prazosin Tablets 1& 5 mg

prazosin Tablets 1& 5 mg

Category :

Antihypertensive : congestive heart failure vasodilator ; antidote ( to ergot alkaloid poisoning ) ; vasospastic therapy adjunct; benign prostatic hyperplasia therapy agent. ( USP DI 2001 )

Composition :

Each tablet contains prazosin hydrochloride equivalent to 1or 2 or 5 mg of prazosin.

Chemistry :

Prazosin hydrochloride ,a quinazoline derivative , is the hydrochloride salt of 1 – ( 4 amino – 6,7 – dimethoxy- 2 – quinazolinyl ) – 4(2-furoyl) piperazine and its structural

formula is :

( C19 H21 N5 0 4. HCL)
Molecular weight = 419.87 (PDR 2002)

Mechanism of Action :

Prazosin is a selective alpha 1 - adrenergic blocking agent . The alpha 1 - adrenergic blocking action is thougth to account primarily for its effects.

1 ) Hypertension:

Prazosin produces vasodilation and reduces peripheral resistance but generally has little effect on cardiac output .Antihypertensive effect is usually not accompanied by reflex tachycardia. There is little or no effect on renal blood flow or glomerular filtration rate.

2 ) congestive heart failure:
Beneficial effects, resulting from vasodilation , are due to decreased systemic resistance , preload and afterload reduction, and resulting improved cardiac output .
3 ) Raynaud’s phenomenon:
Therapeutic effect for vasospasm is due to inhibition of vasoconstriction by blocking of postsynaptic alpha 1 receptors. 4 ) Benign prostatic hyperplasia:
Relaxation of smooth muscle in the bladder neck, prostate, and prostate capsule produced by alpha1 – adrenergic blockade results in a reduction in urethral resistance and pressure, bladder outlet resistance , and urinary symptoms. ( USP DI 2001 ) .

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 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. ( PDR 2002 )

Indications:

Treatment of :
- Hypertension
- Congestive heart failure : Prazosin may be used as an adjunct to digoxin and diuretics for the treatment of congestive heart failure. However, prazosin has not been shown to improve survival in these patients.
- Toxicity , ergot alkaloid: prazosin is used for treatment of peripheral vasospasm caused by ergot alkaloid overdose.
- Pheochromocytoma : prazosin is used for the management of hypertension associated with pheochromocytoma.
- Reynaud’s phenomenon
- Benign prostatic hyperplasia (BPH) : prazosin is used for the treatment of urinary symptoms associated with benign prostatic hyperplasia. Prazosin has been shown to improve urinary flow and symptoms of BPH. However, the long – term effects of prazosin on the incidence of acute urinary obstruction or other complications of BPH or on the need for surgery have not yet been determined . ( USP DI 2001 ) .

Contraindications :

Prazosin is contraindicated in patients with known sensitivity to quinazolines, prazosin , or any of the inert ingredients. (PDR 2002 ) .

Warnings :

As with all alpha – blockers, prazosin 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 about 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 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 the 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. Hypotension may develop in patients given prazosin who are also receiving a beta – blocker such as propranolol. ( PDR 2002 )

Precautions :

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. (PDR 2002)

Usage in pregnancy :

Pregnancy category c. 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. (PDR 2002 )

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 . ( PDR 2002)

Drug Interactions :

- Nonsteroidal anti – inflammatory drugs ( NSAIDs ) , especially indomethacin:
Antihypertensive effects of prazosin may be reduced when it is used concurrently with these agents; indomethacin, and possibly other NSAIDs , may antagonize the antihypertensive effect by inhibiting renal prostaglandin synthesis and by causing sodium and fluid retention, the patient should be carefully monitored to confirm that the desired effect is being obtained.
- Other hypotension – producing medications :
Antihypertensive effects may be potentiated when these medications are used concurrently with prazosin ; although some antihypertensive and / or diuretic combinations are frequently used to therapeutic advantage, dosage adjustments are necessary when these medications are used concurrently.
- Sympathomimetics:
• Antihypertensive effects of prazosin may be reduced when it is used concurrently with these agents; the patient should be carefully monitored to confirm that the desired effect is being obtained.
• Concurrent use of prazosin antagonizes the peripheral vasoconstriction produced by high doses of dopamine.
• Concurrent use of prazosin may decrease the pressor response to ephedrine.
• Concurrent use of prazosin may block the alpah- adrenergic effects of epinephine , possibly resulting in severe hypotension and tachycardia .
• Concurrent use of prazosin usually decreases, but does not reverse or completely block , the pressor effect of metaraminol.
• Prior administration of prazosin may decrease the pressor effect and shorten the duration of action of methoxamine and phenylephrine.( USP DI 2001)
Adverse Reactions :
The following adverse effects have been selected on the basis of their potential clinical significance , not necessarily inclusive:
- Those indicating need for medical attention :
* Incidence more frequent : Dizziness; orthostatic hypotension ( dizziness or lightheadedness when getting up from a lying or sitting position ; sudden fainting ) .
* Incidence less frequent : Edema( swelling of feet or lower legs ) ; palpitations ( pounding heartbeat) ; urinary incotinence (loss of bladder control ) .
* Incidence rare: Angina ( chest pain) ; dyspnea( shortness of breath ) ; priapism ( painful, inappropriate erection of the penis, continuing ) .
- Those indicating need for medical attention only if they continue or rare bothersome :
* Incidence more frequnet : Drowsiness; headache; malaise ( lack of energy) .
* Incidence less frequent: Dryness of mouth; fatigue ( unusual tiredness or weakness ) ; nervouseness.
* Incidence rare: Nausea; urinary frequency ( frequent urge to urinate ) . ( USP DI 2001 )

Overdosage :

Accidental ingestion of at least 50 mg of prazosin 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 that prazosin is not dialyzable because it is protein bound . ( PDR 2002)

Dosage and Administration :

- Usual adult dose:
• Antihypertensive : * Initial : oral, 500 mcg ( 0.5 mg) two or three times a day for at least 3 days . If tolerated, Increase to 1 mg ( base ) two or three times a day for a further 3 days. * Maintenace : oral , adjusted gradually to meet individual requirements , most commonly 6 to 15 mg ( base ) a day in two or three divided daily doses.
•Toxicity , ergot alkaloid : oral , 1 mg three times a day .
•Vasospastic therapy adjunct – Reynaud’s phenomenon : oral , 1 mg three times a day.
• Benign prostatic hyperplasia : * Initial : oral , 1 mg ( base ) two times a day . * Maintenance : Oral , 1 to 5 mg ( base ) two times a day. - Usual adult prescribing limits : Daily doses higher than 20mg ( base ) usually do not have increased efficacy, although some patients respond to up to 40mg a day.
- Usual pediatric dose :
• Antihypertensive : oral, 50 to 400 mcg ( 0.05 to 0.4 mg ) ( base ) per kg of body weight per day in two or three divided doses. Single doses should not exceed 7 mg ,and the total daily dose should not exceed 15 mg per day .(USP DI 2001 )

Storage :

Store below 40 ºc , preferably between 15 and 30 °c. Store in a well – closed, light – resistant container . ( USP DI 2001) .

How supplied :

prazosin hydrochloride 1mg is available as white,oval tablet. prazosin hydrochloride 5 mg is available as light brown , scored, oblong tablet. There are blister of 10’s , Box of 100’s .

Reference :

1) PDR 2002 2) USP DI 2001.