Prazosin hydrochloride

419.86

419.136017

242-903-4

X0Z7454B90

757286|292810

DTXSID50172822

C1507

White to tan powder

2934990002

107

3.17070

white solid

258-259 °C (decomp)

638.4°C at 760 mmHg

339.9ºC

soluble in dimethyl sulfoxide, ethanol, water, methanol.

Store at RT

3.4E-16mmHg at 25°C

193.4 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

III

6.1(b)

3249

3

22-36/37/38-62

28-36

VA1350000

Xn

Prazosin hydrochloride capsules should be stored in well closed, light resistant containers at 15-30 deg C.

P280-P301 + P312 + P330-P305 + P351 + P338

H302-H315-H319-H335-H361

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).|The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl prazosin hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Khoury AF, Kaplan NM; Alpha-blocker Therapy of Hypertension. An Unfulfilled Promise. JAMA 266 (3): 394-8 (1991). For various reasons, the alpha 1-receptor blocker prazosin has been used infrequently as initial therapy for hypertension. A summary of the published data on efficacy, side effects, and special properties of alpha 1-receptor blockers indicates that they will probably be used more extensively, particularly because of their ability to improve lipid and glucose-insulin metabolism.

|Warning|H302 (56.76%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P261, P264, P270, P271, P280, P281, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P314, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 74 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

When prazosin is administered with diuretics or other hypotensive agents, particularly beta-adrenergic blocking agents (eg, propranolol), the hypotensive effect of prazosin may be increased.|... prazosin hydrochloride has been administered without any adverse drug interaction in limited clinical experience to date with the following: cardiac glycosides -- digitalis and digoxin; hypoglycemics -- insulin, chlorpropamide, phenformin, tolazamide, and tolbutamide; tranquilizers and sedatives -- chlordiazepoxide, diazepam, phenobarbital; antigout -- allopurinol, colchicine, and probenecid; antiarrhythmics -- procainamide, propranolol and quinidine; analgesics, antipyretics and anti-inflammatories -- propoxyphene, aspirin, indomethacin, and phenylbutazone.

/Prazosin hydrochloride/ has been shown to be excreted in small amounts in human milk.

Adrenergic alpha-Antagonists; Antihypertensive Agents; Sympatholytics|Prazosin hydrochloride is used in the management of hypertension. Prazosin's efficacy in hypertensive patients is similar to that of thiazide diuretics, beta-adrenergic blocking agents, hydralazine, and centrally acting adrenergic inhibitors (eg, clonidine, methyldopa). ... Prazosin has been shown to be effective in the management of hypertension in patients undergoing chronic hemodialysis, and the drug may be particularly useful in the acute management of severe hypertension in patients with increased concentrations of circulating catecholamines.|Prazosin has been used with good results alone or in combination with a beta-adrenergic blocking agent for the preoperative management of the signs and symptoms of pheochromocytoma in a limited number of patients; however, these patients may be particularly susceptible to a marked hypotensive response to the initial dose of prazosin. Limited data also suggest that prazosin may be useful for the treatment of Raynaud's disease or phenomenon and ergotamine induced peripheral ischemia.|Prazosin may be used as an adjunct to digoxin and diuretics for the treatment of congestive heart failure. However, prazosin has not been shown to improve survival in these patients. /NOT included in US product labeling/|For more Therapeutic Uses (Complete) data for PRAZOSIN HYDROCHLORIDE (11 total), please visit the HSDB record page.

May cause syncope with sudden loss of consciousness, usually attributable to an excessive postural hypotensive effect; risk may be reduced by limiting the initial dose of the drug to 1 mg, and by subsequently increasing the dosage slowly. Adverse reactions include dizziness, drowsiness, and other CNS effects; patients should be cautioned regarding activities such as driving and operating machinery, as well as interactions with other CNS acting drugs including alcohol. Other adverse reactions include palpitations and nausea. The concurrent use of a beta-adrenergic blocking agent may increase the risk of hypotension. /Prazosin hydrochloride/|When prazosin is used as a fixed-combination preparation that includes polythiazide, the cautions, precautions, and contraindications associated with thiazide diuretics must be considered in addition to those associated with prazosin.|Caution should be used when adding prazosin to a preexisting antihypertensive regimen or when adding other hypotensive agents to a prazosin regimen in order to avoid a possible rapid fall in blood pressure. Caution should be used when administering prazosin to patients with chronic renal failure as they may require only small doses of the drug.|Prazosin has been used alone or in combination with other hypotensive agents for the management of severe hypertension in a limited number of pregnant women without apparent adverse effect on the fetus. There are no adequate and well controlled studies to date using prazosin in pregnant women, however, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.|For more Drug Warnings (Complete) data for PRAZOSIN HYDROCHLORIDE (18 total), please visit the HSDB record page.

Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS. (See all compounds classified as Adrenergic alpha-1 Receptor 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.)

