DICHLORPHENAMIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DICHLORPHENAMIDE (DICHLORPHENAMIDE).
Dichlorphenamide is a carbonic anhydrase inhibitor. It inhibits the enzyme carbonic anhydrase in the proximal renal tubule, reducing reabsorption of bicarbonate, leading to metabolic acidosis, and decreasing intraocular pressure by reducing aqueous humor formation.
| Metabolism | Dichlorphenamide is not extensively metabolized; it is excreted unchanged in urine. |
| Excretion | Primarily renal via tubular secretion; 50-70% excreted unchanged in urine; minor biliary/fecal elimination (<20%). |
| Half-life | Terminal elimination half-life of 2-4 hours; increased in renal impairment, up to 12-24 hours in severe insufficiency. |
| Protein binding | 90-95% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.2-0.3 L/kg; low Vd indicates limited extravascular distribution, consistent with high protein binding. |
| Bioavailability | Oral: approximately 80-100% (well absorbed); bioavailability not defined for parenteral routes as not typically given. |
| Onset of Action | Oral: 30-60 minutes for diuretic effect; intravenous (if applicable, though not standard): minutes. |
| Duration of Action | 8-12 hours; diuresis resolves within 12 hours; prolonged in renal impairment. |
| Molecular Weight | 305.16 |
25-50 mg orally twice daily.
| Dosage form | TABLET |
| Renal impairment | CrCl <50 mL/min: not recommended; CrCl 50-80 mL/min: 25 mg once daily; CrCl >80 mL/min: no adjustment. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 25 mg once daily; Child-Pugh C: avoid use. |
| Pediatric use | Not established; safety and efficacy not determined in children. |
| Geriatric use | Start at 25 mg once daily; monitor renal function and electrolytes. |
| 1st trimester | Contraindicated. Risk of teratogenicity based on animal studies and known carbonic anhydrase inhibitor effects. |
| 2nd trimester | Contraindicated. Possible fetal harm. |
| 3rd trimester | Contraindicated. Risk of kernicterus due to albumin binding displacement. |
Clinical note
Comprehensive clinical and safety monograph for DICHLORPHENAMIDE (DICHLORPHENAMIDE).
| Placental transfer | Crosses placenta; concentrations in fetal plasma comparable to maternal. |
| Breastfeeding | Excreted into breast milk; may cause acidosis or sulfonamide-like adverse effects in nursing infants. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
PregnancyHypersensitivity to dichlorphenamide or sulfonamidesHepatic insufficiencySevere renal impairmentAdrenal insufficiencyElectrolyte imbalance (hyponatremia, hypokalemia)Concurrent use of high-dose aspirin
| Precautions | Metabolic acidosis: Can occur, especially in patients with renal impairment or electrolyte disturbances., Hypokalemia: Risk may increase due to bicarbonate loss and metabolic acidosis., Sulfonamide allergy: Cross-sensitivity possible; caution in patients with history of sulfonamide hypersensitivity., Renal impairment: Use with caution; may accumulate and worsen acidosis., Hepatic impairment: Caution due to risk of hepatic encephalopathy., Drug interactions: May increase effects of other carbonic anhydrase inhibitors, furosemide, and decrease effects of lithium., Pregnancy: Weigh risks vs benefits; not recommended., Lactation: Excreted in milk; avoid breastfeeding. |
| Food/Dietary | Avoid high-dose aspirin or salicylates; may increase toxicity. Limit alcohol intake to reduce risk of metabolic acidosis. No specific food restrictions but maintain adequate hydration to prevent renal calculi. Avoid cranberry juice if prone to kidney stones. |
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| L4 - Possibly Hazardous |
| Teratogenic Risk | Dichlorphenamide is a carbonic anhydrase inhibitor. Data in pregnant women are insufficient. In animal studies, it has been associated with fetal skeletal abnormalities and reduced fetal weight at doses similar to human therapeutic doses. First trimester exposure may carry a risk of teratogenicity; second and third trimester risks include possible metabolic acidosis and electrolyte disturbances in the fetus. |
| Fetal Monitoring | Monitor maternal serum electrolytes, bicarbonate, and renal function regularly. Assess fetal growth and well-being via ultrasound and nonstress testing. In neonates, monitor for metabolic acidosis and electrolyte disturbances. |
| Fertility Effects | Dichlorphenamide may cause metabolic acidosis, which could theoretically affect reproductive function. No specific human data on fertility impairment are available. |
| Clinical Pearls | Dichlorphenamide is a carbonic anhydrase inhibitor used for primary open-angle glaucoma and familial periodic paralysis. Monitor serum potassium and perform baseline/periodic blood counts due to risk of hypokalemia and bone marrow suppression. Contraindicated in hepatic cirrhosis due to risk of hepatic encephalopathy. Can cause metabolic acidosis; use cautiously in patients with respiratory acidosis or COPD. Dose adjustment required in renal impairment. May increase urate levels; avoid in gout unless urate-lowering therapy is used. |
| Patient Advice | Take exactly as prescribed; do not skip doses to prevent glaucoma progression. · Report any signs of bleeding, bruising, fever, or sore throat immediately. · May cause drowsiness; avoid driving or operating heavy machinery until effects known. · Take with food or milk to reduce gastrointestinal upset. · Avoid alcohol and aspirin-containing products to reduce risk of metabolic acidosis. · Drink plenty of fluids to prevent kidney stones; maintain adequate hydration. · Notify doctor if you have liver disease, kidney stones, or breathing problems. · This may increase blood sugar; monitor if diabetic. · Taste disturbances or altered sense of taste may occur and are usually reversible. |