Consumer medicine information

Aldactone

Spironolactone

BRAND INFORMATION

Brand name

Aldactone

Active ingredient

Spironolactone

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Aldactone.

What is in this leaflet

This leaflet answers some common questions about Aldactone.

It does not contain all of the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Aldactone against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Aldactone is used for

What Aldactone does

Aldactone is used:

  • To treat essential hypertension (high blood pressure with an unknown cause)
  • To treat oedematous disorders (swelling with fluid), including congestive cardiac failure
  • For the diagnosis and treatment of primary aldosteronism (a hormone disorder causing fluid retention)
  • As add-on therapy in malignant hypertension (a very serious form of high blood pressure)
  • Where there is a low amount of potassium (a mineral) in the blood caused by another diuretic (fluid-removing medicine)
    Aldactone improves the blood pressure lowering action of thiazide diuretics while at the same time reducing or preventing potassium loss due to these medicines.
  • For the prevention of low amounts of potassium in the blood in patients taking digitalis (a type of heart drug)
  • For the treatment of hirsutism (excess body hair in women)

How Aldactone works

Aldactone acts by working against a hormone called aldosterone. Too much aldosterone causes increased amounts of sodium (a mineral) and water to be retained by the kidneys, while too much potassium is removed from the body. Aldactone works against the effects of aldosterone.

Aldactone acts by removing excess fluid and by lowering blood pressure. It may be given alone or with other diuretics (fluid-removing medicines). It improves the effectiveness of other medicines used to lower blood pressure.

Aldactone also has a moderate ability to act against male sex hormones (anti-androgenic effect). Because of this, Aldactone is effective in the treatment of female hirsutism (excess body hair). It reduces hair growth, thickness and hair colour. Increased urine flow is unlikely to be a problem when Aldactone is used to treat hirsutism. This is because aldosterone levels are not normally high in patients with hirsutism.

The safety of Aldactone for the treatment of hirsutism in women of child-bearing age has not been established by specific studies.

Your doctor may recommend combined use with oral contraceptives to provide both regular menstrual cycles and adequate contraception.

Your doctor, however, may prescribe Aldactone for another purpose.

Ask your doctor if you have any questions about why Aldactone has been prescribed for you.

There is no evidence that Aldactone is addictive.

Before you take Aldactone

When you must not take it

Do not use Aldactone if:

  • you are pregnant or think you might be pregnant
    Aldactone should not be used during pregnancy due to possible effects on the developing baby (fetus).
  • you are breast feeding
    The drug may appear in the breast milk and be passed to the infant.
  • you are allergic to Aldactone or to any of the tablet ingredients listed at the end of this leaflet
    If you have an allergic reaction you may get a skin rash, have difficulty in breathing, or become faint.
  • you have severe kidney disease or are not passing urine
  • you have hyperkalaemia (high levels of potassium in the blood)
  • you have Addison's disease (a condition where the adrenal glands do not work properly).

Do not take Aldactone with potassium supplements or potassium containing salt substitutes or with potassium sparing diuretics.

Do not use tablets after the expiry date printed on the pack.

The tablets may have no effect at all, or an entirely unexpected effect, if you use them after the expiry date.

Do not use Aldactone if the packaging shows signs of tampering. If the product has expired or is damaged, return it to your pharmacist for disposal.

Do not use Aldactone to treat any other complaints unless your doctor advises you to.

Before you start to take it

You must tell your doctor if:

  • you are already taking medicines for high blood pressure
  • you are allergic to any other medicines, or any foods, dyes or preservatives
  • you are taking any other medicines, including medicines that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some of the medicines that may affect Aldactone or be affected by Aldactone include:

  • other medicines used to treat high blood pressure
  • diuretics, which are fluid removing medicines also known as water tablets
  • digoxin, a medicine used to treat heart conditions
  • medicines to prevent blood clots.
  • potassium supplements or potassium sparing diuretics
  • dietary salt substitutes. Many of these contain potassium
  • cholestyramine, a medicine used to lower cholesterol levels in the blood
  • ammonium chloride, which is contained in some cough and cold medicines
  • aspirin
  • non-steroidal anti-inflammatory medicines (NSAIDS) or other medicines which are used to relieve pain, swelling and other symptoms of inflammation, including arthritis.
  • regional or general anaesthetics.

These medicines may be affected by Aldactone or may affect how well it works. You may need to take different amounts of your medicine or you may need to take different medicines. Your doctor or pharmacist has a more complete list of medicines to avoid while taking Aldactone.

How to take Aldactone

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

Your doctor or pharmacist will tell you how many tablets you will need to take each day. This depends on your condition and whether or not you are taking any other medicines.

How much to take

Daily doses of Aldactone in adults can range from 25 mg to 400 mg. Depending on the dose and your condition, Aldactone may be taken once a day or divided into separate doses.

In the treatment of hirsutism (excess body hair) in females, your doctor may tell you to take Aldactone every day or in repeating cycles with a break in between.

Follow your doctor's instructions exactly regarding the dose you should take and how often you should take it.

