Methyclothiazide (Enduron) is a thiazide diuretic that acts on the distal tubules of the kidneys to cause fluid, sodium, and potassium loss. It is used in the management of patients with hypertension and fluid overload.
Methyclothiazide Uses:
-
Edema:
- Adjunctive therapy of edema
-
Hypertension:
- Management of hypertension
- Guideline recommendations:
- The 2017 Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults has recommended that if monotherapy is warranted, in the absence of comorbidities (eg, cerebrovascular disease, chronic kidney disease, diabetes, heart failure, ischemic heart disease, etc), that thiazide-like diuretics or dihydropyridine calcium channel blockers, due to better cardiovascular endpoints (eg, prevention of heart failure and stroke), may be preferred options.
- As monotherapy ACE inhibitors and ARBs are also acceptable. For achieving higher blood pressure goals combination therapy may be required and is initially preferred in patients at high risk (stage 2 hypertension or atherosclerotic cardiovascular disease [ASCVD] risk ≥10%).
Methyclothiazide (Enduron) Dose in Adults:
Methyclothiazide (Enduron) Dose in the treatment of Edema:
- Oral: 2.5 to 10 mg once a day
Methyclothiazide (Enduron) Dose in the treatment of Hypertension:
- Oral: 2.5 to 5 mg once a day; another antihypertensive may be added after a trial of 8 to 12 weeks of therapy if 5 mg is not adequate.
Dose in Children:
Not indicated.
Pregnancy Risk Factor B
- Thiazide diuretics may cross the placenta, and can be found in cord blood.
- Maternal use may cause neonatal jaundice, thrombocytopenia or other adverse events in adults.
- Chronic maternal hypertension can lead to adverse events in the fetus/infant.
- Chronic hypertension during pregnancy can increase the likelihood of having a baby with birth defects, low birthweight, premature birth, stillbirth, or neonatal death.
- The severity and length of maternal hypertension may impact the actual risks.
- Diuretics are second-line treatment for chronic hypertension during pregnancy.
Use during breastfeeding:
- Breast milk contains thiazide diuretics.
- The manufacturer recommends that a decision is made regarding whether to stop breastfeeding or discontinue using the drug.
- This is because of the potential for serious adverse reactions in breastfeeding infants.
- Thiazide diuretics can cause decreases in milk volume and suppressions of lactation. Avoid them whenever possible.
Dose in Kidney Disease:
No dosage adjustments are provided in the manufacturer's labeling. However, thiazides usually lose effectiveness with CrCl <30 mL/minute; use cautiously
Dose in Liver disease:
No dosage adjustments are provided in the manufacturer's labeling; use cautiously.
Side effects of Methyclothiazide (Enduron):
-
Cardiovascular:
- Necrotizing Angiitis
- Orthostatic Hypotension
-
Central Nervous System:
- Dizziness
- Headache
- Paresthesia
- Restlessness
- Vertigo
-
Dermatologic:
- Skin Photosensitivity
- Skin Rash
- Stevens-Johnson Syndrome
- Urticaria
-
Endocrine & Metabolic:
- Electrolyte Disturbance
- Glycosuria
- Hypercalcemia
- Hyperglycemia
- Hyperuricemia
- Hypokalemia
-
Gastrointestinal:
- Anorexia
- Constipation
- Diarrhea
- Epigastric Distress
- Gastric Irritation
- Nausea
- Pancreatitis
- Sialadenitis
- Vomiting
-
Hematologic & Oncologic:
- Agranulocytosis
- Aplastic Anemia
- Hemolytic Anemia
- Leukopenia
- Purpura
- Thrombocytopenia
-
Hepatic:
- Jaundice
-
Hypersensitivity:
- Anaphylaxis
-
Neuromuscular & Skeletal:
- Muscle Cramps
- Muscle Spasm
- Weakness
-
Ophthalmic:
- Transient Blurred Vision
- Xanthopsia
-
Respiratory:
- Pneumonitis
- Pulmonary Edema
- Respiratory Distress
-
Miscellaneous:
- Fever
Contraindications to Methyclothiazide (Enduron):
- Hypersensitivity
- Anuria
Warnings and precautions
-
Electrolyte disturbances:
- Hypokalemia, hypochloremic acidkalosis and hyponatremia can occur.
-
Hypersensitivity reactions
- Hypersensitivity reactions can occur.
-
Photosensitivity
- Photosensitization can occur.
-
Allergy to sulfonamide ("sulfa")
- FDA-approved product labels include a wide contraindication for patients who have had an allergic reaction to sulfonamides in the past.
- Cross-reactivity between members of a particular class can occur (e.g, two antibiotics sulfonamides).
- Cross-reactivity concerns have been raised for all compounds with the sulfonamide structural (SO-NH)
- A deeper understanding of allergy mechanisms has shown that cross-reactivity between nonantibiotic and antibiotic sulfonamides is unlikely.
