Instructions Diacarb tablets 250 mg No. 30
Composition
active ingredient: acetazolamide;
1 tablet contains 250 mg of acetazolamide;
Excipients: microcrystalline cellulose, povidone, colloidal anhydrous silica, croscarmellose, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: round biconvex tablets of white color.
Pharmacotherapeutic group
Antiglaucoma drugs and miotics. Carbonic anhydrase inhibitors. ATX code S01E C01.
Pharmacological properties
Pharmacodynamics
Diuretic, antiglaucoma, antiepileptic agent. The mechanism of action is due to selective inhibition of carbonic anhydrase - an enzyme that catalyzes the reversible reaction of carbon dioxide hydration and subsequent dissociation of carbonic acid. The diuretic effect is due to inhibition of carbonic anhydrase activity in the kidneys (mainly in the proximal renal tubules), which leads to a decrease in the reabsorption of bicarbonate, sodium and potassium ions, increased diuresis, increased urine pH, increased ammonia reabsorption. Does not affect the excretion of chlorine ions. As a result of inhibition of carbonic anhydrase of the ciliary body, the secretion of aqueous humor is reduced and intraocular pressure is reduced. Inhibition of carbonic anhydrase in the brain leads to the accumulation of CO2 in the brain and inhibition of excessive paroxysmal discharges of neurons, which determines the antiepileptic activity of the drug. The use of the drug for increased intracranial pressure is associated with inhibition of carbonic anhydrase in the choroid plexuses of the ventricles of the brain and a decrease in the production of cerebrospinal fluid.
Pharmacokinetics
Absorption
Acetazolamide is well absorbed from the gastrointestinal tract. The maximum concentration Cmax in the blood plasma is reached 1-3 hours after administration. Small concentrations of acetazolamide persist in the blood for 24 hours.
Distribution
Acetazolamide is distributed in many tissues. Due to its high affinity for carbonic anhydrase, it accumulates mainly in tissues containing this enzyme, in particular in erythrocytes, kidneys, muscles, tissues of the eyeball and the central nervous system. The drug does not accumulate in tissues.
The protein-bound fraction accounts for 7–90% of the total acetazolamide content in the blood. The half-life is 4–9 hours.
Acetazolamide crosses the placental barrier.
In small quantities, it passes into breast milk.
Metabolism
Acetazolamide is not metabolized.
Breeding
The drug is excreted unchanged by the kidneys. After oral administration, about 90% of the dose is excreted in the urine within 24 hours.
Indication
Glaucoma treatment:
- chronic open-angle glaucoma;
- secondary glaucoma;
- angle-closure glaucoma (for short-term preoperative therapy and before ophthalmic procedures, to reduce intraocular pressure).
Treatment of edema:
- with heart failure;
- edema caused by taking medications.
Treatment of epilepsy (in combination with other anticonvulsants):
- petit mal (small seizures) in children;
- grand mal (major seizures) in adults;
- mixed form.
Treatment of altitude sickness (the drug reduces acclimatization time, but its effect on the manifestations of this disease is insignificant).
Contraindication
Hypersensitivity to the components of the drug and sulfonamides, impaired liver and kidney function, acute renal failure, hepatic failure, hyponatremia and/or hypokalemia, Addison's disease, adrenal insufficiency, hyperchloremic acidosis. Acetazolamide is contraindicated in patients with cirrhosis of the liver, as this may increase the risk of hepatic encephalopathy.
Long-term use of acetazolamide is contraindicated in patients with chronic decompensated angle-closure glaucoma, since in the case of complete closure of the angle of the eye chamber, the worsening of the course of glaucoma will be masked by reduced intraocular pressure.
Urolithiasis (with hypercalciuria), diabetes mellitus, uremia.
Interaction with other medicinal products and other types of interactions
Acetazolamide may enhance the effects of folic acid antagonists, hypoglycemic agents, and anticoagulants administered orally.
Concomitant use of acetazolamide with acetylsalicylic acid may lead to severe acidosis and toxic effects on the central nervous system with the risk of anorexia, tachypnea, lethargy, coma with possible fatal outcome.
When acetazolamide is used simultaneously with cardiac glycosides or drugs that increase blood pressure, the dose of the former must be changed.
Acetazolamide disrupts the metabolism of phenytoin, increasing serum concentrations of the latter. Severe osteomalacia has been observed in patients taking acetazolamide with certain anticonvulsants (phenytoin, primidone).
Acetazolamide may increase or decrease blood glucose levels, which should be taken into account when treating diabetes. It may be necessary to adjust the dose of insulin or oral hypoglycemic agents.
Acetazolamide enhances the excretion of lithium and may reduce plasma lithium levels.
Acetazolamide may increase the plasma concentration of carbamazepine.
With simultaneous use, acetazolamide increases the risk of toxic effects of salicylates, digitalis preparations, carbamazepine, ephedrine, and non-depolarizing muscle relaxants.
