Capozide (Tablets) Instructions for Use

Marketing Authorization Holder

Akrikhin Chemical and Pharmaceutical Plant, JSC (Russia)

Contact Information

AKRIKHIN JSC (Russia)

ATC Code

C09BA01 (Captopril and diuretics)

Active Substances

Hydrochlorothiazide (Rec.INN registered by WHO)

Captopril (Rec.INN registered by WHO)

Dosage Form

Capozide

Tablets 25 mg+50 mg: 28 pcs.

Dosage Form, Packaging, and Composition

Tablets white or white with a creamy tint, oval, biconvex, with a score on one side and a beveled edge on the other side, with a sulfide-like odor; slight “marbling” is allowed.

Excipients: microcrystalline cellulose, pregelatinized starch (corn), stearic acid, magnesium stearate, lactose monohydrate.

14 pcs. – blister packs (2) – cardboard packs.

Clinical-Pharmacological Group

Antihypertensive drug

Pharmacotherapeutic Group

Antihypertensive combination agent (diuretic + ACE inhibitor)

Pharmacological Action

A combined drug that has antihypertensive and diuretic effects.

Captopril is an ACE inhibitor. It reduces the formation of angiotensin II from angiotensin I and decreases aldosterone secretion. It lowers blood pressure, systemic vascular resistance, afterload, and preload. It dilates arteries to a greater extent than veins. It increases coronary and renal blood flow. With long-term use, it reduces the severity of myocardial hypertrophy and hypertrophy of the walls of resistive arteries; improves blood supply to the ischemic myocardium; reduces platelet aggregation.

Hydrochlorothiazide is a thiazide diuretic of moderate potency, it reduces the reabsorption of sodium ions at the level of the cortical segment of the loop of Henle. It does not affect the acid-base status. It reduces blood pressure by changing vascular wall reactivity, reducing the pressor effect of vasoconstrictor substances (epinephrine, norepinephrine) and enhancing the depressor effect on autonomic ganglia (to a lesser extent, by reducing circulating blood volume). It enhances the antihypertensive effect of captopril.

The diuretic effect is noted after 2 hours and reaches a maximum 4 hours after oral administration. The action lasts for 6-12 hours.

Pharmacokinetics

Captopril

When taken orally, it is rapidly absorbed from the gastrointestinal tract, C_max in blood plasma is observed approximately 1 hour after administration. The bioavailability of captopril is 60-70%. Simultaneous food intake slows down the absorption of the drug by 30-40%. Plasma protein binding is 25-30%. T_1/2 is 2-3 hours. The drug is excreted from the body mainly by the kidneys, up to 50% unchanged, the rest in the form of metabolites.

Hydrochlorothiazide

When taken orally, it is relatively rapidly absorbed. T_1/2 in plasma is 2.5 hours when taken on an empty stomach by healthy volunteers. It is excreted by the kidneys, 95% of the dose is unchanged.

Indications

• Arterial hypertension (for patients who require combination therapy).

ICD codes

Dosage Regimen

Take the tablet orally, once daily.

Administer the dose one hour before meals to ensure optimal absorption.

The standard regimen is one tablet containing 50 mg captopril and 25 mg hydrochlorothiazide.

Adjust the dosage based on individual patient response and tolerability.

For patients with impaired renal function (CrCl 30-60 ml/min), use with caution and monitor renal function.

In elderly patients, initiate therapy with caution due to a potentially increased risk of side effects.

Do not use in patients with severe renal impairment (CrCl <30 ml/min).

If a dose is missed, take it as soon as remembered unless it is almost time for the next dose; do not double the dose.

Regularly monitor blood pressure, serum electrolytes (potassium, sodium), renal function, and blood counts during therapy.

Adverse Reactions

The frequency of adverse reactions is classified as follows: common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000), very rare (<1/10,000).

From the cardiovascular system uncommon – tachycardia or tachyarrhythmia, chest pain, angina pectoris, palpitations, myocardial infarction, orthostatic hypotension, syncope, peripheral edema, excessive decrease in blood pressure, Raynaud’s syndrome, flushing; very rare – cardiac arrest, cardiogenic shock.

From the respiratory system common – dry non-productive cough, dyspnea; very rare – bronchospasm, eosinophilic pneumonitis, rhinitis, pulmonary edema.

