MINIPRESS® (prazosin hydrochloride), 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:

It is a white, crystalline substance, slightly soluble in water and isotonic saline, and has a molecular weight of 419.87. Each 1 mg capsule of MINIPRESS for oral use contains drug equivalent to 1 mg free base.

Inert ingredients in the formulations are: hard gelatin capsules (which may contain Blue 1, Red 3, Red 28, Red 40, and other inert ingredients); magnesium stearate; sodium lauryl sulfate; starch; sucrose.

MINIPRESS (prazosin hydrochloride) is indicated in the treatment of hypertension. It can be used alone or in combination with other antihypertensive drugs such as diuretics or beta-adrenergic blocking agents.

The dose of MINIPRESS 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 MINIPRESS should be reduced to 1 mg or 2 mg three times a day and retitration then carried out.

PFIZER INC. Revised September 2000. FDA Rev date: 06/12/01

Clinical trials were conducted on more than 900 patients. During these trials and subsequent marketing experience, the most frequent reactions associated with MINIPRESS 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 MINIPRESS 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, hypertension.
Endocrine: gynecomastia.
Heart Rate/Rhythm: bradycardia.
Psychiatric: insomnia.
Skin/Appendages: urticaria.
Vascular (Extracardiac):vasculitis.
Vision: eye pain.

MINIPRESS (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 MINIPRESS has been shown to cause an additive hypotensive effect. This effect can be minimized by reducing the MINIPRESS dose to 1 to 2 mg three times a day, by introducing additional antihypertensive drugs cautiously and then by retitrating MINIPRESS based on clinical response.

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.

As with all alpha-blockers, MINIPRESS (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 120-160 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 MINIPRESS (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 MINIPRESS 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 MINIPRESS (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 MINIPRESS (prazosin hydrochloride) therapy.

Included as part of the PATIENT INFORMATION section.

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 MINIPRESS at dose levels more than 225 times the usual maximum recommended human dose of 20 mg per day. MINIPRESS 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 studies (one year or more) of MINIPRESS in rats and dogs, testicular changes consisting of atrophy and necrosis occurred at 25 mg/kg/day (75 times the usual maximum recommended human dose). No testicular changes were seen in rats or dogs at 10 mg/kg/day (30 times the usual maximum recommended human dose). In view of the testicular changes observed in animals, 105 patients on long term MINIPRESS therapy were monitored for 17-ketosteroid excretion and no changes indicating a drug effect were observed. In addition, 27 males on MINIPRESS for up to 51 months did not have changes in sperm morphology suggestive of drug effect.

Usage in Pregnancy: Pregnancy Category C. MINIPRESS has been shown to be associated with decreased litter size at birth, 1, 4, and 21 days of age in rats when given doses more than 225 times the usual maximum recommended human dose. No evidence of drug-related external, visceral, or skeletal fetal abnormalities were observed. No drug-related external, visceral, or skeletal abnormalities were observed in fetuses of pregnant rabbits and pregnant monkeys at doses more than 225 times and 12 times the usual maximum recommended human dose respectively.

The use of prazosin and a beta-blocker for the control of severe hypertension in 44 pregnant women revealed no drug-related fetal abnormalities or adverse effects. Therapy with prazosin was continued for as long as 14 weeks.¹

Prazosin has also been used alone or in combination with other hypotensive agents in severe hypertension of pregnancy by other investigators. No fetal or neonatal abnormalities have been reported with the use of prazosin.²

There are no adequate and well controlled studies which establish the safety of MINIPRESS (prazosin HCl) in pregnant women. MINIPRESS should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.

Nursing Mothers: MINIPRESS has been shown to be excreted in small amounts in human milk. Caution should be exercised when MINIPRESS is administered to a nursing woman.

Usage in Children: Safety and effectiveness in children have not been established.

References

1. Lubbe, WF, and Hodge, JV: New Zealand Med J 94 (691) 169-172, 1981.

2. Davey, DA, and Dommisse, J: S.A. Med J, Oct 4, 1980 (551-556).

Accidental ingestion of at least 50 mg of MINIPRESS (prazosin hydrochloride) 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 MINIPRESS is not dialysable because it is protein bound.

MINIPRESS is contraindicated in patients with known sensitivity to quinazolines, prazosin or any of the inert ingredients.

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. Recent animal studies, however, 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 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 a reflex tachycardia. Tolerance has not been observed to develop in long term therapy.

Hemodynamic studies have been carried out in man following acute single dose administration and during the course of long term maintenance therapy. The results confirm that the therapeutic effect is a fall in blood pressure unaccompanied by a clinically significant change in cardiac output, heart rate, renal blood flow and glomerular filtration rate. There is no measurable negative chronotropic effect.

In clinical studies to date, MINIPRESS (prazosin hydrochloride) has not increased plasma renin activity.

In man, blood pressure is lowered in both the supine and standing positions. This effect is most pronounced on the diastolic blood pressure.

Following oral administration, human plasma concentrations reach a peak at about three hours with a plasma half-life of two to three hours. The drug is highly bound to plasma protein. Bioavailability studies have demonstrated that the total absorption relative to the drug in a 20% alcoholic solution is 90%, resulting in peak levels approximately 65% of that of the drug in solution. Animal studies indicate that MINIPRESS (prazosin hydrochloride) is extensively metabolized, primarily by demethylation and conjugation, and excreted mainly via bile and feces. Less extensive human studies suggest similar metabolism and excretion in man.