Doses of Aldactone in children are measured according to body weight and will be calculated by your doctor.

If you forget to take it

If you forget to take Aldactone, do not try to make up for missed doses by taking more than one dose at a time.

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have taken too much Aldactone. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Keep telephone numbers for these places handy.

Overdose may cause nausea and vomiting. Sometimes, drowsiness, mental confusion, rash, diarrhoea or dehydration may occur.

While you are taking Aldactone

Things you must do

Take Aldactone exactly as your doctor has prescribed.

Tell all doctors, dentists and pharmacists who are treating you that you are taking Aldactone. This is especially important if you are going to receive an anaesthetic agent while being treated with Aldactone.

If you are about to have any blood tests tell your doctor that you are taking Aldactone. Aldactone may interfere with the results of some tests.

Tell your doctor if you're taking other types of medicines to treat high blood pressure.

Tell your doctor if you're taking medicines to prevent blood clots

Tell your doctor if you become pregnant while you are taking Aldactone. If it is possible for you to become pregnant, you should use adequate contraception while you are taking Aldactone.

Examples of adequate contraception are oral contraceptives ("the Pill") or intra-uterine devices (IUDs).

Stop taking Aldactone if you become pregnant or you think you may be pregnant.

Go to your doctor regularly for a check-up.

Your doctor may do blood tests to check your sodium and potassium levels and see how your kidneys are working.

Your doctor may do the blood test weekly at the start of your treatment, monthly for the first 3 months of treatment then quarterly for a year, and then every 6 months when increasing your dose.

You may need to stop taking Aldactone if your blood is high in potassium or if your kidneys are not working properly.

Things you must not do

Do not take potassium supplements or use salt substitutes that contain potassium.

Do not consume a diet rich in potassium. Dried fruit, bananas and oranges are some foods that contain high amounts of potassium. Consuming some of these foods is usually safe but do not consume excessive amounts.

If you are taking Aldactone, too much potassium can cause serious problems, such as disturbances to the heart rhythm.

Do not drive or operate machinery until you know how Aldactone affects you. Aldactone may cause drowsiness or dizziness in some people and may affect alertness.

Do not give this medicine to anyone else even if their symptoms seem similar to yours.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Aldactone. Like other medicines, Aldactone can cause some side effects. If they occur, they are most likely to be minor and temporary. However, some may be serious and need medical attention.

Aldactone helps most people with essential hypertension, oedematous disorders, primary aldosteronism, malignant hypertension and hirsutism but it may have unwanted side effects in a few people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Following is a list of possible side effects. Do not be alarmed by this list. You may not experience any of them.

Tell your doctor if...

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • cramping or diarrhoea
  • nausea or vomiting
  • drowsiness, lethargy or generally feeling unwell
  • skin rash or itchiness
  • peeling skin or skin redness
  • fever or sore throat
  • unusual hair loss or thinning
  • excessive hair growth

Tell your doctor as soon as possible if...

Tell your doctor as soon as possible if you notice any of the following:

  • frequent infection such as fever, severe chills, sore throat or mouth ulcers. A few cases of agranulocytosis (lack of white blood cells) have been reported in patients taking Aldactone.
  • breast enlargement. Breast enlargement may occur in men taking Aldactone. This normally goes away when Aldactone is stopped. In rare instances some breast enlargement may persist.
  • breast lumps. Breast lumps and breast cancer have been reported in patients taking Aldactone although Aldactone has not been shown to cause breast cancer.

Go to hospital if...

If any of the following happen, stop taking Aldactone and either tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • stomach bleeding, ulcers or gastritis (inflammation of the stomach)
  • unsteadiness when walking
  • leg cramps
  • headache
  • mental confusion or dizziness
  • change in sex drive
  • impotence (inability to achieve or maintain an erection)
  • breast pain
  • irregular periods or no periods
  • post-menopausal bleeding
  • shortness of breath and swelling of the legs from fluid build (may be due to hyperkalaemia that is very serious)

These are very serious side effects. You may need urgent medical attention or hospitalisation.

Other side effects not listed above may also occur in some people.

After taking Aldactone

Storage

Keep your tablets in their original packaging, including outer carton, until it is time to take them.

If you take the medicine out of the pack it may not keep well.

Keep Aldactone in a cool dry place where the temperature stays below 30°C.

Do not store Aldactone or any other medicines in a bathroom or near a sink. Do not leave it in the car or on window sills.

Heat and dampness can destroy some medicines.

Keep Aldactone where children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking Aldactone, ask your pharmacist what to do with any tablets left over.

Product description

What Aldactone looks like

Aldactone 25 mg tablets are round, biconvex, buff coloured, peppermint flavoured, film coated, stamped SEARLE over 39 on one side and unmarked on the other side. The tablets are available in blister packs of 100 tablets.

Aldactone 100 mg tablets are round, biconvex, buff coloured, peppermint flavoured, film coated, stamped SEARLE over 134 on one side and unmarked on the other side. The tablets are available in blister packs of 100 tablets.

Identification

Aldactone tablets can be identified by the Australian Registration number that appears on the carton.

25 mg tablets: AUST R 68953.

