Phentolamine

281.35

281.35

200-053-1

Z468598HBV

DTXSID4023462

C62066

Crystals

C - Cardiovascular system|V - Various

2933290090

47.9

3.3

Solid

1.2±0.1 g/cm3

174-175 °C

551.0±45.0 °C at 760 mmHg

287.0±28.7 °C

1.626

2.72e-01 g/L

Store in tight container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity.

9.83X10-11 mm Hg at 25 deg C (est)

LD50 orl-rat: 1250 mg/kg PSEBAA 71,70,49

Henry's Law constant = 2.15X10-14 atm-cu m/mol at 25 °C (est)

log Kow = 0.31 at pH 7.5|White or slightly grayish, crystalline powder /Perphanzine hydrochloride/|Crystals; MP 177-181 °C. One gram dissolves in 50 mL water, 23 mL alcohol, 660 mL chloroform. pH of 1% aqueous solution 4.5 to 5.5. Aqueous solutions cannot be stored. /Phentolamine methanesulfonate/|White crystalline powder /Mesylate/|Hydroxyl radical reaction rate constant = 2.82X10-10 cu m/molec-sec at 25 °C (est)

II

8

UN 3264 8/PG 2

3

S26-S36/37/39-S45-S8-S25

SL0700000

Following reconstitution of the commercially available lyophilized powder with sterile water for injection to a concentration of 5 mg/mL, phentolamine mesylate injection is stable for 48 hours at room temperature or 1 week at 2-8 deg C; however, the manufacturer recommends that the reconstituted injection be used immediately and not stored.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including phentolamine mesylate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Phentolamine mesylate/

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P280, P301+P312, P302+P352, P305+P351+P338, P321, P330, P332+P313, P337+P313, P362, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Use a NIOSH-approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.|Wear approved respiratory protection, chemically compatible gloves, and protective clothing.

Water spray, dry chemical, carbon dioxide, or foam as appropriate for surrounding fire and materials.|As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.

Wipe up spillage or collect spillage using a high- efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site.

Engineering controls such as exhaust ventilation are recommended.|This material is assumed to be combustible. As with all dry powders, it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.|As a general rule, when handling USP Reference Standards, avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.|SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.|For more Preventive Measures (Complete) data for Phentolamine (7 total), please visit the HSDB record page.

Possible eye, skin, gastrointestinal, and/or respiratory tract irritation.

PIMOZIDE WAS A POTENT ANTAGONIST OF (+)AMPHETAMINE, DIETHYLPROPION, MAZINDOL & PHENTERMINE ANOREXIA IN MOUSE. PHENTOLAMINE & PROPRANOLOL PRODUCED NO SUCH ANTAGONISM, BUT EITHER POTENTIATED OR HAD NO EFFECT ON DRUG-INDUCED ANOREXIA.

LD50 Rat oral 1250 mg/kg|LD50 Mouse oral 1000 mg/kg

Examples of tyramine-containing food includes aged cheese, red wine, avocados, bananas, chocolate, prepared meats and sauerkraut /Tyramine/

Used as an aid for the diagnosis of pheochromocytoma, and may be administered immediately prior to or during pheochromocytomectomy to prevent or control paroxysmal hypertension resulting from anesthesia, stress, or operative manipulation of the tumor. Phentolamine has also been used to treat hypertensive crisis caused by sympathomimetic amines or catecholamine excess by certain foods or drugs in patients taking MAO inhibitors, or by clonidine withdrawal syndrome. Other indications include the prevention of dermal necrosis and sloughing following IV administration or extravasation of norepinephrine, decrease in impedance to left ventricular ejection and the infarct size in patients with MI associated with left ventricular failure, treatment of erectile dysfunction through self-injection of small doses combined with papaverine hydrochloride into the corpus cavernosum, and as an adjunct to the management of cocaine overdose to reverse coronary vasoconstriction following use of oxygen, benzodiazepines,and nitroglycerin.

