SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Ismelin® ampoules 10 mg/ml

Guanethidine monosulphate Ampoules 10 mg/ml

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Guanethidine monosulphate Ph.Eur. 10mg/ml

3. PHARMACEUTICAL FORM

A colourless solution in a clear glass 1ml ampoule, for intramuscular administration.

4. CLINICAL PARTICULARS

4.1. Therapeutic Indications

Control of hypertensive crises, and to obtain more rapid blood pressure control.

4.2. Posology and Method of Administration

Adults:

Ismelin should be given by intramuscular injection. One injection of 10 to 20mg will generally cause a fall in blood pressure within 30 minutes which reaches a maximum in one to two hours and is maintained for four to six hours. If a further dose of 10 to 20mg is deemed necessary, then three hours should be allowed to elapse between doses.

In hypertensive patients with moderate renal insufficiency, the intervals between dosing should be extended or the dosage reduced to avoid accumulation as the drug is renally excreted. (For patients with renal failure, see Section 4.3, “Contra-indications”).

Children: not recommended.

Elderly: Clinical evidence would indicate that no special dosage regime is necessary, but concurrent coronary or cerebral insufficiency should be taken into account.

4.3. Contra-indications

Cases of phaeochromocytoma and patients previously treated with monoamine oxidase inhibitors (see Section 4.5, “Interactions with other medicaments and other forms of interaction”); in such cases, Ismelin may lead to the release of large quantities of catecholamines, which may cause a hypertensive crisis.

Patients with known hypersensitivity to guanethidine and related derivatives. Heart failure due to causes other than hypertension. Renal failure (creatinine clearance 10 to 40ml/min).

4.4 Special warnings and precautions for use

Heat and physical exertion may increase the antihypertensive effect of Ismelin.

Ismelin should be used with caution in patients with moderate renal insufficiency (creatinine clearance 41 to 65 ml/min), or with coronary and/or cerebral arteriosclerosis; abrupt lowering of blood pressure should be avoided. Caution should be exercised in asthmatic patients or in patients with a history of gastro-intestinal ulceration.

The concurrent administration of guanethidine and ^-blockers may provoke severe bradycardia.

When patients have to undergo surgery, it is recommended that treatment with Ismelin be withdrawn a few days before the operation. To avoid excessive bradycardia during anaesthesia, it is advisable to premedicate with larger than usual doses of atropine.

After prolonged treatment with Ismelin, latent heart failure may develop. This is due to salt and water retention, and mild negative inotropic and chronotropic effects. Concomitant administration of diuretics can readily correct this condition.

If patients develop fever, the dose of Ismelin should be lowered.

Ismelin should be used with caution in patients with Parkinson’s disease with associated autonomic neuropathy because of potential risk of worsening of orthostatic hypotension.

4.5. Interactions with other Medicaments and other forms of Interaction

Monoamine oxidase inhibitors should be withdrawn at least fourteen days before starting treatment with Ismelin (See Section 4.3, “Contra-indications”).

Concurrent administration of Ismelin with anti-arrhythmic agents and digitalis may lead to sinus bradycardia.

The anti-hypertensive action of Ismelin may be enhanced by other antihypertensive agents such as reserpine, methyldopa, vasodilators (especially minoxidil), calcium antagonists, P-blockers, ACE inhibitors and alcohol.

The anti-hypertensive action of Ismelin may be reduced by chlorpromazine, phenothiazine derivatives, tricyclic antidepressants and related anti-psychotic drugs, and oral contraceptives. Consequently if larger doses of Ismelin are prescribed, care must be taken upon the withdrawal of any of the drugs listed, as severe hypotension may ensue if the dose of Ismelin is not adjusted in advance.

After prolonged treatment with Ismelin, it may be necessary to adjust the dosage of insulin or oral anti-diabetic drugs.

Patients on Ismelin may become hypersensitive to adrenaline, amphetamines or other sympathomimetic agents. Therefore caution should be exercised when taking or using preparations containing these drugs.

