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Here’s what to ask a doctor about hereditary angioedema

Prazosin

Pronunciation

Pronunciation

(PRAZ oh sin)

Index Terms

  • Furazosin
  • Prazosin HCl
  • Prazosin Hydrochloride

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Minipress: 1 mg, 2 mg, 5 mg

Generic: 1 mg, 2 mg, 5 mg

Brand Names: U.S.

  • Minipress

Pharmacologic Category

  • Alpha1 Blocker
  • Antihypertensive

Pharmacology

Competitively inhibits postsynaptic alpha-adrenergic receptors which results in vasodilation of veins and arterioles and a decrease in total peripheral resistance and blood pressure

Distribution

Vd: 0.5 L/kg

Metabolism

Extensively hepatic via demethylation and conjugation

Excretion

Feces; urine (6% to 10% as unchanged drug)

Onset of Action

Antihypertensive: Within 2 hours; Peak effect: 2 to 4 hours

Time to Peak

Plasma: ~3 hours; Extended release [Canadian product]: 6 to 10 hours

Duration of Action

10 to 24 hours

Half-Life Elimination

2 to 3 hours, prolonged with CHF

Protein Binding

Highly bound (97%)

Use: Labeled Indications

Hypertension: Treatment of hypertension

The 2014 guideline for the management of high blood pressure in adults (Eighth Joint National Committee [JNC 8]) does not recommend the use of prazosin in the treatment of hypertension (James 2013).

Use: Unlabeled

Post-traumatic stress disorder (PTSD) related nightmares and sleep disruption; benign prostatic hyperplasia; Raynaud's syndrome

Contraindications

Known sensitivity to quinazolines, prazosin, or any component of the formulation

Dosing: Adult

Hypertension:

US labeling: Oral: Initial: 1 mg/dose 2 or 3 times daily, increased slowly to usual dosage range of 6 to 15 mg/day in divided doses or alternatively, 1 to 5 mg twice daily (ASH/ISH [Weber 2014]). Dose may be increased up to 20 mg/day in divided doses; however, some patients may benefit from up to 40 mg/day in divided doses.

Concomitant diuretics or other antihypertensives: When adding a diuretic or other antihypertensive, decrease prazosin dose to 1 or 2 mg 3 times daily and retitrate.

Canadian labeling: Oral:

Immediate release: Initial: 0.5 mg 2 or 3 times daily for ≥3 days; may increase to 1 mg 2 or 3 times daily for ≥3 days and then further increase gradually per response/tolerability to a maximum of 20 mg/day in 2 or 3 divided doses.

Concomitant diuretics or other antihypertensives: Initial: 0.5 mg at bedtime; may increase to 0.5 mg 2 or 3 times daily; increase gradually for patients already on other diuretics or other antihypertensive agents. When adding a diuretic or other antihypertensive agent to prazosin therapy, reduce prazosin dose to 1 or 2 mg 2 or 3 times daily and retitrate.

Extended release: Initial: 2.5 mg once daily; increase slowly over 7 to 14 days per response/tolerability up to a maximum of 20 mg once daily. Monitor response to ensure adequate blood pressure control throughout 24-hour period. Patients receiving immediate-release prazosin as monotherapy or concurrently with other antihypertensives may be switched to extended-release prazosin at an equivalent dose or nearest higher total daily dose.

PTSD-related nightmares and sleep disruption (off-label use): Oral: Initial: 1 mg at bedtime; after 2 to 3 days increase dose to 2 mg at bedtime, then adjust dosage based on response and tolerability in 1 to 2 mg increments every 7 days up to a maximum of 15 mg/day (Raskind, 2003; Raskind, 2007; Taylor, 2008). (Titration as rapid as every 2 to 3 days has been evaluated [Taylor, 2008]). Usual dose range: 3 to 15 mg at bedtime (APA [Benedek, 2009]). Civilian patients, especially females may require lower doses (Taylor 2008).

Raynaud phenomenon (off-label use): Oral: Initial: 0.5 to 1 mg once daily (at bedtime) or 0.5 mg twice daily; gradually adjust dose based on response and tolerability up 12 mg/day in 2 to 3 divided doses (Nielson, 1983; Russell, 1985; Wollersheim, 1988)

Dosing: Geriatric

Refer to adult dosing. In the management of hypertension, consider lower initial doses and titrate to response (Aronow 2011).

Dosing: Pediatric

Hypertension (off-label use): Oral: Children: Initial: 0.05 to 0.1 mg/kg/day in 3 divided doses; maximum: 0.5 mg/kg/day (not to exceed 20 mg) (NHBPEP, Fourth Report)

Canadian labeling: Children ≥12 years and Adolescents: Oral: Refer to adult dosing.

Dosing: Renal Impairment

US labeling: There are no dosage adjustments provided in the manufacturer’s labeling.

Canadian labeling: Moderate to severe impairment: Immediate release: Initial: 0.5 mg daily; increase dose gradually.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Storage

Store at 20°C to 25°C (68°F to 77°F). Protect from moisture and light.

