Rogitine^® ampoules 10mg

Phentolamine mesilate PhEur 10mg.

Colourless to pale yellow solution in 1ml Water for Injections PhEur

Management of hypertensive episodes that may occur in patients with phaeochromocytoma, for example during pre-operative preparation and surgical manipulation.

Diagnosis of phaeochromocytoma by Rogitine blocking test if other more specific tests are not available.

Adults

Management of hypertensive episodes in patients with phaeochromocytoma

For the management of hypertensive crises that arise during the pre-operative phase or during induction of anaesthesia, intubation, or surgical removal of the tumour, 2 to 5mg of Rogitine is injected intravenously and repeated if necessary. The blood pressure response should be monitored.

Diagnosis of phaeochromocytoma - Rogitine blocking test

The test is most reliable in detecting phaeochromocytoma in patients with sustained hypertension and least reliable in those with paroxysmal hypertension. False-positive tests may occur in patients with hypertension without phaeochromocytoma.

Preparation for the test:

Sedatives, analgesics and all other medications except those that might be deemed essential (such as digitalis and insulin) are withheld for at least 24 hours, and preferably 48 to 72 hours, prior to the test. Antihypertensive drugs are withheld until blood pressure returns to the untreated, hypertensive level. This test is not performed on a patient who is normotensive.

Procedure : (intravenous) The patient is kept at rest in the supine position throughout the test, preferably in a quiet, darkened room. Injection of Rogitine is delayed until blood pressure is stabilised, as evidenced by blood pressure readings taken every 10 minutes for at least 30 minutes.

The dose for adults is 5mg. The syringe needle is inserted into the vein and injection delayed until the pressor response to venepuncture has subsided.

Rogitine is injected rapidly. Blood pressure is recorded immediately after injection, at 30-second intervals for the first 3 minutes, and at 60-second intervals for the next 7 minutes.

Interpretation: A positive response, suggestive of phaeochromocytoma, is indicated when the blood pressure is reduced by more than 35mmHg systolic and by 25mmHg diastolic. A typical positive response is a reduction in pressure of 60mmHg systolic and 25mmHg diastolic. Usually, the maximal effect is evident within 2 minutes after injection. A return to preinjection pressure commonly occurs within 15 to 20 minutes but may occur more rapidly.

If blood pressure decreases to a dangerous level, the patient should be treated as outlined under Section 4.9 “Overdose”.

A negative response is indicated when the blood pressure is elevated, unchanged, or reduced by less than 35mmHg systolic and 25mmHg diastolic after injection of Rogitine. A negative response to this test does not exclude the diagnosis of phaeochromocytoma, especially in patients with paroxysmal hypertension, in whom the incidence of false-negative responses is high.

Procedure : (intramuscular) A dose of 5mg is administered intramuscularly.

Interpretation: Blood pressure is recorded every 5 minutes for 30 to 45 minutes following injection. A positive response is indicated when the blood pressure is reduced by 35mmHg systolic and by 25mmHg diastolic, or more, within 20 minutes following injection.

Children:

Management of hypertensive episodes in patients with phaeochromocytoma: The dosage is 1mg given intravenously.

Diagnosis of phaeochromocytoma - Rogitine blocking test: The dosage is 1mg given intravenously or 3mg given intramuscularly.

Elderly: In elderly patients, it is advisable to use the lowest dose or a low infusion rate in case of undiagnosed coronary insufficiency, (see Section 4.3 “Contra-indications”).

Patients with renal impairment: Since no pharmacokinetic studies with Rogitine have been performed in patients with renal impairment, use caution in administering Rogitine to these patients.

Known hypersensitivity to phentolamine and related compounds. Known hypersensitivity to sulphites. Hypotension. Myocardial infarction, history of myocardial infarction, coronary insufficiency, angina, or other evidence of coronary artery disease.

Monitoring of the blood pressure is necessary for appropriate selection of patient, dosage, and duration of therapy. Myocardial infarction, cerebrovascular spasm, and cerebrovascular occlusion have been reported following the administration of Rogitine, usually in association with marked hypotensive episodes.

The presence of sulphites in Rogitine ampoules can lead to isolated hypersensitivity reactions especially in patients with bronchial asthma, which may become manifest as an acute asthma attack, shock, or clouding of consciousness.

For screening tests in patients with hypertension, the generally available urinary assay of catecholamines or other biochemical assays have largely replaced the Rogitine blocking test and other pharmacological tests for reasons of accuracy and safety. Therefore the Rogitine blocking test is not the procedure of choice and should be used only when these other specific tests are not available.