Allergic reactions common – skin itching, with or without rash, sometimes accompanied by fever and arthralgia, skin rash; uncommon – angioedema of the skin and subcutaneous tissue; rare – intestinal angioedema; very rare – urticaria, Stevens-Johnson syndrome, erythema multiforme, photosensitivity, erythroderma, reversible pemphigoid reactions, bullous pemphigus, exfoliative dermatitis, allergic alveolitis, eosinophilic pneumonia, angioedema of the extremities, face, lips, mucous membranes, tongue, pharynx and larynx (including fatal cases).

From the central nervous system common – drowsiness, dizziness; rare – headache, ataxia, paresthesia; very rare – confusion, depression, cerebrovascular disorders, including stroke and syncope, blurred vision.

From the hematopoietic system very rare – neutropenia, agranulocytosis, pancytopenia, lymphadenopathy, eosinophilia, thrombocytopenia, anemia (including aplastic and hemolytic forms), increased titers of antinuclear antibodies, autoimmune diseases.

From the digestive system common – nausea, vomiting, irritation of the gastric mucosa, abdominal pain, diarrhea, constipation, taste disturbance, dry oral mucosa; rare – stomatitis, aphthous stomatitis, anorexia; very rare – glossitis, gastric ulcer, pancreatitis, gingival hyperplasia, impaired liver function and cholestasis (including jaundice), increased activity of liver enzymes, hepatitis (including necrosis), hyperbilirubinemia.

From the musculoskeletal system very rare – myalgia, arthralgia, myasthenia.

From the urinary system uncommon – impaired renal function (including renal failure), polyuria, oliguria, frequent urination, nephrotic syndrome.

From the reproductive system and mammary gland very rare – impotence, gynecomastia.

Other common – alopecia; uncommon – chest pain, increased fatigue, malaise.

Laboratory parameters common – eosinophilia; very rare – proteinuria, hyperkalemia, hyponatremia (including symptomatic), increased blood urea nitrogen, bilirubin and creatinine, decreased hematocrit, decreased hemoglobin, leukocytes, platelets.

Contraindications

• Hereditary or idiopathic angioedema (history of occurrence while taking ACE inhibitors);
• Aortic stenosis;
• Mitral stenosis;
• Hypertrophic obstructive cardiomyopathy;
• Bilateral renal artery stenosis or stenosis of the artery of a single kidney;
• Condition after kidney transplantation;
• Chronic heart failure;
• Cardiogenic shock;
• Arterial hypotension;
• Severe hepatic insufficiency (precomatose state, hepatic coma);
• Severe renal insufficiency (serum creatinine >1.8 mg/dl or CrCl <20-30 ml/min, anuria);
• Primary hyperaldosteronism;
• Concomitant use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or impaired renal function (GFR <60 ml/min);
• Pregnancy;
• Lactation period (breastfeeding);
• Age under 18 years (efficacy and safety not established);
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
• Hypersensitivity to the components of the drug, other ACE inhibitors, thiazide diuretics, sulfonamide derivatives (cross-allergic reactions are possible).

With caution

• Impaired liver function, progressive liver diseases;
• Moderate renal insufficiency (CrCl 30-60 ml/min);
• Proteinuria (more than 1 g/day),
• Hypokalemia (not corrected by medications);
• Hyponatremia;
• Hypovolemia;
• Hypercalcemia;
• Gout, hyperuricemia;
• Systemic connective tissue diseases and other autoimmune diseases (including systemic lupus erythematosus, scleroderma, polyarteritis nodosa);
• Elderly age (over 65 years);
• Concomitant use of drugs that suppress the body’s defense reactions (glucocorticoids, cytostatics, immunosuppressants), allopurinol, procainamide;
• Surgery/general anesthesia;
• Use in patients of the Black race;
• Hemodialysis using high-flux membranes (e.g., AN69^®);
• Concomitant desensitizing therapy;
• Concomitant use of potassium-sparing diuretics, potassium preparations, potassium-containing substitutes;
• Concomitant use of lithium preparations;
• Acute myopia and secondary angle-closure glaucoma.

Use in Pregnancy and Lactation

The use of the drug Capozide^® is contraindicated during pregnancy.

