Methazolamide, a sulfonamide derivative, is a white crystalline powder, weakly acidic, and slightly soluble in water, alcohol and acetone. It is available as 25 mg and 50 mg tablets. The chemical name for methazolamide is N -[5-(aminosulfonyl)-3-methyl-1,3,4-thiadiazol-2(3H )-ylidene]-acetamide and it has the following structural formula:

Methazolamide tablets, USP contain 25mg or 50mg of methazolamide. Inactive ingredients: croscarmellose sodium, hydroxypropyl methylcellulose, lactose (monohydrate), magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate.

Methazolamide is indicated in the treatment of ocular conditions where lowering intraocular pressure is likely to be of therapeutic benefit, such as chronic open-angle glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where lowering the intraocular pressure is desired before surgery.

The effective therapeutic dose administered varies from 50mg to 100mg 2 or 3 times daily. The drug may be used concomitantly with miotic and osmotic agents.

Methazolamide tablets, USP for oral administration are available as:

25mg: Round, white, unscored tablets debossed GG78 on one side and plain on the reverse side, and supplied as:

NDC 0781-1072-01 bottles of 100
NDC 0781-1072-10 bottles of 1000

50mg: Round, white, scored tablets debossed GG181 on one side and plain on the reverse side, and supplied as:

NDC 0781-1071-01 bottles of 100
NDC 0781-1071-10 bottles of 1000

Store at 20°-25°C (68°-77°F) (see USP Controlled Room Temperature).

Dispense in a tight, light-resistant container.

Rev. 01-2007. Sandoz Inc. Princeton, NJ 08540. FDA Rev date: n/a

In a controlled clinical trial, safety data from 141 patients who used MetroLotion® Topical Lotion (n=71), or the lotion vehicle (n=70), twice daily and experienced a local cutaneous adverse event which may or may not have been related to the treatments include: local allergic reaction, MetroLotion® Topical Lotion 2 (3%), lotion vehicle 0; contact dermatitis, MetroLotion® Topical Lotion 2 (3%), lotion vehicle 1 (1%); pruritus, MetroLotion® Topical Lotion 1 (1%), lotion vehicle 0; skin discomfort (burning and stinging), MetroLotion® Topical Lotion 1 (1%), lotion vehicle 2 (3%); erythema, MetroLotion® Topical Lotion 4 (6%), lotion vehicle 0; dry skin, MetroLotion® Topical Lotion 0, lotion vehicle 1 (1%); and worsening of rosacea, MetroLotion® Topical Lotion 1 (1%), lotion vehicle 7 (10%). The following additional adverse experiences have been reported with the topical use of metronidazole: skin irritation, transient redness, metallic taste, tingling or numbness of extremities, and nausea.

Oral metronidazole has been reported to potentiate the anticoagulant effect of warfarin and coumarin anticoagulants, resulting in a prolongation of prothrombin time. The effect of topical metronidazole on prothrombin time is not known.

Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epider-mal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Hypersensitivity reactions may recur when a sulfonamide is readministered, irrespective of the route of administration.

If hypersensitivity or other serious reactions occur, the use of this drug should be discontinued.

Caution is advised for patients receiving high-dose aspirin and metha-zolamide concomitantly, as anorexia, tachypnea, lethargy, coma and death have been reported with concomitant use of high-dose aspirin and carbonic anhydrase inhibitors.

General: Potassium excretion is increased initially upon administration of methazolamide and in patients with cirrhosis or hepatic insufficiency could precipitate a hepatic coma.

In patients with pulmonary obstruction or emphysema, where alveolar ventilation may be impaired methazolamide should be used with caution because it may precipitate or aggravate acidosis.

Laboratory Tests: To monitor for hematologic reactions common to all sulfonamides, it is recommended that a baseline CBC and platelet count be obtained on patients prior to initiating methazolamide therapy and at regular intervals during therapy. If significant changes occur, early discontinuance and institution of appropriate therapy are important. Periodic monitoring of serum electrolytes is also recommended.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies in animals to evaluate methazolamide's carcinogenic potential and its effect on fertility have not been conducted. Methazolamide was not mutagenic in the Ames bacterial test.

