DIAMOX SEQUELS (Acetazolamide Extended-Release Capsules) are an inhibitor of the enzyme carbonic anhydrase.

DIAMOX is a white to faintly yellowish white crystalline, odorless powder, weakly acidic, very slightly soluble in water, and slightly soluble in alcohol. The chemical name for DIAMOX is N-(5-Sulfamoyl-1,3,4-thiadiazol-2-yl) acetamide and has the following chemical structure:

DIAMOX SEQUELS are extended-release capsules, for oral administration, each containing 500 mg of acetazolamide and the following inactive ingredients:

Microcrystalline cellulose, sodium lauryl sulfate and talc.

The ingredients in the capsule shell are D&C red no. 28, D&C yellow no. 10, FD&C red no. 40, gelatin and titanium dioxide.

The ingredients in the imprinting ink are D&C yellow no. 10 aluminum lake, FD&C blue no. 1 aluminum lake, FD&C blue no. 2 aluminum lake, FD&C red no. 40 aluminum lake, pharmaceutical glaze, propylene glycol and synthetic iron oxide.

For adjunctive treatment of: chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where delay of surgery is desired in order to lower intraocular pressure. DIAMOX is also indicated for the prevention or amelioration of symptoms associated with acute mountain sickness despite gradual ascent.

The recommended dosage is 1 capsule (500 mg) two times a day. Usually 1 capsule is administered in the morning and 1 capsule in the evening. It may be necessary to adjust the dose, but it has usually been found that dosage in excess of 2 capsules (1 g) does not produce an increased effect. The dosage should be adjusted with careful individual attention both to symptomatology and intraocular tension. In all cases, continuous supervision by a physician is advisable.

In those unusual instances where adequate control is not obtained by the twice-a-day administration of DIAMOX SEQUELS, the desired control may be established by means of DIAMOX (tablets or parenteral). Use tablets or parenteral in accordance with the more frequent dosage schedules recommended for these dosage forms, such as 250 mg every four hours, or an initial dose of 500 mg followed by 250 mg or 125 mg every four hours, depending on the case in question.

Dosage is 500 mg to 1000 mg daily, in divided doses using tablets or extended-release capsules as appropriate. In circumstances of rapid ascent, such as in rescue or military operations, the higher dose level of 1000 mg is recommended. It is preferable to initiate dosing 24 to 48 hours before ascent and to continue for 48 hours while at high altitude, or longer as necessary to control symptoms.

DIAMOX^Ã? SEQUELS^Ã? (Acetazolamide Extended-Release Capsules) are available as 500 mg:

Orange opaque cap and orange opaque body filled with white to off-white pellets. Imprinted in black ink, Barr 699. Available in bottles of :

100 NDC 51285-754-02

Body as a whole: Headache, malaise, fatigue, fever, pain at injection site, flushing, growth retardation in children, flaccid paralysis, ana-phylaxis.

Digestive: Gastrointestinal disturbances such as nausea, vomiting, diarrhea.

Hematological/Lymphatic: Blood dyscrasias such as aplastic anemia, agranulocytosis, leukopenia, thrombocytopenic purpura, melena.

Hepato-biliary disorders: Abnormal liver function, cholestatic jaundice, hepatic insufficiency, fulminant hepatic necrosis.

Metabolic/Nutritional: Metabolic acidosis, electrolyte imbalance, including hypokalemia, hyponatremia, osteomalacia with long-term phenytoin therapy, loss of appetite, taste alteration, hyper/hypoglycemia.

Nervous: Drowsiness, paresthesia (including numbness and tingling of extremities and face), depression, excitement, ataxia, confusion, convulsions, dizziness.

Skin: Allergic skin reactions including urticaria, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Special senses: Hearing disturbances, tinnitus, transient myopia.

Urogenital: Crystalluria, increased risk of nephrolithiasis with long-term therapy, hema-turia, glycosuria, renal failure, polyuria.

