Neptazane®
Methazolamide · oral tablet
Antiglaucoma
Approved uses
Chronic open-angle glaucoma
50 mg to 100 mg PO two or three times daily
IOP starts falling in 2 to 4 hours, peaks at 6 to 8 hours, and the effect lasts 10 to 18 hours.
Secondary glaucoma, and preoperative acute angle-closure glaucoma
50 mg to 100 mg PO two or three times daily, alone or with miotic and osmotic agents
OFF-LABELNot in the FDA label for this product
Chronic cystoid macular edema in retinitis pigmentosa
50 mg PO BID, the dosage the angiographic responders continued on beyond the 3-week crossover
Masked crossover · n=17
Prospective, double-masked, placebo-controlled crossover trial, N=17, 3 weeks per arm: angiographic macular edema improved in 9 of 17 subjects and visual acuity improved statistically for the group, but a 2 to 4 line gain in at least one eye over placebo occurred in only 3 subjects undilated (4 dilated), and subjective improvement in only 1. Three responders continued at 50 mg BID for a further 6 to 12 weeks and all showed at least partial angiographic rebound. A systematic review of 23 studies concluded oral acetazolamide has the strongest clinical basis and should be first line, with topical dorzolamide the alternative for patients intolerant of it.
Contraindications
- Depressed serum sodium and/or potassium.
- Marked kidney or liver disease or dysfunction.
- Adrenal gland failure.
- Hyperchloremic acidosis.
- Cirrhosis, where use may precipitate hepatic encephalopathy.
- Long-term administration in angle-closure glaucoma, since organic closure of the angle may occur in spite of lowered IOP.
Available Forms25 mg and 50 mg tablets
Mechanism of ActionPotent carbonic anhydrase inhibitor; enzyme inhibition decreases secretion of aqueous humor and lowers IOP. Onset of IOP reduction is 2 to 4 hours, peak effect 6 to 8 hours, total duration 10 to 18 hours, with a mean steady-state plasma half-life near 14 hours and steady state reached after 7 days of BID to TID dosing.
Warnings & Precautions
- Sulfonamide hypersensitivity: Fatalities have occurred, although rarely, from severe sulfonamide reactions; discontinue if hypersensitivity or another serious reaction occurs.
- Cross-sensitivity on rechallenge: Reactions may recur whenever a sulfonamide is readministered, irrespective of route.
- Hematologic monitoring: Baseline CBC and platelet count before starting and at regular intervals during therapy; discontinue early if significant changes occur.
- Onset timing of blood dyscrasias: In a National Registry series of 79 suspected hematopoietic reactions to carbonic anhydrase inhibitors as a class, 68% began within the first 6 months of therapy and 32% of the reported cases were fatal.
- Asian ancestry SJS/TEN risk: In case-control studies of Korean, Japanese, and Han Chinese patients, the HLA-B59 serotype carries a strong association with methazolamide-induced Stevens-Johnson syndrome and toxic epidermal necrolysis; not a labeled warning.
- Serum electrolytes: Periodic monitoring recommended.
- High-dose aspirin: Concomitant use with a carbonic anhydrase inhibitor has caused anorexia, tachypnea, lethargy, coma, and death.
- Steroid therapy: Caution because of the potential for developing hypokalemia.
- Cirrhosis or hepatic insufficiency: Potassium excretion increases initially and could precipitate hepatic coma.
- Pulmonary obstruction or emphysema: Caution where alveolar ventilation may be impaired, since acidosis may be precipitated or aggravated.
Common Side Effects
- Ocular: Transient myopia, which invariably subsides on dose reduction or discontinuation.
- Systemic: Paresthesia, particularly tingling in the extremities, hearing dysfunction or tinnitus, fatigue, malaise, loss of appetite, taste alteration, nausea, vomiting, diarrhea, polyuria, and occasional drowsiness and confusion; occurring most often early in therapy.
- Metabolic: Metabolic acidosis and electrolyte imbalance.
- Severe sulfonamide reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias; rare, with fatalities reported.
- Other occasional reactions: Urticaria, melena, hematuria, glycosuria, hepatic insufficiency, flaccid paralysis, photosensitivity, convulsions, and rarely crystalluria and renal calculi.
- Sulfonamide class reactions: Anaphylaxis, fever, rash including erythema multiforme, crystalluria, renal calculus, bone marrow depression, thrombocytopenic purpura, hemolytic anemia, leukopenia, pancytopenia, agranulocytosis.
Pregnancy & LactationPregnancy: Teratogenic (skeletal anomalies) in rats at approximately 40 times the human dose; no adequate and well controlled studies in pregnant women; use only if the potential benefit justifies the potential risk to the fetus.
Lactation: Excretion in human milk is unknown; because of the potential for serious adverse reactions in nursing infants, decide whether to discontinue nursing or the drug, weighing its importance to the mother.
Pediatric UseSafety and effectiveness in children have not been established.