Part ib summary of product characteristics

SUMMARY OF PRODUCT CHARACTERISTICS
NAME OF THE MEDICINAL PRODUCT
Ismo 20
QUALITATIVE AND QUANTITATIVE COMPOSITION
In terms of the active ingredients:
Ismo 20: 20mg isosorbide-5-mononitrate.
3 PHARMACEUTICAL
Ismo tablets are white, circular, uncoated and contain isosorbide-5-mononitrate. Lactose is present in the formulation. Ismo 20 tablets: Marked with a score line and BM 3B on both faces. 4 CLINICAL
PARTICULARS
4.1 Therapeutic
indications
Ismo products are indicated for use in the treatment and prophylaxis of angina pectoris and as adjunctive therapy in congestive heart failure which does not respond adequately to cardiac glycosides and/or diuretics. Posology and method of administration
Route of administration
Oral.
Adults
The recommended dosage is from 20 to 120mg isosorbide-5-mononitrate daily in
divided doses. The majority of patients will require a dosage in the range of 40 to
60mg daily in divided doses. The tablets should be taken with fluid and swallowed
whole without chewing.
The lowest effective dose should be used. For patients who have not previously received prophylactic nitrate therapy it is recommended that the Ismo Starter Pack be employed. This provides an initial dosage of 10mg isosorbide-5-mononitrate (1 tablet) daily for 2 days followed by a dosage of 20mg daily (1 tablet morning and evening) for a further 3 days. Subsequently the daily dosage may be increased to the normal prophylactic level using the Ismo 20 tablets also included in the Starter Pack. Patients already accustomed to chronic nitrate therapy normally may be transferred directly to a therapeutic dose of Ismo. For those previously treated with isosorbide dinitrate in conventional form the dosage of Ismo should be the same initially. Ismo is effectively twice as potent as sustained release forms of isosorbide dinitrate and patients transferred from such treatment should receive Ismo at half the previous dosage. Therapy should not be discontinued suddenly. Both dosage and frequency should be tapered gradually (see Section 4.4). Elderly
There is no evidence to suggest an adjustment of dose is necessary. However, caution
may be required in elderly patients who are known to be susceptible to the effects of
hypotensive medication.
Children
The safety and efficacy of Ismo in children has not been established.
Renal and hepatic impairment
No dosage reduction is necessary.
4.3 Contraindications
Ismo tablets are contraindicated in patients with a known hypersensitivity to isosorbide-5-mononitrate or isosorbide dinitrate, in cases of marked low blood pressure (BP ≤ 90mm Hg systolic), circulatory collapse, shock, cardiogenic shock, acute myocardial infarction with low left ventricular filling pressure, hypertrophic obstructive cardiomyopathy, constrictive pericarditis, cardiac tamponade, aortic/mitral valve stenosis, severe anaemia, closed-angle glaucoma and conditions associated with raised intracerebral pressure e.g. following head trauma and cerebral haemorrhage. Sildenafil has been shown to potentiate the hypotensive effects of nitrates (see Section 4.8), and its co-administration with nitrates or nitric oxide donors is therefore contraindicated. Special warnings and precautions for use
Ismo is not indicated for relief of an acute attack; sublingual or buccal glyceryl trinitrate tablets or spray should be used. The lowest effective dose should be used (see Section 4.2). Since a rebound phenomenon cannot be excluded, therapy with isosorbide-5-mononitrate should be terminated gradually rather than stopping abruptly (see Section 4.2). Caution should be exercised in patients suffering from hypothyroidism, malnutrition, severe renal or hepatic impairment, hypothermia and recent history of myocardial infarction. Hypotension induced by nitrates may be accompanied by paradoxical bradycardia and increased angina. Severe postural hypotension with light-headedness and dizziness is frequently observed after the consumption of alcohol. Ismo 20 tablets contain 148 mg lactose and are unsuitable for patients with lactase insufficiency, galactosaemia or glucose/galactose malabsorption syndrome. Interaction with other medicinal products and other forms of interaction
The hypotensive effects of other drugs such as alprostadil, aldesleukin and angiotensin II receptor antagonists may be potentiated. In particular, the hypotensive effects of nitrates are potentiated by concurrent co-administration of phosphodiesterase type-5 inhibitors e.g. sildenafil (see Section 4.3); these effects are potentially life threatening. Pregnancy and lactation
