Prazosin Hydrochloride

INDICATIONS AND USAGE Prazosin hydrochloride capsules, USP are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including this drug. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Prazosin hydrochloride capsules, USP can be used alone or in combination with other antihypertensive drugs such as diuretics or beta-adrenergic blocking agents.

DOSAGE AND ADMINISTRATION The dose of prazosin hydrochloride capsules USP should be adjusted according to the patient’s individual blood pressure response. The following is a guide to its administration: Initial Dose 1 mg two or three times a day (see WARNINGS ). Maintenance Dose Dosage may be slowly increased to a total daily dose of 20 mg given in divided doses. The therapeutic dosages most commonly employed have ranged from 6 mg to 15 mg daily given in divided doses. Doses higher than 20 mg usually do not increase efficacy, however a few patients may benefit from further increases up to a daily dose of 40 mg given in divided doses. After initial titration some patients can be maintained adequately on a twice daily dosage regimen. Use With Other Drugs When adding a diuretic or other antihypertensive agent, the dose of prazosin hydrochloride capsules USP should be reduced to 1 mg or 2 mg three times a day and retitration then carried out. Concomitant administration of prazosin hydrochloride capsules USP with a PDE-5 inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension; therefore, PDE-5 inhibitor therapy should be initiated at the lowest dose in patients taking prazosin hydrochloride capsules USP.

CONTRAINDICATIONS Prazosin hydrochloride capsules are contraindicated in patients with known sensitivity to quinazolines, prazosin, or any of the inert ingredients.

ADVERSE REACTIONS Clinical trials were conducted on more than 900 patients. During these trials and subsequent marketing experience, the most frequent reactions associated with prazosin hydrochloride capsules therapy are: dizziness 10.3%, headache 7.8%, drowsiness 7.6%, lack of energy 6.9%, weakness 6.5%, palpitations 5.3%, and nausea 4.9%. In most instances, side effects have disappeared with continued therapy or have been tolerated with no decrease in dose of drug. Less frequent adverse reactions which are reported to occur in 1–4% of patients are: Gastrointestinal: vomiting, diarrhea, constipation. Cardiovascular: edema, orthostatic hypotension, dyspnea, syncope. Central Nervous System: vertigo, depression, nervousness. Dermatologic: rash. Genitourinary: urinary frequency. EENT: blurred vision, reddened sclera, epistaxis, dry mouth, nasal congestion. In addition, fewer than 1% of patients have reported the following (in some instances, exact causal relationships have not been established): Gastrointestinal: abdominal discomfort and/or pain, liver function abnormalities, pancreatitis. Cardiovascular: tachycardia. Central Nervous System: paresthesia, hallucinations. Dermatologic: pruritus, alopecia, lichen planus. Genitourinary: incontinence, impotence, priapism. EENT: tinnitus. Other: diaphoresis, fever, positive ANA titer, arthralgia. Single reports of pigmentary mottling and serous retinopathy, and a few reports of cataract development or disappearance have been reported. In these instances, the exact causal relationship has not been established because the baseline observations were frequently inadequate. In more specific slit-lamp and funduscopic studies, which included adequate baseline examinations, no drug-related abnormal ophthalmological findings have been reported. Literature reports exist associating prazosin hydrochloride capsules therapy with a worsening of pre-existing narcolepsy. A causal relationship is uncertain in these cases. In post-marketing experience, the following adverse events have been reported: Autonomic Nervous System: flushing. Body As A Whole: allergic reaction, asthenia, malaise, pain. Cardiovascular, General: angina pectoris, hypotension. Endocrine: gynecomastia. Heart Rate/Rhythm: bradycardia. Psychiatric: insomnia. Skin/Appendages: urticaria. Vascular (Extracardiac): vasculitis. Vision: eye pain. Special Senses: During cataract surgery, a variant of small pupil syndrome known as Intraoperative Floppy Iris Syndrome (IFIS) has been reported in association with alpha-1 blocker therapy (see PRECAUTIONS ). To report SUSPECTED ADVERSE REACTIONS, contact Lifestar Pharma LLC at 1-888-995-4337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Interactions Drug Interactions Prazosin hydrochloride capsules have been administered without any adverse drug interaction in limited clinical experience to date with the following: (1) cardiac glycosides‒digitalis and digoxin; (2) hypoglycemics‒insulin, chlorpropamide, phenformin, tolazamide, and tolbutamide; (3) tranquilizers and sedatives‒chlordiazepoxide, diazepam, and phenobarbital; (4) antigout‒allopurinol, colchicine, and probenecid; (5) antiarrhythmics‒procainamide, propranolol (see WARNINGS however), and quinidine; and (6) analgesics, antipyretics and anti-inflammatories-propoxyphene, aspirin, indomethacin, and phenylbutazone. Addition of a diuretic or other antihypertensive agent to prazosin hydrochloride capsules have been shown to cause an additive hypotensive effect. This effect can be minimized by reducing the prazosin hydrochloride capsules dose to 1 to 2 mg three times a day, by introducing additional antihypertensive drugs cautiously, and then by retitrating prazosin hydrochloride capsules based on clinical response. Concomitant administration of prazosin hydrochloride capsules with a phosphodiesterase-5 (PDE-5) inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension (see DOSAGE AND ADMINISTRATION ). Drug/Laboratory Test Interactions In a study on five patients given from 12 to 24 mg of prazosin per day for 10 to 14 days, there was an average increase of 42% in the urinary metabolite of norepinephrine and an average increase in urinary VMA of 17%. Therefore, false positive results may occur in screening tests for pheochromocytoma in patients who are being treated with prazosin. If an elevated VMA is found, prazosin should be discontinued and the patient retested after a month.