Epidemiological data regarding the risk of teratogenicity after exposure to ACE inhibitors in the first trimester of pregnancy have not been conclusive, however, a slight increase in risk cannot be excluded. If the use of an ACE inhibitor is considered necessary, patients planning pregnancy should be switched to alternative antihypertensive therapy with an established safety profile for use during pregnancy. It is known that prolonged exposure of the fetus to ACE inhibitors in the II and III trimesters of pregnancy can lead to impaired development (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and the development of complications in the newborn (such as renal failure, arterial hypotension, hyperkalemia). If the patient received the drug Capozide^® in the II and III trimesters of pregnancy, an ultrasound examination is recommended to assess the condition of the fetal skull bones and renal function.

The use of hydrochlorothiazide during pregnancy is not recommended, as it may impair placental perfusion and cause fetal/newborn jaundice, thrombocytopenia, water-electrolyte imbalance and possibly other adverse reactions observed in adults.

The use of ACE inhibitors during pregnancy can cause fetal developmental disorders and death. If pregnancy is confirmed, the use of the drug Capozide^® should be discontinued as soon as possible.

Captopril and Hydrochlorothiazide are detected in breast milk after oral administration by a nursing woman. Due to the risk of developing serious adverse reactions in the child caused by both active substances, breastfeeding should be discontinued or therapy with the drug Capozide^® should be discontinued in the mother during breastfeeding.

Use in Hepatic Impairment

Contraindicated in severe hepatic insufficiency (precomatose state, hepatic coma).

The drug should be prescribed with caution in case of impaired liver function, progressive liver diseases.

Use in Renal Impairment

Contraindicated in severe renal insufficiency (serum creatinine >1.8 mg/dl or CrCl<20-30 ml/min, anuria).

The drug should be prescribed with caution in moderate renal insufficiency (CrCl 30-60 ml/min).

Pediatric Use

The drug is contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Capozide^® should be prescribed with caution to elderly patients (over 65 years of age).

Special Precautions

At the beginning of treatment, an excessive decrease in blood pressure may be observed, especially in patients with chronic heart failure, severe arterial hypertension (including of renal origin) and/or renal insufficiency. Before starting treatment, it is necessary to compensate for the sodium ion deficiency and normalize the circulating blood volume (reduce the dose of previously prescribed diuretics or, in some cases, completely cancel them), and also determine the indicators of renal function.

Regular monitoring of the concentration of potassium and calcium in the blood serum (especially in patients receiving treatment with cardiac glycosides, glucocorticoids, frequently using laxatives, as well as in elderly patients), glucose, uric acid, lipids (cholesterol and triglycerides), urea and creatinine, and the activity of liver enzymes is necessary.

Regular monitoring of blood pressure and laboratory parameters is especially necessary in the following cases: in patients with renal insufficiency; patients with severe arterial hypertension (including of renal origin); in elderly patients (over 65 years of age); in patients with water-electrolyte imbalance and decompensated chronic renal failure; and also those receiving simultaneously allopurinol, lithium salts, procainamide and drugs that reduce immunity.

When using ACE inhibitors, a characteristic non-productive cough is noted, which stops after discontinuation of ACE inhibitor therapy.

In some patients with kidney disease, especially with severe renal artery stenosis, an increase in serum urea nitrogen and creatinine concentrations is observed after a decrease in blood pressure. This phenomenon is usually reversible; a decrease in serum urea nitrogen and creatinine concentrations is noted after discontinuation of the drug.

In some cases, an increase in the concentration of potassium in the blood serum is observed during the use of ACE inhibitors. The risk of developing hyperkalemia when using ACE inhibitors is increased in patients with renal insufficiency and diabetes mellitus, as well as those taking potassium-sparing diuretics, potassium preparations or other drugs that cause an increase in the concentration of potassium in the blood (for example, heparin). The concomitant use of potassium-sparing diuretics and potassium preparations should be avoided. In addition, when using ACE inhibitors simultaneously with thiazide diuretics, the risk of developing hypokalemia is not excluded, therefore, in such cases, regular monitoring of blood potassium concentration should be carried out during therapy.

