 
 
Management 
Severe bradycardia should be treated symptomatically in a specialised environment. In the event of 
bradycardia with poor haemodynamic tolerance, symptomatic treatment including intravenous 
beta-stimulating medicinal products such as isoprenaline may be considered. Temporary cardiac electrical 
pacing may be instituted if required. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Cardiac therapy, other cardiac preparations, ATC code: C01EB17. 
 
Mechanism of action 
 
Ivabradine is a pure heart rate lowering agent, acting by selective and specific inhibition of the cardiac 
pacemaker If current that controls the spontaneous diastolic depolarisation in the sinus node and regulates 
heart rate. The cardiac effects are specific to the sinus node with no effect on intra-atrial, atrioventricular or 
intraventricular conduction times, nor on myocardial contractility or ventricular repolarisation. 
 
Ivabradine can interact also with the retinal current Ih which closely resembles cardiac If. It participates in 
the temporal resolution of the visual system, by curtailing the retinal response to bright light stimuli. Under 
triggering circumstances (e.g. rapid changes in luminosity), partial inhibition of Ih by ivabradine underlies 
the luminous phenomena that may be occasionally experienced by patients. Luminous phenomena 
(phosphenes) are described as a transient enhanced brightness in a limited area of the visual field (see 
section 4.8). 
 
Pharmacodynamic effects 
 
The main pharmacodynamic property of ivabradine in humans is a specific dose dependent reduction in heart 
rate. Analysis of heart rate reduction with doses up to 20 mg twice daily indicates a trend towards a plateau 
effect which is consistent with a reduced risk of severe bradycardia below 40 bpm (see section 4.8). 
At usual recommended doses, heart rate reduction is approximately 10 bpm at rest and during exercise. This 
leads to a reduction in cardiac workload and myocardial oxygen consumption. Ivabradine does not influence 
intracardiac conduction, contractility (no negative inotropic effect) or ventricular repolarisation:  

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- in clinical electrophysiology studies, ivabradine had no effect on atrioventricular or intraventricular 
conduction times or corrected QT intervals; 

- in patients with left ventricular dysfunction (left ventricular ejection fraction (LVEF) between 30 and 
45%), ivabradine did not have any deleterious influence on LVEF. 

 
Clinical efficacy and safety 
 
The antianginal and anti-ischaemic efficacy of ivabradine was studied in five double-blind randomised trials 
(three versus placebo, and one each versus atenolol and amlodipine). These trials included a total of 
4,111 patients with chronic stable angina pectoris, of whom 2,617 received ivabradine. 
 
Ivabradine 5 mg twice daily was shown to be effective on exercise test parameters within 3 to 4 weeks of 
treatment. Efficacy was confirmed with 7.5 mg twice daily. In particular, the additional benefit over 5 mg 
twice daily was established in a reference-controlled study versus atenolol: total exercise duration at trough 
was increased by about 1 minute after one month of treatment with 5 mg twice daily and further improved by 
almost 25 seconds after an additional 3-month period with forced titration to 7.5 mg twice daily. In this 
study, the antianginal and anti-ischaemic benefits of ivabradine were confirmed in patients aged 65 years or 
more. The efficacy of 5 and 7.5 mg twice daily was consistent across studies on exercise test parameters 
(total exercise duration, time to limiting angina, time to angina onset and time to 1 mm ST segment 
depression) 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. 
 
In a 889-patients randomised placebo-controlled study, ivabradine given on top of atenolol 50 mg o.d. 
showed additional efficacy on all ETT parameters at the trough of drug activity (12 hours after oral intake). 
In a 725-patients randomised placebo-controlled study, ivabradine did not show additional efficacy on top of 
amlodipine 10 mg o.d. at the trough of drug activity (12 hours after oral intake) while an additional efficacy 
was shown at peak (3-4 hours after oral intake). 
 
In a 1,277-patients randomised placebo-controlled study, ivabradine demonstrated a statistically significant 
additional efficacy on response to treatment (defined as a decrease of at least 3 angina attacks per week 
and/or an increase in the time to 1 mm ST segment depression of at least 60 s during a treadmill ETT) on top 
of amlodipine 5 mg o.d. or nifedipine GITS 30 mg o.d. at the trough of drug activity (12 hours after oral 
ivabradine intake) over a 6-week treatment period (OR = 1.3, 95% CI [1.0–1.7]; p = 0.012). Ivabradine did 
not show additional efficacy on secondary endpoints of ETT parameters at the trough of drug activity while 
an additional efficacy was shown at peak (3-4 hours after oral ivabradine intake). 
 
Ivabradine efficacy was fully maintained throughout the 3- or 4-month treatment periods in the efficacy 
trials. There was no evidence of pharmacological tolerance (loss of efficacy) developing during treatment nor 
of rebound phenomena after abrupt treatment discontinuation. The antianginal and anti-ischaemic effects of 
ivabradine were associated with dose-dependent reductions in heart rate and with a significant decrease in 
rate pressure product (heart rate x systolic blood pressure) at rest and during exercise. The effects on blood 
pressure and peripheral vascular resistance were minor and not clinically significant. 
 
A sustained reduction of heart rate was demonstrated in patients treated with ivabradine for at least one year 
(n = 713). No influence on glucose or lipid metabolism was observed. 
 
The antianginal and anti-ischaemic efficacy of ivabradine was preserved in diabetic patients (n = 457) with a 
similar safety profile as compared to the overall population. 
 
A large outcome study, BEAUTIFUL, was performed in 10,917 patients with coronary artery disease and 
left ventricular dysfunction (LVEF <40%) on top of optimal background therapy with 86.9% of patients 
receiving beta-blockers. The main efficacy criterion was the composite of cardiovascular death, 
hospitalisation for acute MI or hospitalisation for new onset or worsening heart failure. The study showed no 
difference in the rate of the primary composite outcome in the ivabradine group by comparison to the 
placebo group (relative risk ivabradine: placebo 1.00, p = 0.945). 

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In a post-hoc subgroup of patients with symptomatic angina at randomisation (n = 1,507), no safety signal 
was identified regarding cardiovascular death, hospitalisation for acute MI or heart failure (ivabradine 12.0% 
versus placebo 15.5%, p = 0.05). 
 
A large outcome study, SIGNIFY, was performed in 19,102 patients with coronary artery disease and 
without clinical heart failure (LVEF >40%), on top of optimal background therapy. A therapeutic scheme 
higher than the approved posology was used (starting dose 7.5 mg b.i.d. (5 mg b.i.d, if age ≥75 years) and 
titration up to 10 mg b.i.d). The main efficacy criterion was the composite of cardiovascular death or 
non-fatal MI. The study showed no difference in the rate of the primary composite endpoint (PCE) in the 
ivabradine group by comparison to the placebo group (relative risk ivabradine/placebo 1.08, p = 0.197). 
Bradycardia was reported by 17.9% of patients in the ivabradine group (2.1% in the placebo group). 
Verapamil, diltiazem or strong CYP 3A4 inhibitors were received by 7.1% of patients during the study. 
A small statistically significant increase in the PCE was observed in a pre-specified subgroup of patients 
with angina patients in CCS class II or higher at baseline (n = 12,049) (annual rates 3.4% versus 2.9%, 
relative risk ivabradine/placebo 1.18, p = 0.018), but not in the subgroup of the overall angina population in 
CCS class ≥ I (n=14,286) (relative risk ivabradine/placebo 1.11, p = 0.110). 
The higher than approved dose used in the study did not fully explain these findings. 
The SHIFT study was a large multicentre, international, randomised double-blind placebo controlled outcome 
trial conducted in 6,505 adult patients with stable chronic CHF (for ≥4 weeks), NYHA class II to IV, with a 
reduced left ventricular ejection fraction (LVEF ≤35%) and a resting heart rate ≥70 bpm. 
 
