Prazypor

Uses

Hypertension (Primary and Secondary Hypertension). Raynaud's phenomenon and Raynaud's disease, Congestive heart failure (Prazypor may be used alone or added to the therapeutic regimen in those patients with congestive heart failure who are resistant or refractory to conventional therapy with diuretics and/or cardiac glycosides) & Benign prostatic hyperplasia (For the symptomatic treatment of urinary obstruction due to BPH and in patients awaiting prostatic surgery).

Prazypor is also used to associated treatment for these conditions: Agitation, Benign Prostatic Hyperplasia (BPH), High Blood Pressure (Hypertension), Raynaud's Phenomenon, Disturbed sleep/nightmares

How Prazypor works

Alpha-adrenergic receptors are essential for the regulation of blood pressure in humans. Two types of alpha receptors, alpha 1 and alpha 2, both play a role in regulating blood pressure. Alpha-1 receptors are postsynaptic (located after the nerve junction, or space between a nerve fiber and target tissue). In this case, the target tissue is the vascular smooth muscle . These receptors, when activated, increase blood pressure .

Prazypor inhibits the postsynaptic alpha-1 adrenoceptors. This inhibition blocks the vasoconstricting (narrowing) effect of catecholamines (epinephrine and norepinephrine) on the vessels, leading to peripheral blood vessel dilation. Through blood vessel constriction by adrenergic receptor activation, epinephrine and norepinephrine normally act to increase blood pressure .

Dosage

Prazypor dosage

Hypertension:

• Recommended starting dose is 0.5 mg (in the evening), twice or thrice daily for 3 to 7 days. This dose should be increased to 1 mg twice or three times daily for a further 3 to 7 days. Thereafter, the daily dose should be increased gradually as determined by the patient's response to the blood pressure lowering effect. Most patients are likely to be maintained on a dosage regimen of Prazypor alone of up to 15 mg daily in divided doses.
• Maximum dose: 20 mg in divided doses.

Patients receiving other antihypertensive therapy but with inadequatecontrol:

• The dosage of the other drug should be reduced to a maintenance level and Prazypor initiated at 0.5 mg in the evening, then continuing with 0.5 mg twice or three times daily.
• Subsequent dosage increases should be made gradually depending upon the patient's response.

Congestive heart failure:

• The recommended starting dose is 0.5 mg two, three or four times daily, increasing to 4 mg in divided doses. Dosage should be adjusted according to the patient's response, based on careful monitoring of cardiopulmonary signs and symptoms.
• Usual daily maintenance dosage: 4 mg to 20 mg in divided doses.

Raynaud's disease:

• The recommended starting dosage is 0.5 mg twice daily given for a period of 3 to 7 days and should be adjusted according to the patient's clinical response.
• Usual maintenance dosage is 1 mg or 2 mg twice daily.

Benign prostatic hyperplasia:

• The recommended dosage is 0.5 mg twice daily for a period of 3 to 7 days, with the initial dose administered in the evening. The dosage should then be adjusted according to clinical response.
• The usualmaintenance dosage is 2 mg twice daily.

May be taken with or without food. Starting dose is best taken within dinner, at least 2-3 hr before retiring. Maintenance doses may be taken with or without meals.

Side Effects

The most common side effects of Prazypor are allergic reaction, depression, nervousness, insomnia, Hallucinations, dizziness, drowsiness, headache, faintness, syncope, paraesthesia, worsening of pre-existing narcolepsy, blurred vision, eye pain, reddened sclera, vertigo, tinnitus, palpitations etc.

Toxicity

TDLO, LD50: Oral TDLO (human): 285 μg/kg; Oral TDLO (woman): 10 μg/kg .

Oral LD50 (rat): 1950 mg/kg; Intraperitoneal LD50 (rat): 102 mg/kg .

Overdose information

Accidental ingestion of at least 50 mg of prazosin by a two-year-old child led to severe drowsiness with depressed reflexes. There was no fall in blood pressure, and the child recovered without complication .

Use in pregnancy

There are no adequate and well-controlled studies determining the safety of prazosin use during pregnancy. It is considered a pregnancy category C drug. Prazypor should be used during pregnancy only in cases where the benefit outweighs the possible risk to the mother and fetus . In specific cases where blood pressure control was emergent during pregnancy, prazosin has been used and no effects on the fetus or neonate were reported .