- Particularly with non-antibiotic sulfonamides the mechanisms of anaphylaxis (cross-reaction secondary antibody production) are unlikely.
- T-cell-mediated reactions (type IV), which include maculopapular and other skin reactions, are less well understood.
- These classes are sometimes avoided by some clinicians in severe cases like Stevens-Johnson syndrome/TEN.
-
Insufficiency of the adrenal glands:
- Patients with primary adrenal disease (Addison disease), should avoid diuretics to treat elevated BP.
- Adjustment of glucocorticoid/mineralocorticoid therapy and/or use of alternate antihypertensive agents is preferred for the treatment of hypertension.
-
Diabetes:
- Precautions for diabetics and prediabetics: This could affect glucose control.
-
Gout
- Gout can be precipitated in some patients who have a history of gout, a family predisposition to it, or are suffering from chronic renal failure.
-
Hepatic impairment
- In severe hepatic dysfunction, use caution
- Avoid electrolyte imbalances and acid/base imbalances in cirrhosis to avoid hepatic-encephalopathy.
-
Hypercalcemia:
- Reduced renal calcium excretion may be caused by Thiazide Diuretics.
- Hypercalcemia patients should be avoided.
-
Hypercholesterolemia:
- Patients with high or moderate cholesterol should be cautious.
- There have been reports of an increase in cholesterol and triglyceride.
-
Hypokalemia
- Hypokalemia patients should be treated with caution.
- Before starting therapy, it is important to correct your potassium levels.
-
Parathyroid disease
- Thiazide diuretics reduce calcium excretion.
- Long-term use can lead to pathologic changes in parathyroid glands, including hypophosphatemia and hypercalcemia.
-
Renal impairment
- In severe renal disease (ineffective), it is best to avoid.
- Possible precipitation of azotemia. Stop taking the medication or withhold if you have renal impairment.
-
Systemic lupus erythematosus (SLE):
- Exacerbation/activation of SLE.
Methyclothiazide: Drug Interaction
|
Ajmaline |
Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. |
|
Alcohol (Ethyl) |
May enhance the orthostatic hypotensive effect of Thiazide and Thiazide-Like Diuretics. |
|
Alfuzosin |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Allopurinol |
Thiazide and Thiazide-Like Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinol, an active metabolite of Allopurinol. |
|
Aminolevulinic Acid (Topical) |
Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). |
|
Amphetamines |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Angiotensin-Converting Enzyme Inhibitors |
Thiazide and Thiazide-Like Diuretics may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Anticholinergic Agents |
May increase the serum concentration of Thiazide and Thiazide-Like Diuretics. |
|
Antidiabetic Agents |
Thiazide and Thiazide-Like Diuretics may diminish the therapeutic effect of Antidiabetic Agents. |
|
Antidiabetic Agents |
Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. |
|
Antipsychotic Agents (Second Generation [Atypical]) |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). |
|
Barbiturates |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Benperidol |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Beta2-Agonists |
May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. |
|
Brigatinib |
May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. |
|
Brimonidine (Topical) |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Calcium Salts |
Thiazide and Thiazide-Like Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. |
|
CarBAMazepine |
Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of CarBAMazepine. Specifically, there may be an increased risk for hyponatremia. |
|
Cardiac Glycosides |
Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Cardiac Glycosides. Specifically, cardiac glycoside toxicity may be enhanced by the hypokalemic and hypomagnesemic effect of thiazide diuretics. |
|
Corticosteroids (Orally Inhaled) |
May enhance the hypokalemic effect of Thiazide and ThiazideLike Diuretics. |
|
Corticosteroids (Systemic) |
May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. |
|
Cyclophosphamide |
Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, granulocytopenia may be enhanced. |
|
Dexketoprofen |
May enhance the adverse/toxic effect of Sulfonamides. |
|
Dexmethylphenidate |
May diminish the therapeutic effect of Antihypertensive Agents. |
|
Diacerein |
May enhance the therapeutic effect of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. |
|
Diazoxide |
Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Diazoxide. |
|
Diazoxide |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Dichlorphenamide |
Thiazide and Thiazide-Like Diuretics may enhance the hypokalemic effect of Dichlorphenamide. |
|
DULoxetine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. |
|
Herbs (Hypertensive Properties) |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Herbs (Hypotensive Properties) |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Hypotension-Associated Agents |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. |
|
Ipragliflozin |
May enhance the adverse/toxic effect of Thiazide and Thiazide-Like Diuretics. Specifically, the risk for intravascular volume depletion may be increased. |
|
Ivabradine |
Thiazide and Thiazide-Like Diuretics may enhance the arrhythmogenic effect of Ivabradine. |
|
Levodopa-Containing Products |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. |
|
Licorice |
May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. |
|
Lormetazepam |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Methenamine |
Thiazide and Thiazide-Like Diuretics may diminish the therapeutic effect of Methenamine. |
|
Methylphenidate |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Molsidomine |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Multivitamins/Fluoride (with ADE) |