Patients received standard care including beta-blockers (89%), ACE inhibitors and/or angiotensin II 
antagonists (91%), diuretics (83%), and anti-aldosterone agents (60%). In the ivabradine group, 67% of 
patients were treated with 7.5 mg twice a day. The median follow-up duration was 22.9 months. Treatment 
with ivabradine was associated with an average reduction in heart rate of 15 bpm from a baseline value of 
80 bpm. The difference in heart rate between ivabradine and placebo arms was 10.8 bpm at 28 days, 9.1 bpm 
at 12 months and 8.3 bpm at 24 months. 
 
The study demonstrated a clinically and statistically significant relative risk reduction of 18% in the rate of 
the primary composite endpoint of cardiovascular mortality and hospitalisation for worsening heart failure 
(hazard ratio: 0.82, 95% CI [0.75;0.90] – p <0.0001) apparent within 3 months of initiation of treatment. The 
absolute risk reduction was 4.2%. The results on the primary endpoint are mainly driven by the heart failure 
endpoints, hospitalisation for worsening heart failure (absolute risk reduced by 4.7%) and deaths from heart 
failure (absolute risk reduced by 1.1%). 
 
Treatment effect on the primary composite endpoint, its components and secondary endpoints 
 
 Ivabradine 

(N=3,241) 
n (%) 

Placebo 
(N=3,264) 

n (%) 

Hazard ratio 
[95% CI] 

p-value 

Primary composite 
endpoint 

793 (24.47) 937 (28.71) 0.82 [0.75; 0.90] <0.0001 

Components of the 
composite: 
-CV death 
-Hospitalisation for 
worsening HF 

 
 

449 (13.85) 
514 (15.86) 

 
 

491 (15.04) 
672 (20.59) 

 
 

0.91 [0.80; 1.03] 
0.74 [0.66; 0.83] 

 
 

0.128 
<0.0001 

Other secondary 
endpoints: 
-All cause death 
-Death from HF 
-Hospitalisation for 
any cause 
-Hospitalisation for 
CV reason 

 
 

503 (15.52) 
113 (3.49) 

1231 (37.98) 
 

977 (30.15) 

 
 

552 (16.91) 
151 (4.63) 

1356 (41.54) 
 

1122 (34.38) 

 
 

0.90 [0.80; 1.02] 
0.74 [0.58; 0.94] 
0.89 [0.82; 0.96] 

 
0.85 [0.78; 0.92] 

 
 

0.092 
0.014 
0.003 

 
0.0002 

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The reduction in the primary endpoint was observed consistently irrespective of gender, NYHA class, 
ischaemic or non-ischaemic heart failure aetiology and of background history of diabetes or hypertension. 
 
In the subgroup of patients with HR ≥75 bpm (n = 4,150), a greater reduction was observed in the primary 
composite endpoint of 24% (hazard ratio: 0.76, 95% CI [0.68;0.85] – p <0.0001) and for other secondary 
endpoints, including all cause death (hazard ratio: 0.83, 95% CI [0.72;0.96] – p = 0.0109) and CV death 
(hazard ratio: 0.83, 95% CI [0.71;0.97] – p = 0.0166). In this subgroup of patients, the safety profile of 
ivabradine is in line with the one of the overall population. 
 
A significant effect was observed on the primary composite endpoint in the overall group of patients 
receiving beta-blocker therapy (hazard ratio: 0.85, 95% CI [0.76; 0.94]). In the subgroup of patients with HR 
≥75 bpm and on the recommended target dose of beta-blocker, no statistically significant benefit was 
observed on the primary composite endpoint (hazard ratio: 0.97, 95%CI [0.74; 1.28]) and other secondary 
endpoints, including hospitalisation for worsening heart failure (hazard ratio: 0.79, 95% CI [0.56;1.10]) or 
death from heart failure (hazard ratio: 0.69, 95% CI [0.31;1.53]). 
 
There was a significant improvement in NYHA class at last recorded value, 887 (28%) of patients on 
ivabradine improved versus 776 (24%) of patients on placebo (p = 0.001). 
 
Paediatric population 
 
A randomised, double blind, placebo controlled study was performed in 116 paediatric patients (17 aged 
[6-12]months, 36 aged [1-3]years and 63 aged [3-18]years) with CHF and dilated cardiomyopathy (DCM) on 
top of optimal background treatment. 74 received ivabradine (ratio 2:1). 
The starting dose was 0.02 mg/kg bid in age-subset [6-12]months, 0.05 mg/kg bid in [1-3]years and 
[3-18]years <40 kg, and 2.5 mg bid in [3-18]years and ≥40 kg. The dose was adapted depending on the 
therapeutic response with maximum doses of 0.2 mg/kg bid, 0.3 mg/kg bid and 15 mg bid respectively. In 
this study, ivabradine was administered as oral liquid formulation or tablet twice daily. The absence of 
pharmacokinetic difference between the 2 formulations was shown in an open-label randomised two-period 
cross-over study in 24 adult healthy volunteers. 
A 20% heart rate reduction, without bradycardia, was achieved by 69.9% of patients in the ivabradine group 
versus 12.2% in the placebo group during the titration period of 2 to 8 weeks (Odds Ratio: E = 17.24, 
95% CI [5.91; 50.30]). 
The mean ivabradine doses allowing to achieve a 20% HRR were 0.13 ± 0.04 mg/kg bid, 0.10 ± 0.04 mg/kg 
bid and 4.1 ± 2.2 mg bid in the age subsets [1-3]years, [3-18]years and <40 kg and [3-18] years and ≥40 kg, 
respectively. 
Mean LVEF increased from 31.8% to 45.3% at M012 in ivabradine group versus 35.4% to 42.3% in the 
placebo group. There was an improvement in NYHA class in 37.7% of ivabradine patients versus 25.0% in 
the placebo group. These improvements were not statistically significant. 
The safety profile, over one year, was similar to the one described in adult CHF patients. 
 
The long-term effects of ivabradine on growth, puberty and general development as well as the long-term 
efficacy of therapy with ivabradine in childhood to reduce cardiovascular morbidity and mortality have not 
been studied. 
 
The European Medicines Agency has waived the obligation to submit the results of studies with the 
reference medicinal product containing ivabradine in all subsets of the paediatric population in the treatment 
of angina pectoris (see section 4.2 for information on paediatric use). 
The European Medicines Agency has waived the obligation to submit the results of studies with ivabradine 
in children aged 0 to less than 6 months in the treatment of chronic heart failure. 
 

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5.2 Pharmacokinetic properties 
 
Under physiological conditions, ivabradine is rapidly released from tablets and is highly water-soluble 
(>10 mg/ml). Ivabradine is the S-enantiomer with no bioconversion demonstrated in vivo. The 
N-desmethylated derivative of ivabradine has been identified as the main active metabolite in humans. 
 
Absorption and bioavailability 
Ivabradine is rapidly and almost completely absorbed after oral administration with a peak plasma level 
reached in about 1 hour under fasting condition. The absolute bioavailability of the film-coated tablets is 
around 40%, due to first-pass effect in the gut and liver. 
Food delayed absorption by approximately 1 hour, and increased plasma exposure by 20 to 30%. The intake 
of the tablet during meals is recommended in order to decrease intra-individual variability in exposure (see 
section 4.2). 
 
