Diacarb^® (Tablets) Instructions for Use

ATC Code

S01EC01 (Acetazolamide)

Active Substance

Acetazolamide (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Diuretic. Carbonic anhydrase inhibitor

Pharmacotherapeutic Group

Diuretic agent

Pharmacological Action

Acetazolamide is a systemic carbonic anhydrase inhibitor with weak diuretic activity. Carbonic anhydrase is an enzyme involved in the process of carbon dioxide hydration and carbonic acid dehydration. Inhibition of carbonic anhydrase reduces the formation of bicarbonate ions with a subsequent decrease in sodium transport into the cells. The effects of Diacarb^® are determined by the site of action of the molecule: the choroid plexuses of the brain, the proximal part of the nephron, the ciliary body of the eye, and erythrocytes.

Acetazolamide is used to treat disorders of cerebrospinal fluid dynamics and intracranial hypertension by reducing excessive cerebrospinal fluid production at the level of the choroid plexuses of the brain. Inhibition of carbonic anhydrase in the ependymal cells of the choroid plexus reduces the excessive negative charge in the ependymal cells and decreases the gradient filtration of plasma into the ventricular cavity of the brain.

Acetazolamide is used in the therapy of edematous syndrome due to its weak diuretic effect. As a result of inhibiting carbonic anhydrase activity in the proximal part of the nephron, the formation of carbonic acid decreases and the reabsorption of bicarbonate and Na⁺ by the tubular epithelium is reduced, which significantly increases water excretion. Acetazolamide increases the excretion of bicarbonates, which can lead to the development of metabolic acidosis. Acetazolamide causes the excretion of phosphates, magnesium, and calcium by the kidneys, which can also lead to metabolic disorders. During the subsequent 3 days of therapy, compensatory activation of Na⁺ reabsorption in the distal part of the nephron occurs, reducing the diuretic effect of Diacarb^®.

After 3 days from the start of use, Acetazolamide loses its diuretic properties. After a break in treatment for several days, re-administered Acetazolamide resumes its diuretic action due to the restoration of normal carbonic anhydrase activity in the proximal nephron.

Acetazolamide is used to treat glaucoma. In the process of aqueous humor formation, bicarbonate ions are actively transported into the posterior chamber from the cytoplasm of non-pigmented cells to compensate for the positive ion gradient caused by the active transport of Na⁺ ions. Carbonic anhydrase inhibitors block the formation of carbonic acid, thus reducing the production of HCO^3-. In the absence of a sufficient amount of HCO^3- ions, the positive ion gradient increases, which causes a decrease in the secretion of aqueous humor. Inhibition of carbonic anhydrase in the ciliary body reduces the secretion of aqueous humor in the anterior chamber of the eye, which lowers intraocular pressure. Tolerance to this effect does not develop. Ophthalmic tone begins to decrease 40-60 minutes after taking acetazolamide, the maximum effect is observed after 3-5 hours, and intraocular pressure remains below the initial level for 6-12 hours. On average, intraocular pressure decreases by 40-60% from the initial level.

The drug is used as an adjuvant in the treatment of epilepsy, because inhibition of carbonic anhydrase in the nerve cells of the brain inhibits pathological excitability.

Pharmacokinetics

Absorption

Acetazolamide is well absorbed from the gastrointestinal tract. After oral administration of a 500 mg dose, the C_max of the active substance is 12-27 µg/ml and is achieved in 1-3 hours. The minimum concentration of acetazolamide in plasma is maintained for 24 hours after drug administration.

Distribution and Metabolism

Acetazolamide is distributed in erythrocytes, blood plasma, and kidneys, and to a lesser extent in the liver, muscles, eyeball, and central nervous system. It crosses the placental barrier and is excreted in small amounts in breast milk.

It does not accumulate in tissues and is not metabolized in the body.

Excretion

It is excreted by the kidneys unchanged. About 90% of the dose is excreted in the urine within 24 hours.

Indications

• Edematous syndrome (mild or moderate, combined with alkalosis);
• Relief of an acute attack of glaucoma, preoperative preparation of patients, persistent cases of glaucoma (in complex therapy);
• For epilepsy as an additional therapy to antiepileptic drugs;
• Acute “high-altitude” sickness (the drug reduces acclimatization time);
• Disorders of cerebrospinal fluid dynamics, intracranial hypertension (benign intracranial hypertension, intracranial hypertension after ventricular shunting) in complex therapy.

ICD codes

Dosage Regimen

Tablets

The drug is taken orally, strictly as prescribed by a doctor.

If a dose is missed, the dose should not be increased at the next administration.

Edematous syndrome

At the beginning of treatment, take 250 mg in the morning. To achieve the maximum diuretic effect, it is necessary to take Diacarb^® once daily every other day or for 2 consecutive days with a one-day break. Increasing the dose does not enhance the diuretic effect.

