Composition Acetazolamide:
Composition per tablet:
Active substance:
acetazolamide - 250.00 mg.
Excipients:
microcrystalline cellulose - 120.00 mg,
POVIDON-K25 - 18.00 mg,
croscarmellose sodium - 8.00 mg,
magnesium stearate - 2.00 mg,
colloidal silicon dioxide - 2.00 mg.
Pharmacodynamics Acetazolamide:
Acetazolamide is a systemic carbonic anhydrase inhibitor with weak diuretic activity. Carbo-anhydrase (KA) is an enzyme involved in the process of hydration of carbon dioxide and dehydration of carbonic acid.
Inhibition of carbonic anhydrase reduces the formation of bicarbonate ions, followed by a decrease in sodium transport into cells. The effects of the use of acetazolamide a drugs are determined by the point of application of the molecule: the vascular plexuses of the brain, the proximal nephron, the ciliary body of the eye, red blood cells.
Acetazolamide is used to treat cerebrospinal fluid disorders and intracranial hypertension by reducing excess cerebrospinal fluid production at the level of the vascular plexuses of the brain.
The inhibition of carbonic anhydrase in the ependymocytes of the vascular plexus reduces the excess negative charge in the ependymal cells and reduces the gradient filtration of plasma into the cavity of the ventricles of the brain.
Acetazolamide is used in the treatment of edematous syndrome due to a weak diuretic effect.
As a result of the inhibition of the activity of carbonic anhydrase in the proximal part of the nephron, there is a decrease in the formation of carbonic acid and a decrease in the reabsorption of bicarbonate and sodium ions by the tubular epithelium, and therefore, the release of water increases significantly.
Acetazolamide increases the excretion of bicarbonates, which can lead to the development of metabolic acidosis. Acetazolamide causes the kidneys to excrete phosphates, magnesium, calcium, which can also lead to metabolic disorders.
Over the next three days of therapy, reabsorption of sodium ions in the distal nephron is compensatory activated, reducing the diuretic effect of acetazolamide. After 3 days from the start of use, acetazolamide loses its diuretic properties.
After a break in treatment for several days, the newly prescribed acetazolamide resumes the diuretic effect due to the restoration of the normal activity of carbonic anhydrase of the proximal nephron.
Acetazolamide is used to treat glaucoma. During the formation of aqueous humor of the eye, bicarbonate ions (HCO3-) are actively transported to the posterior chamber from the cytoplasm of non-pigment cells to compensate for the gradient of positive ions due to the active transport of sodium ions.
CA inhibitors block the formation of carbonic acid, thus reducing the production of HCO3 'ions. In the absence of a sufficient amount of HCO3 ions, the positive ion gradient increases, which causes a decrease in the secretion of aqueous humor.
Inhibition of the ciliary carbonic anhydrase reduces the secretion of aqueous humor of the anterior chamber of the eye, which reduces intraocular pressure. Tolerance to this effect does not develop.
When taking acetazolam, the ophthalmotonus begins to decrease after 40-60 minutes, the maximum effect is observed after 3-5 hours, the intraocular pressure remains below the initial level for 6-12 hours. On average, intraocular pressure is reduced by 40-60% of the initial level.
Acetazolamide is used as an adjunct in the treatment of epilepsy, as inhibition of carbonic anhydrase in brain nerve cells inhibits pathological excitability.
Pharmacokinetics Acetazolamide:
Acetazolamide is well absorbed from the gastrointestinal tract. After oral administration in a dose of 500 mg, the maximum concentration (12-27 μg / ml) is achieved after 1-3 hours. In minimal concentrations, it is retained in the blood for 24 hours from the time of administration.
Acetazolamide is distributed in red blood cells, blood plasma and in the kidneys, to a lesser extent - in the liver, muscles, eyeball and central nervous system. Acetazolamide crosses the placental barrier, in a small amount excreted in breast milk.