Distribution 
Ivabradine is approximately 70% plasma protein bound and the volume of distribution at steady-state is close 
to 100 l in patients. The maximum plasma concentration following chronic administration at the 
recommended dose of 5 mg twice daily is 22 ng/ml (CV=29%). The average plasma concentration is 
10 ng/ml (CV=38%) at steady-state. 
 
Biotransformation 
Ivabradine is extensively metabolised by the liver and the gut by oxidation through cytochrome P450 3A4 
(CYP3A4) only. The major active metabolite is the N-desmethylated derivative (S 18982) with an exposure 
about 40% of that of the parent compound. The metabolism of this active metabolite also involves CYP3A4. 
Ivabradine has low affinity for CYP3A4, shows no clinically relevant CYP3A4 induction or inhibition and is 
therefore unlikely to modify CYP3A4 substrate metabolism or plasma concentrations. Inversely, potent 
inhibitors and inducers may substantially affect ivabradine plasma concentrations (see section 4.5). 
 
Elimination 
Ivabradine is eliminated with a main half-life of 2 hours (70-75% of the AUC) in plasma and an effective 
half-life of 11 hours. The total clearance is about 400 ml/min and the renal clearance is about 70 ml/min. 
Excretion of metabolites occurs to a similar extent via faeces and urine. About 4% of an oral dose is excreted 
unchanged in urine. 
 
Linearity/non-linearity 
The kinetics of ivabradine is linear over an oral dose range of 0.5-24 mg. 
 
Special populations 
- Elderly: no pharmacokinetic differences (AUC and Cmax) have been observed between elderly 

(≥65 years) or very elderly patients (≥75 years) and the overall population (see section 4.2). 
- Renal impairment: the impact of renal impairment (creatinine clearance from 15 to 60 ml/min) on 

ivabradine pharmacokinetic is minimal, in relation with the low contribution of renal clearance (about 
20%) to total elimination for both ivabradine and its main metabolite S 18982 (see section 4.2). 

- Hepatic impairment: in patients with mild hepatic impairment (Child Pugh score up to 7) unbound 
AUC of ivabradine and the main active metabolite were about 20% higher than in subjects with 
normal hepatic function. Data are insufficient to draw conclusions in patients with moderate hepatic 
impairment. No data are available in patients with severe hepatic impairment (see sections 4.2 and 
4.3). 

- Paediatric population: The pharmacokinetic profile of ivabradine in paediatric chronic heart failure 
patients aged 6 months to less than 18 years is similar to the pharmacokinetics described in adults 
when a titration scheme based on age and weight is applied. 

 

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Pharmacokinetic/pharmacodynamic (PK/PD) relationship 
PK/PD relationship analysis has shown that heart rate decreases almost linearly with increasing ivabradine 
and S 18982 plasma concentrations for doses of up to 15-20 mg twice daily. At higher doses, the decrease in 
heart rate is no longer proportional to ivabradine plasma concentrations and tends to reach a plateau. High 
exposures to ivabradine that may occur when ivabradine is given in combination with strong CYP3A4 
inhibitors may result in an excessive decrease in heart rate although this risk is reduced with moderate 
CYP3A4 inhibitors (see sections 4.3, 4.4 and 4.5). The PK/PD relationship of ivabradine in paediatric 
chronic heart failure patients aged 6 months to less than 18 years is similar to the PK/PD relationship 
described in adults. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, 
repeated dose toxicity, genotoxicity, carcinogenic potential. Reproductive toxicity studies showed no effect 
of ivabradine on fertility in male and female rats. When pregnant animals were treated during organogenesis 
at exposures close to therapeutic doses, there was a higher incidence of foetuses with cardiac defects in the 
rat and a small number of foetuses with ectrodactylia in the rabbit. 
In dogs given ivabradine (doses of 2, 7 or 24 mg/kg/day) for one year, reversible changes in retinal function 
were observed but were not associated with any damage to ocular structures. These data are consistent with 
the pharmacological effect of ivabradine related to its interaction with hyperpolarisation-activated Ih currents 
in the retina, which share extensive homology with the cardiac pacemaker If current. 
Other long-term repeat dose and carcinogenicity studies revealed no clinically relevant changes. 
 
Environmental Risk Assessment (ERA) 
The environmental risk assessment of ivabradine has been conducted in accordance to European guidelines 
on ERA. 
Outcomes of these evaluations support the lack of environmental risk of ivabradine and ivabradine does not 
pose a threat to the environment. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Core  
Anhydrous lactose 
Magnesium stearate 
Maltodextrin 
Microcrystalline cellulose 
Hydroxypropyl cellulose 
Colloidal anhydrous silica 
 
Film-coating  
Hypromellose 
Titanium dioxide 
Macrogol 400 
Yellow iron oxide (E172) 
Red iron oxide (E172) 
Polysorbate 80 
 
6.2 Incompatibilities 
 
Not applicable. 
 

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16 
 

6.3 Shelf life 
 
2 years 
For bottles only: After first opening, use within 6 months. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
Cold form blisters (OPA/Alu/PVC) in pack sizes of 14, 28, 56, 98 and 112 film-coated tablets. Cold form 
perforated unit dose blisters (OPA/Alu/PVC) in pack sizes of 14 x 1 and 56 x 1 film-coated tablets. 
 
PVC/Aclar-Alu blisters in pack sizes of 14, 28, 56, 98 and 112 film-coated tablets. PVC/Aclar-Alu 
perforated unit dose pack in pack sizes of 14 x 1 and 56 x 1 film-coated tablets. 
 
HDPE bottle with opaque polypropylene screw cap with aluminium induction sealing liner with wad and 
desiccant in sizes of 56, 98, and 100 film-coated tablets. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Jenson R+ Limited 
Fishleigh Court, 
Fishleigh Road, 
Barnstaple, Devon, 
United Kingdom EX31 3UD 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1145/001 
EU/1/16/1145/002 
EU/1/16/1145/003 
EU/1/16/1145/004 
EU/1/16/1145/005 
EU/1/16/1145/006 
EU/1/16/1145/007 
EU/1/16/1145/008 
EU/1/16/1145/009 
EU/1/16/1145/010 
EU/1/16/1145/011 
EU/1/16/1145/012 
EU/1/16/1145/013 
EU/1/16/1145/014 
EU/1/16/1145/015 
EU/1/16/1145/016 
EU/1/16/1145/017 

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EU/1/16/1145/018 
EU/1/16/1145/019 
EU/1/16/1145/020 
EU/1/16/1145/021 
EU/1/16/1145/022 
EU/1/16/1145/023 
EU/1/16/1145/024 
EU/1/16/1145/025 
EU/1/16/1145/026 
EU/1/16/1145/027 
EU/1/16/1145/028 
EU/1/16/1145/029 
EU/1/16/1145/030 
EU/1/16/1145/031 
EU/1/16/1145/032 
EU/1/16/1145/033 
EU/1/16/1145/034 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 
Date of latest renewal: 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
  

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ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
B.  CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 

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A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
McDermott Laboratories Limited 
t/a Gerard Laboratories 
35/36 Baldoyle Industrial Estate 
Grange Road 
Dublin 13 
Ireland 
 
Mylan Hungary Kft. 
Mylan utca. 1  
H-2900 Komárom  
Hungary 
 
The printed package leaflet of the medicinal product must state the name and address of the manufacturer 
responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to medical prescription. 
 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION 
 
 Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set out 
in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE 

OF THE MEDICINAL PRODUCT   
 
 Risk Management Plan (RMP) 

 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the agreed 
RMP presented in Module 1.8.2. of the Marketing Authorisation and any agreed subsequent updates of the 
RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicine Agency; 
• Whenever the risk management system is modified, especially as the result of new information being 
received that may lead to a significant change to the benefit/risk profile or as the result of an important 
(pharmacovigilance or risk minimisation) milestone being reached. 

