prazosin HCl 5 MG Oral Capsule
Generic Name: PRAZOSIN HYDROCHLORIDE
Brand Name: Prazosin Hydrochloride
- Substance Name(s):
- PRAZOSIN HYDROCHLORIDE
WARNINGS
As with all alpha-blockers, prazosin hydrochloride capsules 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 prazosin hydrochloride capsules.
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 prazosin hydrochloride capsules 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 prazosin hydrochloride capsules.
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 prazosin hydrochloride capsules therapy.
Priapism Prolonged erections and priapism have been reported with alpha-1 blockers including prazosin in post marketing experience.
In the event of an erection that persists longer than 4 hours, seek immediate medical assistance.
If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result.
DRUG INTERACTIONS
Drug Interactions Prazosin hydrochloride capsules have 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 prazosin hydrochloride capsules have been shown to cause an additive hypotensive effect.
This effect can be minimized by reducing the prazosin hydrochloride capsules dose to 1 to 2 mg three times a day, by introducing additional antihypertensive drugs cautiously, and then by retitrating prazosin hydrochloride capsules based on clinical response.
Concomitant administration of prazosin hydrochloride capsules with a phosphodiesterase-5 (PDE-5) inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension (see DOSAGE AND ADMINISTRATION ).
OVERDOSAGE
Accidental ingestion of at least 50 mg of prazosin hydrochloride capsules 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 prazosin hydrochloride capsules are not dialysable because it is protein bound.
DESCRIPTION
Prazosin hydrochloride capsules, USP 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: Molecular formula C 19 H 21 N 5 O 4 • HCl It is a white to tan powder, slightly soluble in water and methanol, very slightly soluble in alcohol, practically insoluble in chloroform and acetone and has a molecular weight of 419.87.
Each capsule, for oral use, contains prazosin hydrochloride, USP equivalent (as the polyhydrate) to 1 mg, 2 mg or 5 mg of prazosin.
Inert ingredients in the formulations are: colloidal silicon dioxide, lactose monohydrate, magnesium stearate and microcrystalline cellulose.
The empty gelatin capsules contain black iron oxide, gelatin, red iron oxide, titanium dioxide and yellow iron oxide.
In addition, the 1 mg empty gelatin capsules contain D&C Yellow No.
10 and FD&C Green No.
3; the 2 mg empty gelatin capsules contain D&C Red No.
28, D&C Yellow No.
10, FD&C Blue No.
1 and FD&C Red No.
40; and the 5 mg empty gelatin capsules contain FD&C Blue No.
1.
The imprinting ink also contains ammonium hydroxide, propylene glycol, shellac glaze, simethicone and titanium dioxide.
Prazosin Hydrochloride Structural Formula
HOW SUPPLIED
Prazosin Hydrochloride Capsules, USP are available containing prazosin hydrochloride, USP equivalent to 1 mg, 2 mg, or 5 mg of prazosin.
The 1 mg capsule is a hard-shell gelatin capsule with a dark green opaque cap and a light brown opaque body filled with a white to off-white powder blend.
The capsule is axially printed with MYLAN over 1101 in white ink on both the cap and body.
They are available as follows: NDC 0378-1101-01 bottles of 100 capsules NDC 0378-1101-10 bottles of 1000 capsules The 2 mg capsule is a hard-shell gelatin capsule with a brown opaque cap and a light brown opaque body filled with a white to off-white powder blend.
The capsule is axially printed with MYLAN over 2302 in white ink on both the cap and body.
They are available as follows: NDC 0378-2302-01 bottles of 100 capsules NDC 0378-2302-10 bottles of 1000 capsules The 5 mg capsule is a hard-shell gelatin capsule with a light blue opaque cap and a light brown opaque body filled with a white to off-white powder blend.
The capsule is axially printed with MYLAN over 3205 in white ink on both the cap and body.
They are available as follows: NDC 0378-3205-01 bottles of 100 capsules NDC 0378-3205-25 bottles of 250 capsules Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room Temperature.] Protect from moisture and light.
Dispense in a tight, light-resistant container as defined by the USP using a child-resistant closure.
INDICATIONS AND USAGE
Prazosin hydrochloride capsules are indicated for the treatment of hypertension, to lower blood pressure.
Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.
These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including this drug.
Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake.
Many patients will require more than one drug to achieve blood pressure goals.
For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).
Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits.
The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.
Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit.
Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.
Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease).
These considerations may guide selection of therapy.
Prazosin hydrochloride capsules can be used alone or in combination with other antihypertensive drugs such as diuretics or beta-adrenergic blocking agents.
PREGNANCY
Usage in Pregnancy Prazosin hydrochloride capsules 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 prazosin hydrochloride capsules in pregnant women.
Prazosin hydrochloride capsules should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.
NUSRING MOTHERS
Nursing Mothers Prazosin has been shown to be excreted in small amounts in human milk.
Caution should be exercised when prazosin hydrochloride capsules are administered to a nursing woman.
INFORMATION FOR PATIENTS
Information for Patients 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 prazosin hydrochloride capsules, 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.
DOSAGE AND ADMINISTRATION
The dose of prazosin hydrochloride capsules 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 prazosin hydrochloride capsules should be reduced to 1 mg or 2 mg three times a day and retitration then carried out.
Concomitant administration of prazosin hydrochloride capsules 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 hydrochloride capsules.