Extended-release tablet [Canadian product]: Store between 15°C and 30°C (59°F and 86°F). Protect from moisture.

Drug Interactions

Alpha-/Beta-Agonists: Alpha1-Blockers may diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Similarly, Alpha-/Beta-Agonists may antagonize Alpha1-Blocker vasodilation. Monitor therapy

Alpha1-Agonists: Alpha1-Blockers may diminish the vasoconstricting effect of Alpha1-Agonists. Similarly, Alpha1-Agonists may antagonize Alpha1-Blocker vasodilation. Monitor therapy

Alpha1-Blockers: May enhance the antihypertensive effect of other Alpha1-Blockers. Avoid combination

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Beta-Blockers: May enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Exceptions: Levobunolol; Metipranolol. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Calcium Channel Blockers: Alpha1-Blockers may enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy

Dapoxetine: May enhance the orthostatic hypotensive effect of Alpha1-Blockers. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Alpha1-Blockers. Management: Ensure patient is stable on one agent prior to initiating the other, and always initiate combination using the lowest possible dose of the drug being added. When tadalafil is used for treatment of BPH, concurrent alpha 1-blockers are not recommended. Consider therapy modification

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Test Interactions

Increased urinary VMA 17%, norepinephrine metabolite 42%; therefore, false positives may occur in screening for pheochromocytoma. If elevated VMA is found, discontinue prazosin and retest after one month.

Adverse Reactions

>4%:

Cardiovascular: Palpitation (5%)

Central nervous system: Dizziness (10%), headache (8%), drowsiness (8%)

Endocrine & metabolic: Decreased energy (7%)

Gastrointestinal: Nausea (5%)

Neuromuscular & skeletal: Weakness (7%)

1% to 4%:

Cardiovascular: Edema, orthostatic hypotension, syncope

Central nervous system: Depression, nervousness, vertigo

Dermatologic: Rash

Gastrointestinal: Constipation, diarrhea, vomiting, xerostomia

Genitourinary: Urinary frequency

Ocular: Blurred vision, reddened sclera

Respiratory: Dyspnea, epistaxis, nasal congestion

<1% (Limited to important or life-threatening): Abdominal discomfort, allergic reaction, alopecia, angina, arthralgia, bradycardia, cataplexy, cataracts (both development and disappearance have been reported), diaphoresis, enuresis, eye pain, fever, flushing, gynecomastia, hallucinations, impotence, insomnia, leukopenia, lichen planus, liver function abnormalities, malaise, MI, narcolepsy (worsened), pain, pancreatitis, paresthesia, pigmentary mottling and serous retinopathy, positive ANA titer, priapism, pruritus, systemic lupus erythematosus, tachycardia, tinnitus, urticaria, vasculitis

Reported in association with other alpha1-blockers: Intraoperative floppy iris syndrome (with cataract surgery)

Warnings/Precautions

Concerns related to adverse effects:

• Angina: Discontinue if symptoms of angina occur or worsen.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Floppy iris syndrome: Intraoperative floppy iris syndrome has been observed in cataract surgery patients who were on or were previously treated with alpha1-blockers; modification to surgical technique may be necessary. There appears to be no benefit in discontinuing alpha1-blockers prior to surgery.

• Orthostatic hypotension/syncope: May cause significant orthostatic hypotension and syncope with sudden loss of consciousness, especially within 30 to 90 minutes of the first dose; anticipate a similar effect if therapy is interrupted for a few days, if dosage is rapidly increased, or if another antihypertensive drug (particularly vasodilators or a beta-blocker) or a phosphodiesterase 5 (PDE 5) inhibitor (eg, sildenafil, tadalafil, vardenafil) is introduced. Severe tachycardia (120 to 160 beats/minute) has occasionally been reported prior to a syncopal episode. Patients should be cautioned about alcohol use and performing hazardous tasks when starting new therapy or adjusting dosage upward.

• Priapism: Priapism and prolonged erections have been reported; seek immediate medical assistance for erections lasting longer than 4 hours.

Disease-related concerns:

• Prostate cancer: Should rule out prostatic carcinoma before beginning therapy.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitoring Parameters

Blood pressure, standing and sitting/supine

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies. Prazosin crosses the placenta and its pharmacokinetics may be slightly altered during pregnancy (Bourget 1995; Rubin 1983). Limited use in pregnant women has not demonstrated any fetal abnormalities or adverse effects (Dommisse 1983).

Untreated chronic maternal hypertension is associated with adverse events in the fetus, infant, and mother. If treatment for hypertension during pregnancy is needed, other agents are generally preferred (ACOG 2013).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, loss of strength and energy, headache, or nausea. Have patient report immediately to prescriber severe dizziness, passing out, blurred vision, tachycardia, arrhythmia, depression, shortness of breath, priapism, or swelling of arms or legs (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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