Apo-Prazo

Apo-Prazo

prazosin

Manufacturer:

Apotex

Distributor:

Pharmaforte
Full Prescribing Info
Contents
Prazosin hydrochloride.
Description
Each tablet contains prazosin HCl equivalent to prazosin 1 mg, 2 mg, or 5 mg, respectively.
Gluten- and tartrazine-free.
Excipients/Inactive Ingredients: 1 mg: Lactose, Energy: 2.26 KJ (0.54 kcal), Sodium: <1 mmol. 2 mg: Lactose, Energy: 2.6 KJ (0.62 kcal), Sodium: <1 mmol. 5 mg: Lactose, Energy: 6.49 KJ (1.55 kcal), Sodium: <1 mmol.
Action
Pharmacology: Pharmacodynamics: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 resulls of dog torelimb experiments demonstrate that the peripheral vasodilator effect of prazosin is confined mainly to the level of the resistance vessels (arterioles). Tolerance does not appear to develop and rebound elevation or blood pressure does not seem to occur following abrupt cessation of prazosin therapy. According to hemodynamic studies a fall in blood pressure is unaccompanied by a clinically significant change in heart rate or renal blood flow and glomerular filtration rate.
Prazosin circulated in human plasma highly protein-bound (97%), yet disappeared rapidly with a plasma half-life of 2 to 3 hours. After chronic administration, no apparent drug accumu­lation was observed nor were any obvious decreases in plasma concentrations noted. Secondary plasma drug peaks and shoulders suggested probable enterohepatic circulation.
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.
Plasma drug levels following oral administration of prazosin in humans were generally low and variable.
Indications/Uses
The treatment of hypertension: As an antihypertensive drug it is mild to moderate in activity. It is employed in a general treatment program in conjunction with a diuretic and/or other antihypertensive drugs as needed for proper patient response. It may be employed as the initial agent in the treatment of mild hypertension in those patients in whom, in the judgment of the physician, treatment should be started with a vasodilator rather than a diuretic or a beta-blocker.
Dosage/Direction for Use
Note: When titration is to be undertaken using the tablet formulation it will be necessary to split the 1 mg tablet to obtain the 0.5 mg starting dose.
It is recommended that the starting dose of 0.5 mg be given with food preferable with the evening meal, at least 2 or 3 hours before retiring. The dose should be built up gradually with 0.5 mg being given b.i.d. or t.i.d. for at least 3 days. Unless adverse effects occur and subject to the blood pressure lowering effect, this dose should be increased to 1 mg given b.i.d. to t.i.d for at least a further 3 days.
Thereafter, as determined by the patient's response to the blood pressure lowering effect, the dose should be increased gradually. Response to prazosin is usually seen within 1 to 14 days if it is to occur at any particular dose. When a response is seen, therapy should be continued at that dose until the degree or response has reached the optimum before the next dose increment is added. Incremental increases should be continued until a desired effect is achieved or a maximum daily dose of 20 mg is reached. The maintenance dose or prazosin may be given as a twice daily dosage regimen.
In patients with moderate to severe grades of renal impairment, it is recommended that therapy be initiated at 0.5 mg daily and that dose increases be instituted gradually.
Use With Other Drugs: Patients receiving Diuretic Therapy: The diuretic should be reduced to a maintenance dose level for the particular agent and prazosin initiated at 0.5 mg b.i.d. or t.i.d.
After the initial period of observation, the dose of prazosin should be gradually increased as determined by the patient's response.
Patients receiving Other Antihypertensive Agents: Because some additive effect is anticipated, the other agent (e.g. pro­pranolol or other beta-adrenergic blocking agents, alpha-methyldopa, reserpine, clonidine. etc.) should be reduced and prazosin initiated at 0.5 mg b.i.d. or t.i.d. Subsequent dosage increase should be made depending upon the patient's response.
Appropriate precautions should be observed when the dosage of these other antihypertensive agents is reduced.
Patients on Apo-Prazo to whom Other Antihypertensive Agents are Added: When adding a diuretic or other antihypertensive agent, the dose of prazosin should be reduced to 1 or 2 mg b.i.d. or t.i.d. and retitration then carried out.
Overdosage
Symptoms: Ingestion of 120 mg (60 tablets) of prazosin in a 72 year old man resulted in profound drowsiness, severely depressed blood pressure and minimally elevated heart rate. After appropriate remedial measures were taken, recovery was uneventful.
Treatment: Should overdosage lead to hypoten­sion, support of the cardiovascular system is of first importance. Restoration or blood pressure and normalization of heart rate may be accomplished by keeping the patient in the supine position. If necessary, vasopressors should be used. If this measure is inadequate, shock should then be treated with volume expanders. Renal function should be monitored and supported as needed. Laboratory data indicate that pra­zosin is not dialyzable because it is protein bound.
Contraindications
Known sensitivity to quinazolines.
Warnings
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 associated with about of severe tachycardia with heart rates of 120 to 160 beats/minute. The incidence of syncopal episodes is approximately 0.8% when the gradual dose build-up is described under Dosage is followed. The incidence is higher if the initial dose exceeds 0.5 mg. Syncopal episodes have occurred within 30 to 90 minutes of the initial dose of the drug. They have also been reported in association with dosage increases or the introduction of prazosin into the regimen of a patient taking another antihypertensive agent or a diuretic. Physicians are therefore advised lo limit the initial dose of the drug to 0.5 mg b.i.d. or t.i.d., to subsequently increase the dosage slowly, and to introduce any additional antihypertensive drugs into the patient's regimen with caution.