There is inadequate evidence of safety of isosorbide-5-mononitrate in human pregnancy although nitrates have been in wide use for many years without ill consequence, animal studies having shown no adverse effects on the foetus. There is no information on excretion of isosorbide-5-mononitrate in breast milk. Use in pregnancy and lactation is not recommended unless considered essential by the patient's physician. Effects on ability to drive and use machines
In theory, the ability to drive or to operate machinery may be impaired in patients experiencing hypotensive side effects such as dizziness or blurred vision. 4.8 Undesirable
Central nervous system:
− frequently, particularly at the start of treatment, a transient “nitrate headache” may
occur which normally subsides after some days of continued treatment. − occasionally, particularly when first used, slight states of dizziness or feeling of weakness may occur which normally improve during treatment. Cardiovascular system:
− occasionally, especially at the beginning of treatment, hypotension (including
postural hypotension), tachycardia or flushing, which normally improves on continuation of therapy. − rarely, collapse, in some instances accompanied by bradyarrhythmias and syncope. − in rare cases where there is a significant drop in blood pressure the symptoms of − administration of isosorbide-5-nitrate may produce transient hypoxaemia as a result of redistribution of blood flow with a relative increase in perfusion of poorly ventilated areas of the lung. This may cause ischaemia in patients with coronary heart disease. Gastro-intestinal system:
− occasionally, especially when first used, gastro-intestinal symptoms, e.g. nausea
Haematological:
− formation of methaemoglobin might occur, in particular in susceptible patients
such as those with methaemoglobin reductase deficiency. Skin:
− rarely allergic skin reactions (e.g. exfoliative dermatitis).
4.9 Overdose
Symptoms: Nausea, vomiting, restlessness, warm flushed skin, blurred vision, headache, fainting, tachycardia, hypotension and palpitations. A rise in intracranial pressure with confusion and neurological deficits can sometimes occur. Management: Consider oral activated charcoal if ingestion of a potentially toxic amount has occurred within 1 hour. Observe for at least 12 hours after the overdose. Monitor blood pressure and pulse. Correct hypotension by raising the foot of the bed and/or by expanding the intravascular volume. Other measures as indicated by the patient’s clinical condition. If severe hypotension persists despite the above measures consider use of inotropes such as dopamine or dobutamine. 5 PHARMACOLOGICAL
PROPERTIES
5.1 Pharmacodynamic
properties
The main effect of isosorbide-5-mononitrate is to produce a marked venous vasodilation without a significant effect on the systemic arteries. The venous dilation leads to an accumulation of blood in the capacitance vessels resulting in a reduction of venous return to the heart. This results in a reduction of the ventricular diastolic volume, which produces a reduction in intramural tension (afterload) as well as reductions of filling pressures (preload) and as a result, a reduction in myocardial oxygen requirements from which arises the antianginal effect. 5.2 Pharmacokinetic
properties
Isosorbide-5-mononitrate displays 100% bioavailability on oral administration. Consequently, serum levels are predictable. Isosorbide-5-mononitrate is rapidly absorbed - peak serum concentrations occurring 1 hour after oral administration. Elimination half life is approximately 5 hours. The drug is eliminated solely by the liver and therefore can be used in renal insufficiency. 5.3 Preclinical
6 PHARMACEUTICAL
PARTICULARS
List of excipients
Ismo 20 tablets also contain anhydrous lactose, colloidal silicon dioxide and magnesium stearate. 6.2 Incompatibilities
6.3 Shelf
Special precautions for storage
Nature and contents of container
Ismo Starter Pack: 8 tablets of Ismo 10 and 56 or 60 tablets of Ismo 20 in calendarised blister strips. Ismo 20: Packs of 56, 60 and 100 tablets in blister strips or 100, 250 or 500 tablets in Securitainers. Special precautions for disposal
7 MARKETING
AUTHORISATION
RIEMSER Arzneimittel AG, An der Wiek 7, 17493 Greifswald - Insel Riems, Germany 8 MARKETING
AUTHORISATION
NUMBER(S)
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
04/1999 / 11/2007
DATE OF REVISION OF THE TEXT
08/2008
LEGAL STATUS

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