PHENTOSOL (Phentolamine Mesilate) is an antihypertensive, for intravenous and intramuscular administration. Chemically Phentolamine Mesilate is 3-[[(4,5-Dihydro-1H-imidazol-2-yl)methyl](4-methylphenyl)amino]phenol methanesulfonate. Its molecular formula is C₁₈H₂₃N₃O₄S and molecular weight is 377.5.

STRUCTURAL FORMULA :
Its structural formula is :

PHENTOSOL is a clear colourless to pale yellow solution filled in amber glass ampoule of suitable size.

COMPOSITION :
Each ml contains :
Phentolamine Mesilate B.P.            10 mg
Anhydrous Glucose B.P.                       q.s.
Water for Injections B.P.                        q.s.

ACTIONS :
Phentolamine Mesilate produces an alpha-adrenergic block of relatively short duration. It also has direct, but less marked, positive inotropic and chronotropic effects on cardiac muscle and vasodilator effects on vascular smooth muscle.

PHARMACOKINETICS :
Following intravenous administration, the half-life of phentolamine has been reported to be 19 minutes. It is extensively metabolised and about 13 % of an intravenous dose is excreted unchanged in the urine.

INDICATIONS : 
PHENTOSOL is indicated for the prevention or control of hypertensive episodes that may occur in a patient with pheochromocytoma as a result of stress or manipulation during preoperative preparation and surgical excision. PHENTOSOL is indicated for the prevention or treatment of dermal necrosis and sloughing following intravenous administration or extravasation of norepinephrine. PHENTOSOL is also indicated for the diagnosis of pheochromocytoma by the phentolamine blocking test.

For Intravenous and Intramuscular use only.

INSTRUCTIONS FOR USE OF AMPOULE :

The ampoule used in this product is equipped with O.P.C (One Point Cut) opening system. No ampoule file is needed to open the ampoule. The neck of the ampoule is prescored at the point of constriction. A coloured dot on the ampoule head helps to orientate the ampoule. Take the ampoule and face the coloured dot. Let the solution at the head of the ampoule to flow down by shaking or a gentle stroke. The ampoule opens easily by placing the thumb on the coloured dot and gently pressing downwards as shown.

 

1.Prevention or control of hypertensive episodes in the patient with pheochromocytoma.

For preoperative reduction of elevated blood pressure, 5 mg of Phentolamine Mesilate (1 mg for  children) is injected intravenously or intramuscularly 1 or 2 hours before surgery and repeated if necessary. During surgery, Phentolamine Mesilate (5 mg for adults, 1 mg for children) is administered intravenously as indicated, to help prevent or control paroxysms of hypertension, tachycardia, respiratory depression, convulsions, or other effects of epinephrine intoxication. (Postoperatively, norepinephrine may be given to control the hypotension that commonly follows complete removal of a pheochromocytoma.)

 

2. Prevention or treatment of dermal necrosis and sloughing following intravenous administration or extravasation of norepinephrine.

For Prevention : 10 mg of Phentolamine Mesilate is added to each liter of solution containing norepinephrine. The pressor effect of norepinephrine is not affected.

For Treatment : 5 to 10 mg of Phentolamine Mesilate in 10 ml of saline is injected into the area of extravasation within 12 hours.

 

3.Diagnosis of pheochromocytoma - phentolamine blocking test.

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

 

a.Intravenous

Preparation : 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 preformed on a patient who is normotensive.

Procedure : The patient is kept at rest in a supine position throughout the test, preferably in a quiet, darkened room. Injection of phentolamine is delayed until blood pressure is stabilized, as evidenced by blood pressure readings taken every 10 minutes for at least 30 minutes. The dose for adults is 5 mg; for children, 1 mg. The syringe needle is inserted into the vein and injection is delayed until pressor response to venipuncture has subsided. Phentolamine 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 pheochromocytoma, is indicated when the blood pressure is reduced more than 35 mm Hg systolic and 25 mm Hg diastolic. A typical positive response is a reduction in pressure of 60 mm Hg systolic and 25 mm Hg diastolic. Usually, maximal effect is evident within 2 minutes after injection. A return to preinjection pressure commonly occurs within 15 to 30 minutes but may occur more rapidly. If blood pressure decreases to a dangerous level, the patient should be treated as outlined under OVERDOSAGE. A positive response should always be confirmed by other diagnostic procedures, preferably by measurement of urinary catecholamines or their metabolites. A negative response is indicated when the blood pressure is elevated, unchanged, or reduced less than 35 mm Hg systolic and 25 mm Hg diastolic after injection of phentolamine. A negative response to this test does not exclude the diagnosis of pheochromocytoma, especially in patients with paroxysmal hypertension in whom the incidence of false-negative responses is high.

 

b.Intramuscular

If the intramuscular test for pheochromocytoma is preferred, preparation is the same as for the intravenous test. The dose for adults is 5 mg intramuscularly; for children, 3 mg. 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 35 mm Hg systolic and 25 mm Hg diastolic, or more, within 20 minutes following injection.

 

CONTRAINDICATIONS : 

Myocardial infarction, history of myocardial infarction, coronary insufficiency, angina, or other evidence suggestive of coronary artery disease; hypersensitivity to phentolamine or related compounds.

 

WARNINGS :

Myocardial infarction, cerebrovascular spasm and cerebrovascular occlusion have been reported to occur following the administration of phentolamine, usually in association with marked hypotensive episodes. For screening tests in patients with hypertension, the generally available urinary assay of catecholamines or other biochemical assays have largely replaced the phentolamine and other pharmacological tests for reasons of accuracy and safety. None of the chemical or pharmacological tests is infallible in the diagnosis of pheochromocytoma. The phentolamine blocking test is not the procedure of choice and should be reserved for cases in which additional confirmatory evidence is necessary and the relative risks involved in conducting the test have been considered.

Phentosol contains Sodium Metabisulfite, which may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than non-asthmatic people.

 

PRECAUTIONS :

PHENTOSOL should not generally be given to patients with angina pectoris or other evidence of ischaemic heart disease. Care should be taken in patients with peptic ulcer disease, which may be exacerbated.

 

General :

Tachycardia and cardiac arrhythmias may occur with the use of phentolamine or other alpha-adrenergic blocking agents. When possible, administration of cardiac glycosides should be deferred until cardiac rhythm returns to normal.

Pregnancy : Category C
There are no adequate and well-controlled studies in pregnant women. PHENTOSOL should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

Nursing Mothers : 
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from PHENTOSOL, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

INTERACTIONS :
Since phentolamine only blocks alpha-receptors, concomitant use of drugs such as adrenaline may lead to severe hypotension and tachycardia due to unopposed beta-adrenoreceptor stimulation.

SIDE  EFFECTS :
The adverse effects of phentolamine are primarily due to its alpha-adrenoceptor blocking activity and include orthostatic hypotension and tachycardia. Myocardial infarction and cerebrovascular spasm or occlusion have been reported occasionally, usually in association with marked hypotension; flushing, sweating and feelings of apprehension may accompany hypotensive episodes. Anginal pain and arrhythmias have been reported rarely. Nausea, vomiting and diarrhoea may also occur. Other side effects include weakness, dizziness, flushing and nasal stuffiness.

OVERDOSAGE : 
Acute Toxicity : 
No deaths due to acute poisoning with phentolamine have been reported. Oral LD50s (mg/kg) : mice, 1000; rats, 1250.

Signs and Symptoms :
Overdosage with phentolamine is characterized chiefly by cardiovascular disturbances, such as arrhythmias, tachycardia, hypotension and possibly shock. In addition, the following might occur : excitation, headache, sweating, pupillary contraction, visual disturbances; nausea, vomiting, diarrhoea; hypoglycaemia.

TREATMENT OF OVERDOSAGE : 
There is no specific antidote. A decrease in blood pressure to dangerous levels or other evidence of shock like conditions should be treated vigorously and promptly. The patients legs should be kept raised and a plasma expander should be administered. If necessary, intravenous infusion or norepinephrine, titrated to maintain blood pressure at the normotensive level and all available supportive measures should be included. Epinephrine should not be used, since it may cause a paradoxical reduction in blood pressure.

PHARMACEUTICAL PRECAUTIONS :
Product should be inspected visually for particulate matter and discoloration prior to administration. Discard the solution if it is discoloured or contain particulate matter. 

STORAGE :
Store below 30°C (86°F), protected from light. 
Do not refrigerate.

SHELF LIFE :
24 months from the date of manufacture.

PRESENTATION :
PHENTOSOL is supplied as 10 mg of Phentolamine Mesilate B.P. in 1 ml aqueous solution. 
Such 3 ampoules of 1 ml are packed in a Box.

Disclaimer : For the use of a Registered Medical Practitioner or a Hospital or a Institution only. Also it is not intended to be used by healthcare professionals or patients for the purpose of prescribing or administering these products. Questions regarding the complete and current content of product labeling / specification / presentation should be directed to SGPharma.