Pregnancy: Teratogenic effects. Pregnancy Category C. Methazolamide has been shown to be teratogenic (skeletal anomalies) in rats when given in doses approximately 40 times the human dose. There are no adequate and well controlled studies in pregnant women. Methazolamide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from methazolamide, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use: The safety and effectiveness of methazolamide in children have not been established.

No data are available regarding methazolamide overdosage in humans as no cases of acute poisoning with this drug have been reported. Animal data suggest that even a high dose of methazolamide is nontoxic. No specific antidote is known. Treatment should be symptomatic and supportive.

Electrolyte imbalance, development of an acidotic state, and central nervous system effects might be expected to occur. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored.

Supportive measures may be required to restore electrolyte and pH balance.

Methazolamide therapy is contraindicated in situations in which sodium and/or potassium serum levels are depressed, in cases of marked kidney or liver disease or dysfunction, in adrenal gland failure, and in hyperchloremic acidosis. In patients with cirrhosis, use may precipitate the development of hepatic encephalopathy.

Long-term administration of methazolamide is contraindicated in patients with angle-closure glaucoma, since organic closure of the angle may occur in spite of lowered intraocular pressure.

Methazolamide is a potent inhibitor of carbonic anhydrase.

Methazolamide is well absorbed from the gastrointestinal tract. Peak plasma concentrations are observed 1 to 2 hours after dosing. In a multiple-dose, pharmacokinetic study, administration of methazolamide 25 mg b.i.d., 50 mg b.i.d. and 100 mg b.i.d. demonstrated a linear relationship between plasma methazolamide levels and methazolamide dose. Peak plasma concentrations (Cmax) for the 25mg, 50mg and 100mg b.i.d. regimens were 2.5mcg/mL, 5.1mcg/mL and 10.7mcg/mL, respectively. The area under the plasma concentration-time curves (AUC) were 1130 mcg. min/mL, 2571 mcg. min/mL and 5418 mcg. min/mL for the 25 mg, 50 mg and 100 mg dosage regimens, respectively.

Methazolamide is distributed throughout the body including the plasma, cerebrospinal fluid, aqueous humor of the eye, red blood cells, bile and extra-cellular fluid. The mean apparent volume of distribution (V_area/F) ranges from 17 to 23 L. Approximately 55% is bound to plasma proteins. The steady-state methazolamide red blood cell: plasma ratio varies with dose and was found to be 27:1, 16:1 and 10:1 following the administration of metha-zolamide 25 mg b.i.d., 50 mg b.i.d. and 100 mg b.i.d., respectively.

The mean steady-state plasma elimination half-life for methazolamide is approximately 14 hours. At steady-state approximately 25% of the dose is recovered unchanged in the urine over the dosing interval. Renal clearance accounts for 20 to 25% of the total clearance of drug. After repeated b.i.d.-t.i.d. dosing, methazolamide accumulates to steady state concentrations in seven days.

Methazolamide's secretion of aqueous humor and results in a decrease in intraocular pressure. The onset of the decrease in intraocular pressure generally occurs within two to four hours, has a peak effect in six to eight hours, and a total duration of ten to eighteen hours.

Methazolamide is a sulfonamide derivative; however, it does not have any clinically significant antimicrobial properties. Although methazolamide achieves a high concentration in the cerebrospinal fluid, it is not considered an effective anticonvulsant.

Methazolamide has a weak and transient diuretic effect, therefore use results in an increase in urinary volume, with excretion of sodium, potassium and chloride. The drug should not be used as a diuretic. Inhibition of renal bicarbonate reabsorption produces an alkaline urine. Plasma bicarbonate decreases, and a relative, transient metabolic acidosis may occur due to a disequilibrium in carbon dioxide transport in the red cell. Urinary citrate excretion is decreased by approximately 40% after doses of 100mg every 8 hours. Uric acid output has been shown to decrease 36% in the first 24 hour period.