Aspirin - See WARNINGS

DIAMOX modifies phenytoin metabolism with increased serum levels of phenytoin. This may increase or enhance the occurrence of osteo-malacia in some patients receiving chronic phenytoin therapy. Caution is advised in patients receiving chronic concomitant therapy. By decreasing the gastrointestinal absorption of primidone, DIAMOX may decrease serum concentrations of primidone and its metabolites, with a consequent possible decrease in anticonvulsant effect. Caution is advised when beginning, discontinuing, or changing the dose of DIAMOX in patients receiving primidone.

Because of possible additive effects with other carbonic anhydrase inhibitors, concomitant use is not advisable.

Acetazolamide may increase the effects of other folic acid antagonists.

Acetazolamide decreases urinary excretion of amphetamine and may enhance the magnitude and duration of their effect.

Acetazolamide reduces urinary excretion of quinidine and may enhance its effect.

Acetazolamide may prevent the urinary antiseptic effect of methenamine.

Acetazolamide increases lithium excretion and the lithium may be decreased.

Acetazolamide and sodium bicarbonate used concurrently increase the risk of renal calculus formation.

Acetazolamide may elevate cyclosporine levels.

Sulfonamides may give false negative or decreased values for urinary phenolsulfon-phthalein and phenol red elimination values for urinary protein, serum non-protein, and serum uric acid. Acetazolamide may produce an increased level of crystals in the urine.

Acetazolamide interferes with the HPLC method of assay for theophylline. Interference with the theophylline assay by acetazolamide depends on the solvent used in the extraction; acetazol-amide may not interfere with other assay methods for theophylline.

Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, anaphy-laxis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Sensitizations may recur when a sulfonamide is readministered irrespective of the route of administration. If signs of hypersensitivity or other serious reactions occur, discontinue use of this drug.

Caution is advised for patients receiving concomitant high-dose aspirin and DIAMOX, as anorexia, tachypnea, lethargy, metabolic acidosis, coma, and death have been reported.

Increasing the dose does not increase the diuresis and may increase the incidence of drowsiness and/or paresthesia. Increasing the dose often results in a decrease in diuresis. Under certain circumstances, however, very large doses have been given in conjunction with other diuretics in order to secure diuresis in complete refractory failure.

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 DIAMOX 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 recommended.

Long-term studies in animals to evaluate the carcinogenic potential of DIAMOX have not been conducted. In a bacterial mutagenicity assay, DIAMOX was not mutagenic when evaluated with and without metabolic activation.

The drug had no effect on fertility when administered in the diet to male and female rats at a daily intake of up to 4 times the recommended human dose of 1000 mg in a 50 kg individual.

Acetazolamide, administered orally or parenterally, has been shown to be teratogenic (defects of the limbs) in mice, rats, hamsters, and rabbits. There are no adequate and well-controlled studies in pregnant women. Acetazolamide should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Because of the potential for serious adverse reactions in nursing infants from DIAMOX, 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. Acetazolamide should only be used by nursing women if the potential benefit justifies the potential risk to the child.

The safety and effectiveness of DIAMOX SEQUELS in pediatric patients below the age of 12 years have not been established. Growth retardation has been reported in children receiving long-term therapy, believed secondary to chronic acidosis.

Metabolic acidosis, which can be severe, may occur in the elderly with reduced renal function. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.

No specific antidote is known. Treatment should be symptomatic and supportive.

Electrolyte imbalance, development of an aci-dotic 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 are required to restore electrolyte and pH balance. The acidotic state can usually be corrected by the administration of bicarbonate.

Despite its high intraerythrocytic distribution and plasma protein binding properties, DIAMOX may be dialyzable. This may be particularly important in the management of DIAMOX overdosage when complicated by the presence of renal failure.

Hypersensitivity to acetazolamide or any excipi-ents in the formulation. Since acetazolamide is a sulfonamide derivative, cross sensitivity between acetazolamide, sulfonamides and other sulfonamide derivatives is possible.

Acetazolamide therapy is contraindicated in situations in which sodium and/or potassium blood serum levels are depressed, in cases of marked kidney and liver disease or dysfunction, in suprarenal gland failure, and in hyper-chloremic acidosis. It is contraindicated in patients with cirrhosis because of the risk of development of hepatic encephalopathy.