4.6. Pregnancy and Lactation

No foetal toxicity or fertility studies have been carried out in animals. Therefore the drug should only be used if there is no safer alternative. However, in particular, it should not be used during the first trimester of pregnancy nor within at least two weeks prior to the birth or during labour since it may induce paralytic ileus in the newborn infant.

In mothers receiving Ismelin in therapeutic doses, the active substance passes into the breast milk, but in quantities so small that no undesirable effects on the infant are to be expected.

4.7. Effects on Ability to Drive and Use Machines

Patients should be warned of the potential hazards of driving or operating machinery if they experience side effects such as dizziness, blurred vision or drowsiness.

4.8 Undesirable effects

Blood and lymphatic system disorders

Isolated reports of anaemia, leucopenia, and/or thrombocytopenia

Psychiatric disorders

Depression

Nervous system disorders

Dizziness, paraesthesia or headache may occur, particularly at the start of treatment. Blurred vision.

Rare: Muscular tremor

Cardiac disorders

Sick-sinus syndrome, bradycardia, heart failure.

Rare: Angina pectoris

Vascular disorders

Postural hypotension (which may be associated with cerebral or myocardial ischaemia in severe cases); Exacerbation of intermittent claudication.

Respiratory, thoracic and mediastinal disorders

Nasal congestion

Rare: Asthma

Gastrointestinal disorders

Diarrhoea, gaseous distension, vomiting, nausea, dry mouth.

Rare: Swelling of parotid glands

Skin and subcutaneous tissue disorders

Dermatitis

Rare: Hair loss

Musculoskeletal and connective tissue disorders

Rare: Myalgia

Renal and urinary disorders

Uraemia in patients with latent or manifest renal failure

Reproductive system and breast disorders

Ejaculation disturbances

Erectile dysfunction (including priapism)

General disorders and administration site conditions

Particularly at the start of treatment: Tiredness Particularly at the start of treatment: Lethargy Oedema

Investigations

4.9. Overdose

Symptoms: may include postural hypotension which may cause syncope, sinus bradycardia (although tachycardia has been observed), tiredness, dizziness, blurring of vision, muscular weakness, nausea, vomiting, severe diarrhoea and oliguria.

Treatment: Postural hypotension may be overcome by keeping the patient recumbent, or by instituting fluid and electrolyte replacement, and if necessary, by cautious administration of pressor agents (see Section 4.5, “Interactions with other medicaments and other forms of interaction”). Sinus bradycardia can be treated with atropine, and diarrhoea with an anticholinergic agent.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic Properties

Ismelin is a peripheral sympathetic blocking drug which lowers blood pressure by depleting and inhibiting reformation of noradrenaline in postganglionic nerve endings. Guanethidine, being highly polar, does not cross the blood-brain barrier and is unlikely therefore to exert any effect on the central nervous system. In addition, guanethidine has no effect on the parasympathetic nervous system.

5.2. Pharmacokinetic Properties

Guanethidine may be excreted more slowly in those patients with moderate to severely compromised renal function, therefore the potential for accumulation of the drug will be higher.

5.3. Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to those already included in other sections of the Summary of Product Characteristics.

List of Excipients

Sodium chloride, sulphuric acid and water for injections.

6.2. Incompatibilities

None known.

6.3. Shelf Life

5 years.

6.4. Special Precautions for Storage

None.

6.5. Nature and Contents of Container

Clear glass type I, 1ml ampoules containing 10mg/ml: Boxes of 5.

6.6. Instruction for Use/Handling

None

7 MARKETING AUTHORISATION HOLDER

Amdipharm UK Limited

Regency House

Miles Gray Road

Basildon

Essex

SS14 3AF

United Kingdom.

8. MARKETING AUTHORISATION NUMBER

PL 20072/0027

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

19/02/2009

DATE OF REVISION OF THE TEXT

28/07/2014