May enhance the hypercalcemic effect of Thiazide and Thiazide-Like Diuretics. |
|
Multivitamins/Minerals (with ADEK, Folate, Iron) |
Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Multivitamins/Minerals (with ADEK, Folate, Iron). |
|
Multivitamins/Minerals (with AE, No Iron) |
Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Multivitamins/Minerals (with AE, No Iron). Specifically, thiazide diuretics may decrease the excretion of calcium, and continued concomitant use can also result in metabolic alkalosis. |
|
Naftopidil |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Neuromuscular-Blocking Agents (Nondepolarizing) |
Thiazide and Thiazide-Like Diuretics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). |
|
Nicergoline |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Nicorandil |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Nitroprusside |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. |
|
Nonsteroidal Anti-Inflammatory Agents |
Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. |
|
Opioid Agonists |
May enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. |
|
Oxcarbazepine |
Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of OXcarbazepine. Specifically, there may be an increased risk for hyponatremia. |
|
Pentoxifylline |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Pholcodine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. |
|
Phosphodiesterase 5 Inhibitors |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Porfimer |
Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. |
|
Prostacyclin Analogues |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Quinagolide |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Reboxetine |
May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. |
|
Selective Serotonin Reuptake Inhibitors |
May enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. |
|
Toremifene |
Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Toremifene. |
|
Verteporfin |
Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. |
|
Vitamin D Analogs |
Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Vitamin D Analogs. |
|
Yohimbine |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Risk Factor D (Consider therapy modification) |
|
|
Amifostine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. |
|
Bile Acid Sequestrants |
|
|
Dofetilide |
Thiazide and Thiazide-Like Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Dofetilide. Management: Although hydrochlorothiazide is specifically cited as a contraindication, the risk likely extends to all thiazide and thiazide-like diuretics and may be even greater with chlorthalidone or bendroflumethiazide. Consider alternatives when possible. |
|
Lithium |
Thiazide and Thiazide-Like Diuretics may decrease the excretion of Lithium. |
|
Obinutuzumab |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. |
|
Sodium Phosphates |
Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. |
|
Topiramate |
Thiazide and Thiazide-Like Diuretics may enhance the hypokalemic effect of Topiramate. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Topiramate. Management: Monitor for increased topiramate levels/adverse effects (e.g., hypokalemia) with initiation/dose increase of a thiazide diuretic. Closely monitor serum potassium concentrations with concomitant therapy. Topiramate dose reductions may be necessary. |
|
Risk Factor X (Avoid combination) |
|
|
Aminolevulinic Acid (Systemic) |
Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). |
|
Bromperidol |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. |
|
Fexinidazole [INT] |
Thiazide and Thiazide-Like Diuretics may enhance the arrhythmogenic effect of Fexinidazole [INT]. |
|
Levosulpiride |
Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Levosulpiride. |
|
Mecamylamine |
Sulfonamides may enhance the adverse/toxic effect of Mecamylamine. |
|
Promazine |
Thiazide and Thiazide-Like Diuretics may enhance the QTc-prolonging effect of Promazine. |
Monitoring parameters:
- Assess weight
- Daily intake and output reports for determination of fluid loss
- Blood pressure
- Serum electrolytes, BUN, creatinine
Hypertension: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults:
- Confirmed hypertension & known cardiovascular disease or 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10%: Target BP <130/80 mm Hg is recommended.
- Confirmed hypertension without markers of increased ASCVD risk: Target BP <130/80 mm Hg may be reasonable.
Diabetes and hypertension: The American Diabetes Association (ADA) guidelines:
- Patients 18 to 65 years of age, without ASCVD, and 10-year ASCVD risk <15%: Target BP <140/90 mm Hg is recommended.
- Patients 18 to 65 years of age and known ASCVD or 10-year ASCVD risk >15%: Target BP <130/80 mm Hg may be appropriate if it can be safely attained.
- Patients >65 years of age (healthy or complex/intermediate health): Target BP <140/90 mm Hg is recommended.
- Patients >65 years of age (very complex/poor health): Target BP <150/90 mm Hg is recommended.
How to administer Methyclothiazide (Enduron)?
Oral:
- May be administered with milk or food.
- To avoid nocturia should be administered early in the day.
- In case of multiple doses, the last dose should be administered no later than 6 PM unless instructed otherwise.
Mechanism of action of Methyclothiazide (Enduron):
- Inhibition of sodium reabsorption occurs in the distal tubules, leading to an increase in sodium excretion along with water and potassium.
The onset of action:
- Diuresis: 2 hours
Peak effect:
- 6 hours
Duration:
- Almost 24 hours
Excretion:
- Urine (as unchanged drug)
International Brand Names of Methyclothiazide:
- Enduron
- Urimor
Methyclothiazide Brand Names in Pakistan:
No Brands Available in Pakistan.
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