DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Minizide (Prazosin Hydrochloride / Polythiazide) - Warnings and Precautions

 
 



This fixed combination drug is not indicated for initial therapy of hypertension. Hypertension requires therapy titrated to the individual patient. If the fixed combination represents the dose so determined, its use may be more convenient in patient management. The treatment of hypertension is not static, but must be re-evaluated as conditions in each patient warrant.

 

WARNINGS

MINIPRESS (prazosin hydrochloride)

MINIPRESS 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 MINIPRESS. 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 MINIPRESS 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 MINIPRESS (prazosin hydrochloride). 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 MINIPRESS therapy.

RENESE (polythiazide)

RENESE should be used with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Sensitivity reactions may occur in patients with a history of allergy or bronchial asthma.

The possibility of exacerbation or activation of systemic lupus erythematosus has been reported.

Thiazides may be additive or potentiative of the action of other antihypertensive drugs.

Potentiation occurs with ganglionic or peripheral adrenergic blocking drugs.

Periodic determinations of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.

All patients receiving thiazide therapy should be observed for clinical signs of fluid or electrolyte imbalance, namely, hyponatremia, hypochloremic alkalosis, and hypokalemia. Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids. Medications such as digitalis may also influence serum electrolytes. Warning signs, irrespective of cause, are: dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.

Hypokalemia may develop with thiazides as with any potent diuretic, especially with brisk diuresis, when severe cirrhosis is present, or during concomitant use of corticosteroids or ACTH.

Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Digitalis therapy may exaggerate the metabolic effects of hypokalemia, especially with reference to myocardial activity.

Any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in hepatic or renal disease). Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction rather than administration of salt, except in rare instances when the hyponatremia is life-threatening. In actual salt depletion, appropriate replacement is the therapy of choice.

Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.

Insulin requirements in diabetic patients may be either increased, decreased, or unchanged. Latent diabetes mellitus may become manifest during thiazide administration.

Thiazide drugs may increase responsiveness to tubocurarine.

The antihypertensive effects of the drug may be enhanced in the post-sympathectomy patient.

Thiazides may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use.

If progressive renal impairment becomes evident, as indicated by a rising nonprotein nitrogen or blood urea nitrogen, a careful reappraisal of therapy is necessary with consideration given to withholding or discontinuing diuretic therapy.

Thiazides may decrease serum protein-bound iodine levels without signs of thyroid disturbance.

PRECAUTIONS

Drug/Laboratory Test Interactions

In a study on five patients given from 12 to 24 mg of prazosin per 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenic or mutagenic studies have been conducted with MINIZIDE. However, no carcinogenic potential was demonstrated in 18 month studies in rats with either MINIPRESS or RENESE at dose levels more than 100 times the usual maximum human doses. MINIPRESS was not mutagenic in in vivo genetic toxicology studies.

MINIZIDE produced no impairment of fertility in male or female rats at 50 and 25 mg/kg/day of MINIPRESS and RENESE respectively. In chronic studies (one year or more) of MINIPRESS in rats and dogs, testicular changes consisting of atrophy and necrosis occurred at 25 mg/kg/day (60 times the usual maximum recommended human dose). No testicular changes were seen in rats or dogs at 10 mg/kg/day (24 times the usual maximum recommended human dose). In view of the testicular changes observed in animals, 105 patients on long term MINIPRESS therapy were monitored for 17-ketosteroid excretion and no changes indicating a drug effect were observed. In addition, 27 males on MINIPRESS alone for up to 51 months did not have changes in sperm morphology suggestive of drug effect.

Use in Pregnancy

Pregnancy Category C. MINIZIDE was not teratogenic in either rats or rabbits when administered in oral doses more than 100 times the usual maximum human dose. Studies in rats indicated that the combination of RENESE (40 times the usual maximum recommended human dose) and MINIPRESS (8 times the usual maximum recommended human dose) caused a greater number of stillbirths, a more prolonged gestation, and a decreased survival of pups to weaning than that caused by MINIPRESS alone. There are no adequate and well controlled studies in pregnant women. Therefore, MINIZIDE should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether MINIPRESS or RENESE is excreted in human milk. Thiazides appear in breast milk. Thus, if use of the drug is deemed essential the patient should stop nursing.

Pediatric Use

Safety and effectiveness in children has not been established.

Page last updated: 2006-10-05

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017