Tachycardia and cardiac arrhythmias may occur with the use of Rogitine.

Due to its stimulatory effect on the gastro-intestinal tract, including gastric secretion, Rogitine should be used with caution in patients with gastritis and peptic ulcer. Excessive cardiac stimulation and hypertensive crisis may occur during surgical removal of a tumour due to manipulation of the phaeochromocytoma, despite the fact that phentolamine had been given as pre-medication to prevent such an occurrence. In the event of this complication, use a ₁-selective, -adrenergic blocking agent in slow i.v. injection.

Rogitine may augment the hypotensive effect of other antihypertensive agents. Antipsychotics may enhance the hypotensive effect of -adrenergic blocking agents.

Experience with Rogitine in pregnant women is not available. Do not use in pregnancy unless treatment is considered essential.

No information is available as to whether phentolamine passes into breast milk. For safety reasons, it is not recommended to use Rogitine during lactation.

Patients should be warned of the potential hazards of driving or operating machinery if they experience side effects such as dizziness and sedation.

Cardiovascular system: Frequent: Orthostatic hypotension and tachycardia. Occasional: Acute or prolonged hypotensive episodes (flushing, sweating and feelings of apprehension). Myocardial infarction, cerebrospasm, and cerebrovascular occlusion may occur under these circumstances. Rare: Anginal pain and cardiac arrhythmias.

Central nervous system: Occasional: Dizziness and weakness.

Gastro-intestinal tract: Occasional: Nausea, vomiting and diarrhoea.

Other organ systems: Occasional: Nasal stuffiness and flushing. Rare: Chest pain.

Symptoms: Arterial hypotension, reflex tachycardia, cardiac stimulation, arrhythmia, increase of systemic venous capacity, and possibly shock. These effects may be accompanied by headache, hyperexcitability and disturbances of vision, sweating, increased gastric motility, vomiting and diarrhoea, hypoglycaemia.

Treatment: Hypotension, excessive peripheral vasodilation: noradrenaline, in cautiously titrated continuous i.v. infusion, can be considered the physiological antagonist; the effect of Rogitine may wear off in a short time, and administration of noradrenaline may have to be adjusted accordingly. When a pressor agent is used, ECG should be monitored, as major arrhythmias may occur. Alternative measures such as keeping the patient's legs raised and administering a plasma expander should be implemented concomitantly. Do not use adrenaline since this may cause a further fall of blood pressure under the given conditions.

Disturbances of cardiac rhythm: adjust treatment to the nature of the arrhythmia.

Hypoglycaemia: Provide glucose iv until reaction is compensated.

Phentolamine is a competitive non-selective ₁ and ₂-adrenergic receptor blocker of relatively short duration. It causes vasodilation and a fall in blood pressure which is based upon the blockade of both postjunctional vascular ₁ and ₂-adrenoceptors. It also antagonises the vasoconstrictor response to noradrenaline and adrenaline infusions. Enhanced neural release of noradrenaline due to presynaptic ₂-blockade may contribute to the positive inotropic and chronotropic effects of Rogitine on cardiac muscle.

The administration of Rogitine intravenously to man produces transient declines in mean systemic vascular resistance and mean systemic arterial pressure as a result of dilatation in the arterial as well as in the venous vascular bed. These effects of Rogitine are accompanied by tachycardia, triggered by the baroreceptor reflex system and the autonomic nervous system.

The elimination of phentolamine from blood is rapid and does not follow first order kinetics. After two to four hours the concentration has fallen to about 15% of the peak value. At concentrations of 0.02 to 109μg/ml, 54% of phentolamine is bound to human serum proteins. Phentolamine is extensively metabolised, on average about 13% of a dose given by intravenous infusion is excreted unchanged in the urine. Phentolamine metabolism is more pronounced following oral administration than after intravenous administration.

According to the experimental data available, phentolamine did not reveal either a mutagenic or a teratogenic potential. Long-term carcinogenicity studies have not been conducted with phentolamine.

Water, sodium metabisulphite and glucose.

Rogitine should not be mixed with alkaline solutions.

5 Years

Store ampoules in the outer carton at 2 to 8°C. Do not freeze.

Glass ampoules in boxes of 5.

None

Alliance Pharmaceuticals Ltd

Avonbridge House

Bath Road

Chippenham

Wiltshire

SN15 2BB

PL16853/0012

25 June 1998

17/02/2006

Alliance, Alliance Pharmaceuticals and associated devices are registered Trademarks of Alliance Pharmaceuticals Ltd.