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.

It has the following molecular formula C₉H₁₁Cl₂N₃O₄S₂ with a molecular weight of 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.

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.

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 (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.

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.

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.

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 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:

Store at controlled room temperature 15°-30°C (59°-86°F).

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Rx only

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 (See PRECAUTIONS section), hypercalcemia.

Nervous System: Vertigo, dizziness, paresthesias, muscle spasm, restlessness.

Special Senses: Transient blurred vision, xanthopsia.

Urogenital System: Glycosuria.

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.

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 nonthiazide 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.

General

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.

Information for Patients

See PATIENT INFORMATION section.

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.

Drug Interactions

See DRUG INTERACTIONS section.

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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No data are 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).

Pregnancy

Teratogenic Effects

Pregnancy Category B: 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.

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.

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.

Methyclothiazide is contraindicated in patients with anuria and in patients with a history of hypersensitivity to this compound or other sulfonamide-derived drugs.

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 are approximately 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.

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.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

METHYCLOTHIAZIDE - ORAL

(meth-i-kloe-THIGH-uh-zide)

USES: This medication is used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. Methyclothiazide is a "water pill" (diuretic) that causes your body to get rid of extra salt and water. This increases the amount of urine you make.

This medication also reduces extra fluid in the body (edema) caused by conditions such as congestive heart failure, liver disease, and kidney disease. Getting rid of extra water helps to reduce fluid in the lungs so that you can breathe easier. It also helps to decrease swelling of the arms, legs, and stomach/abdomen.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This medication may also be used to treat a condition known as "water diabetes" (diabetes insipidus) and to help prevent calcium kidney stones.

HOW TO USE: Take this medication by mouth with or without food, usually once daily or as directed by your doctor. It is best to avoid taking this medication within 4 hours of your bedtime to avoid having to get up to urinate. Consult your doctor or pharmacist if you have questions about your dosing schedule.

The dosage is based on your medical condition and response to therapy. The manufacturer recommends that you do not take more than 10 milligrams as a single daily dose to treat edema or more than 5 milligrams daily to treat high blood pressure.

Use this medication regularly in order to get the most benefit from it. To help you remember, take it at the same time each day or as prescribed. Do not increase your dose, skip doses, or stop taking this medication unless directed by your doctor. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick. For the treatment of high blood pressure, it may take up to several weeks before the full benefit of this drug takes effect.

Cholestyramine and colestipol can decrease the absorption of this medication by your body. If you are taking either of these drugs, separate them from methyclothiazide by at least 4 hours.

Inform your doctor if your condition does not improve or if it worsens (e.g., swelling increases, your routine blood pressure readings increase).

SIDE EFFECTS: Dizziness, lightheadedness, headache, blurred vision, loss of appetite, stomach upset, diarrhea, or constipation may occur as your body adjusts to the medication. You may also experience decreased sexual ability or increased sensitivity to the sun. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

This medication may cause a loss of too much body water (dehydration) and salt/minerals. Tell your doctor immediately if you have any of these unlikely but serious symptoms of dehydration or mineral loss: very dry mouth, thirst, muscle cramps, weakness, fast/irregular heartbeat, nausea, vomiting, severe dizziness, unusual drowsiness, unusual decrease in the amount of urine, fainting, confusion, seizures.

Tell your doctor immediately if any of these unlikely but serious side effects occur: numbness/tingling of the arms/legs, joint pain (e.g., big toe pain).

Tell your doctor immediately if any of these rare but very serious side effects occur: signs of infection (e.g., fever, persistent sore throat), easy bruising/bleeding, stomach/abdominal pain, persistent nausea/vomiting, unusual/persistent tiredness, yellowing eyes/skin, dark urine, unusual change in the amount of urine (not including the normal increase in urine when you first start this drug).

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking methyclothiazide, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: severe kidney disease (inability to make urine).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease, untreated salt/mineral imbalance (e.g., imbalance of sodium, potassium, calcium, magnesium), loss of too much body water (dehydration), high levels of fats in the blood (high cholesterol/triglycerides), gout, lupus, certain recent nerve surgery (sympathectomy).

If you have diabetes, methyclothiazide may affect your blood sugar levels. Check your blood sugar levels regularly as directed and share the results with your doctor. Tell your doctor immediately if you have symptoms of high blood sugar such as increased thirst/urination. Your doctor may need to adjust your anti-diabetic medication or diet.

This drug may reduce the potassium levels in your blood. Ask your doctor about increasing the amount of potassium in your diet (e.g., bananas, orange juice) or about using a salt substitute containing potassium. A potassium supplement may be prescribed by your doctor.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen and wear protective clothing when outdoors.

Before having surgery, tell your doctor or dentist that you are taking this medication.

This drug may make you dizzy or cause blurred vision; use caution engaging in activities requiring alertness such as driving or using machinery. Limit alcoholic beverages.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position. Significant loss of body water from too much sweating, vomiting, or diarrhea can also lower your blood pressure and worsen dizziness. Drink plenty of fluids to prevent these effects and dehydration. If you are on restricted fluid intake, consult your doctor for further instructions. Contact your doctor if you are unable to drink fluids or if you have persistent diarrhea/vomiting.

Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, the elderly may be more sensitive to the effects of this drug, especially dizziness.

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

This drug passes into breast milk. While there have been no reports of harm to nursing infants, consult your doctor before breast-feeding.

DRUG INTERACTIONS: See also the How to Use section.

Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medications because very serious interactions may occur: cisapride, dofetilide.

If you are currently using any of these medications, tell your doctor or pharmacist before starting methyclothiazide.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: corticosteroids (e.g., prednisone), diazoxide, digoxin, lithium, nonsteroidal anti-inflammatory drugs (e.g., ibuprofen, indomethacin), drugs that can increase dizziness (e.g., phenobarbital, narcotic pain relievers such as codeine).

Check the labels on all your medicines (e.g., cough-and-cold products, diet aids, nonsteroidal anti-inflammatory drugs-NSAIDs for pain/fever reduction) because they may contain ingredients that could increase your blood pressure (e.g., pseudoephedrine, phenylephrine) or reduce the effect of this medication (e.g., ibuprofen, naproxen). Ask your pharmacist about the safe use of those products.

Low-dose aspirin, as prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually at dosages of 81-325 milligrams per day) should be continued. Consult your doctor or pharmacist for more details.

This product can affect the results of certain lab tests. Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include: severe dizziness, severe weakness, fainting.

NOTES: Do not share this medication with others.

Lifestyle changes such as stress reduction programs, exercise, and dietary changes may increase the effectiveness of this medicine. Talk to your doctor or pharmacist about lifestyle changes that might benefit you.

Laboratory and/or medical tests (e.g., blood mineral levels such as potassium, kidney and liver function tests) should be performed from time to time to monitor your progress or check for side effects. Consult your doctor for more details.

Have your blood pressure checked regularly while taking this medication. Learn how to monitor your own blood pressure, and share the readings with your doctor.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store in a tightly closed container at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For enrollment information call MedicAlert at 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.