It does not accumulate in tissues and is not metabolized and is metabolized in the body. It is excreted by the kidneys unchanged. After oral administration, about 90% of the dose taken is excreted by the kidneys within 24 hours.
Side effects Acetazolamide:
Adverse reactions are classified according to frequency of occurrence and according to organs and systems.
The following definition of the frequency of occurrence of adverse reactions is adopted: very often> 1/10, often from> 1/100 to <1/10, infrequently from> 1/1000 to <1/100, rarely from> 1/10000 to <1/1000 , very rarely from <1/10000, the frequency is unknown (cannot be determined based on available data).
Disorders from the blood and lymphatic system: rarely - aplastic anemia, thrombocytopenia, agranulocytosis, leukopenia, thrombocytopenic purpura, myelosuppression, pancytopenia.
Immune system disorders: frequency unknown - anaphylactic reactions.
Disorders from metabolism and nutrition: often - loss of appetite, taste disturbance, metabolic acidosis, metabolic acidosis and electrolyte disturbances (usually can be corrected by using sodium bicarbonate); infrequently - thirst; rarely - glucosuria; frequency unknown - hypokalemia, hyponatremia.
Mental disorders: infrequently - depression, irritability; frequency unknown - agitation, confusion, disorientation.
Violations of the nervous system: often dizziness, paresthesia, in particular a feeling of "tingling" in the limbs; infrequently - “hot flashes”, headache; very rarely - drowsiness, peripheral paresis, convulsions; frequency unknown - ataxia.
Disorders from the side of the organ of vision: rarely - transient myopia (this condition completely disappeared when the dose was reduced or acetazolamide was canceled).
Hearing impairment and labyrinth disorders: rarely - hearing impairment and ringing in the ears.
Disorders of the gastrointestinal tract: infrequently nausea, vomiting, diarrhea, melena; frequency unknown - dry mouth, dysgeusia.
Violations of the liver and biliary tract: rarely - fulminant necrosis of the liver, impaired liver function, hepatitis, cholestatic jaundice; frequency unknown - liver failure, hepatic colic.
Disorders from the skin and subcutaneous tissues: rarely - photosensitivity; frequency unknown - pruritus, skin rash, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria. Violations of the musculoskeletal and connective tissue: frequency unknown - arthralgia.
Disorders from the kidneys and urinary tract: the frequency is unknown - the formation of calculi in the kidneys, crystalluria, renal and ureteric colic, kidney damage, polyuria, hematuria, renal failure. Violations of the genitals and mammary gland: infrequently - decreased libido. General disorders and disorders at the injection site: often - fatigue; infrequently - fever, weakness.
Special conditions Acetazolamide:
With prolonged use of acetazolamide, safety precautions must be observed. It is recommended to conduct a general blood test (the number of red blood cells, white blood cells and platelets) before the appointment of acetazolamide and regularly monitor the blood picture during treatment.
Periodic monitoring of serum electrolytes is also recommended. Life-threatening hypersensitivity reactions to casetazolamide (sulfonamides), such as Stevens-Johnson syndrome, Lyell-la syndrome, fulminant liver necrosis, agranulocytosis, aplastic anemia and hemorrhagic diathesis, are described.
In the event of toxic skin reactions and / or a decrease in the number of blood cells, it is necessary to immediately stop taking acetazolamide.
If any skin rashes appear, consult a doctor. Increasing the dose of acetazolamide does not enhance the diuretic effect, but may increase the incidence of adverse reactions (such as dizziness and / or paresthesia).
The use of acetazolamide in high doses often leads to a decrease in diuresis. When using acetazolamide for more than 5 days, the risk of developing metabolic acidosis increases. Acetazolamide should be used with caution in patients with bronchial obstruction and emphysema (conditions accompanied by impaired alveolar ventilation) due to the possibility of increased acidosis.
Caution should be exercised with the simultaneous use of high doses of acetylsalicylic acid (more than 300 mg per day) and acetazolamide, since there have been reports of anorexia, tachypnea, lethargy, coma and death of patients with the use of these drugs.