Long-term administration of DIAMOX is contraindicated in patients with chronic non-congestive angle-closure glaucoma since it may permit organic closure of the angle to occur while the worsening glaucoma is masked by lowered intraocular pressure.

DIAMOX is a potent carbonic anhydrase inhibitor, effective in the control of fluid secretion (e.g., some types of glaucoma), in the treatment of certain convulsive disorders (e.g., epilepsy), and in the promotion of diuresis in instances of abnormal fluid retention (e.g., cardiac edema).

DIAMOX is not a mercurial diuretic. Rather, it is a non-bacteriostatic sulfonamide possessing a chemical structure and pharmacological activity distinctly different from the bacteriostatic sulfonamides.

DIAMOX is an enzyme inhibitor that acts specifically on carbonic anhydrase, the enzyme that catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. In the eye, this inhibitory action of acetazolamide decreases the secretion of aqueous humor and results in a drop in intraocular pressure, a reaction considered desirable in cases of glaucoma and even in certain non-glaucomatous conditions. Evidence seems to indicate that DIAMOX has utility as an adjuvant in treatment of certain dysfunctions of the central nervous system (e.g., epilepsy). Inhibition of carbonic anhydrase in this area appears to retard abnormal, paroxysmal, excessive discharge from central nervous system neurons. The diuretic effect of DIAMOX is due to its action in the kidney on the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. The result is renal loss of HCO₃ ion, which carries out sodium, water, and potassium. Alkalinization of the urine and promotion of diuresis are thus affected. Alteration in ammonia metabolism occurs due to increased reabsorption of ammonia by the renal tubules as a result of urinary alkalinization. DIAMOX SEQUELS provide prolonged action to inhibit aqueous humor secretion for 18 to 24 hours after each dose, whereas tablets act for only eight to 12 hours. The prolonged continuous effect of SEQUELS permits a reduction in dosage frequency.

Plasma concentrations of acetazolamide peak from three to six hours after administration of DIAMOX SEQUELS, compared to one to four hours with tablets. Food does not affect bioavailability of DIAMOX SEQUELS.

Placebo-controlled clinical trials have shown that prophylactic administration of DIAMOX at a dose of 250 mg every eight to 12 hours (or a 500 mg controlled-release capsule once daily) before and during rapid ascent to altitude results in fewer and/or less severe symptoms of acute mountain sickness (AMS) such as headache, nausea, shortness of breath, dizziness, drowsiness, and fatigue. Pulmonary function (e.g., minute ventilation, expired vital capacity, and peak flow) is greater in the DIAMOX treated group, both in subjects with AMS and asymptomatic subjects. The DIAMOX treated climbers also had less difficulty in sleeping.

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. Caution is advised for early detection of such reactions and the drug should be discontinued and appropriate therapy instituted.

In patients with pulmonary obstruction or emphysema where alveolar ventilation may be impaired, DIAMOX which may precipitate or aggravate acidosis should be used with caution. Gradual ascent is desirable to try to avoid acute mountain sickness. If rapid ascent is undertaken and DIAMOX is used, it should be noted that such use does not obviate the need for prompt descent if severe forms of high altitude sickness occur, i.e., high altitude pulmonary edema (HAPE) or high altitude cerebral edema.

Caution is advised for patients receiving concomitant high-dose aspirin and DIAMOX, as anorexia, tachypnea, lethargy, metabolic acidosis, coma, and death have been reported (see WARNINGS).

Both increases and decreases in blood glucose have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus.

Acetazolamide treatment may cause electrolyte imbalances, including hyponatremia and hypokalemia, as well as metabolic acidosis. Therefore, periodic monitoring of serum electrolytes is recommended. Particular caution is recommended in patients with conditions that are associated with, or predispose a patient to, electrolyte and acid/base imbalances, such as patients with impaired renal function (including elderly patients; see PRECAUTIONS, Geriatric Use), patients with diabetes mellitus, and patients with impaired alveolar ventilation.

