1. Name Of The Medicinal Product
Ismelin®ampoules l0mg/ml
2. Qualitative And Quantitative Composition
Guanethidine monosulphate Ph.Eur. 10mg/ml
3. Pharmaceutical Form
A colourless solution in a clear glass l ml 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
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 Contraindications
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 65ml/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
The concurrent administration of guanethidine and β
When patients have to undergo surgery, it is recommended that treatment with Ismelin be withdrawn a few days before the operation.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.
4.5 Interaction 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
Concurrent administration of Ismelin with anti
The anti-hypertensive action of Ismelin may be enhanced by other anti-hypertensive agents such as reserpine, methyldopa, vasodilators (especially minoxidil), calcium antagonists, β
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
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
Side effects are often an indication of excessive dosage. The following effects may occur:
Central nervous system: Particularly at the start of treatment: dizziness, tiredness, lethargy, paraesthesia and headache. Occasional: blurred vision and depression. Rare: myalgia and muscular tremor.
Cardiovascular system: Postural hypotension (which may be associated with cerebral or myocardial ischaemia in severe cases) especially when getting up in the morning or after physical exertion, sick
Gastro Diarrhoea and gaseous distension. Occasional: vomiting, nausea and dry mouth. Rare: swelling of parotid glands.
Respiratory tract: Nasal congestion. Rare: asthma.
Urogenital system: Raised BUN levels or uraemia in patients with latent or manifest renal failure, and ejaculation disturbances.
Skin and hair: Occasional: dermatitis. Rare: hair loss.
Blood: Isolated reports of anaemia, leucopenia, and/or thrombocytopenia.
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
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
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
5 years.
6.4 Special Precautions For Storage
None.
6.5 Nature And Contents Of Container
Clear glass type I, l ml ampoules containing l0mg/ml: Boxes of 5.
6.6 Special Precautions For Disposal And Other Handling
None
Administrative Data
7. Marketing Authorisation Holder
Amdipharm Plc
Regency House
Miles Gray Road
Basildon
Essex SS14 3AF
United Kingdom
8. Marketing Authorisation Number(S)
PL 20072/0027
9. Date Of First Authorisation/Renewal Of The Authorisation
18th April 2005
10. Date Of Revision Of The Text
Legal Status
POM
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