Patients whose blood pressure is not adequately controlled by high doses of a beta-adrenergic blocking agent such as propranolol may develop acute hypotension when prazosin is added. To minimize the incidence of acute hypotension in such patients, the dose of beta-adrenergic blocking agent should be reduced before prazosin is administered. A low initial dose of prazosin is also strongly recommended (see Dosage & Administrtion).
If syncope occurs, the patient should be placed in the recumbent position and supportive measures instituted. This adverse effect is self-limiting and in most cases does not recur once a steady maintenance level is initiated. Patients should be cautioned to avoid situations where injury could result should syncope occur during prazosin therapy especially in the initial dose adjustment period.
Occupational Hazards: The patient should be cautioned about possible adverse effects often associated with lowering of blood pressure. Dizziness, lightheadedness or drowsiness may occur after the first dose of prazosin, or when rising from a lying or sitting position, standing for long periods of time, exercising, drinking alcohol, or if the weather is hot. The patient should be advised to avoid driving or performing hazardous tasks for the first 24 hours after taking prazosin or when the dose is increased, to stand up slowly and to use extra care during exercise, hot weather or if standing for long periods of time. While taking prazosin the patient should be careful in the amount of alcohol consumed.
Children: Prazosin is not recommended for the treatment of children under the age of 12 years since safe conditions for its use have not been established in this group.
Special Precautions
Patients with Moderate to Severe Grades of Renal Impairment: Because some patients with moderate to severe grades of renal impairment have responded to smaller than usual doses of prazosin, it is recommended that therapy be initiated at 0.5 mg daily and that dose increases be instituted cautiously.
Use In Pregnancy & Lactation
Pregnancy: 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 abnormalitles were observed. No drug related external, visceral or skeletal abnormalities were observed in fetuses of pregnant rabbits at doses more than 225 times the usual maximum recommended human dose.
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.
Lactation: 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.
Adverse Reactions
The most common reactions associated with prazosin therapy are postural dizziness (11%), nausea (9.5%), drowsiness (8.7%), headache (8.4%), palpitations (6.6%), dry mouth (5.6%), weakness (4.6%) and fatigue/malaise (4.5%). In most instances side effects have disappeared with continued therapy or have been tolerated with no decrease in dose of drug. The following reactions have also been observed during prazosin administration, some of them rarely (1 to 4%).
Gastrointestinal: vomiting, diarrhea, constipation, abdominal discomfort and/or pain, liver function abnormalities, pancre­atitis.
Cardiovascular: syncope (see Warnings), edema, dyspnea, orthostatic hypotension, tachycardia.
CNS: nervousness, vertigo, depression, paresthesia, halluci­nations.
Dermatologic: rash, pruritus, alopecia, lichen planus.
Genitourinary: urinary frequency, incontinence, impotence, priapism.
EENT: blurred vision, reddened sclera, epistaxis, tinnitus, nasal congestion, dry mouth.
Other: diaphoresis, fever, positive ANA titer, arthralgia.
Single reports of pigmentary mottling and serious retinop­athy, and a few reports of cataract development 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.
Published reports indicate that the administration of pra­zosin in cases of pre-existing narcolepsy increases the frequency of cataplectic attacks; a causal relationship has not been established in all cases.
Drug Interactions
Prazosin has been administered without any adverse drug interaction in limited clinical experience to date with the following: cardiac glycosides: digitalis and digoxin; hypoglycemic agents: insulin, chlorpropamide, tolazamide and tolbutamide; tranquilizers and sedatives: chlordiaze­poxide, diazepam and phenobarbital; agents for the treatment of gout: allopurinol, colchicine and probenecid; antiarrhythmic agents: procainamide and quinidine; and analgesic, antipyretic and anti-inflammatory agents: propoxyphene, ASA, indomethacin and phenylbutazone.
Addition of a diuretic or other antihypertensive agents to prazosin has been shown to cause an additive hypotensive effect (see Warnings and Dosage & Administration).
Drug/Laboratory Test Interactions: In a. study on 5 patients given from 12 to 24 mg of prazosin/day for 10 to 14 days, there was an average increase of 42% in the urinary metabolite of norepinephrine and an average increase in urinary VMA of 17%. Therefore, false positive results may occur in screening tests for pheochromocytoma in patients who are being treated with prazosin. If an elevated VMA is found, pra­zosin should be discontinued; and the patient retested after a month.
ATC Classification
C02CA01 - prazosin ; Belongs to the class of alpha-adrenoreceptor antagonists, peripherally-acting antiadrenergic agents. Used in the treatment of hypertension.
Presentation/Packing
Tab 1 mg (capsule-shaped, peach, flat faced with beveled edge, scored and engraved APO/P1 on on side) x 100's. 2 mg (round, white, biconvex, scored and engraved APO/P2 on one side) x 100's. 5 mg (diamond shaped, white, biconvex, scored and engraved APO/PS on one side) x 100's.
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