Acetazolamide should be used with caution in patients with diabetes mellitus due to the increased risk of hyperglycemia.
If transient hearing loss occurs, you should stop taking acetazolamide.
Acetazolamide blocks urine. In patients with a history of urolithiasis, a balance of the benefits of treatment and the risk of stone formation should be assessed. There was a slight increase in the risk of suicidal ideation and suicidal behavior in patients treated with antiepileptic drugs.
The mechanism of this phenomenon is unknown, but existing data do not exclude such a risk with the use of acetazolamide. Therefore, when using acetazolamide, patients should be monitored and possible signs of suicidal behavior or thinking identified.
Patients (and carers) should be warned of the need to seek medical attention if signs of suicidal behavior or thinking appear. The effect on the ability to drive vehicles and mechanisms of Acetazolamide, especially in high doses, can cause drowsiness, less often fatigue, dizziness, ataxia and disorientation, therefore, during treatment, patients should not drive vehicles and work with mechanisms that require an increased concentration of attention and speed of psychomotor reactions
Indications Acetazolamide:
• Edema syndrome (mild or moderate severity, in combination with alkalosis);
• Relief of an acute attack of glaucoma, preoperative preparation of patients, persistent cases of glaucoma (in complex therapy);
• With epilepsy as an additional therapy for antiepileptic drugs;
• Acute “high-altitude” disease (the drug reduces the time of acclimatization);
• Liquorodynamic disturbances, intracranial hypertension (benign intracranial hypertension, intracranial hypertension after ventricular bypass surgery) in complex therapy.
Contraindications Acetazolamide:
• Hypersensitivity to acetazole amide, other sulfonamides and / or components of the drug;
• acute renal failure;
• severe chronic renal failure (creatinine clearance less than 10 ml / min); • uremia;
• liver failure (risk of developing encephalopathy);
• refractory hypokalemia;
• refractory hyponatremia;
• metabolic acidosis;
• hypocorticism;
• Addison's disease;
• decompensated diabetes mellitus;
• long-term use in chronic angle-closure glaucoma, since reduced intraocular pressure can mask the deterioration of glaucoma and allow the development of an organic angle closure;
• pregnancy (I trimester); • period of breastfeeding;
• children's age up to 3 years. Carefully
• edema of hepatic and renal origin;
• simultaneous administration with acetylsalicylic acid (doses above 300 mg / day);
• pulmonary embolism and emphysema (risk of acidosis);
• pregnancy (II and III trimester); • elderly age;
• violation of the water-electrolyte balance; • impaired liver function;
• in patients at risk of urinary tract obstruction;
• diabetes.
Use during pregnancy and during breastfeeding Well-controlled clinical trials of the use of the drug in pregnant women have not been conducted.
Therefore, during pregnancy, the drug is contraindicated in the first trimester, 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 in a small amount is excreted in breast milk, so if it is necessary to use the drug Acetazolamide, breastfeeding should be stopped.
Drug Interactions Acetazolamide:
Acetazolamide may enhance the effects of folic acid antagonists, hypoglycemic agents and oral anticoagulants.
The simultaneous use of acetazolamide and acetylsalicylic acid can cause metabolic acidosis and enhance toxic effects in relation to the central nervous system.
When combined with cardiac glycosides or drugs that increase blood pressure, the dose of acetazolamide should be adjusted. Acetazolamide increases the content of phenytoin in the blood serum. Acetazolamide enhances the manifestations of osteomalacia caused by the use of antiepileptic drugs.
The simultaneous use of acetazolamide and amphetamine, atropine or quinidine can enhance their side effects. Potentiation of the diuretic effect of acetazolamide occurs when combined with methylxanthines (aminophylline).
A decrease in the diuretic effect of acetazolamide occurs when combined with ammonium chloride and other acid-forming diuretics. An increase in the hypotensive effect with respect to intraocular pressure is possible with simultaneous use with cholinergic drugs and beta-adrenergic blockers.