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

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 MINIPRESS, 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.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

PRAZOSIN - ORAL

(PRAY-zoh-sin)

COMMON BRAND NAME(S): Minipress

WARNING: Prazosin can occasionally cause sudden fainting after the first dose. To reduce your risk of fainting, the first dose prescribed by your doctor will be the smallest dose available. You should take this first dose as you are going to bed. This will decrease the possibility of fainting. Your dose will then be gradually increased. Any other medicines for high blood pressure should be started with caution after you are on a stable dose of prazosin.

USES: Prazosin is used with or without other medications to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems.

Prazosin belongs to a class of medications called alpha blockers. It works by relaxing and widening blood vessels so blood can flow more easily.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug may also be used to treat certain blood circulation disorders (Raynaud's phenomenon, ergotamine-induced peripheral ischemia), as well as problems urinating due to an enlarged prostate (benign prostatic hyperplasia).

HOW TO USE: See also Warnings.

Take this medication by mouth with or without food, usually two or three times daily or as directed by your doctor. If stomach upset occurs, take with food or milk. The dosage is based on your age, medical condition and response to therapy.

Use this medication regularly in order to get the most benefit from it. To help you remember, take it at the same time each day. If you are taking this medication for high blood pressure, it is important to continue taking it even if you feel well. Most people with high blood pressure do not feel sick. It may take up to several weeks before the full benefit of this drug takes effect.

Do not stop taking this medication without first consulting your doctor. Some conditions may become worse when the drug is abruptly stopped. Your dose may need to be gradually decreased.

Inform your doctor if your condition worsens (e.g., your routine blood pressure readings increase).

SIDE EFFECTS: Headache, drowsiness, tiredness, weakness, blurred vision, nausea, vomiting, constipation, or a feeling in your chest of a pounding/irregular heartbeat (palpitation) may occur as your body adjusts to the medication.

Lightheadedness or dizziness upon standing may also occur, especially after the first dose and shortly after taking a dose of the drug during the first week of treatment. To minimize dizziness and reduce the risk of fainting, get up slowly when rising from a seated or lying position. If dizziness occurs, sit or lie down immediately. If any of these effects persist or worsen, notify your doctor or pharmacist promptly. Your dose may need to be adjusted.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: decreased sexual ability, very fast/irregular heartbeat, fainting, frequent urination, inability to control urination (incontinence), diarrhea, mental/mood changes (e.g., depression, hallucinations), swelling of the feet/ankles, shortness of breath, hair loss, ringing in the ears.

For males, in the very unlikely event you have a painful, prolonged erection (lasting more than 4 hours), stop using this drug and seek immediate medical attention, or permanent problems could occur.

Tell your doctor immediately if any of these rare but very serious side effects occur: severe nausea/vomiting, abdominal pain, eye pain.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: See also Warnings.

Before taking prazosin, tell your doctor or pharmacist if you are allergic to it; or to other alpha blockers (e.g., doxazosin, terazosin); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: heart disease, kidney disease, uncontrolled attacks of deep sleep (narcolepsy), low blood pressure, prostate cancer.

Before having surgery (including cataract eye surgery), tell your doctor or dentist that you are taking this medication.

This drug may make you dizzy or drowsy or cause blurred vision; use caution while engaging in activities requiring alertness or clear vision such as driving or using machinery. Do not drive or participate in hazardous activities for 24 hours after your first dose, any increase in your dosage, or restarting treatment. If your doctor prescribes any additional blood pressure drugs, avoid driving and hazardous activities for 24 hours after your first dose of the new medication. Limit alcoholic beverages.

To reduce the risk of dizziness and fainting, be careful when standing for long periods. Avoid getting overheated during exercise and hot weather. When first starting this drug, avoid situations where you may be injured if you faint.

Caution is advised when using this drug in the elderly because they may be more sensitive to its effects, especially dizziness and fainting.

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

Prazosin passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: beta blockers (e.g., atenolol, metoprolol, propranolol), verapamil, drugs for sexual function problems (e.g., sildenafil, tadalafil, vardenafil).

If you are taking sildenafil at doses greater than 25 milligrams, you can decrease your risk of fainting by taking sildenafil at least four hours apart from your prazosin. Consult your doctor or pharmacist if you have any questions.

Tell your doctor or pharmacist if you also take drugs that can cause drowsiness, lower your blood pressure, or make it difficult for you to urinate such as: certain antihistamines (e.g., diphenhydramine), anti-anxiety drugs (e.g., diazepam), anti-seizure drugs (e.g., carbamazepine), medicine for sleep (e.g., sedatives), muscle relaxants (e.g., carisoprodol), narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., phenothiazines such as chlorpromazine or tricyclic antidepressants such as amitriptyline), tranquilizers.

Check the labels on all your medicines (e.g., cough-and-cold products, diet aids, nonsteroidal anti-inflammatory drugs-NSAIDs for pain/fever reduction) because they may contain ingredients that could increase your blood pressure or cause a fast heartbeat (e.g., pseudoephedrine, phenylephrine, chlorpheniramine, diphenhydramine, clemastine, ibuprofen, naproxen). Ask your pharmacist about the safe use of those products.

This product can affect the results of certain lab tests (pheochromocytoma screening test). Make sure laboratory personnel and your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include: severe drowsiness, slow reactions.

NOTES: Do not share this medication with others.

Lifestyle changes such as stress reduction programs, exercise, and dietary changes may increase the effectiveness of this medicine. Talk to your doctor or pharmacist about lifestyle changes that might benefit you.

Have your blood pressure and heart rate checked regularly while taking this medication. Learn how to monitor your own blood pressure, and share the results with your doctor.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.