Summary of medicine characteristics - GUANETHIDINE MONOSULPHATE AMPOULES 10 MG / ML, ISMELIN AMPOULES 10 MG / ML
1 NAME OF THE MEDICINAL PRODUCT
1 NAME OF THE MEDICINAL PRODUCTIsmelin® ampoules l0 mg/ml
Guanethidine monosulphate Ampoules 10 mg/ml
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Guanethidine monosulphate Ph.Eur. 10mg/ml
3. PHARMACEUTICAL FORM
3. PHARMACEUTICAL FORMA colourless solution in a clear glass 1ml ampoule, for intramuscular administration.
4.
4.1. Therapeutic indications
Control of hypertensive crises, and to obtain more rapid blood pressure control.
4.2. Posology and method of administration
Posology
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”).
Elderly:
Clinical evidence would indicate that no special dosage regime is necessary, but concurrent coronary or cerebral insufficiency should be taken into account.
Paediatric population
Not recommended.
Method of administration
Intramuscular administration.
4.3. Contraindications
Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.
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.
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 P-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.
This medicine contains less than 1 mmol sodium (23 mg) per dosage, that is to say essentially ‘sodium-free’.
4.5. Interactions with other medicinal products 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, ß-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. Fertility, pregnancy and lactation
Pregnancy
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.
Breast-feeding
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.
Fertility
No foetal toxicity or fertility studies have been carried out in animals.
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
The following adverse reactions are classified by system organ class and ranked under heading of frequency using the following convention:
Common (>1/100 to <1/10)
Rare (>1/10,000 to <1/1,000)
Not known (cannot be estimated from the available data)
| System organ class | Frequency | Undesirable effects |
| Psychiatric disorders | Not known | Depression |
| Nervous system disorders | Rare | Muscular tremor |
| Common | Dizziness, paraesthesia or headache may occur, particularly at the start of treatment. | |
| Eye disorders | Not known | Blurred vision |
| Cardiac disorders | Rare | Angina pectoris |
| Common | Sick-sinus syndrome, bradycardia, heart failure. | |
| Vascular disorders | Common | Postural hypotension (which may be associated with cerebral or myocardial ischaemia in severe cases); Exacerbation of intermittent claudication. |
| Respiratory, thoracic and mediastinal disorders | Rare | Asthma |
| Not known | Nasal congestion | |
| Gastrointestinal disorders | Rare | Swelling of parotid glands |
| Common | Diarrhoea, gaseous distension, vomiting, nausea, dry mouth. | |
| Skin and subcutaneous | Rare | Hair loss |
| tissue disorders | Not known | Dermatitis |
| Musculoskeletal and connective tissue disorders | Rare | Myalgia |
| Renal and urinary disorders | Not known | Uraemia in patients with latent or manifest renal failure |
| Reproductive system and breast disorders | Common | Ejaculation disturbances Erectile dysfunction (including priapism) |
| General disorders and administration site conditions | Common | Particularly at the start of treatment: Tiredness, lethargy, oedema |
| Investigations | Not known | Raised BUN levels in patients with latent or manifest renal failure. |
Isolated reports of anaemia, leucopenia, and/or thrombocytopenia
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 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
4.9. OverdoseSymptoms
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.
Management
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. PHARMACOLOGICAL PROPERTIESPharmacotherapeutic group: Guanidine derivatives, ATC code: C02CC02
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 bloodbrain 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
Elimination
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
5.3. Preclinical safety dataThere 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.
6. PHARMACEUTICAL PARTICULARS
6.1. List of excipients
Sodium chloride, sulphuric acid and water for injections.
6.2. Incompatibilities
None known.
6.3. Shelf life
6.3. Shelf life5 years.
6.4. Special precautions for storage
None.
6.5. Nature and contents of container and special equipment for use, administration or implantation
Clear glass type I, 1ml ampoules containing 10mg/ml: Boxes of 5.
6.6. Special precautions for disposal and other handling
None
7 MARKETING AUTHORISATION HOLDER
Amdipharm UK Limited
Capital House, 85 King William Street,
London EC4N 7BL, UK.
8. MARKETING AUTHORISATION NUMBER(S)
PL 20072/0027
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
19/02/2009