When performing hemodialysis in patients receiving ACE inhibitors, the use of dialysis membranes with high permeability (for example, AN69) should be avoided, as in such cases the risk of developing anaphylactoid reactions increases. Anaphylactoid reactions have also been observed in patients undergoing LDL apheresis with dextran sulfate. The use of either antihypertensive drugs of another class or another type of dialysis membrane should be considered.

In case of angioedema development, the drug is discontinued and careful medical observation is carried out until the symptoms completely disappear. Angioedema of the larynx can be fatal. If the edema is localized on the face, special treatment is usually not required (antihistamines can be prescribed to reduce the severity of symptoms); if the edema spreads to the tongue, pharynx or larynx and there is a threat of airway obstruction, epinephrine (adrenaline) should be administered immediately subcutaneously (0.3-0.5 ml in a 1:1000 dilution). In rare cases, patients after taking ACE inhibitors have experienced intestinal angioedema, which was accompanied by abdominal pain (with or without nausea and vomiting), sometimes with normal C1-esterase activity and without preceding facial edema. Intestinal edema should be included in the spectrum of differential diagnosis in patients complaining of abdominal pain while taking ACE inhibitors. In two patients undergoing desensitization with hymenoptera venom, life-threatening anaphylactoid reactions were noted while taking captopril. With temporary discontinuation of the ACE inhibitor in the same patients, anaphylactoid reactions were avoided. Caution should be exercised when performing desensitization in patients taking ACE inhibitors.

In patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose concentration should be carefully monitored, especially during the first month of ACE inhibitor therapy.

ACE inhibitors are less effective in Black patients than in Caucasian patients, which may be associated with a higher prevalence of low renin activity in Black patients.

During major surgical interventions or during therapy with anesthetics in patients taking ACE inhibitors, an excessive decrease in blood pressure may be noted. In these cases, measures aimed at increasing the circulating blood volume are carried out.

In rare cases, when taking ACE inhibitors, a syndrome has been noted that begins with the appearance of cholestatic jaundice, progressing to fulminant hepatonecrosis, sometimes with a fatal outcome. The mechanism of development of this syndrome is unknown. If a patient receiving ACE inhibitor therapy develops jaundice or a marked increase in liver enzyme activity, ACE inhibitor treatment should be discontinued and the patient should be monitored.

Neutropenia/agranulocytosis, thrombocytopenia and anemia have been observed in patients taking ACE inhibitors. In patients with normal renal function and in the absence of other disorders, neutropenia is rare.

The drug Capozide^® should be used very cautiously in patients with autoimmune connective tissue diseases, in patients taking immunosuppressants, allopurinol and procainamide, especially in the presence of pre-existing renal impairment. Since most fatal cases of neutropenia during the use of ACE inhibitors developed in such patients, their white blood cell count should be monitored before starting treatment, in the first 3 months – every 2 weeks, then – every 2 months.

In all patients, the white blood cell count should be monitored monthly during the first 3 months after the start of therapy, then – every 2 months. If the white blood cell count is below 4000/µl, a repeat complete blood count is indicated; if it is below 1000/µl, the drug should be discontinued, continuing to monitor the patient. Usually, the neutrophil count recovers within 2 weeks after discontinuation of captopril. In 13% of cases of neutropenia, a fatal outcome was noted. In almost all cases, fatal neutropenia was observed in patients with connective tissue diseases, renal or heart failure, while taking immunosuppressants, or a combination of these factors.

When using ACE inhibitors, proteinuria may occur, mainly in patients with impaired renal function, as well as when using the drugs in high doses. In most cases, proteinuria when taking captopril disappeared or its severity decreased within 6 months, regardless of whether the drug was discontinued or not. Renal function parameters (blood urea nitrogen and creatinine concentrations) in patients with proteinuria were almost always within the normal range. In patients with kidney disease, urine protein concentration should be determined before starting treatment and periodically during the course of therapy.

Sulfonamide derivatives (including Hydrochlorothiazide) can cause transient myopia and acute angle-closure glaucoma; risk factors include a history of allergy to sulfonylurea drugs or penicillin. Symptoms (sudden decrease in visual acuity, eye pain) are usually observed from several hours to several weeks after starting treatment. If symptoms appear, the drug should be discontinued immediately; if necessary, drugs to correct intraocular pressure should be prescribed.

