Aldactone

Package Leaflet: Information for the User

Aldactone 20 mg/ml Solution for Injection

Potassium canrenoate

Read the package leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this package leaflet, please inform your doctor or pharmacist. See section 4.

Package Leaflet Contents:

• 1. What is Aldactone and what is it used for
• 2. Important information before using Aldactone
• 3. How to use Aldactone
• 4. Possible side effects
• 5. How to store Aldactone
• 6. Contents of the pack and other information

1. What is Aldactone and what is it used for

Aldactone is an aldosterone antagonist, which blocks the binding of aldosterone to its receptor, thereby preventing the reabsorption of sodium and the excretion of potassium ions. Potassium canrenoate exhibits its properties only in the presence of aldosterone, and its action may be inhibited by increasing aldosterone concentrations. It inhibits aldosterone biosynthesis only at very high doses. Potassium canrenoate increases sodium and chloride excretion, slightly increases calcium excretion, inhibits the excretion of ammonium, magnesium, and potassium ions, and causes urine alkalization. Potassium canrenoate has too weak a diuretic effect to be used as a common diuretic. The diuretic effect can be increased only by concurrent administration with loop or thiazide diuretics. By reducing glomerular filtration, potassium canrenoate may increase blood urea levels. Depending on the severity of hyperaldosteronism, the diuretic effect becomes apparent within 3 to 6 hours after intravenous administration and may persist for up to 72 hours. Stabilized diuretic effect occurs after 2 weeks of treatment. Indications:

• Primary hyperaldosteronism;
• Secondary hyperaldosteronism in the course of severe, chronic liver diseases, accompanied by edema and ascites;
• Secondary hyperaldosteronism in chronic heart failure with edema; in cases where oral administration of aldosterone antagonists is not possible and the action of other diuretics is insufficient.

2. Important information before using Aldactone

When not to use Aldactone

If it is determined that:

• the patient is allergic to the active substance, spironolactone, or to any of the other ingredients of this medicine (listed in section 6),
• there is hyperkalemia (elevated potassium ion levels in the blood) or hyponatremia (reduced sodium ion levels in the blood),
• there are renal function disorders with serum creatinine levels above 1.8 mg/dl and creatinine clearance below 30 ml/min,
• there is acute renal failure and anuria (anuria - cessation of urine production in the kidneys or lack of urine in the bladder due to ureteral obstruction). Do not use during pregnancy and breastfeeding.

Warnings and precautions

Before starting Aldactone, discuss it with your doctor, pharmacist, or nurse. Close medical supervision is particularly required in the following cases:

• renal function disorders (serum creatinine levels between 1.2 mg/dl and 1.8 mg/dl or creatinine clearance between 60 ml/min and 30 ml/min),
• patients prone to acidosis and/or hyperkalemia due to their underlying disease (e.g., diabetes),
• hypotension, hypovolemia

Fluid and electrolyte balance:The state of fluids and electrolytes should be regularly monitored, especially in the elderly with renal and hepatic function disorders. Hyperkalemia may occur in patients with impaired renal function or after excessive potassium intake and may cause irregular heart rhythm, which can lead to death. If hyperkalemia develops, Aldactone treatment should be discontinued, and if necessary, active measures should be taken to reduce potassium levels to normal. Hyponatremia may occur, especially if Aldactone is administered in combination with other diuretics. Reversible hyperchloremic metabolic acidosis, usually in combination with hyperkalemia, occurred in a few patients with decompensated liver cirrhosis, even if renal function was normal. Urea:Reversible increase in blood urea levels occurred during Aldactone therapy, mainly in patients with renal function disorders. Caution should be exercised when using Aldactone in patients who are at risk of acidosis and hyperkalemia (e.g., in diabetes). Close monitoring of serum potassium levels is required in patients with renal function disorders with serum creatinine levels between 1.2 and 1.8 mg/dl or creatinine clearance below 60 ml/min per 1.73 m² body surface area, as well as when using Aldactone in combination with other medicines that may increase potassium levels (see "Aldactone and other medicines"). The results of radioimmunological tests used to determine digoxin levels in the blood may be falsely elevated in patients treated with Aldactone. Aldactone may falsely elevate the results of cortisol determination by the Mattingly method. In animal studies, carcinogenic effects were found with long-term administration; therefore, Aldactone treatment should be carried out for as short a period as possible and always considering the need for further administration. The use of Aldactone may lead to positive results in doping tests. The use of Aldactone as a doping agent can endanger health.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult her doctor before using this medicine. Use during pregnancy and breastfeeding is contraindicated. There is no available information on the impact of Aldactone on human fertility.

Driving and using machines

Aldactone, even when used as recommended, may alter the patient's reaction time to the extent of impairing the ability to drive vehicles and operate machinery. This applies particularly to the initial treatment period, to situations where previously used medicines have been replaced by others, when additional medicines have been started, and in cases of concurrent alcohol consumption.

Aldactone and other medicines:

Inform your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take. Concurrent administration of Aldactone and:

• diuretics may enhance their effect,
• carbenoxolone may weaken the effect of the latter,
• non-steroidal anti-inflammatory drugs may increase the risk of hyperkalemia,
• other potassium-sparing diuretics (triamterene, amiloride), potassium supplements, or angiotensin-converting enzyme inhibitors (ACE inhibitors) may lead to life-threatening increases in blood potassium levels,
• angiotensin-converting enzyme inhibitors (ACE inhibitors) may cause increased serum creatinine levels,
• concurrent use of furosemide and ACE inhibitors may cause acute renal failure,
• acetylsalicylic acid, indomethacin, and other prostaglandin synthesis inhibitors may weaken the effect of potassium canrenoate,
• digoxin may lead to increased digoxin levels in the blood
• epinephrine or norepinephrine reduces the effect of these on the cardiovascular system.

