Acetazolamide
Mechanism :
Acetazolamide is a potent carbonic anhydrase inhibitor. It acts by increasing the pH of the urine and releasing bicarbonate in urine. It is used as a diuretic in instances of abnormal fluid retention (e. g., cardiac edema), to decrease CSF production in increased intracranial tension and to alkalinize the urine in renal tubular acidosis. It also decreases the intraocular tension by decreasing formation of aqueous humor and used in the treatment of glaucoma. It is used in the treatment of certain convulsive disorders (e. g., epilepsy).
Indication :
- Epilepsy, partial seizures and refractory absence seizures
- Glaucoma
- Diuresis
- Raised intracranial pressure
- Acute altitude sickness
- Urine alkalinisation
- Pseudotumor cerebri
Contraindications :
Acetazolamide is a sulfonamide derivative, cross sensitivity between acetazolamide, sulphonamides and other sulfonamide derivatives is possible.
Therapy is contraindicated in situations in which sodium and/or potassium blood serum levels are depressed, in marked kidney and liver disease or dysfunction, in suprarenal gland failure, and in hyperchloremic acidosis. It is contraindicated in patients with cirrhosis because of the risk of development of hepatic encephalopathy. Long term use is not recommended in chronic closed angle glaucoma.
Dosing :
Diuretic (PO, IV):
Child:
5 mg/kg/dose once daily or every other day.
Adult:
250-375 mg/dose once daily or every other day.
Glaucoma:
Children <12 years:
IM/IV: 20-40 mg/kg/day divided in 6 hourly dose. PO: 8-30 mg/kg/day divided in 6-8 hours. Maximum dose: 1000 mg/24 hours.
Children ≥12 years:
15 to 30 mg/kg/day in divided doses every 6 to 8 hours. Maximum dose: 1000 mg/24 hours.
Adult:
PO (Simple chronic; open angle) 1000 mg/24 hours in divided doses every 6 to 8 hours. IV (Acute secondary; closed angle): 500 mg/dose IV for rapid reduction in intraocular pressure.
Seizure:
<12 years:
Safety and efficacy not established.
>12 years:
8-30 mg/kg/day orally or every 6-12 hours in divided doses; dose to not exceed 30 mg/kg/day or 1 g/day (tablet).
Urine Alkalinisation:
Adult: 5 mg/kg/dose PO repeated two-three times over 24 hours.
Management of hydrocephalus:
Start with 20 mg/kg/24 hours in divided doses every 6 to 8 hours PO/IV. Can increase to 100 mg/kg/24 hours upto a maximum of 2 g/24 hours.
Pseudotumor cerebri (PO):
Children:
Start with 25 mg/kg/24 hours divided 1-4 times daily, increase by 25 mg/kg/24 hours until clinical response or as tolerated up to maximum of 100 mg/kg/24 hours.
Adolescent:
Start with 1 g/24 hours divided 1-4 times daily, increase by 250 mg/24 hours until clinical response or as tolerated up to a maximum of 4 g/24 hours.
For prevention of altitude sickness:
<12 years:
Safety and efficacy not established.
>12 years:
500-1000 mg/day orally every 8-12 hours in divided doses. To be started 24-48 hours before the ascent and continued during the ascent and/or at least 48 hours after arrival at high altitude if necessary, to control symptoms.
For treatment of altitude sickness:
2.5 mg/kg every 8-12 hours. Max: 250 mg/dose.
Adverse Effect :
Flushing, drowsiness, ataxia, confusion, fatigue, vertigo, fever, seizures, dizziness, depression, malaise, headache, excitement, rash, erythema multiforme, photosensitivity, Stevens-Johnson syndrome, urticaria, toxic epidermal necrolysis, hypokalemia, hyperchloremic metabolic acidosis, hyperglycemia, hypoglycemia, growth retardation, GI irritation, anorexia, nausea, vomiting, xerostomia, melena, metallic taste, black stools, diarrhoea, dysuria, polyuria, reduced urate secretion, development of renal calculi, hematuria, glycosuria, bone marrow suppression, thrombocytopenia, hemolytic anaemia, pancytopenia, hepatic insufficiency, cholestatic jaundice, hepatic necrosis, pain at injection site, paresthesia, muscle weakness, myopia (transient), tinnitus.
Interaction :
Alcohol (Ethyl): May enhance the CNS depressant effect of Alcohol.
Alpha-/Beta-Agonists: Carbonic Anhydrase Inhibitors may decrease the excretion of Alpha-/Beta-Agonists.
Amphetamines: Carbonic Anhydrase Inhibitors may decrease the excretion of Amphetamines.
Anticonvulsants (Barbiturate, phenytoin, carbamazepine): Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Anticonvulsants specifically, osteomalacia and rickets.
Diazoxide: May enhance the hypotensive effect of Antihypertensives.
Salicylates: May enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination.
Quinidine: Reduces its excretion.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | 250 mg up to 4 times a day |
| 10-20 | 250 mg up to twice a day |
| <10 | 250 mg daily |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Not dialysed. Dose as in GFR<10 mL/min |
| HD | Unlikely dialysability. Dose as in GFR<10 mL/min. |
| HDF/High flux | Unknown dialysability. Dose as in GFR<10 mL/min |
| CAV/VVHD | Unknown dialysability. Dose as in GFR=10–20 mL/min |
Hepatic Dose :
Contraindicated in cirrhosis and severe hepatic impairment due to risk of hepatic encephalopathy.