All patients taking thiazide diuretics should be monitored for clinical signs of water-electrolyte imbalance (hyponatremia, hypochloremic alkalosis, hypokalemia). It is especially important to determine the electrolyte content in blood serum and urine in case of excessive prolonged vomiting or when administering infusion solutions. Signs of water-electrolyte imbalance may include dry mouth, thirst, weakness, lethargy, confusion, restlessness, muscle pain or cramps, muscle weakness, excessive decrease in blood pressure, oliguria, tachycardia, nausea, vomiting.

Hypokalemia can provoke or enhance the cardiotoxic effect of cardiac glycosides.

Chloride ion deficiency is usually mild and does not require correction.

In patients with edema in hot weather, hyponatremia caused by an increase in blood volume may be observed. Fluid intake should be restricted. In cases of life-threatening hyponatremia, a sodium chloride solution is prescribed.

During therapy with thiazide diuretics, hyperuricemia or gout attacks may occur; latent diabetes mellitus may also become manifest.

Thiazide derivatives can cause a decrease in the concentration of bound iodine in the blood serum without signs of thyroid dysfunction.

While taking thiazide diuretics, the degree of calcium excretion decreases; cases of pathological changes in the parathyroid glands, accompanied by hypercalcemia and hypophosphatemia, have been reported. Thiazide diuretic intake should be discontinued before testing parathyroid function.

While taking thiazide diuretics, an increase in the degree of magnesium excretion has been observed, which can lead to hypomagnesemia.

The drug Capozide^® can cause a false-positive reaction in urine analysis for ketone bodies and distort the results of the bentiromide test.

If fever, enlarged lymph nodes and/or development of signs of laryngitis and/or pharyngitis occur, the number of leukocytes should be determined immediately.

The use of thiazide diuretics may be the cause of a positive result in doping control.

Effect on the ability to drive vehicles and mechanisms

During treatment, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms sharp decrease in blood pressure, shock, stupor, bradycardia, water-electrolyte imbalance, renal failure, lethargy (which may progress to coma within a few hours), not accompanied by water-electrolyte imbalance and causing only slight suppression of respiratory and cardiovascular functions. Irritation of the mucous membrane and increased contractile activity of the gastrointestinal tract may be observed.

Treatment measures to bring out of coma or stupor; gastric lavage, administration of adsorbents and sodium sulfate within 30 minutes after taking the drug, administration of 0.9% sodium chloride solution or other plasma-substituting solutions, hemodialysis. For bradycardia or pronounced vagal reactions – administration of atropine. The use of an artificial pacemaker may be considered. Peritoneal dialysis is not effective for removing captopril from the body.

Drug Interactions

Captopril

In patients taking diuretics, especially at the beginning of therapy, as well as in combination with strict sodium restriction (salt-free diets) or hemodialysis, an excessive decrease in blood pressure may sometimes be observed, which usually occurs within the first hour after taking the first prescribed dose of the drug Capozide^®. The patient’s condition should be monitored for 1 hour after taking the first dose of the drug. If an excessive decrease in blood pressure is noted, the patient should be placed in a horizontal position with a low headboard and, if necessary, 0.9% sodium chloride solution should be administered intravenously. Transient excessive decrease in blood pressure is not a contraindication to further therapy, which can be continued after normalization of blood pressure by increasing the blood volume.

Vasodilators (for example, nitroglycerin) in combination with the drug Capozide^® should be used in the lowest effective doses due to the risk of excessive decrease in blood pressure.

Caution should be exercised when using the drug Capozide^® concomitantly with drugs that affect the sympathetic nervous system (for example, ganglion blockers, alpha-adrenergic blockers).

During therapy with drugs containing Captopril, potassium-sparing diuretics (for example, triamterene, spironolactone, amiloride), potassium preparations, potassium supplements, salt substitutes (contain significant amounts of potassium ions) should be prescribed only for proven hypokalemia, as their use increases the risk of hyperkalemia.

The drug Capozide^® increases the plasma concentration of digoxin by 15-20%, increases the bioavailability of propranolol.

The risk of developing an immunosuppressive effect increases with combined use with procainamide, as well as with drugs that block tubular secretion (decrease in the number of leukocytes and granulocytes).

