Methyclothiazide is administered orally. Therapy should be individualized according to patient response. This therapy should be titrated to gain maximal therapeutic response as well as the minimal dose possible to maintain that therapeutic response.<br/>For edematous conditions: 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.<br/>For the treatment of hypertension: The usual adult dose ranges from 2.5 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 will usually not result in further lowering of blood pressure. Methyclothiazide 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.
Methyclothiazide, a diuretic-antihypertensive agent, is a member of the benzothiadiazine (thiazide) class of drugs. It is an analogue of hydrochlorothiazide and occurs as a white to practically white crystalline powder which is basically odorless. Methyclothiazide is very slightly soluble in water and chloroform, and slightly soluble in alcohol. Chemically, methyclothiazide is represented as 6-chloro-3-(chloromethyl)-3,4-dihydro-2-methyl-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. The structural formula is: CHClNOSM.W. 360.23 Each methyclothiazide tablet for oral administration contains 5 mg methyclothiazide and the following inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, pregelatinized starch, sodium lauryl sulfate, sodium starch glycolate and FD&C Blue #1.
The diuretic and saluretic effects of methyclothiazide result from a drug-induced inhibition of renal tubular reabsorption of electrolytes. The excretion of sodium and chloride is greatly enhanced. Potassium excretion is also enhanced to a variable degree, as it is with the other thiazides. Although urinary excretion of bicarbonate is increased slightly, there is usually no significant change in urinary pH. Methyclothiazide has a per mg natriuretic activity approximately 100 times that of the prototype thiazide, chlorothiazide. At maximal therapeutic dosages, all thiazides areapproximately equal in their diuretic/natriuretic effects. There is significant natriuresis and diuresis within two hours after administration of a single dose of methyclothiazide. These effects reach a peak in about six hours and persist for 24 hours following oral administration of a single dose. Like other benzothiadiazines, methyclothiazide also has antihypertensive properties, and may be used for this purpose either alone or to enhance the antihypertensive action of other drugs. The mechanism by which the benzothiadiazines, including methyclothiazide, produce a reduction of elevated blood pressure is not known. However, sodium depletion appears to be involved. Methyclothiazide is rapidly absorbed and slowly eliminated by the kidneys as intact drug but primarily as an inactive metabolite. Additional information on the pharmacokinetics is not known at this time.
Methyclothiazide is contraindicated in patients with anuria and in patients with a history of hypersensitivity to this compound or other sulfonamide-derived drugs.
Methyclothiazide Tablets, USP are available containing 5 mg of methyclothiazide, USP. The tablets are blue, round, scored tablets. They are debossed with M29 on the scored side. They are available as follows: NDC 0378-0160-01bottles of 100 tablets STORE AT CONTROLLED ROOM TEMPERATURE 15�����30��C (59�����86��F). PROTECT FROM LIGHT. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
Symptoms of overdosage include electrolyte imbalance and signs of potassium deficiency such as confusion, dizziness, muscular weakness, and gastrointestinal disturbances. General supportive measures including replacement of fluids and electrolytes may be indicated in treatment of overdosage.
Adverse reactions are usually reversible upon reduction of dosage or discontinuation of methyclothiazide tablets. Whenever adverse reactions are moderate or severe, it may be necessary to discontinue the drug. The following adverse reactions have been observed, but there has not been enough systematic collection of data to support an estimate of their frequency. Consequently the reactions are categorized by organ system and are listed in decreasing order of severity and not frequency. Body as a Whole: Headache, cramping, weakness. Cardiovascular System: Orthostatic hypotension (may be potentiated by alcohol, barbiturates, or narcotics). Digestive System: Pancreatitis, jaundice (intrahepatic cholestatic), sialadenitis, vomiting, diarrhea, nausea, gastric irritation, constipation, anorexia. Hemic and Lymphatic System: Aplastic anemia, hemolytic anemia, agranulocytosis, leukopenia, thrombocytopenia. Hypersensitivity Reactions: Anaphylactic reactions, necrotizing angiitis (vasculitis, cutaneous vasculitis), Stevens-Johnson syndrome, respiratory distress including pneumonitis and pulmonary edema, fever, purpura, urticaria, rash, photosensitivity. Metabolic and Nutritional Disorders: Hyperglycemia, hyperuricemia, electrolyte imbalance , hypercalcemia. Nervous System: Vertigo, dizziness, paresthesias, muscle spasm, restlessness. Special Senses: Transient blurred vision, xanthopsia. Urogenital System: Glycosuria.
Methyclothiazide shares with other thiazides the propensity to deplete potassium reserves to an unpredictable degree. There have been isolated reports that certain non-edematous individuals developed severe fluid and electrolyte derangements after only brief exposure to normal doses of thiazide and non-thiazide diuretics. Thiazides should be used with caution in patients with renal disease or significant impairment of renal function, since azotemia may be precipitated and cumulative drug effects may occur. 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. Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.
Methyclothiazide is indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in the more severe forms of hypertension. Methyclothiazide tablets are indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Methyclothiazide tablets have also been found useful in edema due to various forms of renal dysfunction such as the nephrotic syndrome, acute glomerulonephritis, and chronic renal failure.<br/>Usage in Pregnancy: 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 . 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 beappropriate.