Prazosin

Prazosin
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

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Overview

Prazosin is a alpha-adrenergic blocker that is FDA approved for the {{{indicationType}}} of treatment of hypertension. Common adverse reactions include orthostatic hypotension, palpitations, nausea, asthenia, dizziness, headache, lethargy and somnolence.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Hypertension

• Initial dose:

• 1 mg two or three times a day

• 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 should be reduced to 1 mg or 2 mg three times a day and retitration then carried out.
• Concomitant administration of prazosin 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.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Benign prostatic hyperplasia

• Class of Recommendation: Class IIb

• Strength of Evidence: Category B

• Dosing Information/Recommendation

• (Dosage)

Dream disorder - posttraumatic stress disorder

• Class of Recommendation: Class IIb

• Strength of Evidence: Category B

• A 6-week open-label trial, with 5 patients, with history of exposure to civilian trauma, in a non-military environment, who subsequently developed posttraumatic stress disorder (PTSD):

• 1 to 4 mg/day

• An 8-week open-label trial, with 4 patients, with history of combat trauma nightmares and chronic DSM-IV posttraumatic stress disorder (PTSD) with concomitant severe intractable combat trauma nightmares:

• 2 to 10 mg/day

Erectile dysfunction

• Class of Recommendation: Class IIb

• Strength of Evidence: Category B

• Dosing Information/Recommendation

• (Dosage)

Poisoning due to scorpion venom

• Class of Recommendation: Class IIb

• Strength of Evidence: Category B

• Dosing Information/Recommendation

• (Dosage)

Raynaud's phenomenon

• Class of Recommendation: Class IIb

• Strength of Evidence: Category B

• Dosing Information/Recommendation

• (Dosage)

Non–Guideline-Supported Use

Condition 1

• Dosing Information

• (Dosage)

Condition 2

• Dosing Information

• (Dosage)

Condition 3

• Dosing Information

• (Dosage)

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition 1

• Dosing Information

• (Dosage)

Condition 2

• Dosing Information

• (Dosage)

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition 1

• Developed by: (Organisation)

• Class of Recommendation: (Class) (Link)

• Strength of Evidence: (Category A/B/C) (Link)

• Dosing Information/Recommendation

• (Dosage)

Condition 2

• Developed by: (Organisation)

• Class of Recommendation: (Class) (Link)

• Strength of Evidence: (Category A/B/C) (Link)

• Dosing Information/Recommendation

• (Dosage)

Non–Guideline-Supported Use

Condition 1

• Dosing Information

• (Dosage)

Condition 2

• Dosing Information

• (Dosage)

Condition 3

• Dosing Information

• (Dosage)

Contraindications

• Prazosin is contraindicated in patients with known sensitivity to:

• Quinazolines
• Prazosin
• Any of the inert ingredients

Warnings

• Prazosin, as other alpha-blockers, may cause:

• Syncope with sudden loss of consciousness:

• May be due to an excessive postural hypotensive effect
• 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
• These have often 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.
• 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.
• 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.

• Hypotension may develop in patients given prazosin who are also receiving a beta-blocker such as propranolol.
• Patients should always be started on the 1 mg capsules of prazosin. 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
• 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 therapy.

Adverse Reactions

Clinical Trials Experience

• Clinical trials were conducted on more than 900 patients. During these trials and subsequent marketing experience, the most frequent reactions associated with prazosin therapy are:

• Dizziness 10.3%
• Headache 7.8%
• Drowsiness 7.6%
• Lack of energy 6.9%
• Weakness
• Palpitations 5.3%
• 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:

Central Nervous System

• Vertigo
• Depression
• Nervousness

Cardiovascular

• Edema
• Orthostatic hypotension
• Dyspnea
• Syncope

Gastrointestinal

• Vomiting
• Diarrhea
• Constipation

Miscellaneous

• Rash
• Urinary frequency
• Blurred vision
• Reddened sclera
• Epistaxis
• Dry mouth
• Nasal congestion

• Fewer than 1% of patients have reported the following:

Gastrointestinal

• Abdominal discomfort
• Liver function abnormalities
• Pancreatitis

Cardiovascular

• Tachycardia

Central Nervous System

• Paresthesia
• Hallucinations

Dermatologic

• Pruritus
• Alopecia
• Lichen planus

Genitourinary

• Incontinence
• Impotence
• Priapism

EENT

• Tinnitus

Miscellaneous

• 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 therapy with a worsening of pre-existing narcolepsy. A causal relationship is uncertain in these cases.

