Prazosin Hydrochloride 5 mg Capsule, 250-count — NDC 46708-693-61 (Billing 46708-0693-61)

WARNINGS As with all alpha-blockers, prazosin hydrochloride may cause syncope with sudden loss of consciousness. In most cases, this is believed to be due to an excessive postural hypotensive effect, although occasionally the syncopal episode has been preceded by a bout of severe tachycardia with heart rates of 120 to 160 beats per minute. Syncopal episodes have usually occurred within 30 to 90 minutes of the initial dose of the drug; occasionally, they have been reported in association with rapid dosage increases or the introduction of another antihypertensive drug into the regimen of a patient taking high doses of prazosin hydrochloride.

The incidence of syncopal episodes is approximately 1% in patients given an initial dose of 2 mg or greater. Clinical trials conducted during the investigational phase of this drug suggest that syncopal episodes can be minimized by limiting the initial dose of the drug to 1 mg, by subsequently increasing the dosage slowly, and by introducing any additional antihypertensive drugs into the patient’s regimen with caution (see DOSAGE AND ADMINISTRATION). Hypotension may develop in patients given prazosin hydrochloride who are also receiving a beta-blocker such as propranolol.

If syncope occurs, the patient should be placed in the recumbent position and treated supportively as necessary. This adverse effect is self-limiting and in most cases does not recur after the initial period of therapy or during subsequent dose titration. Patients should always be started on the 1 mg capsules of prazosin hydrochloride.

The 2 and 5 mg capsules are not indicated for initial therapy. More common than loss of consciousness are the symptoms often associated with lowering of the blood pressure, namely, dizziness and lightheadedness. The patient should be cautioned about these possible adverse effects and advised what measures to take should they develop.

The patient should also be cautioned to avoid situations where injury could result should syncope occur during the initiation of prazosin hydrochloride therapy. Priapism Prolonged erections and priapism have been reported with alpha-1 blockers including prazosin in post marketing experience. In the event of an erection that persists longer than 4 hours, seek immediate medical assistance.

If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result.

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 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 to 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 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 FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions Prazosin hydrochloride has 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 has been shown to cause an additive hypotensive effect. This effect can be minimized by reducing the prazosin hydrochloride dose to 1 to 2 mg three times a day, by introducing additional antihypertensive drugs cautiously, and then by retitrating prazosin hydrochloride based on clinical response. Concomitant administration of prazosin hydrochloride 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.

Laboratory Tests In clinical studies in which lipid profiles were followed, there were generally no adverse changes noted between pre- and post-treatment lipid levels.

PRECAUTIONS General Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in some patients treated with alpha-1 blockers. This variant of small pupil syndrome is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs, and potential prolapse of the iris toward the phacoemulsification incisions. The patient’s ophthalmologist should be prepared for possible modifications to the surgical technique, such as the utilization of iris hooks, iris dilator rings, or viscoelastic substances.

There does not appear to be a benefit of stopping alpha-1 blocker therapy prior to cataract surgery. Information for Patients: Dizziness or drowsiness may occur after the first dose of this medicine. Avoid driving or performing hazardous tasks for the first 24 hours after taking this medicine or when the dose is increased.

Dizziness, lightheadedness, or fainting may occur, especially when rising from a lying or sitting position. Getting up slowly may help lessen the problem. These effects may also occur if you drink alcohol, stand for long periods of time, exercise, or if the weather is hot.

While taking prazosin hydrochloride, be careful in the amount of alcohol you drink. Also, use extra care during exercise or hot weather, or if standing for long periods. Check with your physician if you have any questions.

Drug Interactions Prazosin hydrochloride has 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 has been shown to cause an additive hypotensive effect. This effect can be minimized by reducing the prazosin hydrochloride dose to 1 to 2 mg three times a day, by introducing additional antihypertensive drugs cautiously, and then by retitrating prazosin hydrochloride based on clinical response. Concomitant administration of prazosin hydrochloride 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.

Laboratory Tests In clinical studies in which lipid profiles were followed, there were generally no adverse changes noted between pre- and post-treatment lipid levels. Carcinogenesis, Mutagenesis, Impairment of Fertility: No carcinogenic potential was demonstrated in an 18 month study in rats with prazosin hydrochloride at dose levels more than 225 times the usual maximum recommended human dose of 20 mg per day. Prazosin hydrochloride was not mutagenic in in vivo genetic toxicology studies.

In a fertility and general reproductive performance study in rats, both males and females, treated with 75 mg/kg (225 times the usual maximum recommended human dose), demonstrated decreased fertility, while those treated with 25 mg/kg (75 times the usual maximum recommended human dose) did not. In chronic st… [Excerpted — this section continues on DailyMed.]