Increases the neurotoxicity of salicylates, enhances the effect of competitive non-depolarizing muscle relaxants, ethanol.

Reduces the excretion of quinidine, reduces the effect of oral hypoglycemic drugs, norepinephrine, epinephrine and anti-gout drugs.

Enhances the side effects of cardiac glycosides, especially when prescribed simultaneously with drugs that increase the excretion of potassium and magnesium ions and/or retain calcium ions (for example, diuretics, adrenal cortex hormones, laxatives, amphotericin B, carbenoxolone, penicillin G, salicylates).

Dual blockade of the RAAS, caused by the simultaneous use of ACE inhibitors and angiotensin II receptor blockers or aliskiren and aliskiren-containing drugs, was associated with an increased frequency of side effects, such as arterial hypotension, hyperkalemia, decreased renal function (including acute renal failure).

Cimetidine, by slowing down the metabolism of captopril in the liver, increases its plasma concentration.

Hydrochlorothiazide

Indomethacin and other NSAIDs, including COX-2 inhibitors, as well as table salt can reduce the antihypertensive effect of the drug, especially in arterial hypertension accompanied by low renin activity, and also reduce the absorption of hydrochlorothiazide. In patients with risk factors (old age, hypovolemia, use of diuretics, impaired renal function), simultaneous use of NSAIDs (including COX-2 inhibitors) and ACE inhibitors (including Captopril) can lead to deterioration of renal function, up to acute renal failure. Usually, renal function impairment in such cases is reversible. Renal function should be periodically checked in patients taking the drug Capozide^® and NSAIDs.

Hydrochlorothiazide can enhance the effect of non-depolarizing muscle relaxants, general anesthetics used in surgery (for example, tubocurarine chloride and gallamine triethiodide), so dose adjustment of these drugs may be required. Monitoring and, if possible, correction of water-electrolyte balance before surgery is recommended.

Hydrochlorothiazide reduces the effect of therapeutically used pressor amines (for example, norepinephrine) on the arteries, but does not completely prevent it.

Anesthetics and premedication agents should be used in the lowest possible doses. If possible, Hydrochlorothiazide should be discontinued one week before surgery.

Combination with nitrates, thiazide diuretics, verapamil, beta-blockers and other antihypertensive drugs, MAO inhibitors, ganglion blockers, as well as tricyclic antidepressants, hypnotics and ethanol enhances the severity of the hypotensive effect.

With simultaneous use of ACE inhibitors with lithium preparations, a slowdown in the excretion of lithium ions, an increase in the concentration of lithium in the blood serum and, as a consequence, an enhancement of the damaging effect on the heart and central nervous system may occur. In addition, Hydrochlorothiazide also increases the risk of lithium toxicity. When using such combination therapy, regular monitoring of the lithium concentration in the blood serum should be carried out.

Drugs that intensively bind to proteins enhance the diuretic effect. Dose adjustment of indirect anticoagulants, probenecid and sulfinpyrazone may be required, since Hydrochlorothiazide may suppress their action.

Hydrochlorothiazide has a hyperuricemic effect, so adjustment of anti-uricosuretic drugs may be required with simultaneous use.

Diazoxide enhances the hyperglycemic, hyperuricemic and antihypertensive effects of thiazide diuretics, so the concentration of uric acid and glucose in the blood serum should be monitored.

With simultaneous use of oral hypoglycemic agents and insulin, an increase in their doses may be required, since Hydrochlorothiazide increases blood glucose concentration.

With simultaneous use of methyldopa, hemolysis of erythrocytes may develop.

Cholestyramine and colestipol hydrochloride may delay or reduce the absorption of hydrochlorothiazide.

Potassium salts, potassium-sparing diuretics (triamterene, amiloride and spironolactone) and heparin contribute to the development of hyperkalemia.

Methenamine may reduce the effect of hydrochlorothiazide due to an increase in urine pH.

Carbamazepine increases the risk of symptomatic hyponatremia when used concomitantly with hydrochlorothiazide.

With the combined use of calcium salts and thiazide diuretics, the concentration of calcium in the blood serum may increase due to a slowdown in its excretion. Control of the calcium concentration in the blood serum and, if necessary, adjustment of its dose is required.

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 3 years.

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.