METHYCLOTHIAZIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for METHYCLOTHIAZIDE (METHYCLOTHIAZIDE).
Thiazide-like diuretic that inhibits sodium-chloride symporter in distal convoluted tubule, increasing excretion of sodium, chloride, and water. Reduces peripheral vascular resistance.
| Metabolism | Not extensively metabolized; undergoes some hepatic metabolism via CYP450 enzymes (minor pathway). Primarily excreted unchanged in urine. |
| Excretion | Primarily renal (70-80% as unchanged drug via tubular secretion and glomerular filtration); minor biliary/fecal (<10%) |
| Half-life | Terminal elimination half-life: ~40 hours (range 30-50 h); due to extensive tubular reabsorption, half-life is prolonged in renal impairment and elderly, allowing once-daily dosing |
| Protein binding | ~78% bound primarily to albumin (and some to other plasma proteins) |
| Volume of Distribution | 0.2-0.5 L/kg (confined mainly to extracellular fluid; low distribution into tissues due to high protein binding) |
| Bioavailability | Oral: approximately 70-80% (well absorbed; first-pass metabolism minimal) |
| Onset of Action | Oral: diuresis begins within 2 hours; peak effect at 6-12 hours |
| Duration of Action | 24 hours (antihypertensive effect persists up to 24 h); diuretic effect may last 12-24 h. Single daily dosing is sufficient |
2.5-10 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if GFR <30 mL/min. For GFR 30-50 mL/min, use with caution and monitor renal function; no dose adjustment specified. For GFR >50 mL/min, no adjustment needed. |
| Liver impairment | No specific dose adjustment guidelines for Child-Pugh classes. Use with caution in severe hepatic impairment due to electrolyte imbalances. |
| Pediatric use | Not recommended for use in children. Safety and efficacy not established. |
| Geriatric use | Initiate at 2.5 mg once daily due to increased sensitivity; monitor for hypotension and electrolyte imbalances. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for METHYCLOTHIAZIDE (METHYCLOTHIAZIDE).
| Breastfeeding | Methyclothiazide is excreted into breast milk in low amounts. M/P ratio is not reported. Thiazides may suppress lactation. Use during breastfeeding is not recommended due to potential for neonatal electrolyte disturbances and thrombocytopenia. Consider alternative agents if diuresis is required. |
| Teratogenic Risk | Thiazide diuretics are generally avoided in pregnancy due to risk of maternal hypovolemia, electrolyte imbalances, and potential for neonatal thrombocytopenia, jaundice, and electrolyte disturbances. Methyclothiazide is classified as FDA Pregnancy Category B, but limited human data. Use during first trimester is not recommended unless benefit outweighs risk. Second and third trimester use may cause fetal or neonatal thrombocytopenia, jaundice, and electrolyte disturbances. Avoid for treatment of gestational hypertension due to decreased plasma volume. |
■ FDA Black Box Warning
No FDA boxed warning
| Common Effects | Fatigue Nasopharyngitis inflammation of the throat and nasal passages |
| Serious Effects |
["Anuria","Hypersensitivity to methyclothiazide or sulfonamide-derived drugs","Severe renal disease (creatinine clearance <30 mL/min)","Hepatic coma or pre-coma"]
| Precautions | ["Hypokalemia","Hyperuricemia","Sulfonamide allergy cross-reactivity","Electrolyte imbalance (hyponatremia, hypomagnesemia)","Diabetes mellitus: may increase blood glucose","Systemic lupus erythematosus exacerbation","Orthostatic hypotension","Renal impairment (risk of azotemia)"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (especially potassium, sodium, chloride), renal function, and urine output. Assess for signs of maternal hypovolemia. Fetal monitoring include ultrasound for growth restriction and amniotic fluid volume (thiazides may cause oligohydramnios). Monitor neonatal for thrombocytopenia, jaundice, and electrolyte disturbances after delivery. |
| Fertility Effects | No known adverse effects on fertility in males or females. Thiazides do not affect ovulation or spermatogenesis. |