Drug Interactions Prazosin hydrochloride capsules have been administered without any adverse drug interaction in limited clinical experience to date with the following: (1) cardiac glycosides‒digitalis and digoxin; (2) hypoglycemics‒insulin, chlorpropamide, phenformin, tolazamide, and tolbutamide; (3) tranquilizers and sedatives‒chlordiazepoxide, diazepam, and phenobarbital; (4) antigout‒allopurinol, colchicine, and probenecid; (5) antiarrhythmics‒procainamide, propranolol (see WARNINGS however), and quinidine; and (6) analgesics, antipyretics and anti-inflammatories-propoxyphene, aspirin, indomethacin, and phenylbutazone. Addition of a diuretic or other antihypertensive agent to prazosin hydrochloride capsules have been shown to cause an additive hypotensive effect. This effect can be minimized by reducing the prazosin hydrochloride capsules dose to 1 to 2 mg three times a day, by introducing additional antihypertensive drugs cautiously, and then by retitrating prazosin hydrochloride capsules based on clinical response. Concomitant administration of prazosin hydrochloride capsules with a phosphodiesterase-5 (PDE-5) inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension (see DOSAGE AND ADMINISTRATION ).

DESCRIPTION Prazosin hydrochloride, USP a quinazoline derivative, is the first of a new chemical class of antihypertensives. It is the hydrochloride salt of 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furoyl) piperazine and its structural formula is: Molecular formula C 19 H 21 N 5 O 4 •HCl It is a white to tan powder, slightly soluble in water, practically insoluble in chloroform and acetone and has a molecular weight of 419.87. Each capsule, for oral administration, contains prazosin hydrochloride, USP equivalent (as the polyhydrate) to 1 mg, 2 mg or 5 mg of prazosin. Inert ingredients in the formulations are: colloidal silicon dioxide, lactose monohydrate, lactose anhydrous, magnesium stearate and microcrystalline cellulose. The empty hard gelatin capsules contain black iron oxide, gelatin, red iron oxide, titanium dioxide and yellow iron oxide. In addition, the 1 mg empty gelatin capsules contain D&C Yellow No. 10 and FD&C Green No. 3; the 2 mg empty gelatin capsules contain D&C Red No. 28, D&C Yellow No. 10, FD&C Blue No. 1 and FD&C Red No. 40; and the 5 mg empty gelatin capsules contain FD&C Blue No. 1. The capsules shells are imprinted in edible ink which contains concentrated ammonium solution, potassium hydroxide, propylene glycol, shellac and titanium dioxide. The structural formula for Prazosin hydrochloride, USP a quinazoline derivative, is the first of a new chemical class of antihypertensives. It is the hydrochloride salt of 1-(4-amino-6,7-dimethoxy-2-q