  

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20 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 

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A. LABELLING 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
CARTON/BOTTLE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ivabradine JensonR 5 mg film-coated tablets 
 
ivabradine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE) 
 
Each film-coated tablet contains 5 mg ivabradine (as hydrochloride) 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
Blister 
14 film-coated tablets 
14 x 1 film-coated tablets 
28 film-coated tablets 
56 film-coated tablets 
56 x 1 film-coated tablets 
98 film-coated tablets 
112 film-coated tablets 
 
Bottle 
56 film-coated tablets 
98 film-coated tablets 
100 film-coated tablets 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use.  
Oral use. 
 
 

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6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 
THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP 
 
Bottle: After first opening, use within 6 months. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Jenson R+ Limited 
Fishleigh Court, 
Fishleigh Road, 
Barnstaple, Devon, 
United Kingdom EX31 3UD 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1145/001 
EU/1/16/1145/002 
EU/1/16/1145/003 
EU/1/16/1145/004 
EU/1/16/1145/005 
EU/1/16/1145/006 
EU/1/16/1145/007 
EU/1/16/1145/008 
EU/1/16/1145/009 
EU/1/16/1145/010 
EU/1/16/1145/011 
EU/1/16/1145/012 
EU/1/16/1145/013 
EU/1/16/1145/014 
EU/1/16/1145/015 

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24 
 

EU/1/16/1145/016 
EU/1/16/1145/017 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Ivabradine JensonR 5 mg film-coated tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Applicable only for the outer packaging component: 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
Applicable only for the outer packaging component: 
PC: 
SN: 
NN: 
 
 
  

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25 
 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 

 
 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
Ivabradine JensonR 5 mg film-coated tablets 
 
ivabradine 
 
 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Jenson R+ Limited 
 
 

3. EXPIRY DATE 
 
EXP 
 
 

4. BATCH NUMBER 
 
Lot 
 
 

5. OTHER 
 
Mon → Tue → Wed → Thu → Fri → Sat → Sun  
 
 
  

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
CARTON/BOTTLE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ivabradine JensonR 7.5 mg film-coated tablets 
 
ivabradine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Each film-coated tablet contains 7.5 mg ivabradine (as hydrochloride) 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose.  
See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
Blister 
14 film-coated tablets 
14 x 1 film-coated tablets 
28 film-coated tablets 
56 film-coated tablets 
56 x 1 film-coated tablets 
98 film-coated tablets 
112 film-coated tablets 
 
Bottle 
56 film-coated tablets 
98 film-coated tablets 
100 film-coated tablets 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use.  
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 

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27 
 

 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP 
 
Bottle: After first opening, use within 6 months. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Jenson R+ Limited 
Fishleigh Court, 
Fishleigh Road, 
Barnstaple, Devon, 
United Kingdom EX31 3UD 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1145/018 
EU/1/16/1145/019 
EU/1/16/1145/020 
EU/1/16/1145/021 
EU/1/16/1145/022 
EU/1/16/1145/023 
EU/1/16/1145/024 
EU/1/16/1145/025 
EU/1/16/1145/026 
EU/1/16/1145/027 
EU/1/16/1145/028 
EU/1/16/1145/029 
EU/1/16/1145/030 
EU/1/16/1145/031 
EU/1/16/1145/032 
EU/1/16/1145/033 
EU/1/16/1145/034 
 
 

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13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Ivabradine JensonR 7.5 mg film-coated tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Applicable only for the outer packaging component: 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
Applicable only for the outer packaging component: 
PC: 
SN: 
NN: 
 
 
  

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 

 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
Ivabradine JensonR 7.5 mg film-coated tablets 
 
ivabradine 
 
 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Jenson R+ Limited 
 
 

3. EXPIRY DATE 
 
EXP 
 
 

4. BATCH NUMBER 
 
Lot 
 
 

5. OTHER 
 
Mon → Tue → Wed → Thu → Fri → Sat → Sun  
 
 
  

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B. PACKAGE LEAFLET 

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Package leaflet: Information for the patient 

 
Ivabradine JensonR 5 mg film-coated tablets 

 
ivabradine 

 
Read all of this leaflet carefully before you start taking this medicine because it contains important 
information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if 

their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
 
What is in this leaflet 
1. What Ivabradine JensonR is and what it is used for 
2. What you need to know before you take Ivabradine JensonR 
3. How to take Ivabradine JensonR 
4. Possible side effects 
5. How to store Ivabradine JensonR 
6. Contents of the pack and other information 
 
 
1. What Ivabradine JensonR is and what it is used for 
 
Ivabradine JensonR (ivabradine) is a heart medicine used to treat: 
- Symptomatic stable angina pectoris (which causes chest pain) in adult patients whose heart rate is over 

or equal to 70 beats per minute. It is used in adult patients who do not tolerate or cannot take heart 
medicines called beta-blockers. It is also used in combination with beta-blockers in adult patients 
whose condition is not fully controlled with a beta-blocker. 

- Chronic heart failure in adult patients whose heart rate is over or equal to 75 beats per minute. It is 
used in combination with standard therapy, including beta-blocker therapy or when beta-blockers are 
contraindicated or not tolerated. 

 
About stable angina pectoris (usually referred to as “angina”): 
Stable angina is a heart disease which happens when the heart does not receive enough oxygen. It usually 
appears between 40 and 50 years of age. The most common symptom of angina is chest pain or discomfort. 
Angina is more likely to happen when the heart beats faster in situations such as exercise, emotion, exposure 
to the cold or after eating. This increase in heart rate can cause the chest pain in people who suffer from 
angina. 
 
About chronic heart failure: 
Chronic heart failure is a heart disease which happens when your heart cannot pump enough blood to the rest 
of your body. The most common symptoms of heart failure are breathlessness, fatigue, tiredness and ankle 
swelling. 
 
How does Ivabradine JensonR work 
Ivabradine JensonR mainly works by reducing the heart rate by a few beats per minute. This lowers the 
heart’s need for oxygen especially in the situations when an angina attack is more likely to happen. In this 
way Ivabradine JensonR helps to control and reduce the number of angina attacks. 
 

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Furthermore as elevated heart rate adversely affects the heart functioning and vital prognosis in patients with 
chronic heart failure, the specific heart rate lowering action of ivabradine helps to improve the heart 
functioning and vital prognosis in these patients. 
 