If the previously achieved response to acetazolamide therapy decreases, the drug should be discontinued for one day (to restore kidney carbonic anhydrase activity).

The use of acetazolamide does not cancel the need for the use of other medications, adherence to bed rest (if recommended by a doctor), and restriction of sodium chloride intake.

Glaucoma

Diacarb^® should be taken as part of complex therapy.

Adults with open-angle glaucoma are prescribed the drug at a dose of 250 mg 1-4 times/day. Doses exceeding 1000 mg do not increase the therapeutic effect.

For secondary glaucoma, the drug is prescribed at a dose of 250 mg every 4 hours during the day. In some patients, the therapeutic effect is manifested after short-term use of the drug at a dose of 250 mg twice daily.

For acute attacks of glaucoma – 250 mg 4 times/day.

Children over 3 years with glaucoma attacks – 10-15 mg/kg body weight/day in 3-4 divided doses.

After 5 days of use, take a break for 2 days. During long-term treatment, it is necessary to prescribe potassium preparations and a potassium-sparing diet.

For preoperative preparation, 250-500 mg is prescribed the day before and in the morning on the day of surgery.

Epilepsy

Doses for adults: 250-500 mg/day in a single dose for 3 days, with a break on the 4th day.

When acetazolamide is used simultaneously with other anticonvulsant drugs, 250 mg once daily is used at the beginning of treatment, gradually increasing the dose if necessary. The maximum daily dose for adults is 1000 mg.

Doses for children over 3 years: 8-30 mg/kg/day, divided into 1-4 doses. The maximum daily dose is 750 mg.

Acute “high-altitude” sickness

It is recommended to use the drug at a dose of 500-1000 mg/day. In case of rapid ascent – 1000 mg/day.

The drug should be used 24-48 hours before ascent. If symptoms of the disease appear, treatment is continued for the next 48 hours or longer if necessary.

Disorders of cerebrospinal fluid dynamics, intracranial hypertension

It is recommended to use the drug at a dose of 250 mg/day or 125-250 mg every 8-12 hours. The maximum therapeutic effect is achieved when taking a dose of 750 mg/day. To achieve the optimal therapeutic effect, daily use of the drug without intervals may be required.

Adverse Reactions

Adverse effects are classified according to frequency of occurrence and by organs and systems. The following definition of the frequency of adverse effects is accepted: very common (>1/10); common (>1/100, <1/10); uncommon (>1/1000, <1/100); rare (>1/10,000, <1/1000); very rare (<1/10,000), frequency unknown (cannot be estimated from the available data).

From the hematopoietic system rare – aplastic anemia, thrombocytopenia, agranulocytosis, leukopenia, thrombocytopenic purpura, myelosuppression, pancytopenia.

From the immune system frequency unknown – anaphylactic reactions.

From metabolism and nutrition common – decreased appetite, taste disturbances, metabolic acidosis and electrolyte disturbances (usually can be corrected by prescribing bicarbonate); uncommon – thirst; rare – glucosuria; frequency unknown – hypokalemia, hyponatremia.

Psychiatric disorders uncommon – depression, irritability; frequency unknown – agitation, confusion, disorientation.

From the nervous system common – dizziness, paresthesia, in particular a tingling sensation in the limbs; uncommon – “flushing”, headache; very rare – drowsiness, peripheral paresis, convulsions; frequency unknown – ataxia.

From the organ of vision rare – transient myopia (this condition completely disappeared when the dose was reduced or the drug was discontinued).

From the organ of hearing rare – hearing impairment and tinnitus.

From the digestive system uncommon – nausea, vomiting, diarrhea, melena; rare – fulminant liver necrosis, liver function disorders, hepatitis, cholestatic jaundice; frequency unknown – dry mouth, dysgeusia, liver failure, hepatic colic.

From the skin and subcutaneous tissue rare – photosensitivity; frequency unknown – itching, rash, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria.

From the musculoskeletal system frequency unknown – arthralgia.

From the urinary system frequency unknown – kidney stone formation, crystalluria, renal and ureteral colic and kidney damage, polyuria, hematuria, renal failure.

From the reproductive system and mammary gland uncommon – decreased libido.

General disorders and administration site conditions common – fatigue; uncommon – fever, weakness.

Contraindications

• Acute renal failure;
• Uremia;
• Hepatic failure (risk of encephalopathy);
• Refractory hypokalemia and hyponatremia;
• Metabolic acidosis;
• Hypocorticism;
• Addison’s disease;
• Decompensated diabetes mellitus;
• First trimester of pregnancy;
• Lactation period;
• Children under 3 years of age;
• Hypersensitivity to acetazolamide (or other sulfonamides), as well as any other component of the drug.