Adverse reactions common to all sulfonamide derivatives may occur: anaphylaxis, fever, rash (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), crystalluria, renal calculus, bone marrow depression, thrombocytopenic purpura, hemolytic anemia, leukopenia, pancytopenia and agranulocytosis. Precaution is advised for early detection of such reactions and the drug should be discontinued and appropriate therapy instituted.

Caution is advised for patients receiving high-dose aspirin and methazolamide concomitantly.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

METHAZOLAMIDE - ORAL

(meth-uh-ZOHL-uh-mide)

COMMON BRAND NAME(S): Glauctabs, Neptazane

USES: This medication is used in combination with other medications to treat high pressure inside the eye due to certain types of glaucoma. Lowering high pressure inside the eye helps to prevent blindness, vision loss, and nerve damage. Methazolamide belongs to a class of drugs known as carbonic anhydrase inhibitors. It works by decreasing the production of fluid inside the eye.

HOW TO USE: Take this medication by mouth, usually 2 or 3 times daily or as directed by your doctor. This medication may be taken with food if stomach upset occurs. To decrease the risk for certain side effects (e.g., kidney stones), drink plenty of fluids unless otherwise directed by your doctor.

Dosage is based on your medical condition and response to therapy.

Use this medication regularly to get the most benefit from it. Most people with glaucoma or high pressure in the eyes do not have any symptoms. To help you remember, take it at the same time(s) each day.

SIDE EFFECTS: Nausea, loss of appetite, change in taste, vomiting, diarrhea, frequent urination, dizziness, drowsiness, or tiredness may occur. These effects may be temporary and decrease as your body adjusts to the medication. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: blood in urine, numbness or tingling of hands/feet, painful urination, ringing in the ears, sudden decrease in amount of urine.

Tell your doctor immediately if any of these rare but very serious side effects occur: confusion, easy bleeding/bruising, fast/pounding heartbeat, persistent nausea/vomiting, signs of infection (e.g., fever, persistent sore throat), seizure, stomach/abdominal pain, dark urine, yellowing of eyes/skin.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking methazolamide, tell your doctor or pharmacist if you are allergic to it; or to sulfa drugs (e.g., sulfamethoxazole); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: adrenal gland problems (e.g., Addison's disease), severe kidney disease, severe liver disease (e.g., cirrhosis), untreated mineral imbalance (e.g., low sodium/potassium, hyperchloremic acidosis).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: breathing problems (e.g., chronic obstructive pulmonary disease-COPD, emphysema, lung infection), diabetes, gout, kidney problems (e.g., history of kidney stones), overactive thyroid (hyperthyroidism).

This drug may make you dizzy or drowsy. Use caution while driving, using machinery, or doing any activity that requires alertness. Limit alcoholic beverages.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen and wear protective clothing when outdoors.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known if this medication passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

This drug should not be used with the following medications because very serious interactions may occur: cisapride, methenamine.

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting methazolamide.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: large doses of aspirin and aspirin-like drugs (salicylates), anti-seizure drugs (e.g., phenytoin, phenobarbital), carbonic anhydrase inhibitor eye drops (e.g., dorzolamide, brinzolamide), diabetes medications, digoxin, drugs that may cause potassium loss (e.g., diuretics such as furosemide/hydrochlorothiazide, corticosteroids such as prednisone), lithium, stimulant drugs (e.g., amphetamine, ephedrine), topiramate.

Check the labels on all your medicines because they may contain aspirin or aspirin-like drugs (salicylates), which can cause serious side effects if taken in large doses with this medication. Low-dose aspirin should be continued if prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually at dosages of 81-325 milligrams per day). Consult your doctor or pharmacist for more details.

This medication can affect the results of certain lab tests, possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., serum potassium level, complete blood count, liver function tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.