 
2. What you need to know before you take Ivabradine JensonR 
 
Do not take Ivabradine JensonR 
- if you are allergic to ivabradine or any of the other ingredients of this medicine (listed in section 6); 
- if your resting heart rate before treatment is too slow (below 70 beats per minute); 
- if you are suffering from cardiogenic shock (a heart condition treated in hospital); 
- if you suffer from a heart rhythm disorder; 
- if you are having a heart attack; 
- if you suffer from very low blood pressure; 
- if you suffer from unstable angina (a severe form in which chest pain occurs very frequently and with 

or without exertion); 
- if you have heart failure which has recently become worse; 
- if your heart beat is exclusively imposed by your pacemaker; 
- if you suffer from severe liver problems; 
- if you are already taking medicines for the treatment of fungal infections (such as ketoconazole, 

itraconazole), macrolide antibiotics (such as josamycin, clarithromycin, telithromycin or erythromycin 
given orally), medicines to treat HIV infections (such as nelfinavir, ritonavir) or nefazodone (medicine 
to treat depression) or diltiazem, verapamil (used for high blood pressure or angina pectoris); 

- if you are a woman able to have children and not using reliable contraception; 
- if you are pregnant or trying to become pregnant; 
- if you are breast-feeding. 
 
Warnings and precautions 
Talk to your doctor or pharmacist before taking Ivabradine JensonR 
- if you suffer from heart rhythm disorders (such as irregular heartbeat, palpitation, increase in chest 

pain) or sustained atrial fibrillation (a type of irregular heartbeat), or an abnormality of 
electrocardiogram (ECG) called ‘long QT syndrome’, 

- if you have symptoms such as tiredness, dizziness or shortness of breath (this could mean that your 
heart is slowing down too much), 

- if you suffer from symptoms of atrial fibrillation (pulse rate at rest unusually high (over 110 beats per 
minute) or irregular, without any apparent reason, making it difficult to measure), 

- if you have had a recent stroke (cerebral attack), 
- if you suffer from mild to moderate low blood pressure, 
- if you suffer from uncontrolled blood pressure, especially after a change in your antihypertensive 

treatment, 
- if you suffer from severe heart failure or heart failure with abnormality of ECG called ‘bundle branch 

block’, 
- if you suffer from chronic eye retinal disease, 
- if you suffer from moderate liver problems, 
- if you suffer from severe renal problems 
 
If any of the above applies to you, talk straight away to your doctor before or while taking Ivabradine 
JensonR. 
 
Children and adolescents 
Ivabradine JensonR is not intended for use in children and adolescents younger than 18 years. 
 
Other medicines and Ivabradine JensonR 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 

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Make sure to tell your doctor if you are taking any of the following medicines, as a dose adjustment of 
Ivabradine JensonR or monitoring should be required: 
- fluconazole (an antifungal medicine) 
- rifampicin (an antibiotic) 
- barbiturates (for difficult sleeping or epilepsy) 
- phenytoin (for epilepsy) 
- Hypericum perforatum or St John’s wort (herbal treatment for depression) 
- QT prolonging medicines to treat either heart rhythm disorders or other conditions: 

- quinidine, disopyramide, ibutilide, sotalol, amiodarone (to treat heart rhythm disorders) 
- bepridil (to treat angina pectoris) 
- certain types of medicines to treat anxiety, schizophrenia or other psychoses (such as pimozide, 

ziprasidone, sertindole) 
- anti-malarial medicines (such as mefloquine or halofantrine) 
- intravenous erythromycin (an antibiotic) 
- pentamidine (an antiparasitic medicine) 
- cisapride (against the gastro-oesophageal reflux) 

- Some types of diuretics which may cause decrease in blood potassium level, such as furosemide, 
hydrochlorothiazide, indapamide (used to treat oedema, high blood pressure). 

 
Ivabradine JensonR with food and drink 
Avoid grapefruit juice during treatment with Ivabradine JensonR. 
 
Pregnancy and breast-feeding 
Do not take Ivabradine JensonR if you are pregnant or are planning to have a baby (see “Do not take 
Ivabradine JensonR”). 
If you are pregnant and have taken Ivabradine JensonR, talk to your doctor. 
Do not take Ivabradine JensonR if you are able to become pregnant unless you use reliable contraceptive 
measures (see “Do not take Ivabradine JensonR”). 
Do not take Ivabradine JensonR if you are breast-feeding (see “Do not take Ivabradine JensonR”). Talk to 
your doctor if you are breast-feeding or intending to breast-feed as breast-feeding should be discontinued if 
you take Ivabradine JensonR. 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your 
doctor or pharmacist for advice before taking this medicine. 
 
Driving and using machines 
Ivabradine JensonR may cause temporary luminous visual phenomena (a temporary brightness in the field of 
vision, see “Possible side effects”). If this happens to you, be careful when driving or using machines at 
times when there could be sudden changes in light intensity, especially when driving at night. 
 
Ivabradine JensonR contains lactose 
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before 
taking this medicine. 
 
 
3. How to take Ivabradine JensonR 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure. 
 
Ivabradine JensonR should be taken during meals. 
 
If you are being treated for stable angina pectoris 
The starting dose should not exceed one tablet of Ivabradine JensonR 5 mg twice daily. If you still have 
angina symptoms and if you have tolerated the 5 mg twice daily dose well, the dose may be increased. The 
maintenance dose should not exceed 7.5 mg twice daily. Your doctor will prescribe the right dose for you. 

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The usual dose is one tablet in the morning and one tablet in the evening. In some cases (e.g. if you are 
elderly), your doctor may prescribe half the dose i.e., one half 5 mg tablet of Ivabradine JensonR 5 mg 
(corresponding to 2.5 mg ivabradine) in the morning and one half 5 mg tablet in the evening. 
 
If you are being treated for chronic heart failure 
The usual recommended starting dose is one tablet of Ivabradine JensonR 5 mg twice daily increasing if 
necessary to one tablet of Ivabradine JensonR 7.5 mg twice daily. Your doctor will decide the right dose for 
you. The usual dose is one tablet in the morning and one tablet in the evening. In some cases (e.g. if you are 
elderly), your doctor may prescribe half the dose i.e., one half 5 mg tablet of Ivabradine JensonR 5 mg 
(corresponding to 2.5 mg ivabradine) in the morning and one half 5 mg tablet in the evening. 
 
If you take more Ivabradine JensonR than you should: 
A large dose of Ivabradine JensonR could make you feel breathless or tired because your heart slows down 
too much. If this happens, contact your doctor immediately. 
 
If you forget to take Ivabradine JensonR: 
If you forget to take a dose of Ivabradine JensonR, take the next dose at the usual time. Do not take a double 
dose to make up for the forgotten dose. 
The calendar printed on the blister containing the tablets should help you remember when you last took a 
tablet of Ivabradine JensonR. 
 
If you stop taking Ivabradine JensonR: 
As the treatment for angina or chronic heart failure is usually life-long, you should discuss with your doctor 
before stopping this medicinal product. 
If you think that the effect of Ivabradine JensonR is too strong or too weak, talk to your doctor or pharmacist. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most common adverse reactions with this medicine are dose dependent and related to its mode of action: 
 
Very common (may affect more than 1 in 10 people): 
Luminous visual phenomena (brief moments of increased brightness, most often caused by sudden changes 
in light intensity). They can also be described as a halo, coloured flashes, image decomposition or multiple 
images. They generally occur within the first two months of treatment after which they may occur repeatedly 
and resolve during or after treatment. 
 
Common (may affect up to 1 in 10 people): 
Modification in the heart functioning (the symptoms are a slowing down of the heart rate). They particularly 
occur within the first 2 to 3 months of treatment initiation. 
 
Other side effects have also been reported: 
 
Common (may affect more than 1 in 10 people): 
Irregular rapid contraction of the heart, abnormal perception of heartbeat, uncontrolled blood pressure, 
headache, dizziness and blurred vision (cloudy vision). 
 