The diuretic effect of acetazolamide is enhanced by theophylline and weakened by acid-forming diuretics.
There have been isolated reports of decreased serum levels of pramidone and increased levels of carbamazepine when administered concomitantly with acetazolamide.
Due to possible additive effects, concomitant use with other carbonic anhydrase inhibitors is not recommended.
Cyclosporine: Acetazolamide may increase cyclosporine levels.
Methenamine: Acetazolamide may interfere with the antiseptic effect of methenamine on the urine.
Sodium bicarbonate: Concomitant use of acetazolamide with sodium bicarbonate increases the risk of kidney stone formation.
Application features
Suicidal ideation and behavior have been reported in patients treated with antiepileptic drugs for various indications. A meta-analysis of randomized placebo-controlled trials also showed a small increased risk of suicidal ideation and behavior. The mechanism of this risk is unknown, and the available data do not exclude the possibility of an increased risk for acetazolamide.
Therefore, monitoring for signs of suicidal ideation and behavior should be considered, and the need for appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice immediately if signs of suicidal ideation or behavior emerge.
Acetazolamide, when given in doses higher than recommended, does not increase diuresis, but may cause drowsiness and paresthesia, and may sometimes even decrease diuresis. Under certain conditions, however, very high doses must be used in combination with other diuretics to provide diuresis in complete refractory heart failure.
During treatment with acetazolamide, both a decrease and an increase in blood plasma glucose levels were noted; this should be taken into account when prescribing the drug to patients with impaired glucose tolerance or diabetes mellitus.
Special precautions are necessary during prolonged therapy. The patient should be warned about the need to report all cases of skin changes. It is recommended to periodically monitor the blood picture and serum electrolyte levels (especially potassium and blood pH), as well as control of the peripheral blood picture. Fatalities have occurred due to serious reactions to sulfonamides, although such cases were rare. In the event of a sharp decrease in the number of formed blood elements or the appearance of toxic skin changes, the drug should be urgently canceled.
Use with caution in pulmonary embolism and pulmonary emphysema, lower airway obstruction/obstruction where alveolar ventilation may be reduced, renal failure, and in elderly patients due to increased risk of metabolic acidosis.
In patients with a history of kidney stones, the risk/benefit ratio for further stone deposition should be assessed.
The drug alkalizes urine.
The development of generalized erythema during drug use, accompanied by the appearance of pustules and fever, may be a symptom of acute generalized eczematous pustulosis. If this condition is diagnosed, treatment with acetazolamide should be discontinued, and further use of the drug is contraindicated.
In case of hypersensitivity, symptoms that may threaten the patient's life may occur, such as Stevens-Johnson syndrome, Lyell's syndrome, fulminant hepatic necrosis, agranulocytosis, aplastic anemia and hemorrhagic diathesis.
In case of development of skin or hematological manifestations, the drug should be discontinued immediately.
Acetazolamide should be administered with caution to patients taking acetylsalicylic acid (high doses), as there is a possibility of anorexia, rapid breathing, lethargy, coma, and even death.
If you miss a dose, do not increase the dose at the next dose.
If a patient takes acetazolamide for longer than 5 days, there is a risk of developing metabolic acidosis.
Choroidal effusion/detachment has been reported following the use of acetazolamide. Symptoms include acute onset of decreased visual acuity or eye pain and usually occur within hours to weeks of starting the drug. If choroidal effusion/detachment is suspected, acetazolamide should be discontinued as soon as possible.
Laboratory studies
It is recommended to monitor blood counts and platelet levels at the beginning of treatment and periodically during treatment, and it is also recommended to monitor plasma electrolyte levels.
Use during pregnancy or breastfeeding
Acetazolamide crosses the placental barrier. Use of the drug during pregnancy is contraindicated.
Breast-feeding
Acetazolamide passes into breast milk in small amounts. Breastfeeding should be discontinued during use of the drug.
Ability to influence reaction speed when driving vehicles or other mechanisms
Acetazolamide in high doses can cause drowsiness, and less commonly fatigue, dizziness, ataxia, and disorientation. Therefore, during treatment with acetazolamide, you should not drive or operate potentially dangerous machinery.
Method of administration and doses
The drug is taken orally.
Glaucoma treatment
The dose of the drug should be determined individually depending on the intraocular pressure.
