METHAZOLAMIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for METHAZOLAMIDE (METHAZOLAMIDE).

How it works

Carbonic anhydrase inhibitor; reduces aqueous humor secretion by inhibiting carbonic anhydrase in ciliary processes, decreasing intraocular pressure.

What the body does with it

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

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for METHAZOLAMIDE (METHAZOLAMIDE).

Breastfeeding	Methazolamide is excreted into breast milk; M/P ratio not established. Potential for metabolic acidosis or sulfonamide-related adverse effects in nursing infant. Use only if benefit outweighs risk; consider alternative agents.
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.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hyponatremia or hypokalemia; severe renal or hepatic impairment; adrenal insufficiency; hypersensitivity to sulfonamides or thiazide diuretics; concurrent use with high-dose aspirin.

Clinical Precautions

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).

Clinical Tips & Counseling

Drug interactions

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METHAZOLAMIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for METHAZOLAMIDE (METHAZOLAMIDE).

How it works

Carbonic anhydrase inhibitor; reduces aqueous humor secretion by inhibiting carbonic anhydrase in ciliary processes, decreasing intraocular pressure.

What the body does with it

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

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for METHAZOLAMIDE (METHAZOLAMIDE).

Breastfeeding	Methazolamide is excreted into breast milk; M/P ratio not established. Potential for metabolic acidosis or sulfonamide-related adverse effects in nursing infant. Use only if benefit outweighs risk; consider alternative agents.
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.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hyponatremia or hypokalemia; severe renal or hepatic impairment; adrenal insufficiency; hypersensitivity to sulfonamides or thiazide diuretics; concurrent use with high-dose aspirin.