With caution: edema of hepatic and renal origin, simultaneous use with acetylsalicylic acid (doses more than 300 mg/day), pulmonary embolism and pulmonary emphysema (risk of acidosis), second and third trimesters of pregnancy, elderly age, water-electrolyte imbalance, impaired liver function, in patients at risk of urinary tract obstruction.

Use in Pregnancy and Lactation

Diacarb^® is contraindicated in the first trimester of pregnancy, and in the second and third trimesters it is used with caution and only in cases where the potential benefit to the mother outweighs the potential risk to the fetus.

Acetazolamide is excreted in small amounts in breast milk, so if it is necessary to use Diacarb^® during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

Contraindicated in hepatic failure (risk of encephalopathy).

The drug should be used with caution in edema of hepatic origin.

Use in Renal Impairment

Contraindicated in acute renal failure.

The drug should be used with caution in edema of renal origin.

Pediatric Use

The use of the drug is contraindicated in children under 3 years of age.

Geriatric Use

The drug should be prescribed with caution to elderly patients.

Special Precautions

In case of hypersensitivity to the drug, life-threatening adverse reactions may occur, for example, Stevens-Johnson syndrome, Lyell’s syndrome, fulminant liver necrosis, agranulocytosis, aplastic anemia, and hemorrhagic diathesis. If these symptoms appear, the drug should be discontinued immediately.

Diacarb^®, used in doses exceeding the recommended ones, does not increase diuresis, may enhance drowsiness and paresthesia, and sometimes also reduce diuresis.

In case of using the drug for more than 5 days, there is a high risk of developing metabolic acidosis. Monitoring of blood picture and platelets at the beginning of treatment, and at regular intervals during treatment, as well as periodic monitoring of serum electrolytes is recommended.

Acetazolamide should be used with caution in patients with bronchial obstruction and pulmonary emphysema (conditions accompanied by impaired alveolar ventilation) due to the possibility of increased acidosis.

Acetazolamide alkalinizes the urine. In patients with a history of urolithiasis, the balance of treatment benefit and the risk of stone formation should be assessed.

If transient hearing impairment occurs, acetazolamide should be discontinued.

Concomitant use of acetazolamide with high doses of acetylsalicylic acid (more than 300 mg/day) is not recommended due to the high risk of severe adverse events.

Against the background of epilepsy treatment with specific antiepileptic drugs, a slight increase in the risk of suicidal thoughts and suicidal behavior is noted. The mechanism of this phenomenon is unknown, but available data do not exclude such a risk when using acetazolamide. Therefore, when using acetazolamide for the treatment of epilepsy, patients should be monitored for possible signs of suicidal behavior and thoughts and, if necessary, seek immediate medical help.

Diacarb^® should be used with caution in patients with diabetes mellitus due to an increased risk of hyperglycemia.

Effect on ability to drive vehicles and operate machinery

Diacarb^®, especially in high doses, may cause drowsiness, less often fatigue, dizziness, ataxia, and disorientation. During treatment, patients should not drive vehicles or work with mechanisms requiring increased concentration and speed of psychomotor reactions.

Overdose

Symptoms of overdose have not been described. Probable symptoms of overdose may include water-electrolyte imbalance, metabolic acidosis, as well as disorders of the central nervous system.

Treatment there is no specific antidote. Symptomatic and supportive therapy is carried out. The content of electrolytes in the blood, especially potassium, sodium, as well as blood pH should be monitored. In case of metabolic acidosis, sodium bicarbonate is used. Acetazolamide is removed by hemodialysis.

Drug Interactions

Acetazolamide may enhance the effect of folic acid antagonists, hypoglycemic agents, and oral anticoagulants.

Concomitant use of acetazolamide and acetylsalicylic acid may cause metabolic acidosis and enhance toxic effects on the central nervous system.

When used concomitantly with cardiac glycosides or drugs that increase blood pressure, the dose of acetazolamide should be adjusted.

Acetazolamide increases the serum concentration of phenytoin.

Acetazolamide enhances the manifestations of osteomalacia caused by the use of antiepileptic drugs.

Concomitant use of acetazolamide and amphetamine, atropine, or quinidine may enhance their side effects.

Potentiation of the diuretic effect occurs when used concomitantly with methylxanthines (aminophylline).

Reduction of the diuretic effect occurs when combined with ammonium chloride and other acid-forming diuretics.

Enhancement of the hypotensive effect on intraocular pressure is possible with simultaneous use with cholinergic drugs and beta-blockers.

Acetazolamide enhances the effect of ephedrine.

Increases the plasma concentration of carbamazepine, non-depolarizing muscle relaxants.

Acetazolamide may increase the concentration of cyclosporine.

Increases the excretion of lithium.

Acetazolamide may reduce the antiseptic effect of methenamine on the genitourinary system.

Concomitant use of acetazolamide and sodium bicarbonate increases the risk of kidney stone formation.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 2 years. Do not use the drug after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.