Some adverse reactions to acetazolamide, such as drowsiness, fatigue, and myopia, may impair the ability to drive and operate machinery.

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.

ACETAZOLAMIDE - ORAL

(a-SEET-a-ZOLE-a-mide)

COMMON BRAND NAME(S): Diamox

USES: Acetazolamide is used to prevent and reduce the symptoms of altitude sickness. This medication can decrease headache, tiredness, nausea, dizziness, and shortness of breath that can occur when you climb quickly to high altitudes (generally above 10,000 feet/3,048 meters). It is particularly useful in situations when you cannot make a slow ascent. The best ways to prevent altitude sickness are climbing slowly, stopping for 24 hours during the climb to allow the body to adjust to the new height, and taking it easy the first 1 to 2 days.

This drug is also used with other medications to treat a certain type of eye problem (open-angle glaucoma). Acetazolamide is a "water pill" (diuretic). It decreases the amount of fluid that can build up in the eye. It is also used to decrease a buildup of body fluids (edema) caused by congestive heart failure or certain medications. Acetazolamide can work less well over time, so it is usually used only for a short period.

It has also been used with other medications to treat certain types of seizures (petit mal and unlocalized seizures).

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

Acetazolamide may also be used to treat periodic paralysis.

HOW TO USE: If you are taking the tablets, take this medication by mouth, usually 1 to 4 times daily or as directed by your doctor. If you are taking the long-acting capsules, take this medication by mouth, usually 1 or 2 times daily or as directed by your doctor. Swallow the long-acting capsules whole. Do not open, break, or chew the capsules. Doing so can destroy the long action of the drug and may increase side effects.

Acetazolamide may be taken with or without food. Drink plenty of fluids unless otherwise directed by your doctor. Your dosage is based on your medical condition and response to therapy.

To prevent altitude sickness, start taking acetazolamide 1 to 2 days before you start to climb. Continue taking it while you are climbing and for at least 48 hours after you have reached your final altitude. You may need to continue taking this medication while staying at the high altitude to control your symptoms. If you develop severe altitude sickness, it is important that you climb down as quickly as possible. Acetazolamide will not protect you from the serious effects of severe altitude sickness. (See also Precautions.)

If you are taking this drug for another condition (e.g., glaucoma, seizures), use this medication regularly as directed to get the most benefit from it. To help you remember, take it at the same time(s) each day. Taking your last dose in the early evening will help prevent you from having to get up in the middle of the night to urinate. Consult your doctor or pharmacist if you have questions about your dosing schedule.

Do not increase or decrease your dose or stop using this medication without first consulting your doctor. Some conditions may become worse when this drug is suddenly stopped. Your dose may need to be gradually decreased.

When used for an extended period, this medication may not work as well and may require different dosing. Your doctor will be monitoring your condition. Tell your doctor if your condition does not improve or if it worsens (e.g., more frequent seizures).

This drug may reduce the potassium levels in your blood. Your doctor may recommend that you eat foods rich in potassium (e.g., bananas or orange juice) while you are taking this medication. Your doctor may also prescribe a potassium supplement for you to take during treatment. Consult your doctor for more information.

SIDE EFFECTS: Dizziness, lightheadedness, and an increased amount of urine may occur, especially during the first few days as your body adjusts to the medication. Blurred vision, dry mouth, drowsiness, loss of appetite, stomach upset, headache and tiredness may also occur. If any of these symptoms persist or worsen, notify your doctor or pharmacist.

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 very unlikely but serious side effects occur: increased body hair, hearing loss, ringing in the ears, unusual tiredness, persistent nausea/vomiting, severe stomach/abdominal pain.

