Isomex XL 30 mg prolonged-release tablets – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Isomex XL 30 mg prolonged-release tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 30 mg isosorbide mononitrate

Excipient(s) with known effect

Each tablet contains 113 mg lactose

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Prolonged-release tablet.

White to off-white oval tablet, approximately 7mm x 13 mm.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Prophylactic treatment of angina pectoris

4.2 Posology and method of administration

Posology

Adults

The usual dose is 60 mg (two tablets) taken once daily in the morning. The dose may be increased to 120 mg (four tablets) taken once daily in the morning. The dose can be titrated to minimise the possibility of headache, by initiating the treatment with 30mg (one tablet) for the first 2 - 4 days.

Paediatric population

The safety and efficacy of Isomex XL 30mg prolonged release tablets in children (less than 18 years old) has not yet been established.

Older People

No evidence of a need for routine dosage adjustment in older people has been found, but special care may be needed in those with increased susceptibility to hypotension or marked hepatic or renal insufficiency.

The core of the tablet is insoluble in the digestive juices but disintegrates into small particles when all active substance has been released. Very occasionally the matrix may pass through the gastrointestinal tract without disintegrating and be found visible in the stool, but all active substance has been released.

Method of administration

The tablets must not be chewed or crushed. They should be swallowed whole with half a glass of water.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Co-administration with riociguat (see section 4.5).

Constrictive cardiomyopathy and pericarditis, aortic stenosis, cardiac tamponade, mitral stenosis and severe anaemia.

Patients treated with Isomex XL 30mg prolonged release tablets must not take phosphodiesterase type-5 inhibitors (e.g. sildenafil,)

Severe cerebrovascular insufficiency or hypotension are relative contraindications to the use of Isomex XL 30mg prolonged release tablets.

4.4 Special warnings and precautions for use

Isosorbide mononitrate is not indicated for relief of acute angina attacks, in the event of an acute attack, sublingual or buccal glyceryl trinitrate tablets should be used.

Excipients

This medicinal product contains lactose. Patients with any of the following rare hereditary conditions: galactose intolerance, total lactase deficiency or glucose-galactose malabsorption; should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Concomitant administration of Isomex XL 30mg prolonged release tablets and phosphodiesterase type 5 Inhibitors can potentiate the vasodilatory effect of isosorbide mononitrate with the potential result of serious side effects such as syncope or myocardial infarction. Therefore, this medicinal product and phosphodiesterase type 5 inhibitors (e.g. sildenafil) must not be given concomitantly. The use of isosorbide mononitrate with riociguat, a stimulator of soluble guanylate cyclase, is contra-indicated (see section 4.3), since concomitant use can cause hypotension.

4.6 Fertility, pregnancy and lactation

The safety and efficacy of isosorbide mononitrate during pregnancy or lactation has not been established.

4.7 Effects on ability to drive and use machines

Patients may develop dizziness when first using isosorbide mononitrate. Patients should be advised to determine how they react to this medicinal product before they drive or operate machinery

4.8 Undesirable effects

Most of the undesirable effects are pharmacodynamically mediated and dose-dependent.

Headache may occur when the treatment is initiated but usually disappears after 1-2 weeks of treatment. The dose can be titrated to minimise the possibility of headache, by initiating treatment with 30mg.

Hypotension with symptoms such as dizziness and nausea, with syncope in isolated cases has been occasionally been reported. These symptoms generally disappear during continued treatment.

Tabulated list of adverse reactions

The incidence of undesirable effects is classified as follows: 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) and Very rare (<1/10,000), Rate not known (cannot be estimated from available data).

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 Yellow Card Scheme Website:www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Symptoms

Pulsing headache. More serious symptoms are excitation, redness, cold sweats, nausea, vomiting, vertigo, syncope, tachycardia and a fall in blood pressure.

