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:
- In the absence of comorbidities (such as cerebrovascular disease, chronic kidney disease, diabetes, heart failure, ischemic heart disease, etc.), thiazide-like diuretics or dihydropyridine calcium channel blockers may be preferred due to better cardiovascular endpoints (such as the prevention of heart failure and stroke). This recommendation comes from the 2017 Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults.
- ARBs and ACE inhibitors are also acceptable for monotherapy. Combination therapy may be needed to reach higher blood pressure objectives and is initially favoured in individuals at high risk (stage 2 hypertension or an atherosclerotic cardiovascular disease [ASCVD] risk of 10% or above).
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 can be detected in cord blood and may cross the placenta.
- Neonatal jaundice, thrombocytopenia, or other negative consequences in adults may result from maternal usage.
- Events that are harmful to the foetus or infant can result from chronic maternal hypertension.
- Pregnant women with chronic hypertension run a higher risk of giving birth to children who have birth abnormalities, low birth weight, early birth, stillbirth, or neonatal mortality.
- 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.
- The mechanisms of anaphylaxis (cross-reaction secondary antibody formation), especially with non-antibiotic sulfonamides, appear unlikely.
- Less is known about T-cell-mediated reactions (type IV), which include maculopapular and other skin reactions.
- 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.
- For the management of hypertension, it is preferable to modify glucocorticoid/mineralocorticoid therapy and/or employ other antihypertensive medications.
-
Diabetes:
- Precautions for diabetics and prediabetics: This could affect glucose control.
-
Gout
- Patients with a history of gout, a familial history of gout, or chronic renal insufficiency may get gout that is triggered.
-
Hepatic impairment
- Be cautious in cases of severe hepatic impairment.
- To prevent hepatic encephalopathy in cirrhosis, minimise acid/base imbalances and electrolyte imbalances.
-
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 might make ajmaline more harmful or poisonous. In particular, there may be an elevated risk for cholestasis. |
|
Alcohol (Ethyl) |
Increases the effectiveness of thiazide and thiazide-like diuretics in lowering orthostatic blood pressure. |
|
Alfuzosin |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Allopurinol |
The possibility of allergic or hypersensitive reactions to allopurinol may be increased by thiazide and thiazide-like diuretics. The serum concentration of Allopurinol may rise in response to thiazides and thiazide-like diuretics. In particular, Thiazide Diuretics may raise Oxypurinol's levels, an active metabolite of Allopurinol. |
|
Aminolevulinic Acid (Topical) |
Aminolevulinic Acid's photosensitizing impact may be enhanced by photosensitizing agents (Topical). |
|
Amphetamines |
May lessen the effectiveness 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 |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Benperidol |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
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) |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
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 lessen the effectiveness 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 |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
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 lessen the effectiveness of antihypertensive agents. |
|
Herbs (Hypotensive Properties) |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Hypotension-Associated Agents |
The hypotensive action of hypotension-associated agents may be strengthened by blood pressure lowering medications. |
|
Ipragliflozin |
The toxic and harmful effects of thiazide and thiazide-like diuretics may be increased. In particular, there may be an elevated risk for intravascular volume depletion. |
|
Ivabradine |
The arrhythmogenic impact of ivabradine may be enhanced by thiazide and thiazide-like diuretics. |
|
Levodopa-Containing Products |
Levodopa-Containing Products' hypotensive effects may be strengthened by blood pressure-lowering medications. |
|
Licorice |
Thiazide and Thiazide-Like Diuretics might have an enhanced hypokalemic impact. |
|
Lormetazepam |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Methenamine |
The therapeutic effects of methenamine may be diminished by thiazide and thiazide-like diuretics. |
|
Methylphenidate |
May lessen the effectiveness of antihypertensive agents. |
|
Molsidomine |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Multivitamins/Fluoride (with ADE) |
Thiazide and Thiazide-Like Diuretics might have an enhanced hypokalemic impact. |
|
Multivitamins/Minerals (with ADEK, Folate, Iron) |
The effect of multivitamins and minerals on hypercalcemia may be enhanced by thiazide and thiazide-like diuretics (with ADEK, Folate, Iron). |
|
Multivitamins/Minerals (with AE, No Iron) |
The serum concentration of multiple vitamins and minerals may rise after taking thiazide and thiazide-like diuretics (with AE, No Iron). Particularly, thiazide diuretics may reduce calcium excretion, and long-term concurrent usage may result in metabolic alkalosis. |
|
Naftopidil |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Neuromuscular-Blocking Agents (Nondepolarizing) |
The neuromuscular-blocking action of neuromuscular-blocking agents may be enhanced by thiazide and thiazide-like diuretics (Nondepolarizing). |
|
Nicergoline |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Nicorandil |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Nitroprusside |