Uncommon (may affect up to 1 in 100 people): 
Palpitations and cardiac extra beats, feeling sick (nausea), constipation, diarrhoea, abdominal pain, spinning 
sensation (vertigo), difficulty breathing (dyspnoea), muscle cramps, changes in laboratory parameters: high 
blood levels of uric acid, an excess of eosinophils (a type of white blood cell) and elevated creatinine in 

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blood (a breakdown product of muscle), skin rash, angioedema (such as swollen face, tongue or throat, 
difficulty in breathing or swallowing), low blood pressure, fainting, feeling of tiredness, feeling of weakness, 
abnormal ECG heart tracing, double vision, impaired vision. 
 
Rare (may affect up to 1 in 1,000 people):  
Urticaria, itching, skin reddening, feeling unwell. 
 
Very rare (may affect up to 1 in 10,000 people):  
Irregular heart beats. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed 
in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects you can help provide more information on the safety of this medicine. 
 
 
5. How to store Ivabradine JensonR 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton, bottle and blister after ‘EXP’. 
The expiry date refers to the last day of that month.  
 
This medicine does not require any special storage conditions.  
 
For bottles, use within 6 months after first opening. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw 
away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Ivabradine JensonR contains  
- The active substance is ivabradine (as hydrochloride). Each film-coated tablet contains 5 mg 

ivabradine (as hydrochloride).  
- The other ingredients in the tablet core are: lactose anhydrous, magnesium stearate, maltodextrin, 

microcrystalline cellulose, colloidal anhydrous silica, hydroxypropyl cellulose, and in the tablet 
coating are : hypromellose, titanium dioxide, macrogol, polysorbate 80, yellow iron oxide (E172), red 
iron oxide (E172).  

 
What Ivabradine JensonR looks like and contents of the pack  
Ivabradine JensonR 5 mg tablets are pink-coloured, oval shaped film-coated tablets scored on both sides, 
marked with “ I 5” on one side and “M” on the other side of the tablet. 
 
Ivabradine JensonR is available in blister packs of 14, 14 x 1, 28, 56, 56 x 1, 98 and 112 film-coated tablets. 
The pack sizes 14 x 1 and 56 x 1 film-coated tablets are presented in unit dose blisters. 
Ivabradine JensonR is also available in bottles with a screw cap and a desiccant of 56, 98 and 
100 film-coated tablets. Do not eat the desiccant. 
 
Not all pack sizes may be marketed.  
 

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Marketing Authorisation Holder 
Jenson R+ Limited 
Fishleigh Court, 
Fishleigh Road, 
Barnstaple, Devon, 
United Kingdom EX31 3UD 
 
Manufacturer 
McDermott Laboratories Limited 
t/a Gerard Laboratories 
35-36 Baldoyle Industrial Estate 
Grange Road 
Dublin 13 
Ireland 
 
Mylan Hungary Kft 
Mylan utca 1 
2900 Komárom 
Hungary 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder. 
 
België/Belgique/Belgien 
Mylan bvba/sprl 
Tél/Tel: + 32 02 658 61 00 
 

Lietuva 
Generics [UK] Ltd 
Tel: +44 1707 853000 
(Jungtinė Karalystė) 
 

България 
Майлан ЕООД 
Тел: +359 2 44 55 400 
 

Luxembourg/Luxemburg 
Mylan bvba/sprl 
Tel: + 32 02 658 61 00 
(Belgique/Belgien) 
 

Česká republika 
Mylan Pharmaceuticals.s.r.o. 
Tel: +420 274 770 201 

Magyarország 
Mylan EPD Kft 
Tel: + 36 1 465 2100 
 

Danmark 
Mylan AB 
Tlf: + 46 855 522 750 
(Sverige) 
 

Malta 
George Borg Barthet Ltd. 
Tel: + 356 212 44205 / +356 212 44206 
 

Deutschland 
Mylan dura GmbH 
Tel: + 49-(0) 6151 9512 0 
 

Nederland 
Mylan BV 
Tel: + 31 33 299 7080 

Eesti 
Generics [UK] Ltd 
Tel: +44 1707 853000 
(Ühendkuningriik) 
 

Norge 
Mylan AB 
Tel: + 46 855 522 750 
(Sverige) 
 

Ελλάδα 
Generics Pharma Hellas ΕΠΕ 
Τηλ: +30 210 993 6410 
 

Österreich 
Arcana Arzneimittel GmbH 
Tel: +43 1 416 2418 
 

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España 
Mylan Pharmaceuticals, S.L 
Tel: + 34 900 102 712 
 

Polska 
Mylan Sp. z.o.o. 
Tel: + 48 22 546 64 00 
 

France 
Mylan S.A.S 
Tel: +33 4 37 25 75 00 
 

Portugal 
Mylan, Lda. 
Tel: + 351 21 412 72 56 
 

Hrvatska 
Mylan EPD d.o.o. 
Tel: +385 1 23 50 599 
 

România 
A&G Med Trading SRL 
Tel: + 4021 332 49 91 
 

Ireland 
Generics [UK] Ltd. 
Tel: + 44 1707 853000 
(United Kingdom) 
 

Slovenija 
GSP Proizvodi d.o.o. 
Tel: + 386 1 236 31 85 
 

Ísland 
Mylan AB 
Tel: + 46 855 522 750 
(Svíþjóð) 
 

Slovenská republika 
Mylan s.r.o. 
Tel: +421 2 326 04 910 / +421 917 206 274 

Italia 
Mylan S.p.A 
Tel: + 39 02 612 46923 
 

Suomi/Finland 
Mylan OY 
Puh/Tel: + 358 9-46 60 03 
 

Κύπρος 
Pharmaceutical Trading Co. Ltd. 
Τηλ: + 357 99403969 
 

Sverige 
Mylan AB 
Tel: + 46 855 522 750 
 

Latvija 
Generics [UK] Ltd 
Tel: +44 1707 853000 
(Lielbritānija) 
 

United Kingdom 
Generics [UK] Ltd 
Tel: +44 1707 853000 

 
This leaflet was last revised in 
 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  

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Package leaflet: Information for the patient 
 

Ivabradine JensonR 7.5 mg film-coated tablets 
 

ivabradine 
 
Read all of this leaflet carefully before you start taking this medicine because it contains important 
information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if 

their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
 
What is in this leaflet 
1. What Ivabradine JensonR is and what it is used for 
2. What you need to know before you take Ivabradine JensonR 
3. How to take Ivabradine JensonR 
4. Possible side effects 
5. How to store Ivabradine JensonR 
6. Contents of the pack and other information 
 
 
1. What Ivabradine JensonR is and what it is used for 
 
Ivabradine JensonR (ivabradine) is a heart medicine used to treat: 
- Symptomatic stable angina pectoris (which causes chest pain) in adult patients whose heart rate is over 

or equal to 70 beats per minute. It is used in adult patients who do not tolerate or cannot take heart 
medicines called beta-blockers. It is also used in combination with beta-blockers in adult patients 
whose condition is not fully controlled with a beta-blocker. 

- Chronic heart failure in adult patients whose heart rate is over or equal to 75 beats per minute. It is 
used in combination with standard therapy, including beta-blocker therapy or when beta-blockers are 
contraindicated or not tolerated. 

 
About stable angina pectoris (usually referred to as “angina”): 
Stable angina is a heart disease which happens when the heart does not receive enough oxygen. It usually 
appears between 40 and 50 years of age. The most common symptom of angina is chest pain or discomfort. 
Angina is more likely to happen when the heart beats faster in situations such as exercise, emotion, exposure 
to the cold or after eating. This increase in heart rate can cause the chest pain in people who suffer from 
angina. 
 