Seek immediate medical attention if any of these unlikely but very serious side effects occur: easy bleeding/bruising, fast/irregular heartbeat, signs of infection (e.g., fever, persistent sore throat), mental/mood changes (e.g., confusion, difficulty concentrating), severe muscle cramps/pain, tingling of the hands/feet, blood in the urine, dark urine, painful urination, yellowing of the eyes/skin.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: blisters/sores in the mouth, 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 acetazolamide, tell your doctor or pharmacist if you are allergic to it; or to other sulfa medications; 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), low blood levels of sodium or potassium, severe kidney disease, severe liver disease (e.g., cirrhosis), certain metabolic problems (e.g., hyperchloremic acidosis).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: breathing problems (e.g., emphysema, chronic bronchitis), high levels of calcium, dehydration, diabetes mellitus, gout, narrow-angle glaucoma, overactive thyroid (hyperthyroidism).

While this medication can help you get used to high altitudes and help you tolerate quick climbs, it cannot completely prevent serious altitude sickness. Symptoms of serious altitude sickness may include: severe shortness of breath, mental/mood changes (e.g., confusion, difficulty concentrating), lack of coordination/staggering walk, extreme tiredness, severe headache.

If you develop any of these symptoms, it is very important that you descend to a lower altitude as quickly as possible to prevent serious, possibly fatal problems.

This drug may cause blurred vision or make you dizzy or drowsy. Use caution engaging in activities requiring alertness such as driving or using machinery. Limit alcoholic beverages.

To minimize dizziness and lightheadedness, get up slowly when rising from a seated or lying position.

This drug may infrequently make your blood sugar levels rise, causing or worsening diabetes. Tell your doctor immediately if you develop symptoms of high blood sugar such as increased thirst or tiredness.

If you already have diabetes, be sure to check your blood sugar levels regularly. This medication may also cause your blood sugar levels to fall. Symptoms of low blood sugar include fast/pounding heartbeat, shakiness, hunger and sweating. It is a good habit to carry glucose tablets or gel to treat low blood sugar. If you are in a situation where you don't have these reliable forms of glucose, eat a quick source of sugar such as table sugar, honey, or candy, or drink a glass of orange juice or non-diet soda to quickly raise your blood sugar level. Tell your doctor immediately about the reaction.

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.

This medication should not be used in children less than 12 because it may affect normal growth.

This medication should be used with caution in the elderly because they may be more sensitive to its side effects, especially low potassium or sodium levels.

This medication should be used during pregnancy only if clearly needed. Discuss the risks and benefits with your doctor.

Acetazolamide passes into breast milk. Breast-feeding while using this medication is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., 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 them first.

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

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

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially: anticonvulsants (e.g., phenytoin, primidone, phenobarbital), other diuretics similar to this medication (carbonic anhydrase inhibitors such as brinzolamide, dorzolamide), cyclosporine, digoxin, drugs for diabetes (e.g., glyburide, insulin), drugs that cause loss of potassium (e.g., diuretics such as furosemide, corticosteroids such as prednisone, amphotericin B), folic acid antagonists (e.g., methotrexate, trimethoprim), lithium, memantine, procainamide, quinidine, salicylates (e.g., aspirin, bismuth subsalicylate), sodium bicarbonate, stimulants (e.g., amphetamines, ephedrine), topiramate, tricyclic antidepressants (e.g., amitriptyline).

Check all prescription and nonprescription labels carefully since they may contain medications (e.g., anti-diarrhea drugs, pain relievers/fever reducers) similar to aspirin, which can cause serious side effects when taken with acetazolamide. Low-dose aspirin, as prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually at dosages of 81-325 milligrams per day), should be continued. Consult your doctor or pharmacist for more details.

This medication may interfere with certain laboratory tests, possibly causing false test results. Make sure laboratory personnel and your doctor 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. Canadian residents should call their local poison control center directly.

NOTES: Do not change brands or dosage forms of this medication without consulting your doctor or pharmacist. Not all forms of this medication work the same way.

Do not share this medication with others.

Laboratory and/or medical tests (e.g., blood count, minerals such as potassium and sodium, liver function tests) may be performed from time to time to monitor your progress and 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 for your 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 moisture and sunlight. Do not store in the bathroom. Keep all medications 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.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For enrollment information call MedicAlert at 1-800-854-1166 (USA), or 1-800-668-1507 (Canada).

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