Nitroprusside's hypotensive impact may be strengthened by blood pressure-lowering medications. |
|
Nonsteroidal Anti-Inflammatory Agents |
Nonsteroidal Anti-Inflammatory Agents' nephrotoxic effects may be intensified by thiazide and thiazide-like diuretics. Thiazide and Thiazide-Like Diuretics may have less of a therapeutic impact when used with nonsteroidal anti-inflammatory drugs. |
|
Opioid Agonists |
Could make diuretics' harmful or toxic effects worse. Opioid antagonists may reduce diuretics' therapeutic benefit. |
|
Oxcarbazepine |
Thiazide and Thiazide-Like Diuretics may intensify OXcarbazepine's negative/toxic effects. Particularly, there could be a higher risk of hyponatremia. |
|
Pentoxifylline |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Pholcodine |
Pholcodine's hypotensive impact may be strengthened by blood pressure lowering medications. |
|
Phosphodiesterase 5 Inhibitors |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Porfimer |
The photosensitizing effect of Porfimer may be strengthened by photosensitizing agents. |
|
Prostacyclin Analogues |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Quinagolide |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Reboxetine |
Thiazide and Thiazide-Like Diuretics might have an enhanced hypokalemic impact. |
|
Selective Serotonin Reuptake Inhibitors |
Thiazide and Thiazide-Like Diuretics might have an enhanced hypokalemic impact. |
|
Toremifene |
Toremifene's hypercalcemic impact may be enhanced by thiazide and thiazide-like diuretics. |
|
Verteporfin |
Verteporfin's photosensitizing effect may be strengthened by photosensitizing agents. |
|
Vitamin D Analogs |
The hypercalcemic impact of vitamin D analogues may be enhanced by thiazides and thiazide-like diuretics. |
|
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 |
The absorption of thiazide and thiazide-like diuretics may be reduced. Also reduced is the diuretic reaction. |
|
Dofetilide |
The QTc-prolonging action of dofetilide may be enhanced by thiazide and thiazide-like diuretics. The blood concentration of Dofetilide may rise in response to thiazide and thiazide-like diuretics. Management: Despite the fact that hydrochlorothiazide is clearly listed as being contraindicated, the risk certainly applies to all thiazide and thiazide-like diuretics and may even be larger when using chlorthalidone or bendroflumethiazide. When feasible, take into account alternatives. |
|
Lithium |
The excretion of lithium may be reduced by thiazide and thiazide-like diuretics. |
|
Obinutuzumab |
The hypotensive effects of blood pressure-lowering medications may be strengthened. Management: Take into account temporarily stopping blood pressure-lowering drugs 12 hours before the start of the obinutuzumab infusion and keeping them off until 1 hour after the infusion is finished. |
|
Sodium Phosphates |
The nephrotoxic effects of sodium phosphates may be increased by diuretics. In particular, there may be an increased risk of acute phosphate nephropathy. Treatment: You might want to temporarily stop taking diuretics or look for an alternative to the oral sodium phosphate bowel preparation in order to prevent this combo. If the combination cannot be avoided, drink well and keep an eye on your kidney and fluid levels. |
|
Topiramate |
The hypokalemic impact of topiramate may be enhanced by thiazide and thiazide-like diuretics. The blood concentration of topiramate may rise in response to thiazide and thiazide-like diuretics. When using a thiazide diuretic, monitor for elevated topiramate levels and any negative consequences (such as hypokalemia). Serum potassium levels should be closely watched when receiving concurrent treatment. There may be a need to lower topiramate dosage. |
|
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] |
Fexinidazole [INTability ]'s to induce arrhythmias may be enhanced by the use of thiazide and thiazide-like diuretics. |
|
Levosulpiride |
Thiazide and Thiazide-Like Diuretics may intensify Levosulpiride's negative/toxic effects. |
|
Mecamylamine |
Sulfonamides may intensify Mecamylamine's harmful or hazardous effects. |
|
Promazine |
Promazine's ability to prolong QTc may be enhanced by thiazide and thiazide-like diuretics. |
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:
- Target blood pressure of 130/80 mm Hg is advised if you have confirmed hypertension, a history of cardiovascular disease, or a 10-year atherosclerotic cardiovascular disease (ASCVD) risk of 10% or less.
- Confirmed hypertension without signs of a higher risk for ASCVD: A target blood pressure of 130/80 mm Hg might be adequate.
Diabetes and hypertension: The American Diabetes Association (ADA) guidelines:
- Target blood pressure of 140/90 mm Hg is advised for patients aged 18 to 65 who do not have ASCVD and have a 10-year ASCVD risk of less than 15%.
- Patients between the ages of 18 and 65 with known ASCVD or a 10-year ASCVD risk more than 15% may benefit from a target blood pressure of 130/80 mm Hg if it can be safely achieved.
- Patients over 65 who are in good or complex/intermediate health should aim for a target blood pressure of 140/90 mm Hg.
- Patients over 65 who are very complex or in poor health should aim for a target blood pressure of 150/90 mm Hg.
How to administer Methyclothiazide (Enduron)?
Oral:
- Po
- Early in the day should be used to avoid nocturia.
- If there are numerous doses, the last dose, unless otherwise advised, should be given no later than 6 PM.
Mechanism of action of Methyclothiazide (Enduron):
- At the distal end, sodium reabsorption is inhibited.
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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