Methyclothiazide

Methyclothiazide
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gerald Chi

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Overview

Methyclothiazide is a thiazide-like diuretic that is FDA approved for the {{{indicationType}}} of hypertension and edema associated with congestive heart failure, hepatic cirrhosis, renal dysfunction, and corticosteroid and estrogen therapy. Common adverse reactions include hypotension, rash, hyperuricemia, hypokalemia, nausea, cramp, dizziness, and headache.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

• Methyclothiazide tablets are 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.

Edema

• Dosing Information

• 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.

Hypertension

• Dosing Information

• 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.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Methyclothiazide in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Methyclothiazide in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Safety and effectiveness in children have not been established.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Methyclothiazide in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Methyclothiazide in pediatric patients.

Contraindications

• Anuria
• Hypersensitivity to this compound or other sulfonamide-derived drugs

Warnings

• 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.

Precautions

• 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.

Laboratory Tests

• 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.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Methyclothiazide in the drug label.

Postmarketing Experience

• 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

Orthostatic hypotension (may be potentiated by alcohol, barbiturates, or narcotics).

Hematologic

Aplastic anemia, hemolytic anemia, agranulocytosis, leukopenia, thrombocytopenia.

Gastrointestinal

Pancreatitis, jaundice (intrahepatic cholestatic), sialadenitis, vomiting, diarrhea, nausea, gastric irritation, constipation, anorexia.

Hypersensitivity

Anaphylactic reactions, necrotizing angiitis (vasculitis, cutaneous vasculitis), Stevens-Johnson syndrome, respiratory distress including pneumonitis and pulmonary edema, fever, purpura, urticaria, rash, photosensitivity.

Metabolic

Hyperglycemia, hyperuricemia, electrolyte imbalance, hypercalcemia.

Neurologic

Vertigo, dizziness, paresthesias, muscle spasm, restlessness.

Special Senses

Transient blurred vision, xanthopsia.

Urogenital

Glycosuria.

Drug Interactions

• 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.

Drug/Laboratory Test Interactions

• Thiazides may decrease serum PBI levels without signs of thyroid disturbance.
• Thiazides should be discontinued before carrying out tests for parathyroid function.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category B

• Tteratogenic Effects

• Reproduction studies performed in rats and rabbits at doses up to 4 mg/kg/day have revealed no evidence of harm to the fetus due to methyclothiazide. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

• Nonteratogenic Effects

• Thiazides cross the placental barrier and appear in cord blood. The use of thiazides in pregnant women requires that the anticipated benefit be weighed against possible hazards to the fetus. These hazards include fetal or neonatal jaundice, thrombocytopenia and possible other adverse reactions that have occurred in the adult.

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Methyclothiazide in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Methyclothiazide during labor and delivery.

Nursing Mothers

• 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.

Pediatric Use

• Safety and effectiveness in children have not been established.

Geriatic Use

There is no FDA guidance on the use of Methyclothiazide with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Methyclothiazide with respect to specific gender populations.

Race

There is no FDA guidance on the use of Methyclothiazide with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Methyclothiazide in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Methyclothiazide in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Methyclothiazide in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Methyclothiazide in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

Monitoring

There is limited information regarding Monitoring of Methyclothiazide in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Methyclothiazide in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• Symptoms of overdosage include electrolyte imbalance and signs of potassium deficiency such as confusion, dizziness, muscular weakness, and gastrointestinal disturbances.

Management

• General supportive measures including replacement of fluids and electrolytes may be indicated in treatment of overdosage.

Chronic Overdose

There is limited information regarding Chronic Overdose of Methyclothiazide in the drug label.

Pharmacology

Mechanism of Action

• 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.

Structure

• 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:

This image is provided by the National Library of Medicine.

• Each methyclothiazide tablet, USP for oral administration contains 5 mg methyclothiazide, USP and the following inactive ingredients: colloidal silicon dioxide, FD&C Blue No. 1 Aluminum Lake, magnesium stearate, microcrystalline cellulose, pregelatinized starch, sodium lauryl sulfate and sodium starch glycolate.

Pharmacodynamics

• Methyclothiazide has a per mg natriuretic activity approximately 100 times that of the prototype thiazide, chlorothiazide. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic/natriuretic effects.
• There is significant natriuresis and diuresis within 2 hours after administration of a single-dose of methyclothiazide. These effects reach a peak in about 6 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.

Pharmacokinetics

• 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.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

• 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).

Clinical Studies

There is limited information regarding Clinical Studies of Methyclothiazide in the drug label.

How Supplied

• Methyclothiazide Tablets, USP are available containing 5 mg of methyclothiazide, USP.
• The 5 mg tablets are blue tablets debossed with M above the score and 29 below the score on one side of the tablet and blank on the other side. They are available as follows:

NDC 0378-0160-01

Bottles of 100 tablets

• Store at 20° to 25°C (68° to 77° F). [See USP Controlled Room Temperature.]
• Protect from light and moisture.
• Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Storage

There is limited information regarding Methyclothiazide Storage in the drug label.

Images

Drug Images

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Patient Counseling Information

• Patients should inform their doctor if they have:

• Had an allergic reaction to methyclothiazide or other diuretics
• Asthma
• Kidney disease
• Liver disease
• Gout
• Systemic lupus erythematosus
• Had 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.

Precautions with Alcohol

• Orthostatic hypotension may be potentiated by alcohol.
• Alcohol can increase the chance of dizziness.

Brand Names

• Aquatensen®
• Enduron®

Look-Alike Drug Names

• N/A

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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