OVERDOSAGE Accidental ingestion of at least 50 mg of prazosin hydrochloride capsules in a two year old child resulted in profound drowsiness and depressed reflexes. No decrease in blood pressure was noted. Recovery was uneventful. Should overdosage lead to hypotension, support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by keeping the patient in the supine position. If this measure is inadequate, shock should first be treated with volume expanders. If necessary, vasopressors should then be used. Renal function should be monitored and supported as needed. Laboratory data indicate prazosin hydrochloride capsules are not dialysable because it is protein bound.

HOW SUPPLIED Prazosin Hydrochloride Capsules, USP are available containing prazosin hydrochloride, USP equivalent to 1 mg, 2 mg, or 5 mg of prazosin. The 1 mg capsule is White opaque cap/ white opaque body, hard gelatin capsule imprinted with on cap and "429" on body with black ink containing white to off white powder. They are available as follows: NDC 76420-523-10 bottles of 10 capsules. (repackaged from NDC 70756-429-XX) NDC 76420-523-20 bottles of 20 capsules. (repackaged from NDC 70756-429-XX) NDC 76420-523-30 bottles of 30 capsules. (repackaged from NDC 70756-429-XX) NDC 76420-523-60 bottles of 60 capsules. (repackaged from NDC 70756-429-XX) NDC 76420-523-90 bottles of 90 capsules. (repackaged from NDC 70756-429-XX) NDC 76420-523-01 bottles of 100 capsules. (relabeled from NDC 70756-429-11) The 2 mg capsule is Pink opaque cap/ Pink opaque body, hard gelatin capsule imprinted with on cap and "430" on body with black ink containing white to off white powder. They are available as follows: NDC 76420-525-10 bottles of 10 capsules. (repackaged from NDC 70756-430-XX) NDC 76420-525-20 bottles of 20 capsules. (repackaged from NDC 70756-430-XX) NDC 76420-525-30 bottles of 30 capsules. (repackaged from NDC 70756-430-XX) NDC 76420-525-60 bottles of 60 capsules. (repackaged from NDC 70756-430-XX) NDC 76420-525-90 bottles of 90 capsules. (repackaged from NDC 70756-430-XX) NDC 76420-525-01 bottles of 100 capsules. (relabeled from NDC 70756-430-11) The 5 mg capsule is Blue opaque cap/ Blue opaque body, hard gelatin capsule imprinted with on cap and "440" on body with black ink containing white to off white powder. They are available as follows: NDC 76420-526-10 bottles of 10 capsules. (repackaged from NDC 70756-440-XX) NDC 76420-526-20 bottles of 20 capsules. (repackaged from NDC 70756-440-XX) NDC 76420-526-30 bottles of 30 capsules. (repackaged from NDC 70756-440-XX) NDC 76420-526-60 bottles of 60 capsules. (repackaged from NDC 70756-440-XX) NDC 76420-526-90 bottles of 90 capsules. (repackaged from NDC 70756-440-XX) NDC 76420-526-01 bottles of 100 capsules. (relabeled from NDC 70756-440-11) Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from light. Dispense in a tight, light-resistant container as defined in the USP Keep this and all medication out of the reach of children. Image Image Image