Use in nursing

This drug is found excreted in small concentrations in human milk. This drug should be used with caution when used during nursing .

Precaution

In patients with benign prostatic hyperplasia: Prazypor is not recommended for patients with a history of micturition syncope. It should not normally be administered to patients already receiving another alpha-1-antagonist.

In patients with congestive heart failure: Prazypor is not recommended in the treatment of congestive cardiac failure due to mechanical obstruction such as aortic valve stenosis, mitral valve stenosis, pulmonary embolism and restrictive pericardial disease.

In patients with hypertension: Postural hypotension evidenced by dizziness and weakness, or rarely loss of consciousness, has been reported, particularly with the commencement of therapy

Interaction

Use with phosphodiesterase-5 inhibitors (PDE-5 Inhibitors): Concomitant useo f PDE-5 inhibitors (e.g. Sildenafil, Tadalafil, Vardenafil) and Prazypor may lead to symptomatic hypotension in some patients. Adding Prazypor to beta-adrenergic antagonist or calcium antagonist therapy may produce a substantial reduction in blood pressure.

Food Interaction

• Avoid alcohol.
• Avoid natural licorice.
• Take with or without food. The absorption is unaffected by food.

Prazypor Alcohol interaction

[Moderate] GENERALLY AVOID:

The concurrent use of ethanol and alpha-1 adrenergic blockers may cause increased hypotensive effects.

Patients with aldehyde dehydrogenase deficiencies (primarily Asians) may be at a higher risk of this interaction.

The mechanism has not been determined.

Data exist for prazosin and other alpha adrenergic blockers are expected to interact also.

In addition, any patients taking alpha adrenergic blockers may experience excessive orthostatic hypotension with ethanol ingestion, due to ethanol's unopposed vasodilatory effects in the presence of alpha adrenergic blockade.

Patients who develop

a flushing reaction after ethanol ingestion (indicates a possible aldehyde dehydrogenase deficiency) should be advised to avoid ethanol or limit their intake.

All patients should be warned about the possibility of orthostatic hypotension with concurrent ethanol use.

Prazypor Drug Interaction

Moderate: aripiprazole, zolpidem, diphenhydramine, lurasidone, quetiapine, bupropion, alprazolamUnknown: amphetamine / dextroamphetamine, duloxetine, omega-3 polyunsaturated fatty acids, clonazepam, lamotrigine, escitalopram, pregabalin, fluoxetine, topiramate, cyanocobalamin, cholecalciferol, sertraline, cetirizine

Prazypor Disease Interaction

Moderate: hypotension, liver disease

Volume of Distribution

About 0.6 L/kg .

Elimination Route

After administration of an oral dose, peak plasma concentrations are attained at approximately 3 hours . There is a linear association between the prazosin dose given and plasma concentration at steady state .

Half Life

The plasma half-life is about 2-3 hours .

Clearance

In patients with congestive heart failure, the clearance of this drug is decreased. Impairment of renal function does not have relevant effects on elimination .

Elimination Route

This drug is mainly excreted in the bile and the feces .

Pregnancy & Breastfeeding use

Pregnancy category C. It should be used only when, in the opinion of the physician, potential benefit outweighs potential risk. Prazypor has been shown to be excreted in small amounts in human milk. Caution should be exercised when Prazypor is administered to nursing mothers.

Contraindication

Prazypor is contraindicated in patients with known sensitivity to Prazypor & other quinazolines or any of the excipients.

Special Warning

Patients with moderate to severe grades of renal impairment: Evidence to date shows that Prazypor does not further compromise renal function when used in patients with renal impairment. As some patients in this category have responded to small doses of Prazypor, it is recommended that therapy be initiated at 0.5 mg daily and that dosage increases be instituted cautiously.

Patients with hepatic dysfunction: it is recommended that therapy should be initiated at 0.5 mg daily and that dosage should be increased cautiously.

Use in the elderly: Since the elderly may be more susceptible to hypotension, therapy should be initiated with the lowest possible dose.

Acute Overdose

Symptoms: Hypotension, profound drowsiness, depressed reflexes.

Management: Symptomatic and supportive treatment. May be treated with activated charcoal if patient presents within 1 hr of ingestion. Postural measures and parenteral fluid volume replacement for severe hypotension and if necessary, cautious IV infusion of a vasopressor.

Storage Condition

Keep away from light and moisture, store below 30° C. Keep away from reach out of the children.

Innovators Monograph

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