METHAZOLAMIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for METHAZOLAMIDE (METHAZOLAMIDE).
Carbonic anhydrase inhibitor; reduces aqueous humor secretion by inhibiting carbonic anhydrase in ciliary processes, decreasing intraocular pressure.
| Metabolism | Hepatic metabolism via CYP3A4; metabolites include N-demethylated and S-oxidized products. |
| Excretion | Renal: 70-90% as unchanged drug; minor biliary/fecal (<10%) |
| Half-life | Terminal half-life: 14-20 hours; approximately 15 hours in adults, prolonged in renal impairment |
| Protein binding | ~95% bound to plasma proteins (primarily albumin) |
| Volume of Distribution | 0.2-0.3 L/kg; indicates distribution primarily in extracellular fluid |
| Bioavailability | Oral: ~90% (well absorbed); IM: not typically used; IV: 100% |
| Onset of Action | Oral: 2-4 hours for peak IOP reduction; IV: 30-60 minutes |
| Duration of Action | Oral: 10-18 hours; IV: 4-6 hours; tolerance may develop with chronic use |
| Molecular Weight | 222.25 |
Oral: 50-100 mg two to three times daily.
| Dosage form | TABLET |
| Renal impairment | GFR 10-50 mL/min: Administer every 12 hours; GFR <10 mL/min: Not recommended. |
| Liver impairment | No specific guidelines; use with caution in severe hepatic impairment. |
| Pediatric use | Oral: 5-10 mg/kg/day divided every 6-8 hours; maximum 30 mg/kg/day. |
| Geriatric use | Initiate at low end of dosing range due to age-related renal function decline; monitor electrolytes and renal function. |
| 1st trimester | Avoid: teratogenic in animal studies; associated with metabolic acidosis; use only if benefit outweighs risk. |
| 2nd trimester | Caution: may cause fetal acidosis; limited human data. |
| 3rd trimester | Caution: risk of neonatal metabolic acidosis and electrolyte disturbances if used near term. |
Clinical note
Comprehensive clinical and safety monograph for METHAZOLAMIDE (METHAZOLAMIDE).
| Placental transfer | Crosses placenta; measured in fetal plasma at 80-100% of maternal levels. |
| Breastfeeding | Excreted in breast milk; potential for infant metabolic acidosis and sulfonamide-related adverse effects; consider alternative or monitor infant for acidosis. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to methazolamide or sulfonamidesSevere hepatic insufficiencySevere renal impairment (CrCl <10 mL/min)Adrenocortical insufficiencyMetabolic acidosisHypokalemia
| Precautions | Sulfonamide hypersensitivity reactions; metabolic acidosis; electrolyte disturbances (hypokalemia); drowsiness and confusion; potentiation of acidosis in renal impairment; risk of nephrolithiasis; caution with concomitant use of high-dose aspirin (risk of toxicity). |
| Food/Dietary | No specific food interactions. Maintain adequate hydration. Avoid excessive intake of sodium bicarbonate or antacids containing bicarbonate. |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Crosses placenta; based on animal studies, may cause skeletal and soft tissue malformations. Human data limited but caution advised. Second and third trimesters: Risk of fetal acidosis and electrolyte disturbances due to carbonic anhydrase inhibition. Avoid if possible. |
| Fetal Monitoring | Monitor renal function, serum electrolytes (especially potassium, bicarbonate), and arterial blood gases for metabolic acidosis. In fetus, assess growth and amniotic fluid volume periodically. |
| Fertility Effects | No significant impairment reported. Animal studies show no adverse effects on fertility. Limited human data. |
| Clinical Pearls |
| Methazolamide is a carbonic anhydrase inhibitor used for glaucoma. Monitor serum electrolytes, especially potassium, as hypokalemia is common. Contraindicated in patients with hepatic cirrhosis due to risk of hepatic encephalopathy. Avoid in patients with adrenal insufficiency. Adjust dose in renal impairment. Use with caution in patients with pulmonary obstruction or emphysema as it can cause metabolic acidosis. |
| Patient Advice | Take this medication exactly as prescribed, usually twice a day. · You may experience tingling in the fingers or toes, which is common and usually harmless. · Drink plenty of fluids to prevent kidney stones. · Avoid alcohol as it may increase side effects. · Report any signs of infection, easy bruising, or bleeding. · Do not drive or operate heavy machinery until you know how this medication affects you. · This medication may cause sensitivity to sunlight; use sunscreen and protective clothing. · If you miss a dose, take it as soon as you remember unless it is almost time for the next dose; do not double dose. |