Acetazolamide enhances the effects of ephedrine. Increases the concentration in the blood plasma of carbamase-pin, non-depolarizing muscle relaxants. Acetazolamide increases the excretion of lithium. Acetazolamide can increase the concentration of cyclosporine.
Acetazolamide may decrease the antiseptic effect of methenamine on the urinary system. The simultaneous use of acetazolamide and sodium bicarbonate increases the risk of kidney stones.
Acetazolamide reduces the absorption of primidone in the gastrointestinal tract, which can lead to a decrease in the concentration of primidone and its metabolites in the blood plasma and reduce the anticonvulsant effect of the drug.
Caution should be exercised in the appointment, dose adjustment and withdrawal of acetazolamide in patients receiving primidone therapy.
Dosage Acetazolamide:
The drug is taken orally, strictly as prescribed by the doctor. In case of missing the drug, do not increase the dose at the next dose. Edema syndrome At the beginning of treatment, 250 mg is taken in the morning.
To achieve the maximum diuretic effect, it is necessary to take the drug Acetazolamide once a day every other day or 2 days in a row with a one-day break. Increasing the dose does not enhance the diuretic effect.
With a decrease in the previously achieved response to acetazolamide therapy, the drug should be discontinued for a day (to restore the activity of renal carbonic anhydrase).
The use of acetazolamide does not eliminate the need for other drugs, bed rest and restriction of sodium chloride intake. Hpaucoma Acetazolamide should be taken as part of complex therapy. For adults with open-angle glaucoma, the drug is prescribed in a dose of 250 mg 1-4 times a day. Doses in excess of 1000 mg do not increase the therapeutic effect.
In secondary glaucoma, the drug is prescribed in a dose of 250 mg every 4 hours during the day. In some patients, the therapeutic effect is manifested after short-term administration of the drug in a dose of 250 mg 2 times a day. With acute attacks of glaucoma; the drug is prescribed 250 mg 4 times a day.
For children older than 3 years with glaucoma attacks, the drug is prescribed at a dose of 10-15 mg / kg body weight per day in 3-4 doses. After 5 days of admission, take a break for 2 days. With prolonged treatment, it is necessary to prescribe potassium preparations, a potassium-sparing diet.
In preparation for the operation, 250-500 mg are prescribed on the eve and in the morning on the day of the operation. Epilepsy Doses for adults: 250-500 mg / day in one dose for 3 days, on the 4th day a break.
With the simultaneous use of Acetazolamide with other anticonvulsants, 250 mg 1 time per day is used at the beginning of treatment, gradually increasing the dose if necessary. The maximum daily dose in adults is 1000 mg. Doses for children over 3 years: 8-30 mg / kg per day, divided into 1-4 doses.
The maximum daily dose is 750 m. Acute "high-altitude" disease. The use of the drug in a dose of 500-1000 mg per day is recommended. In the case of rapid climbing -1000 mg per day. The drug should be used 24-48 hours before the ascent.
In case of symptoms of the disease, treatment is continued for the next 48 hours or longer if necessary. Liquorodynamic disturbances, intracranial hypertension. The use of the drug at a dose of 250 mg per day or 125-250 mg every 8-12 hours is recommended.
The maximum therapeutic effect is achieved when taking a dose of 750 mg per day. To achieve the optimal effect, a daily non-interval intake of the drug may be required.
Overdose Acetazolamide:
Symptoms of an overdose are not described.
Possible symptoms of an overdose may be disturbances in the water-electrolyte balance, metabolic acidosis, as well as disorders of the central nervous system.
Treatment There is no specific antidote. Treatment should be symptomatic and supportive.
Plasma electrolytes should be monitored, especially potassium, sodium, as well as blood pH.
In the case of metabolic acidosis, sodium bicarbonate is used. Acetazolamide is excreted by hemodialysis.