About chronic heart failure: 
Chronic heart failure is a heart disease which happens when your heart cannot pump enough blood to the rest 
of your body. The most common symptoms of heart failure are breathlessness, fatigue, tiredness and ankle 
swelling. 
 
How does Ivabradine JensonR work 
Ivabradine JensonR mainly works by reducing the heart rate by a few beats per minute. This lowers the 
heart’s need for oxygen especially in the situations when an angina attack is more likely to happen. In this 
way Ivabradine JensonR helps to control and reduce the number of angina attacks. 
 

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Furthermore as elevated heart rate adversely affects the heart functioning and vital prognosis in patients with 
chronic heart failure, the specific heart rate lowering action of ivabradine helps to improve the heart 
functioning and vital prognosis in these patients. 
 
 
2. What you need to know before you take Ivabradine JensonR 
 
Do not take Ivabradine JensonR 
- if you are allergic to ivabradine or any of the other ingredients of this medicine (listed in section 6); 
- if your resting heart rate before treatment is too slow (below 70 beats per minute); 
- if you are suffering from cardiogenic shock (a heart condition treated in hospital); 
- if you suffer from a heart rhythm disorder; 
- if you are having a heart attack; 
- if you suffer from very low blood pressure; 
- if you suffer from unstable angina (a severe form in which chest pain occurs very frequently and with 

or without exertion); 
- if you have heart failure which has recently become worse; 
- if your heart beat is exclusively imposed by your pacemaker; 
- if you suffer from severe liver problems; 
- if you are already taking medicines for the treatment of fungal infections (such as ketoconazole, 

itraconazole), macrolide antibiotics (such as josamycin, clarithromycin, telithromycin or erythromycin 
given orally), medicines to treat HIV infections (such as nelfinavir, ritonavir) or nefazodone (medicine 
to treat depression) or diltiazem, verapamil (used for high blood pressure or angina pectoris); 

- if you are a woman able to have children and not using reliable contraception; 
- if you are pregnant or trying to become pregnant; 
- if you are breast-feeding. 
 
Warnings and precautions 
Talk to your doctor or pharmacist before taking Ivabradine JensonR 
- if you suffer from heart rhythm disorders (such as irregular heartbeat, palpitation, increase in chest 

pain) or sustained atrial fibrillation (a type of irregular heartbeat), or an abnormality of 
electrocardiogram (ECG) called ‘long QT syndrome’, 

- if you have symptoms such as tiredness, dizziness or shortness of breath (this could mean that your 
heart is slowing down too much), 

- if you suffer from symptoms of atrial fibrillation (pulse rate at rest unusually high (over 110 beats per 
minute) or irregular, without any apparent reason, making it difficult to measure), 

- if you have had a recent stroke (cerebral attack), 
- if you suffer from mild to moderate low blood pressure, 
- if you suffer from uncontrolled blood pressure, especially after a change in your antihypertensive 

treatment, 
- if you suffer from severe heart failure or heart failure with abnormality of ECG called ‘bundle branch 

block’, 
- if you suffer from chronic eye retinal disease, 
- if you suffer from moderate liver problems, 
- if you suffer from severe renal problems 
 
If any of the above applies to you, talk straight away to your doctor before or while taking Ivabradine 
JensonR. 
 
Children and adolescents 
Ivabradine JensonR is not intended for use in children and adolescents younger than 18 years. 
 
Other medicines and Ivabradine JensonR 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 

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Make sure to tell your doctor if you are taking any of the following medicines, as a dose adjustment of 
Ivabradine JensonR or monitoring should be required: 
- fluconazole (an antifungal medicine) 
- rifampicin (an antibiotic) 
- barbiturates (for difficult sleeping or epilepsy) 
- phenytoin (for epilepsy) 
- Hypericum perforatum or St John’s wort (herbal treatment for depression) 
- QT prolonging medicines to treat either heart rhythm disorders or other conditions: 

- quinidine, disopyramide, ibutilide, sotalol, amiodarone (to treat heart rhythm disorders) 
- bepridil (to treat angina pectoris) 
- certain types of medicines to treat anxiety, schizophrenia or other psychoses (such as pimozide, 

ziprasidone, sertindole) 
- anti-malarial medicines (such as mefloquine or halofantrine) 
- intravenous erythromycin (an antibiotic) 
- pentamidine (an antiparasitic medicine) 
- cisapride (against the gastro-oesophageal reflux) 

- Some types of diuretics which may cause decrease in blood potassium level, such as furosemide, 
hydrochlorothiazide, indapamide (used to treat oedema, high blood pressure). 

 
Ivabradine JensonR with food and drink 
Avoid grapefruit juice during treatment with Ivabradine JensonR. 
 
Pregnancy and breast-feeding 
Do not take Ivabradine JensonR if you are pregnant or are planning to have a baby (see “Do not take 
Ivabradine JensonR”). 
If you are pregnant and have taken Ivabradine JensonR, talk to your doctor. 
Do not take Ivabradine JensonR if you are able to become pregnant unless you use reliable contraceptive 
measures (see “Do not take Ivabradine JensonR”). 
Do not take Ivabradine JensonR if you are breast-feeding (see “Do not take Ivabradine JensonR”). Talk to 
your doctor if you are breast-feeding or intending to breast-feed as breast-feeding should be discontinued if 
you take Ivabradine JensonR. 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your 
doctor or pharmacist for advice before taking this medicine. 
 
Driving and using machines 
Ivabradine JensonR may cause temporary luminous visual phenomena (a temporary brightness in the field of 
vision, see “Possible side effects”). If this happens to you, be careful when driving or using machines at 
times when there could be sudden changes in light intensity, especially when driving at night. 
 
Ivabradine JensonR contains lactose 
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before 
taking this medicine. 
 
 
3. How to take Ivabradine JensonR 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure. 
 
Ivabradine JensonR should be taken during meals. 
 
If you are being treated for stable angina pectoris 
The starting dose should not exceed one tablet of Ivabradine JensonR 5 mg twice daily. If you still have 
angina symptoms and if you have tolerated the 5 mg twice daily dose well, the dose may be increased. The 
maintenance dose should not exceed 7.5 mg twice daily. Your doctor will prescribe the right dose for you. 

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41 
 

The usual dose is one tablet in the morning and one tablet in the evening. In some cases (e.g. if you are 
elderly), your doctor may prescribe half the dose i.e., one half 5 mg tablet of Ivabradine JensonR 5 mg 
(corresponding to 2.5 mg ivabradine) in the morning and one half 5 mg tablet in the evening. 
 
If you are being treated for chronic heart failure 
The usual recommended starting dose is one tablet of Ivabradine JensonR 5 mg twice daily increasing if 
necessary to one tablet of Ivabradine JensonR 7.5 mg twice daily. Your doctor will decide the right dose for 
you. The usual dose is one tablet in the morning and one tablet in the evening. In some cases (e.g. if you are 
elderly), your doctor may prescribe half the dose i.e., one half 5 mg tablet of Ivabradine JensonR 5 mg 
(corresponding to 2.5 mg ivabradine) in the morning and one half 5 mg tablet in the evening. 
 
If you take more Ivabradine JensonR than you should: 
A large dose of Ivabradine JensonR could make you feel breathless or tired because your heart slows down 
too much. If this happens, contact your doctor immediately. 
 