Management

Induction of emesis, activated charcoal. In the case of pronounced hypotension, the patient should first be placed in the supine position with the legs highly elevated. If necessary, administer intravenous fluids.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Vasodilators used in cardiovascular disease, organic nitrates, ATC code: C01DA14

The principal pharmacological action of isosorbide mononitrate, an active metabolite of isosorbide dinitrate, is relaxation of vascular smooth muscle, producing vasodilation of both arteries and veins with the latter effect predominating. The effect of the treatment is dependent on the dose. Low plasma concentrations lead to venous dilatation, resulting in peripheral pooling of blood, decreased venous return and reduction in left ventricular end-diastolic pressure (preload). High plasma concentrations also dilate the arteries reducing systemic vascular resistance and arterial pressure leading to a reduction in cardiac afterload. Isosorbide mononitrate may also have a direct dilatory effect on the coronary arteries. By reducing the end diastolic pressure and volume, the preparation lowers the intramural pressure, thereby leading to an improvement in the subendocardial blood flow.

The net effect when administering isosorbide mononitrate is therefore a reduced workload of the heart and an improved oxygen supply/demand balance in the myocardium.

5.2 Pharmacokinetic properties

Isosorbide mononitrate is completely absorbed and is not subject to first pass metabolism by the liver. This reduces the intra- and inter-individual variations in plasma levels and leads to predictable and reproducible clinical effects.

The elimination half-life of Isomex XL 30mg prolonged release tablets is around 5 hours. The plasma protein binding is less than 5%. The volume of distribution for Isomex XL 30mg prolonged release tablets is about 0.6 l/kg and total clearance around 115 ml/minute. Elimination is primarily by denitration and conjugation in the liver. The metabolites are excreted mainly via the kidneys. Only about 2% of the dose given is excreted intact via the kidneys.

Impaired liver or kidney function have no major influence on the pharmacokinetic properties.

This medicinal product is a prolonged release formulation. The active substance is released independently of pH, over a 10-hour period. Compared to ordinary tablets the absorption phase is prolonged and the duration of effect is extended.

The extent of bioavailability is about 90% compared to immediate release tablets. Absorption is not significantly affected by food intake and there is no accumulation during steady state. The medicinal product exhibits dose proportional kinetics up to 120mg. After repeated peroral administration with 60mg once daily, maximal plasma concentration (around 3000 nmol/l) is achieved after around 4 hours. The plasma concentration then gradually falls to under 500 nmol/l at the end of the dosage interval (24 hours after dose intake).

In placebo-controlled studies, isosorbide mononitrate in once daily tablets has been shown to effectively control angina pectoris both in terms of exercise capacity and symptoms, and also in reducing signs of myocardial ischaemia. The duration of the effect is at least 12 hours, at this point the plasma concentration is at the same level as at around 1 hour after dose intake (around 1300 nmol/l).

Isomex XL 30mg prolonged release tablets are effective as monotherapy as well as in combination with chronic β

-blocker therapy.

The clinical effects of nitrates may be attenuated during repeated administration owing to high and/or even plasma levels. This can be avoided by allowing low plasma levels for a certain period of the dosage interval. The medicinal product, when administered once daily in the morning, produces a plasma profile of high levels during the day and low levels during the night. With a 60mg or 120mg dose once daily no development of tolerance with respect to antianginal effect has been observed. Rebound phenomenon between doses as described with intermittent nitrate patch therapy has not been seen with this medicinal product.

5.3 Preclinical safety data

The accessible data indicate that isosorbide mononitrate has expected pharmacodynamic properties of an organic nitrate ester, has simple pharmacokinetic properties, and is devoid of toxic, mutagenic or oncogenic effects.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Hypromellose.

Lactose monohydrate.

Pregelatinised starch

Magnesium stearate

Silica, colloidal anhydrous

6.2 Incompatibilities

Not applicable

6.3 Shelf life

3 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

PVC/PVDC/Alu blister packs with 28 or 98 tablets.

HDPE bottle and PP cap with 100 tablets, child resistant

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

RPH Pharmaceuticals AB

Box 603

101 32 Stockholm

Sweden

8 MARKETING AUTHORISATION NUMBER(S)

PL 36301/0066

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

Date of first authorisation: 23 June 2025

10 DATE OF REVISION OF THE TEXT

06/08/2026