Adrenergic alpha-Antagonists; Antihypertensive Agents; Sympatholytics|Phentolamine is used mainly in the diagnosis of pheochromocytoma and to control or prevent paroxysmal hypertension immediately prior to or during pheochromocytomectomy. /Use included in US product label/|OraVerse is indicated for the reversal of soft-tissue anesthesia, i.e., anesthesia of the lip and tongue, and the associated functional deficits resulting from an intraoral submucosal injection of a local anesthetic containing a vasoconstrictor. /Use included in US product label/|Although no single chemical or pharmacological test is completely reliable, determinations of blood concentrations of catecholamines and/or urinary excretion of catecholamines or their metabolites are the safest and most reliable methods for the diagnosis of pheochromocytoma. The phentolamine test may be used when additional confirmatory evidence of pheochromocytoma is required and the potential benefits of the test outweigh the possible risks. The phentolamine test is more reliable in detecting pheochromocytomas in patients with sustained hypertension than in those with paroxysmal hypertension and is of no value in patients who are not hypertensive at the time of the test. Sudden and marked reduction in blood pressure following parenteral administration of phentolamine to a hypertensive patient suggests the presence of a pheochromocytoma. However, false-negative and false-positive responses to the phentolamine test occur frequently. /Use included in US product label/|For more Therapeutic Uses (Complete) data for Phentolamine (10 total), please visit the HSDB record page.

Phentolamine may cause acute and prolonged hypotension, tachycardia, cardiac arrhythmias, and angina, especially after parenteral administration. Myocardial infarction and cerebrovascular spasm or occlusion, usually in association with marked hypotension and a shock-like state, have been reported occasionally following parenteral administration of phentolamine. Deaths have occurred after IV administration of phentolamine for the diagnosis of pheochromocytoma.|Weakness, dizziness, flushing, orthostatic hypotension, and nasal congestion have been reported in patients receiving phentolamine. Adverse GI effects are common and include abdominal pain, nausea, vomiting, diarrhea, and exacerbation of peptic ulcer; these adverse effects generally prevent long-term administration of phentolamine.|Intracavernous injection /not approved in the US/ of combined phentolamine and papaverine for the treatment of impotence occasionally has caused priapism. Priapism is a medical emergency that could result in penile tissue damage and permanent loss of potency if not treated immediately, and therefore, patients should be advised to report promptly to their physician or, if unavailable, to seek alternative immediate medical attention if an erection that persists longer than 4 hours or that is extremely painful occurs. ... Other complications of intracavernous injection of combined phentolamine and papaverine have included transient pain, including referred pain to the glans, burning, and paresthesia. Penile ecchymosis has occurred in many patients, and superficial hematoma and bruising of the penis also have occurred. Fibrotic changes (e.g., induration, lumpy areas of the penis but not necessarily at the injection site), including bilateral fibrosis of the corpora cavernosa, also have been reported. Embolus in the glans has been reported rarely, and the development of priapism, deep vein thrombosis, and fatal pulmonary embolus occurred in one patient. Adverse systemic effects of the drugs (e.g., facial flushing, dizziness, decreased systemic blood pressure, metallic taste) also have occurred.|It is not known whether phentolamine mesylate is distributed into milk. Because of the potential for serious adverse reactions to phentolamine mesylate in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.|For more Drug Warnings (Complete) data for Phentolamine (7 total), please visit the HSDB record page.

Phentolamine is indicated for the control of episodes of hypertension and sweating that occur with a disease called pheochromocytoma. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly. Phentolamine is a long-acting, adrenergic, alpha-receptor blocking agent which can produce and maintain "chemical sympathectomy" by oral administration. It increases blood flow to the skin, mucosa and abdominal viscera, and lowers both supine and erect blood pressures. It has no effect on the parasympathetic system. Phentolamine works by blocking alpha receptors in certain parts of the body. Alpha receptors are present in the muscle that lines the walls of blood vessels. When the receptors are blocked by Phentolamine, the muscle relaxes and the blood vessels widen. This widening of the blood vessels results in a lowering of blood pressure.

Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma. (See all compounds classified as Adrenergic alpha-Antagonists.)|Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)

10-13% of the drug is excreted unchanged in urine, and the fate of the remainder of the drug is unknown.|The Tmax is 30 to 60 minutes. Protein binding is less than 72%. It undergoes extensive hepatic metabolism, 80% renal excretion (10% to 13% excreted as unchanged drug) and 20% fecal excretion.|Phentolamine is only about 20% as active after oral administration as after parenteral administration. About 10% of a parenteral dose can be recovered in the urine as active drug; the fate of the remainder is not known. It is not known whether the drug crosses the placenta or appears in milk.

