ISMO Retard prolonged-release tablet Ref.[49794] Active ingredients: Isosorbide mononitrate

ISMO 40 tablets should not be used after the expiry date specified on the pack.

Isosorbide-5-mononitrate may only be used with caution in the following cases:

• hypertrophic obstructive cardiomyopathy, constrictive pericarditis and pericardial tamponade.
• low filling pressures, e.g. in cases of acute myocardial infarction, impaired left ventricular function (left-heart failure). Any fall in blood pressure below 90 mmHg systolic should be avoided.
• aortic and/or mitral stenosis.
• susceptibility to orthostatic circulatory dysregulation.
• disorders associated with increased intracranial pressure (to date, any further increase in pressure has only been observed with high-dose IV administration of glyceryl trinitrate).

ISMO 40 retard is not suitable for the treatment of acute attacks of angina pectoris or acute myocardial infarction.

Due to their pharmacological effect (inhibition of cGMP degradation), phosphodiesterase-5 inhibitors – including sildenafil – potentiate the hypotensive effect of nitrates and other NOdonors, which can lead to serious and often therapy-resistant hypotension. Use of phosphodiesterase-5 inhibitors during treatment with ISMO 40 retard is therefore contraindicated. Patients must be informed about this potentially life-threatening interaction. If the phosphodiesterase-5 inhibitor has already been taken, intake of isosorbide-5-mononitrate within the next 24 hours is contraindicated.

Patients with rare hereditary problems of glucose-galactose malabsorption should not take ISMO 40 retard.

Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take ISMO 40 retard.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency should not take ISMO 40 retard.

Safety, effectiveness and dosage of isosorbide-5-nitrate in children have not been established.

The following interactions of this medicinal product must be considered:

Concomitant intake of other vasodilators, antihypertensives, ACE inhibitors, beta-blockers, calcium antagonists, diuretics, neuroleptics or tricyclic antidepressants and alcohol can potentiate the antihypertensive effect of ISMO 40 retard.

This particularly applies to the concomitant use of phosphodiesterase-5 inhibitors, e.g. sildenafil, vardenafil and tadalafil (see Contraindications).

With concomitant use of dihydroergotamine, ISMO 40 retard can lead to a rise in the DHE level and thereby potentiate its hypertensive effect.

Pregnancy

For special precautionary reasons, ISMO 40 retard should only be taken during pregnancy on the express instructions of a doctor, as there are no adequate data on the use of ISMO 40 retard in pregnant women. Studies in animals have revealed no evidence of any embryofoetal damage (see section 5.3 Preclinical Safety Data).

Breast feeding

For special precautionary reasons, ISMO 40 retard should only be taken during lactation on the express instructions of a doctor, as there is insufficient experience with use in lactating women and it is not known whether ISMO 40 retard passes into breast milk. If ISMO 40 retard is taken during breast-feeding, vigilance is required for possible drug effects in the infant.

Even when used as directed, this medicinal product can alter responsiveness to such an extent that the ability to drive, use machines or perform dangerous tasks is impaired. This particularly applies at the start of treatment, whenever there is a dose increase or change in medication and in interaction with alcohol.

The following categories are used when stating the frequency of undesirable effects: 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 (frequency cannot be estimated from the available data).

Nervous system disorders

Very common: At the start of treatment, headache (“nitrate-induced headache”) may occur, which – based on experience – mostly resolves after a few days of continued intake.

Vascular disorders

Common: During initial use – but also upon dose escalation – a fall in blood pressure and/or orthostatic hypotension have been observed, which may be accompanied by a reflex increase in the pulse rate, stupor, as well as feelings of dizziness and weakness. Such symptoms generally recede during treatment.

Uncommon: a significant drop in blood pressure with exacerbation of angina pectoris symptoms has been observed, as well as states of collapse, sometimes with bradyarrhythmias and syncope.

Not known: Severe hypotensive responses including nausea, vomiting, restlessness, pallor, and hyperhidrosis have been reported for organic nitrates.

Skin and subcutaneous tissue disorders

Uncommon: transient erythema (flush) and allergic skin reactions have been observed. Very

Rare: exfoliative dermatitis may occur.

Blood and lymphatic system disorders

Methaemoglobin formation may occur, particularly in patients with methaemoglobin reductase deficiency or in patients with diaphorase deficiency and abnormal haemoglobin structure.

Gastrointestinal disorders

Uncommon: nausea and/or vomiting have been observed.

Not known: heartburn

Tolerance development and occurrence of cross-tolerance with other nitrate compounds have been described. In order to avoid any attenuation or loss of the effect, high continuous dosing regimens should be avoided.

Note:

During administration of ISMO 40 retard, transient hypoxaemia may occur due to a relative redistribution of blood flow into hypoventilated alveolar areas, which may precipitate myocardial hypoxia in patients with coronary heart disease.

Dose escalation and/or changes in the dosing interval can lead to an attenuation or loss of the effect.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions via https://nzphvc.otago.ac.nz/reporting/.

None are known.