Aldactone

Package leaflet: Information for the user

Warning! Keep this leaflet! Information on the immediate packaging in a foreign language.
Aldactone (Aldactone 10 ml Canrenoate)
20 mg/ml (200 mg/10 ml), solution for injection
Potassium canrenoate
Aldactone and Aldactone 10 ml Canrenoate are different trade names for the same medicinal product.
Please read this leaflet carefully before using this medicine, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any further questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents:

1. What Aldactone is and what it is 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 Aldactone is and what it is used for

Aldactone is an aldosterone antagonist, meaning it blocks aldosterone from binding to its receptor, thereby preventing reabsorption of sodium and promoting retention of potassium ions.
Potassium canrenoate exerts its effects 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 enhances excretion of sodium and chlorides, slightly increases calcium excretion, and reduces excretion of ammonium, magnesium, and potassium ions. It also causes urine alkalization.
The diuretic effect of potassium canrenoate is too weak for the drug to be used as a conventional diuretic. Its diuretic action can only be enhanced by concomitant administration with loop or thiazide diuretics.
By reducing glomerular filtration, potassium canrenoate may increase blood urea nitrogen levels.
Depending on the severity of hyperaldosteronism, the diuretic effect becomes apparent within 3 to 6 hours after intravenous administration and may last up to 72 hours. A stable diuretic effect is achieved after 2 weeks of treatment.

Indications:

• Primary hyperaldosteronism;
• Secondary hyperaldosteronism associated with 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 feasible and when the effect of other diuretics is insufficient.

2. Important information before using Aldactone

When not to use Aldactone
Do not use Aldactone if:

• the patient is allergic to the active substance, spironolactone, or to any of the other ingredients of this medicine (listed in section 6),
• hyperkalaemia (increased potassium ion concentration in the blood) or hyponatraemia (reduced sodium ion concentration in the blood) is present,
• renal impairment with serum creatinine concentration above 1.8 mg/dL and creatinine clearance below 30 mL/min,
• acute renal failure or anuria (anuria - cessation of urine production by the kidneys or absence of urine in the bladder due to blocked ureters).
  Do not use during pregnancy or while breastfeeding.

Warnings and precautions
Before starting treatment with Aldactone, discuss this with your doctor, pharmacist, or nurse.
Close medical supervision is particularly required in the following cases:

• impaired kidney function (serum creatinine concentration between 1.2 mg/dL and 1.8 mg/dL or creatinine clearance between 60 mL/min and 30 mL/min),
• patients predisposed to acidosis and/or hyperkalaemia due to their underlying disease (e.g. diabetes),
• hypotension,
• hypovolemia.

Fluid and electrolyte balance: The fluid and electrolyte status should be monitored regularly, especially in elderly patients and in patients with impaired kidney or liver function.
Hyperkalaemia may occur in patients with impaired kidney function or after excessive potassium intake and may cause irregular heartbeat, which can lead to death.
If hyperkalaemia develops, treatment with Aldactone should be discontinued and, if necessary, active measures should be taken to reduce potassium concentration to normal levels.
Hyponatraemia may occur, particularly when Aldactone is used concomitantly with other diuretic medicines.
Reversible hyperchloremic metabolic acidosis, usually in combination with hyperkalaemia, has occurred in several patients with decompensated liver cirrhosis, even when kidney function was normal.
Urea: Reversible increase in blood urea concentration has occurred during treatment with Aldactone, mainly in patients with impaired kidney function.
Caution should be exercised when using Aldactone in patients who are at risk of acidosis and in whom there is a risk of hyperkalaemia (e.g. in diabetes).
Close monitoring of serum potassium concentration is required in patients with impaired kidney function and serum creatinine concentration 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 Aldactone is used concomitantly with other medicines that may increase potassium concentration (see "Aldactone and other medicines").
Results of radioimmunoassays used to measure blood digoxin concentration may be falsely elevated in patients treated with Aldactone. This is thought to be due to the use of insufficiently specific antibodies.
Aldactone may falsely elevate cortisol assay results when measured by the Mattingly method.
Carcinogenic effects were observed in animal studies with long-term administration; therefore, treatment with Aldactone should be as short as possible, and the necessity of continued administration should always be considered.
Use of Aldactone may lead to positive results in doping tests.
Using Aldactone as a doping agent may endanger health.

Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult her doctor before using this medicine.
Use during pregnancy and breastfeeding is contraindicated.
There is no available information on the effect of Aldactone on fertility in humans.

Driving and operating machinery
Aldactone, even when used as directed, may alter the patient's reaction time to an extent that impairs the ability to drive vehicles or operate machinery. This is particularly relevant during the initial period of treatment, when previously used medicines are replaced with others, when additional medicines are started, and when alcohol is consumed concurrently.

Aldactone and other medicines:
Inform your doctor about all medicines currently or recently taken, as well as any medicines the patient plans to take.
Concomitant use of Aldactone and:

• diuretics may enhance their effect,
• carbenoxolone may reduce the effect of the latter,
• non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of hyperkalaemia,
• other potassium-sparing diuretics (triamterene, amiloride), potassium supplements, or angiotensin-converting enzyme (ACE) inhibitors may lead to a potentially life-threatening increase in serum potassium concentration,
• angiotensin-converting enzyme (ACE) inhibitors may increase serum creatinine concentration,
• concomitant use of furosemide and ACE inhibitors may lead to acute renal failure,
• acetylsalicylic acid, indomethacin, and other compounds inhibiting prostaglandin synthesis may reduce the effect of potassium canrenoate,
• digoxin may lead to increased digoxin serum concentration,
• epinephrine or norepinephrine may reduce the cardiovascular effects of these agents.