Potassium canrenoate may modify the results of radioimmunological tests used to determine digoxin levels in the blood.

Aldactone contains sodium and potassium

The medicine contains 37.1 mg of sodium (the main component of common salt) in one ampoule. This corresponds to 1.9% of the maximum recommended daily sodium intake in the diet for adults. The medicine contains less than 1 mmol (39 mg) of potassium per dose, which means the medicine is considered "potassium-free". The medicine may cause pain at the injection site.

3. How to use Aldactone

This medicine should always be used as directed by your doctor. If you are unsure, consult your doctor. The recommended dose is 200 mg to 400 mg (1-2 ampoules) per day, depending on the severity of hyperaldosteronism. In exceptional cases, the dose can be increased to 800 mg (4 ampoules) per day. Usually, a single dose of 200 mg (one ampoule) is administered.

Use in children and adolescents

For newborns, infants, and children, the daily dose should be administered in an amount of solution appropriate for their age and condition, divided into three separate doses administered by slow, short intravenous infusion, at hourly intervals. The recommended dosage is usually:

• children with a body weight up to 50 kg - initial dose up to 4-5 mg/kg/day, then up to 2-3 mg/kg/day.
• infants - maximum initial dose 2-3 mg/kg/day, then up to 1.5-2 mg/kg/day.

The medicine should be injected intravenously at a rate not exceeding 1 ampoule (10 ml) over 2-3 minutes to avoid local irritation of the vein and nausea. The medicine should not be injected into thin veins. In patients receiving high doses of Aldactone or when it is necessary to improve the patient's tolerance to the medicine, potassium canrenoate can be administered in divided doses or by intravenous infusion lasting about 30 minutes. In patients with renal function disorders with serum creatinine levels between 1.2 mg/dl and 1.8 mg/dl and creatinine clearance below 60 ml/min, Aldactone treatment may be carried out under the condition of frequent monitoring of serum potassium levels. The ampoule should be opened immediately before injection. Longer storage of an opened ampoule may lead to clouding of the solution. Any residue in the ampoule cannot be reused. Slight opalescence of the solution does not affect the tolerance of the medicine. If the solution shows distinct clouding, which may result from improper storage, the solution should not be administered. Only a clear solution without visible impurities can be used. Accidental intravenous injection of the medicine may be harmful; therefore, before starting administration, ensure that the needle is in the vein.

Use of a higher than recommended dose of Aldactone

Overdose of potassium canrenoate may lead to drowsiness, impaired consciousness, and electrolyte disturbances. There is no specific antidote. Drowsiness and impaired consciousness usually resolve after reducing the dose or discontinuing the medicine.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Possible side effects are listed below by system organ class. Frequency is defined as: very common (≥ 1/10); common (≥ 1/100 to <1>Common(may affect up to 1 in 10 people)

• headache, excessive drowsiness (lethargy), ataxia

Uncommon(may affect up to 1 in 100 people)

• hyperkalemia
• In women - breast tension, menstrual disorders (amenorrhea or intermenstrual bleeding), postmenopausal bleeding. In men - sensitivity of the nipples and gynecomastia. Sexual potency disorders and decreased libido may occur.

Rare(may affect up to 1 in 1000 people)

• hyperchloremic metabolic acidosis, hyponatremia, increased blood uric acid levels. Electrolyte balance disorders may cause the following symptoms: cardiac arrhythmias, fatigue, muscle weakness, muscle cramps, dizziness.
• hypotension
• bone demineralization, osteomalacia
• hirsutism
• voice disorders (hoarseness) or deepening of the voice. In some cases, both in men and women, voice disorders may not resolve despite discontinuation of treatment. Therefore, in individuals for whom voice is particularly important (e.g., actors or teachers), the therapeutic benefits should be carefully weighed against the risk of treatment.
• nausea, vomiting, diarrhea, abdominal cramps, stomach or intestinal ulcers, with possible bleeding.
• thrombocytopenia, eosinophilia in patients with liver cirrhosis
• dizziness
• transient confusion syndrome, which resolves after dose reduction or temporary discontinuation of treatment.
• pain at the injection site

Not known(frequency cannot be estimated from the available data)

• vasculitis
• redness, urticaria, exfoliation, vasculitis, erythema multiforme, pseudo-lupus-like and lichen planus-like changes, alopecia, alopecia areata
• agranulocytosis
• liver damage, hepatitis

Reporting side effects

If you experience any side effects, including those not listed in this package leaflet, please inform your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, PL-02 222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, e-mail: ndl@urpl.gov.pl. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Aldactone

Keep the medicine out of the sight and reach of children. Store in the original package. Protect from light. Do not use this medicine after the expiry date stated on the package.

6. Contents of the pack and other information

What Aldactone contains

• The active substance is potassium canrenoate (1 ampoule of 10 ml contains 200 mg of potassium canrenoate)
• The other ingredients are: anhydrous sodium carbonate, sodium chloride, potassium hydroxide, water for injections

What Aldactone looks like and contents of the pack

Ampoule made of type I glass with a capacity of 10 ml. 10 ampoules in a cardboard box. Clear, colorless to slightly yellowish solution in a colorless glass ampoule

Marketing authorization holder and manufacturer

Marketing authorization holder

Esteve Pharmaceuticals GmbH, Hohenzollerndamm 150-151, 14199 Berlin, Germany

Manufacturer

Cenexi, 52, rue Marcel et Jacques Gaucher, 94120 Fontenay-sous-Bois, France

Date of last revision of the package leaflet: