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 |
| Molecular Weight | 376.5 |
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 | Methyclothiazide crosses the placenta and may cause fetal or neonatal jaundice, thrombocytopenia, and electrolyte disturbances. Use only if clearly needed. |
| 2nd trimester | Associated with maternal volume depletion and electrolyte imbalance, which may compromise placental perfusion. Avoid if possible. |
| 3rd trimester | May cause fetal or neonatal jaundice, thrombocytopenia, and electrolyte disturbances. Avoid use in pregnancy-induced hypertension due to decreased placental perfusion. |
Clinical note
Comprehensive clinical and safety monograph for METHYCLOTHIAZIDE (METHYCLOTHIAZIDE).
| Placental transfer | Crosses the placenta; detected in cord blood and amniotic fluid. |
| Breastfeeding | Methyclothiazide is excreted into breast milk in low amounts. Monitor the infant for electrolyte disturbances, dehydration, and diuretic effects. Use caution, especially in nursing newborns or preterm infants. |
■ FDA Black Box Warning
No FDA boxed warning
| Common Effects | Fatigue Nasopharyngitis inflammation of the throat and nasal passages |
| Serious Effects |
AnuriaRenal failure (creatinine clearance <30 mL/min)Hypersensitivity to methyclothiazide or sulfonamide-derived drugs
| 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) |
| Food/Dietary | Avoid excessive intake of potassium-rich foods (bananas, oranges, spinach) unless directed; this drug increases potassium loss. Limit alcohol as it may enhance hypotensive effects. Take with food or milk to reduce gastrointestinal upset. |
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| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| Clinical Pearls | Monitor serum potassium and glucose; may cause hypokalemia and hyperglycemia. Effective in hypertension and edema. Onset of diuresis within 2 hours, peak at 6 hours, duration 24 hours. Avoid in severe renal impairment (CrCl <30 mL/min). |
| Patient Advice | Take exactly as prescribed, usually once daily in the morning to avoid nighttime urination. · May cause dizziness or lightheadedness; rise slowly from sitting or lying positions. · Report symptoms of low potassium (muscle cramps, weakness, irregular heartbeat) or high blood sugar (increased thirst, frequent urination). · Avoid prolonged sun exposure and use sunscreen; may increase sensitivity to sunlight. · Do not stop taking without consulting your doctor, even if you feel well. |