There is intraindividual and interindividual variation in the rate of absorption and plasma concentrations of prazosin. The absolute oral bioavailability of prazosin is also variable but is reported to average about 60% (range: 43-82%). Results of one study indicate that the presence of food may delay absorption of the drug in some patients, but does not affect the extent of absorption.|Following oral administration of prazosin hydrochloride, plasma concentrations of the drug reach a peak in 2-3 hrs in most fasting patients. Plasma concentrations of prazosin generally do not correlate with therapeutic effect. One manufacturer reports that plasma concentrations of the drug after a single 5 mg dose range from 0.01-0.075 ug/ml. Blood pressure begins to decrease within 2 hr after an oral dose; the maximum decrease occurs in 2-4 hr. The hypotensive effect of prazosin lasts less than 24 hr.|Animal studies indicate that prazosin is widely distributed in body tissues. After iv administration in dogs, highest concentrations of the drug are found in the lungs, coronary arteries, aorta, paw arteries and heart; the lowest concentrations are in the brain. During prazosin therapy, approximately 97% of the drug in plasma is bound to proteins. It is not known whether the drug crosses the placenta. Prazosin is distributed into milk in small amounts.|Approximately 6-10% of a dose is excreted in urine and the remainder in feces via bile.|The drug /prazosin hydrochloride/ is tightly bound to plasma proteins (primarily alpha1-acid glycoprotein), and only 5% of the drug is free in the circulation; diseases that modify the concentration of this protein (e.g., inflammatory processes) may change the free fraction. Prazosin is extensively metabolized in the liver, and little unchanged drug is excreted by the kidneys.

Animal studies show that prazosin hydrochloride is metabolized extensively in the liver, principally by demethylation and conjugation, and excreted as unchanged drug (5-11%) and metabolites. Four of the metabolites have been shown to possess 10-25% of the hypotensive activity of prazosin and they may contribute to the antihypertensive effect of the drug.|The 6-O-demethyl and 7-O-demethyl analogues of the new antihypertensive drug prazosin [2-[4-(2-furoyl)-piperazin-1-yl]-4-amino-6,7-dimethoxyquinazoline hydrochloride] have been unequivocally synthesized via separate 10-step reaction sequences starting from isovanillin and vanillin, respectively. The 6-O-demethyl derivative was found to be identical with the major prazosin metabolite formed in dog and rat, while the 7-O-demethyl derivative was identical with another, less prevalent but significant metabolite. Two minor metabolites of prazosin, 2-(1-piperazinyl)-4-amino-6,7-dimethoxyquinazoline and 2,4-diamino-6,7-dimethoxyquinazoline, are also described. All 4 metabolites are less potent blood pressure lowering agents in dogs than prazosin but may contribute to its antihypertensive effect, since they account for a major portion of the administered dose.

Elimination half-life approx 3 hr.|The plasma half-life of prazosin after oral administration has been reported to be 2-4 hr.

Animal studies indicate that prazosin does not have its antihypertensive effect in the CNS. Prazosin does not interfere with nerve impulse transmission across sympathetic ganglia nor does it cause adrenergic neuronal blockade.|The exact mechanism of the hypotensive action of prazosin is unknown. Prazosin causes a decrease in total peripheral resistance and was originally thought to have a direct relaxant action on vascular smooth muscle. Animal studies have suggested that the vasodilator effect of prazosin is also related to blockade of postsynaptic alpha-adrenoceptors. The results of dog forelimb experiments demonstrate that that the peripheral vasodilator effect of prazosin is confined mainly to the level of the resistance vessels (arterioles). Unlike conventional alpha- blockers, the antihypertensive action of prazosin is usually not accompanied by reflex tachycardia.|Prazosin ... is a very potent and selective alpha 1-adrenergic antagonist. ... Interestingly, the drug also is a relatively potent inhibitor of cyclic nucleotide phosphodiesterases...

Treatment with supportive care including intravenous fluid boluses and vasopressors such as dopamine were effective in the few overdose cases reported.|Maintain an open airway and assist ventilation if necessary.Hypotension usually respondes to supine positioning and iv crystalloid fluids. Occasionally pressor therapy is needed. there is no specific antidote. Administer activated charcoal.

/HUMAN EXPOSURE STUDIES/ In overdosage, hypotension and CNS depression ranging from lethargy to coma are reported. In addition, priapism may occur.|/CASE REPORTS/ Ingestion of at least 50 mg of prazosin by a 2 yr old child produced profound drowsiness and depressed reflexes. There was no decrease in blood pressure and recovery was uneventful. A 19 yr old man who ingested approximately 200 mg of prazosin had normal CNS responses and slightly decreased blood pressure.

Furazosin

Oral Capsules, 1 mg (of prazosin), Minipress, Pifizer; 2 mg (of prazosin), Minipress, Pifzer; 5 mg (of prazosin), Minipress, Pifizer.|Oral Capsules, 1 mg (of prazosin) with Polythiazide 0.5 mg, Minizide 1, Pifizer; 2 mg (of prazosin) with Polythiazide 0.5 mg, Minizide 2, Pfizer; 5 mg (of prazosin) with Polythiazide 0.5 mg, Minizide 5, Pfizer.|Capsules, 1, 2, and 5 mg /Prazosin HCl/|1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furanylcarbonyl)piperazine.|2-(4-(2-FUROYL)PIPERAZIN-1-YL)-4-AMINO-6,7-DIMETHOXYQUINAZOLINE

Analyte: prazosin hydrochloride; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: prazosin hydrochloride; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards|Analyte: prazosin hydrochloride; matrix: chemical identification; procedure: thin-layer chromatography with detection using short-wavelength ultraviolet light and comparison to standards|Analyte: prazosin hydrochloride; matrix: chemical identification; procedure: visual reaction (precipitate) with silver nitrate|For more Analytic Laboratory Methods (Complete) data for PRAZOSIN HYDROCHLORIDE (7 total), please visit the HSDB record page.

HPLC-fluorescence analysis of prazosin in plasma.|Determination of prazosin in plasma or serum using a HPLC method with a fluorescence detector at 246 nm and an emission filter with a cutoff wavelength of 389 nm. Flow rate is 2.5 ml/min.

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