Phentolamine has known human metabolites that include [3-[N-(4,5-dihydro-1H-imidazol-2-ylmethyl)-4-methylanilino]phenyl] hydrogen sulfate.

19 minutes|The elimination half life /of phentolamine/ is 19 minutes after intravenous administration, 5 to 7 hours after oral administration.

Phentolamine produces its therapeutic actions by competitively blocking alpha-adrenergic receptors (primarily excitatory responses of smooth muscle and exocrine glands), leading to a muscle relaxation and a widening of the blood vessels. This widening of the blood vessels results in a lowering of blood pressure. The action of phentolamine on the alpha adrenergic receptors is relatively transient and the blocking effect is incomplete. The drug is more effective in antagonizing responses to circulating epinephrine and/or norepinephrine than in antagonizing responses to mediator released at the adrenergic nerve ending. Phentolamine also stimulates β-adrenergic receptors and produces a positive inotropic and chronotropic effect on the heart and increases cardiac output.|Phentolamine inhibits responses to adrenergic stimuli by competitively blocking a-adrenergic receptors (primarily excitatory responses of smooth muscle and exocrine glands), but the action of the drug is relatively transient and a-adrenergic blockade is incomplete. Phentolamine has greater a-adrenergic blocking effects than does tolazoline. Phentolamine is more effective in antagonizing responses to circulating epinephrine and/or norepinephrine than in antagonizing responses to mediator released at the adrenergic nerve ending. The drug causes peripheral vasodilation and decreases peripheral resistance, primarily by direct relaxation of vascular smooth muscle, but a-adrenergic blockade also contributes to vasodilation. Phentolamine also stimulates beta-adrenergic receptors and produces a positive inotropic and chronotropic effect on the heart and increases cardiac output.|DIFFERENCES IN PLASMA GLUCOSE & LACTOSE OBSERVED SUGGEST PROTECTION OF HEPATIC METABOLISM IN PHENTOLAMINE-TREATED ENDOTOXIC RATS (FASTED MALE RATS ADMIN E COLI ENDOTOXIN 25 MG/KG/IP) BY PREVENTION OF EXCESSIVE HEPATIC HYPOXIA.|INFUSION OF PHENTOLAMINE AUGMENTED ACUTE INSULIN RESPONSE & GLUCOSE TOLERANCE.|COMPARISON OF CARDIOVASCULAR ACTIONS OF DIHYDRALAZINE, PHENTOLAMINE, & PRAZOSIN IN SPONTANEOUSLY HYPERTENSIVE RATS IS DISCUSSED.|For more Mechanism of Action (Complete) data for Phentolamine (8 total), please visit the HSDB record page.

Treatment. There is no specific antidote. A decrease in blood pressure to dangerous levels or other evidence of shocklike conditions should be treated vigorously and promptly. The patient's legs should be kept raised and a plasma expander should be administered. If necessary, intravenous infusion of 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.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ Phentolamine may cause acute and prolonged hypotension, tachycardia, cardiac arrhythmias, and angina, especially after parenteral administration. Myocardial infarction and cerebrovascular spasm or occlusion, usually in association with marked hypotension and a shock-like state, have been reported occasionally following parenteral administration of phentolamine. Deaths have occurred after IV administration of phentolamine for the diagnosis of pheochromocytoma.|/SIGNS AND SYMPTOMS/ Overdosage with Regitine 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, diarrhea; hypoglycemia.|/SIGNS AND SYMPTOMS/ Intracavernous injection /not approved in the US/ of combined phentolamine and papaverine for the treatment of impotence occasionally has caused priapism. Priapism is a medical emergency that could result in penile tissue damage and permanent loss of potency if not treated immediately, and therefore, patients should be advised to report promptly to their physician or, if unavailable, to seek alternative immediate medical attention if an erection that persists longer than 4 hours or that is extremely painful occurs. ...

Fentolamin

For injection, powder, lyophilized, for suspension: vials each containing 5 mg of phentolamine mesylate for injection, USP, and 25 mg of mannitol, USP, inlyophilized form, Regitine (Novartis).|For injection, solution for submucosal use: 0.4 mg/1.7 mL solution per cartridge, OraVerse (Novalar).|Parenteral: For injection: 5 mg Phentolamine Mesylate for Injection (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name). /Phentolamine mesylate/

No longer widely used because of its side effects /which include arrhythmia and tachycardia/.

HPLC determination in biological samples

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals