CARBONICANHYDRASE INHIBITORS (Systemic)

Some commonly used brand names are:

In the U.S.?

• Ak-Zol ¹
• Daranide ²
• Dazamide ¹
• Diamox ¹
• Diamox Sequels ¹
• MZM ³
• Neptazane ³
• Storzolamide ¹

In Canada?

• Acetazolam ¹
• Apo-Acetazolamide ¹
• Diamox ¹
• Diamox Sequels ¹
• Neptazane ³

Another commonly used name for dichlorphenamide is diclofenamide.

Category

• Altitude sickness, acute, prophylactic and therapeutic agent?Acetazolamide
• Anticonvulsant?Acetazolamide
• Antiglaucoma agent, systemic?Acetazolamide; Dichlorphenamide; Methazolamide
• Antiparalytic,familial periodic paralysis?Acetazolamide
• Antiurolithic, cystine calculi?Acetazolamide
• Antiurolithic,uric acid calculi?Acetazolamide
• Diuretic, urinary alkalinizing?Acetazolamide

Description

Carbonic anhydrase inhibitors are used to treat glaucoma. Acetazolamideis also used as an anticonvulsant to control certain seizures in the treatmentof epilepsy. It is also sometimes used to prevent or lessen some effects inmountain climbers who climb to high altitudes, and to treat other conditionsas determined by your doctor.

These medicines are available only with your doctor's prescription, inthe following dosage forms:

Oral
• Acetazolamide
  • Extended-release capsules (U.S. and Canada)
  • Tablets (U.S. and Canada)
• Dichlorphenamide
  • Tablets (U.S.)
• Methazolamide
  • Tablets (U.S. and Canada)

Parenteral
• Acetazolamide
  • Injection (U.S. and Canada)

Before Using This Medicine

In deciding to use a medicine,the risks of taking the medicine must be weighed against the good it willdo. This is a decision you and your doctor will make. For carbonic anhydraseinhibitors, the following should be considered:

Allergies?Tell your doctor if you have ever had any unusual orallergic reaction to carbonic anhydrase inhibitors, sulfonamides (sulfa drugs),or thiazide diuretics (a type of water pill). Also tell your health care professionalif you are allergic to any other substances, such as foods, preservatives,or dyes.

Pregnancy?Carbonic anhydrase inhibitors have not been studiedin pregnant women. However, studies in animals have shown that carbonic anhydraseinhibitors cause birth defects. Before taking this medicine, make sure yourdoctor knows if you are pregnant or if you may become pregnant.

Breast-feeding?Carbonic anhydrase inhibitors may pass into thebreast milk. These medicines are not recommended during breast-feeding, becausethey may cause unwanted effects in nursing babies. It may be necessary foryou to use another medicine or to stop breast-feeding during treatment. Besure you have discussed this with your doctor.

Children?Although there is no specific information comparinguse of carbonic anhydrase inhibitors in children with use in other age groups,these medicines are not expected to cause different side effects or problemsin children than they do in adults.

Older adults?Many medicines have not been studied specificallyin older people. Therefore, it may not be known whether they work exactlythe same way they do in younger adults. Although there is no specific informationcomparing use of carbonic anhydrase inhibitors in the elderly with use inother age groups, these medicines are not expected to cause different sideeffects or problems in older people than they do in younger adults.

Other medicines?Although certain medicines should not be usedtogether at all, in other cases two different medicines may be used togethereven if an interaction might occur. In these cases, your doctor may want tochange the dose, or other precautions may be necessary. When you are usingcarbonic anhydrase inhibitors, it is especially important that your healthcare professional know if you are using any of the following:

• Amphetamines or
• Mecamylamine (e.g., Inversine) or
• Quinidine (e.g., Quinidex)?Use of carbonic anhydrase inhibitorsmay increase the chance of side effects

• Methenamine (e.g., Mandelamine)?Use of carbonic anhydrase inhibitorsmay decrease the effectiveness of methenamine

Other medical problems?The presence of other medicalproblems may affect the use of carbonic anhydrase inhibitors. Make sure youtell your doctor if you have any other medical problems, especially:

• Type 2 diabetes mellitus?Use of carbonic anhydrase inhibitorsmay increase the patient's blood and urine sugar concentrations

• Emphysema or other chronic lung disease?Use of carbonic anhydraseinhibitors may increase the risk of acidosis (shortness of breath, troubledbreathing)

• Gout or
• Low blood levels of potassium or sodium?Use of carbonic anhydraseinhibitors may make the condition worse

• Kidney disease or stones?Higher blood levels of carbonic anhydraseinhibitors may result, which may increase the chance of side effects; also,these medicines may make the condition worse

• Liver disease?Use of carbonic anhydrase inhibitors may increasethe risk of electrolyte imbalance and may make the condition worse

• Underactive adrenal gland (Addison's disease)?Use of carbonicanhydrase inhibitors may increase the risk of electrolyte imbalance

Proper Use of This Medicine

Take this medicine only as directed. Do not take more of it and donot take it more often than your doctor ordered. To do so may increase thechance of side effects without increasing the effectiveness of this medicine.

This medicine may be taken with meals to lessen the chance of stomach upset.However, if stomach upset (nausea or vomiting) continues, check with yourdoctor.

This medicine may cause an increase in the amount of urine or in your frequencyof urination. If you continue to take the medicine every day, these effectsshould lessen or stop. To keep the increase in urine from affecting your nighttimesleep:

• If you are to take a single dose a day, take it in the morning afterbreakfast.
• If you are to take more than one dose a day, take the last dose nolater than 6 p.m., unless otherwise directed by your doctor.

However, it is best to plan your dose or doses according to a schedulethat will least affect your personal activities and sleep. Ask your healthcare professional to help you plan the best time to take this medicine.

Dosing?The doses of carbonic anhydrase inhibitorswill be different for different patients. Follow yourdoctor's orders or the directions on the label. The following informationincludes only the average doses of these medicines. If your dose is different, do not change it unless your doctor tellsyou to do so.

The number of capsules or tablets that you take depends on the strengthof the medicine. Also, the number of doses you take eachday, the time allowed between doses, and the length of time you take the medicinedepend on the medical problem for which you are taking the carbonic anhydraseinhibitor.

For acetazolamide
• For oral dosage form (extended-releasecapsules):
  • For glaucoma:
    • Adults?500 milligrams (mg) two times a day, in the morningand evening.
    • Children?Use and dose must be determined by your doctor.
  • For altitude sickness:
    • Adults?500 mg one or two times a day.
    • Children?Use and dose must be determined by your doctor.
• For oral dosage form (tablets):
  • For glaucoma:
    • Adults?250 mg one to four times a day.
    • Children?Dose is based on body weight and must be determinedby your doctor. The usual dose is 10 to 15 mg per kilogram (kg) (4.5 to 6.8mg per pound) of body weight a day in divided doses.
  • For epilepsy:
    • Adults and children?Dose is based on body weight and must bedetermined by your doctor. The usual dose is 10 mg per kg (4.5 mg per pound)of body weight a day in divided doses.
  • For altitude sickness:
    • Adults?250 mg two to four times a day.
    • Children?Use and dose must be determined by your doctor.
• For injection dosage form:
  • For glaucoma:
    • Adults?500 mg, injected into a muscle or vein, for one dose.
    • Children?Dose is based on body weight and must be determinedby your doctor. The usual dose is 5 to 10 mg per kg (2.3 to 4.5 mg per pound)of body weight every six hours, injected into a muscle or vein.

For dichlorphenamide
• For oral dosage form (tablets):
  • For glaucoma:
    • Adults?25 to 50 milligrams (mg) one to three times a day.
    • Children?Use and dose must be determined by your doctor.

For methazolamide
• For oral dosage form (tablets):
  • For glaucoma:
    • Adults?50 to 100 milligrams (mg) two or three times a day.
    • Children?Use and dose must be determined by your doctor.

Missed dose?If you miss a dose of this medicine, take it assoon as possible. However, if it is almost time for your next dose, skip themissed dose and go back to your regular dosing schedule. Do not double doses.

Storage?To store this medicine:

• Keep out of the reach of children.
• Store away from heat and direct light.
• Do not store the capsule or tablet form of this medicine in the bathroom,near the kitchen sink, or in other damp places. Heat or moisture may causethe medicine to break down.
• Do not keep outdated medicine or medicine no longer needed. Be surethat any discarded medicine is out of the reach of children.

Precautions While Using This Medicine

Thismedicine may cause some people to feel drowsy, dizzy, lightheaded, or moretired than they are normally. Make sure you know howyou react to this medicine before you drive, use machines, or do anythingelse that could be dangerous if you are not alert.

It is important that your doctor check your progress at regular visits.Your doctor may want to do certain tests to see if the medicine is workingproperly or to see if certain side effects may be occurring without your knowingit.

This medicine may cause a loss of potassium from yourbody. To help prevent this, your doctor may want you to eat or drinkfoods that have a high potassium content (for example, orange or other citrusfruit juices) or take a potassium supplement. It is very important to followthese directions. Also, it is important not to change your diet on your own.This is more important if you are already on a special diet (as for diabetes)or if you are taking a potassium supplement. Extra potassium may not be necessaryand, in some cases, too much potassium could be harmful.

For diabetic patients:

• This medicine may raise blood and urine sugar levels. While you areusing this medicine, be especially careful in testing for sugar in your bloodor urine. If you have any questions about this, check with your doctor.

Your doctor may want you to increase the amount of fluids you drink whileyou are taking this medicine. This is to prevent kidney stones. However, donot increase the amount of fluids you drink without first checking with yourdoctor.

For patients taking acetazolamide as an anticonvulsant:

• If you have been taking acetazolamide regularlyfor several weeks or more, do not suddenly stop taking it. Your doctormay want you to reduce gradually the amount you are taking before stoppingcompletely.

Side Effects of This Medicine

Along with its needed effects, a medicine may cause some unwanted effects.Although not all of these side effects may occur, if they do occur they mayneed medical attention.

Check with your doctorimmediately if either of the following side effects occurs:

Rare

Shortness of breath or trouble in breathing

Also, check with your doctoras soon as possible if any of the following side effects occur:

More common

Unusual tiredness or weakness

Less common

Blood in urine; difficult urination; mental depression; painin lower back; pain or burning while urinating; sudden decrease in amount of urine

Rare

Bloody or black, tarry stools; clumsinessor unsteadiness; confusion; convulsions (seizures); darkening of urine; fever; hives, itching of skin, skinrash, or sores; muscle weakness (severe); pale stools; ringing or buzzing in theears; sore throat; trembling; unusual bruising or bleeding; yellow eyes or skin

Symptoms of too much potassium loss

Dryness of mouth; increased thirst; irregular heartbeats; mood or mentalchanges; muscle cramps or pain; nausea or vomiting; unusual tiredness or weakness; weak pulse

Also, check with your doctor if you have any changesin your vision (especially problems with seeing faraway objects) when youfirst begin taking this medicine.

Other side effects may occur that usually donot need medical attention. These side effects may go away during treatmentas your body adjusts to the medicine. However, check with your doctor if anyof the following side effects continue or are bothersome:

More common

Diarrhea; general feeling of discomfortor illness; increase in frequency of urination oramount of urine (rare with methazolamide); loss ofappetite; metallic taste in mouth; nausea or vomiting; numbness, tingling, or burningin hands, fingers, feet, toes, mouth, lips, tongue, or anus; weight loss

Less common or rare

Constipation; dizziness or lightheadedness; drowsiness; feeling ofchoking or lump in the throat; headache; increased sensitivity of eyes to sunlight; loss of taste and smell; nervousness or irritability

Other side effects notlisted above may also occur in some patients. If you notice any other effects,check with your doctor.