If you forget to take Ivabradine JensonR: 
If you forget to take a dose of Ivabradine JensonR, take the next dose at the usual time. Do not take a double 
dose to make up for the forgotten dose. 
The calendar printed on the blister containing the tablets should help you remember when you last took a 
tablet of Ivabradine JensonR. 
 
If you stop taking Ivabradine JensonR: 
As the treatment for angina or chronic heart failure is usually life-long, you should discuss with your doctor 
before stopping this medicinal product. 
If you think that the effect of Ivabradine JensonR is too strong or too weak, talk to your doctor or pharmacist. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most common adverse reactions with this medicine are dose dependent and related to its mode of action: 
 
Very common (may affect more than 1 in 10 people): 
Luminous visual phenomena (brief moments of increased brightness, most often caused by sudden changes 
in light intensity). They can also be described as a halo, coloured flashes, image decomposition or multiple 
images. They generally occur within the first two months of treatment after which they may occur repeatedly 
and resolve during or after treatment. 
 
Common (may affect up to 1 in 10 people): 
Modification in the heart functioning (the symptoms are a slowing down of the heart rate). They particularly 
occur within the first 2 to 3 months of treatment initiation. 
 
Other side effects have also been reported: 
 
Common (may affect more than 1 in 10 people): 
Irregular rapid contraction of the heart, abnormal perception of heartbeat, uncontrolled blood pressure, 
headache, dizziness and blurred vision (cloudy vision). 
 
Uncommon (may affect up to 1 in 100 people): 
Palpitations and cardiac extra beats, feeling sick (nausea), constipation, diarrhoea, abdominal pain, spinning 
sensation (vertigo), difficulty breathing (dyspnoea), muscle cramps, changes in laboratory parameters: high 
blood levels of uric acid, an excess of eosinophils (a type of white blood cell) and elevated creatinine in 

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42 
 

blood (a breakdown product of muscle), skin rash, angioedema (such as swollen face, tongue or throat, 
difficulty in breathing or swallowing), low blood pressure, fainting, feeling of tiredness, feeling of weakness, 
abnormal ECG heart tracing, double vision, impaired vision. 
 
Rare (may affect up to 1 in 1,000 people): 
Urticaria, itching, skin reddening, feeling unwell. 
 
Very rare (may affect up to 1 in 10,000 people): 
Irregular heart beats. 
 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed 
in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects you can help provide more information on the safety of this medicine. 
 
 
5. How to store Ivabradine JensonR 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton, bottle and blister after ‘EXP’. 
The expiry date refers to the last day of that month. 
 
This medicine does not require any special storage conditions. 
 
For bottles, use within 6 months after first opening. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw 
away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Ivabradine JensonR contains 
- The active substance is ivabradine (as hydrochloride).Each film-coated tablet contains 7.5 mg 

ivabradine (as hydrochloride). 
- The other ingredients in the tablet core are: lactose anhydrous, magnesium stearate, maltodextrin, 

microcrystalline cellulose, colloidal anhydrous silica, hydroxypropyl cellulose and in the tablet 
coating: hypromellose, titanium dioxide, macrogol, polysorbate 80, yellow iron oxide (E172), red iron 
oxide (E172). 

 
What Ivabradine JensonR looks like and contents of the pack 
Ivabradine JensonR 7.5 mg tablets are pink-coloured, round film-coated tablets marked with “I 7” on one 
side and “M” on the other side of the tablet. 
 
Ivabradine JensonR is available in blister packs of 14, 14 x 1, 28, 56, 56 x 1, 98, and 112 film-coated tablets. 
The pack sizes 14 x 1 and 56 x 1 film-coated tablets are presented in unit dose blisters. 
Ivabradine JensonR is also available in bottles with a screw cap and a desiccant of 56, 98 and 
100 film-coated tablets. Do not eat the desiccant. 
 
Not all pack sizes may be marketed. 
 

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43 
 

Marketing Authorisation Holder 
Jenson R+ Limited 
Fishleigh Court, 
Fishleigh Road, 
Barnstaple, 
Devon, 
United Kingdom EX31 3UD 
 
Manufacturer 
McDermott Laboratories Limited 
t/a Gerard Laboratories 
35-36 Baldoyle Industrial Estate 
Grange Road 
Dublin 13 
Ireland 
 
Mylan Hungary Kft 
Mylan utca 1 
2900 Komárom 
Hungary 
 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder. 
 
België/Belgique/Belgien 
Mylan bvba/sprl 
Tél/Tel: + 32 02 658 61 00 
 

Lietuva 
Generics [UK] Ltd 
Tel: +44 1707 853000 
(Jungtinė Karalystė) 
 

България 
Майлан ЕООД 
Тел: +359 2 44 55 400 
 

Luxembourg/Luxemburg 
Mylan bvba/sprl 
Tel: + 32 02 658 61 00 
(Belgique/Belgien) 
 

Česká republika 
Mylan Pharmaceuticals.s.r.o. 
Tel: +420 274 770 201 

Magyarország 
Mylan EPD Kft 
Tel: + 36 1 465 2100 
 

Danmark 
Mylan AB 
Tlf: + 46 855 522 750 
(Sverige) 
 

Malta 
George Borg Barthet Ltd. 
Tel: + 356 212 44205 / +356 212 44206 
 

Deutschland 
Mylan dura GmbH 
Tel: + 49-(0) 6151 9512 0 
 

Nederland 
Mylan BV 
Tel: + 31 33 299 7080 

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44 
 

Eesti 
Generics [UK] Ltd 
Tel: +44 1707 853000 
(Ühendkuningriik) 
 

Norge 
Mylan AB 
Tel: + 46 855 522 750 
(Sverige) 
 

Ελλάδα 
Generics Pharma Hellas ΕΠΕ 
Τηλ: +30 210 993 6410 
 

Österreich 
Arcana Arzneimittel GmbH 
Tel: +43 1 416 2418 
 

España 
Mylan Pharmaceuticals, S.L 
Tel: + 34 900 102 712 
 

Polska 
Mylan Sp. z.o.o. 
Tel: + 48 22 546 64 00 
 

France 
Mylan S.A.S 
Tel: +33 4 37 25 75 00 
 

Portugal 
Mylan, Lda. 
Tel: + 351 21 412 72 56 
 

Hrvatska 
Mylan EPD d.o.o. 
Tel: +385 1 23 50 599 
 

România 
A&G Med Trading SRL 
Tel: + 4021 332 49 91 
 

Ireland 
Generics [UK] Ltd. 
Tel: + 44 1707 853000 
(United Kingdom) 
 

Slovenija 
GSP Proizvodi d.o.o. 
Tel: + 386 1 236 31 85 
 

Ísland 
Mylan AB 
Tel: + 46 855 522 750 
(Svíþjóð) 
 

Slovenská republika 
Mylan s.r.o. 
Tel: +421 2 326 04 910 / +421 917 206 274 

Italia 
Mylan S.p.A 
Tel: + 39 02 612 46923 
 

Suomi/Finland 
Mylan OY 
Puh/Tel: + 358 9-46 60 03 
 

Κύπρος 
Pharmaceutical Trading Co. Ltd. 
Τηλ: + 357 99403969 
 

Sverige 
Mylan AB 
Tel: + 46 855 522 750 
 

Latvija 
Generics [UK] Ltd 
Tel: +44 1707 853000 
(Lielbritānija) 
 

United Kingdom 
Generics [UK] Ltd 
Tel: +44 1707 853000 

 
This leaflet was last revised in 
 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  

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	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USEOF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET