Methyclothiazide

The routine use of diuretics in an otherwise healthy pregnant woman is inappropriate and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy, and there is no satisfactory evidence that they are useful in the treatment of developed toxemia.

Edema during pregnancy may arise from pathological causes or from the physiological and mechanical consequences of pregnancy. Thiazides are indicated in pregnancy when edema is due to pathological causes, just as they are in the absence of pregnancy (see PRECAUTIONS: Pregnancy). Dependent edema in pregnancy, resulting from restriction of venous return by the expanded uterus, is properly treated through elevation of the lower extremities and use of support hose; use of diuretics to lower intravascular volume in this case is illogical and unnecessary. There is hypervolemia during normal pregnancy that is harmful to neither the fetus nor the mother (in the absence of cardiovascular disease), but that is associated with edema, including generalized edema, in the majority of pregnant women. If this edema produces discomfort, increased recumbency will often provide relief. In rare instances, this edema may cause extreme discomfort that is not relieved by rest. In these cases, a short course of diuretics may provide relief and may be appropriate.

All patients should be observed for clinical signs of electrolyte imbalances such as 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, especially with brisk diuresis, when severe cirrhosis is present, during concomitant use of corticosteroids or ACTH, or after prolonged therapy.

Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia may be avoided or treated by use of potassium supplements or foods with a high potassium content.

Any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease 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.

Latent diabetes mellitus may become manifest during thiazide administration.

The antihypertensive effects of the drug may be enhanced in the postsympathectomy patient.

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 urinary calcium excretion. Thiazides may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.

Thiazides may cause increased concentrations of total serum cholesterol, total triglycerides, and low-density lipoproteins in some patients. Use thiazides with caution in patients with moderate or high cholesterol concentrations and in patients with elevated triglyceride levels.

Patients should inform their doctor if they have:

1) had an allergic reaction to methyclothiazide or other diuretics 2) asthma 3) kidney disease 4) liver disease 5) gout 6) systemic lupus erythematosus, or 7) been taking other drugs such as cortisone, digitalis, lithium carbonate, or drugs for diabetes.

The physician should inform patients of possible side effects and caution the patient to report any of the following symptoms of electrolyte imbalance; dryness of mouth, thirst, weakness, tiredness, drowsiness, restlessness, muscle pains or cramps, nausea, vomiting or increased heart rate.

The physician should advise the patient to take this medication every day as directed. Physicians should also caution patients that drinking alcohol can increase the chance of dizziness.

Initial and periodic determinations of serum electrolytes should be performed at appropriate intervals for the purpose of detecting possible electrolyte imbalances such as hyponatremia, hypochloremic alkalosis, and hypokalemia. Serum and urine electrolyte determinations are particularly important when a patient is vomiting excessively or receiving parenteral fluids.

Hypokalemia can sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability).

Hypokalemia may develop during concomitant use of steroids or ACTH.

Insulin requirements in diabetic patients may be increased, decreased, or unchanged.

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

Thiazide drugs may increase the responsiveness of tubocurarine.

Lithium renal clearance is reduced by thiazides, increasing the risk of lithium toxicity.

Thiazides may add to or potentiate the action of other antihypertensive drugs. Potentiation occurs with ganglionic or peripheral adrenergic blocking drugs.

Thiazides may decrease serum PBI levels without signs of thyroid disturbance.

Thiazides should be discontinued before carrying out tests for parathyroid function.

No data is available concerning the potential for carcinogenicity or mutagenicity in animals or humans. Methyclothiazide did not impair fertility in rats receiving up to 4 mg/kg/day (at least 20 times the maximum recommended human dose of 10 mg, assuming patient weight equal to or greater than 50 kg).

Thiazides are excreted in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother.

Safety and effectiveness in children have not been established.

The usual adult dose ranges from 2.5 mg to 10 mg once daily. Maximum effective single-dose is 10 mg; larger single doses do not accomplish greater diuresis, and are not recommended.

The usual adult dose ranges from 2.5 mg to 5 mg once daily.

If control of blood pressure is not satisfactory after 8 to 12 weeks of therapy with 5 mg once daily, another antihypertensive drug should be added. Increasing the dosage of methyclothiazide tablets will usually not result in further lowering of blood pressure.

Methyclothiazide tablets may be either employed alone for mild to moderate hypertension or concurrently with other antihypertensive drugs in the management of more severe forms of hypertension. Combined therapy may provide adequate control of hypertension with lower dosage of the component drugs and fewer or less severe side effects.

When other antihypertensive agents are to be added to the regimen, this should be accomplished gradually. Ganglionic blocking agents should be given at only half the usual dose since their effect is potentiated by pretreatment with methyclothiazide tablets.