Recommended doses for adults:
| In open-angle glaucoma | 250 mg (1 tablet) 1–4 times a day. Doses above 1000 mg (4 tablets) do not increase therapeutic efficacy. |
| In secondary glaucoma | 250 mg (1 tablet) every 4 hours. In some patients, a therapeutic effect is observed after taking 250 mg (1 tablet) twice a day (long-term administration is not indicated). |
| In acute attacks of angle-closure glaucoma | 250 mg (1 tablet) 4 times a day. |
Epilepsy treatment
| Adults and children | Typically, 8–30 mg/kg body weight per day. The dose should be administered in 1–4 divided doses. The optimal dose is 250–1000 mg (1–4 tablets). |
| When using acetazolamide simultaneously with other anticonvulsants, the initial dose of the first should be 250 mg (1 tablet) per day. The dose should be increased gradually if necessary. For children, the dose should not exceed 750 mg per day. |
Treatment of edema in heart failure and edema caused by medication
The initial dose is 250 mg per day (1 tablet) in the morning.
The best diuretic effect is observed if the drug is used every other day or every 2 days with a one-day break.
In the treatment of heart failure, acetazolamide should be prescribed in conjunction with standard therapy (e.g., digitalis glycosides, low-salt diet, and potassium supplementation).
Treatment of altitude sickness
The recommended daily dose is 500–1000 mg (2–4 tablets), divided into several doses. In case of anticipated rapid ascent to altitude (more than 500 m per day), the recommended dose is 1000 mg (4 tablets), divided into several doses.
The drug should be taken 24–48 hours before ascending, and if symptoms of the disease appear, treatment should be continued for another 48 hours or more if necessary.
Children
The drug should be used for the treatment of children aged 3 years and older only as an adjunctive therapy for epilepsy.
Overdose
Symptoms of overdose and acute poisoning in humans have not been described. In case of overdose, electrolyte imbalance, acidosis and central nervous system disorders (drowsiness, paresthesia) are possible; sometimes - decreased diuresis. Therefore, it is necessary to monitor the concentration of electrolytes in the blood plasma, especially potassium, as well as urine pH.
Treatment.
Drug withdrawal, symptomatic therapy, in case of acidosis, administer bicarbonates. Effective hemodialysis. There is no specific antidote.
Adverse reactions
The following adverse reactions have been observed during treatment with acetazolamide, listed below, with the following frequencies: very common (≥ 1/10), common (≥ 1/100, <1/10), uncommon (≥ 1/1000, <1/100), rare (≥ 1/10000, <1/1000), very rare (≥ 1/100000, <1/10000), frequency unknown (cannot be estimated from the available information).
From the blood system
Rare: aplastic anemia, thrombocytopenia, agranulocytosis, leukopenia, thrombocytopenic purpura, bone marrow depression, pancytopenia.
In some cases, with prolonged use, hemolytic anemia.
Metabolic
Common: anorexia, metabolic acidosis, fluid and electrolyte imbalance (in combination with hyponatremia and hypokalemia).
Frequency unknown: hypocalcemia, weight loss (with long-term use).
From the psyche
Uncommon: depression.
From the nervous system and sensory organs
Common: dizziness, taste disturbance, paresthesia (sensation of crawling in the limbs).
Uncommon: hot flashes, thirst, headache, irritability, decreased libido.
Isolated cases have been reported: drowsiness, confusion, flaccid paralysis, convulsions.
Frequency unknown: ataxia; with prolonged use - disorientation, impaired touch and sensitivity, general weakness, peripheral paralysis; in rare cases - a sensation of hair on the tongue.
From the organs of vision
Rare: reversible myopia.
Frequency unknown: choroidal effusion, choroidal detachment.
Hearing and balance disorders
Rare: tinnitus, hearing impairment.
Gastrointestinal tract
Uncommon: nausea, vomiting, diarrhoea, melena.
Liver and biliary tract disorders
Uncommon: liver dysfunction.
Rare: fulminant hepatic necrosis, hepatitis, mechanical jaundice.
Frequency unknown: hepatic failure, hepatic colic.
Skin and skin derivatives
Frequency unknown: acute generalized eczematous pustulosis, pruritus, erythema.
From the urinary system
Uncommon: nephrolithiasis, crystalluria, renal colic, kidney damage, polyuria, hematuria, renal failure.
Rare: glycosuria.
Frequency unknown: frequent urination.
General disorders
Common: fatigue.
Uncommon: fever.
On the part of the immune system
Rare: hypersensitivity reactions, including anaphylactic reactions.
Research
Very rare: hypoglycemia, hyperglycemia.
Acetazolamide, as a sulfonamide derivative, can cause adverse reactions typical of sulfonamides.
Expiration date
5 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging.
Keep out of reach of children.
Packaging
10 tablets in a blister; 3 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Production of the finished medicinal product, primary and secondary packaging, quality control and batch release:
Pharmaceutical Works «Polpharma» SA, Poland.
Primary, secondary packaging, quality control and batch release:
Pharmaceutical Works POLPHARMA SA Medana Branch in Sieradz.
Location of the manufacturer and its business address
19, Pelplinska Str., 83-200 Starogard Gdanski, Poland.
57, Polskiej Organizacji Wojskowej Str., 98-200 Sieradz, Poland.