Potassium canrenoate may modify the results of radioimmunoassays used to measure digoxin concentration in blood.

Aldactone contains sodium and potassium
The medicine contains 37.1 mg of sodium (a major component of table salt) per ampoule. This corresponds to 1.9% of the maximum recommended daily dietary sodium intake for adults.
The medicine contains less than 1 mmol (39 mg) of potassium per dose, meaning 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 the physician. If in doubt, 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 may be increased up to 800 mg (4 ampoules) per day.
Typically, a single dose of 200 mg (one ampoule) is administered.

Use in children and adolescents
In neonates, infants, and children, the daily dose should be adjusted according to age and clinical condition, divided into three separate doses administered as slow, short intravenous infusions at hourly intervals.

Recommended dosing is usually:

• Children with body weight up to 50 kg – initial dose up to 4 to 5 mg/kg/day, followed by up to 2 to 3 mg/kg/day,
• Infants – maximum initial dose of 2 to 3 mg/kg/day, followed by up to 1.5 to 2 mg/kg/day.

The medicine must be administered intravenously at a rate not exceeding 1 ampoule (10 ml) over 2 to 3 minutes to avoid local venous irritation and nausea. The medicine should not be injected into thin veins.

In patients receiving high doses of Aldactone or when improved drug tolerance is required, potassium canrenoate may be administered in divided doses or via intravenous infusion lasting approximately 30 minutes.

In patients with renal impairment and serum creatinine levels between 1.2 mg/dl and 1.8 mg/dl, or creatinine clearance below 60 ml/min, treatment with Aldactone may be continued provided that serum potassium levels are monitored frequently.

Ampoules should be opened immediately before administration. Prolonged storage of an opened ampoule may lead to solution turbidity. Any unused portion remaining in the ampoule must not be reused.

Slight opalescence of the solution does not affect drug tolerance. However, if distinct turbidity is visible in the solution—which may exceptionally result from improper storage—the solution must not be administered. Only a clear solution, free from visible particles, should be used.

Accidental intra-arterial injection may be harmful; therefore, prior to administration, ensure that the needle is properly positioned within a vein.

Overdose of Aldactone
Overdose of potassium canrenoate may lead to drowsiness, disturbances in consciousness, and electrolyte imbalances.
There is no specific antidote.
Drowsiness and disturbances in consciousness usually resolve upon dose reduction or discontinuation of the medicine.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone experiences them.
The possible adverse reactions listed below are classified according to system organ classes. The frequency of occurrence is defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10000 to < 1/1000); very rare (< 1/10000); not known (frequency cannot be estimated from the available data).

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 tenderness, menstrual disorders (amenorrhea or intermenstrual bleeding), postmenopausal bleeding; in men – breast nipple hypersensitivity and gynecomastia. Impotence and decreased libido may also occur.

Rare (may affect up to 1 in 1000 people):

• hyperchloremic metabolic acidosis, hyponatremia, increased serum uric acid levels. Electrolyte imbalance may cause the following symptoms: cardiac arrhythmias, fatigue, muscle weakness, muscle cramps, dizziness,
• hypotension,
• bone demineralization, osteomalacia,
• hirsutism,
• voice disorders (hoarseness) or lowering of voice pitch. In some cases, voice changes may persist despite discontinuation of treatment. Therefore, in individuals for whom voice quality is particularly important (e.g. actors or teachers), the therapeutic benefits should be carefully weighed against the risks of treatment,
• nausea, vomiting, diarrhea, cramping abdominal pain, gastric or intestinal ulcers, possibly with bleeding,
• thrombocytopenia, eosinophilia in patients with liver cirrhosis,
• dizziness,
• transient confusional state, 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,
• erythema, urticaria, exfoliation, vasculitis, erythema annulare, lupus-like and lichenoid skin lesions, alopecia, alopecia areata,
• agranulocytosis,
• liver damage, hepatitis.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181 C, 02-222 Warsaw, tel.: + 48 22 49 21 301, fax: + 48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Reporting adverse reactions helps to provide more information on the safe use of the medicine.

5. How to store Aldactone

Keep this medicine out of the sight and reach of children.
Do not store above 25°C.
Store ampoules in the outer packaging to protect from light.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Aldactone contains

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

What Aldactone looks like and contents of the pack
Ampoules made of colourless glass with a capacity of 10 ml.
10 ampoules in a cardboard box.
Clear, colourless to slightly yellow solution in a colourless glass ampoule.
For further information, please contact the marketing authorisation holder or the parallel importer.
Marketing authorisation holder in Germany, the country of export:
Esteve Pharmaceuticals GmbH
Hohenzollerndamm 150-151
14199 Berlin
Germany
Manufacturer:
Cenexi
52, rue Marcel et Jacques Gaucher
94120 Fontenay-sous-Bois
France
Parallel importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw
Repackaged in:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
German marketing authorisation number, country of export: 6618119.00.00
Parallel import authorisation number: 294/20