METAHYDRIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for METAHYDRIN (METAHYDRIN).
Metahydrin (trichlormethiazide) is a thiazide diuretic that inhibits the sodium-chloride symporter (NCC) in the distal convoluted tubule of the nephron, reducing sodium and chloride reabsorption and increasing excretion of water, sodium, chloride, and potassium.
| Metabolism | Metahydrin is not extensively metabolized; primarily excreted unchanged by the kidneys. |
| Excretion | Renal: 30% (fecal: 70% as unabsorbed drug, primarily biliary elimination; <1% unchanged in urine) |
| Half-life | 18-30 hours (clinically relevant for once-daily dosing in hypertension; prolonged in renal impairment) |
| Protein binding | 90-95% (bound to albumin and alpha-1-acid glycoprotein) |
| Volume of Distribution | 1.5-2.5 L/kg (indicates extensive tissue distribution, binding to vascular smooth muscle) |
| Bioavailability | Oral: 90-100% (well absorbed, minimal first-pass metabolism) |
| Onset of Action | Oral: 1-2 hours; peak effect at 4-6 hours |
| Duration of Action | 12-24 hours (antihypertensive effect persists for 24 hours, allowing once-daily dosing) |
| Molecular Weight | 378.9 |
Oral, 50-100 mg once daily. Maximum 200 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-<60 mL/min: 50 mg once daily. GFR <30 mL/min: 25 mg once daily or every other day. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: 50 mg once daily. Child-Pugh C: avoid use. |
| Pediatric use | Not recommended for pediatric use; safety not established. |
| Geriatric use | Start at 25 mg once daily; titrate slowly. Monitor renal function. |
| 1st trimester | Avoid due to potential teratogenic effects; animal studies show fetal abnormalities. |
| 2nd trimester | Avoid; may cause fetal harm (growth retardation, hypoglycemia). Use only if clearly needed. |
| 3rd trimester | Contraindicated; can cause prolonged hypoglycemia, electrolyte disturbances, and hypoglycemia in neonate. |
Clinical note
Comprehensive clinical and safety monograph for METAHYDRIN (METAHYDRIN).
| Placental transfer | Crosses the placenta; detected in fetal blood at levels approximating maternal serum. |
| Breastfeeding | Excreted into breast milk; may cause hypoglycemia in nursing infant. Avoid breastfeeding or discontinue drug. |
| Lactation Rating |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to chlorthalidone or sulfonamidesAnuriaHepatic coma or precomaSevere renal impairment (CrCl <30 mL/min)Electrolyte imbalance (e.g., hyponatremia, hypokalemia)
| Precautions | Electrolyte disturbances (hypokalemia, hyponatremia, hypochloremic alkalosis), Hyperuricemia and gout, Hypotension and orthostatic hypotension, Sulfonamide hypersensitivity reactions, Exacerbation of systemic lupus erythematosus, Photosensitivity, Increased risk of non-melanoma skin cancer, Acute angle-closure glaucoma (rare) |
| Food/Dietary | Avoid high-potassium foods and salt substitutes containing potassium chloride. Limit alcohol intake as it may increase hypotensive effects and risk of electrolyte disturbances. |
Loading safety data…
| L4 (Possibly Hazardous) |
| Teratogenic Risk | First trimester: Thiazide diuretics are generally avoided due to potential teratogenic effects, including neural tube defects and cardiovascular anomalies. Second and third trimesters: Associated with fetal or neonatal jaundice, thrombocytopenia, electrolyte imbalances, and possibly hypoglycemia. May cause decreased placental perfusion. |
| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (especially potassium, sodium), uric acid, blood glucose, and renal function. Fetal monitoring includes ultrasound for growth and amniotic fluid volume, as thiazides can cause oligohydramnios. |
| Fertility Effects | Limited data. Thiazides may interfere with placental hormone function but no direct evidence of impaired fertility. Long-term use may affect menstrual regularity due to electrolyte disturbances. |
| Clinical Pearls | Monitor serum potassium and renal function frequently, especially in patients with diabetes or impaired renal function. Avoid use with potassium supplements or potassium-sparing diuretics to prevent hyperkalemia. May cause azotemia and electrolyte imbalances; elderly patients are more susceptible. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily in the morning to avoid nighttime urination. · Avoid potassium-rich foods (e.g., bananas, oranges, salt substitutes) unless directed by your doctor. · Do not take any other medications, including over-the-counter products, without consulting your healthcare provider. · Report signs of electrolyte imbalance such as muscle cramps, weakness, irregular heartbeat, or unusual fatigue. · This medication may cause dizziness or lightheadedness; avoid driving or operating machinery until you know how it affects you. |