Postmarketing Experience

General

• Allergic reaction
• Asthenia
• Malaise
• Pain

Autonomic Nervous System

• Flushing

Cardiovascular

• Angina pectoris
• Hypotension
• Bradycardia

Endocrine

• Gynecomastia

Psychiatric

• Insomnia

Skin/Appendages

• Urticaria

Vascular

• 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

Drug Interactions

• Prazosin has been administered without any adverse drug interaction in limited clinical experience to date with the following:

• Cardiac glycosides:

• Digitalis
• Digoxin

• Hypoglycemics:

• Insulin
• Chlorpropamide
• Phenformin
• Tolazamide
• Tolbutamide

• Tranquilizers and sedatives:

• Chlordiazepoxide
• Diazepam
• Phenobarbital

• Antigout

• Allopurinol
• Colchicine
• Probenecid

• Antiarrhythmics

• Procainamide
• Propranolol
• Quinidine

• Analgesics, antipyretics and anti-inflammatories

• Propoxyphene
• Aspirin
• Indomethacin
• Phenylbutazone

• Addition of a diuretic or other antihypertensive agent to prazosin has been shown to cause an additive hypotensive effect. This effect can be minimized by reducing the prazosin dose to 1 to 2 mg three times a day, by introducing additional antihypertensive drugs cautiously, and then by retitrating prazosin based on clinical response.

• Concomitant administration of prazosin with a phosphodiesterase-5 inhibitor can result in:

• Additive blood pressure lowering effects
• Symptomatic hypotension

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

• Prazosin 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. 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.

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

Pregnancy Category (AUS): B2 There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of prazosin in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Prazosin during labor and delivery.

Nursing Mothers

• Prazosin has been shown to be excreted in small amounts in human milk. Caution should be exercised when prazosin is administered to a nursing woman.

Pediatric Use

• Safety and effectiveness in children have not been established.

Geriatic Use

There is no FDA guidance on the use of Prazosin in geriatric settings.

Gender

There is no FDA guidance on the use of Prazosin with respect to specific gender populations.

Race

There is no FDA guidance on the use of Prazosin with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Prazosin in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Prazosin in patients with hepatic impairment.

Females of Reproductive Potential and Males

• No carcinogenic potential was demonstrated in an 18 month study in rats with prazosin at dose levels more than 225 times the usual maximum recommended human dose of 20 mg per day.

• Prazosin 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 prazosin 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 prazosin therapy were monitored for 17-ketosteroid excretion and no changes indicating a drug effect were observed. In addition, 27 males on prazosin for up to 51 months did not have changes in sperm morphology suggestive of drug effect.

Immunocompromised Patients

There is no FDA guidance one the use of Prazosin in patients who are immunocompromised.

Administration and Monitoring

Administration

Oral

Monitoring

Hypotension

• Hypotension may develop in patients given prazosin who are also receiving a beta-blocker such as propranolol.

IV Compatibility

There is limited information regarding the compatibility of Prazosin and IV administrations.

Overdosage

• Accidental ingestion of at least 50 mg of prazosin in a two year old child resulted in:

• Profound drowsiness
• Depressed reflexes
• No decrease in blood pressure was noted.
• Recovery was uneventful.

Acute Overdose

Hypotension

• Should overdosage lead to hypotension, support of the cardiovascular system is of first importance.

Management

• 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.

Pharmacology

Mechanism of Action

• 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.

Structure

Prazosin, 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:

This image is provided by the National Library of Medicine.

Molecular formula C19H21N5O4•HCl 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 prazosin 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.

Pharmacodynamics

• 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, 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.

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

Pharmacokinetics

• 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 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.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of prazosin in the drug label.

Clinical Studies

Condition 1

(Description)

Condition 2

(Description)

Condition 3

(Description)

How Supplied

(Description)

Storage

There is limited information regarding Prazosin Storage in the drug label.

Images

Drug Images

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Patient Counseling Information

(Patient Counseling Information)

Precautions with Alcohol

Alcohol-Prazosin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Prazosin Brand Names in the drug label.

Look-Alike Drug Names

• (Paired Confused Name 1a) — (Paired Confused Name 1b)
• (Paired Confused Name 2a) — (Paired Confused Name 2b)
• (Paired Confused Name 3a) — (Paired Confused Name 3b)

Drug Shortage Status

Drug Shortage

Price

References

The contents of this FDA label are provided by the National Library of Medicine.