100 mg tablets: AUST R 68954.

Ingredients

The active ingredient in Aldactone tablets is spironolactone. Aldactone 25 mg tablets contain 25 mg spironolactone and Aldactone 100 mg tablets contain 100 mg spironolactone.

The tablets also contain:

  • calcium sulfate
  • maize starch
  • povidone
  • magnesium stearate
  • hypromellose
  • macrogol 400
  • peppermint flavour
  • Opaspray yellow

Supplier

Aldactone is supplied in Australia by:

Pfizer Australia Pty Ltd
Sydney NSW 2000
Toll free number: 1800 675 229

Date of preparation

This leaflet was prepared in February 2020

® Registered Trademark

© Pfizer Australia Pty Ltd 2020

Published by MIMS May 2020

BRAND INFORMATION

Brand name

Aldactone

Active ingredient

Spironolactone

Schedule

S4

 

1 Name of Medicine

Spironolactone.

6.7 Physicochemical Properties

Chemical structure.


CAS number.

52-01-7.

2 Qualitative and Quantitative Composition

The 25 mg Aldactone tablets contain 25 mg spironolactone.
The 100 mg Aldactone tablets contain 100 mg spironolactone.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Film-coated tablets.

25 mg Aldactone tablets.

8.7 mm in diameter, round, biconvex, buff coloured, peppermint flavoured, film coated, stamped SEARLE over 39 on one side and unmarked on the other.

100 mg Aldactone tablets.

11.2 mm in diameter, round, biconvex, buff coloured, peppermint flavoured, film coated, stamped SEARLE over 134 on one side and unmarked on the other.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Aldactone (spironolactone) is a specific pharmacologic antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone dependent sodium potassium exchange site in the distal convoluted renal tubule. Aldactone causes increased amounts of sodium and water to be excreted, while potassium is retained. Aldactone acts both as a diuretic and as an antihypertensive agent. It may be given alone or with other diuretic agents that act more proximally in the renal tubule.
Increased levels of the mineralocorticoid, aldosterone, are present in primary and secondary hyperaldosteronism. Oedematous states in which secondary aldosteronism is usually involved include congestive cardiac failure, hepatic cirrhosis, and nephrotic syndrome. By competing with aldosterone for receptor sites, Aldactone provides effective therapy for oedema and ascites in those conditions.
Aldactone is effective in lowering the systolic and diastolic blood pressure in patients with primary hyperaldosteronism. It is also effective in most cases of essential hypertension despite the fact that aldosterone secretion may be within normal limits in benign essential hypertension.
Through its action in antagonising the effect of aldosterone, Aldactone inhibits the exchange of sodium for potassium in the distal renal tubule and helps to prevent potassium loss.
Aldactone has not been demonstrated to elevate serum uric acid, to precipitate gout or to alter carbohydrate metabolism.
Aldactone has moderate antiandrogenic activity in humans by inhibition of the interaction between dihydrotestosterone and the intracellular androgen receptor. It also inhibits several steps in ovarian steroidogenesis resulting in lowered plasma levels of testosterone and some other weak androgenic steroids. Through this activity Aldactone is effective in the treatment of female hirsutism.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

In the human, the bioavailability of spironolactone from orally administered Aldactone tablets exceeds 90% when compared with an optimally absorbed solution (spironolactone in polyethylene glycol 400).
Food may increase the bioavailability of spironolactone; the clinical relevance of this effect is uncertain.

Metabolism.

Spironolactone is rapidly and extensively metabolised.
Approximately 25% to 30% of the dose administered is converted to canrenone. Sulfur containing products are the predominant metabolites and together with spironolactone are thought to be primarily responsible for the therapeutic effects of the drug. Canrenone attains peak serum levels at two to four hours following single oral administration. Canrenone plasma concentrations decline in two distinct phases, being rapid in the first 12 hours and slower from 12 to 96 hours. The log linear phase half-life of canrenone, following multiple doses of Aldactone, is between 13 and 24 hours. Both spironolactone and canrenone are more than 90% bound to plasma proteins.

Excretion.

The metabolites of spironolactone are excreted primarily in urine, but also in bile.

5.3 Preclinical Safety Data

Genotoxicity.

See Section 5.3 Preclinical Safety Data, Carcinogenicity.

Carcinogenicity.

Spironolactone has been shown to be tumorigenic in chronic toxicity studies performed in rats. It should be used only for approved indications. Unnecessary use of this drug should be avoided.
In chronic toxicity studies of spironolactone in rats, changes were observed in the endocrine organs, and the liver. In one study using dietary doses of 50 mg/kg/day, 150 mg/kg/day and 500 mg/kg/day there was a statistically significant dose related increase in benign adenomas of thyroid follicular cells and testicular interstitial cells. In female rats, there was a statistically significant increase in malignant mammary tumours at the mid-dose only. In male rats, there was a dose related increase in proliferative changes in the liver, which included hyperplastic nodules and hepatocellular carcinomas at the mid and high doses.
In a 2 year oral carcinogenicity study in which rats were administered 10 mg/kg/day, 30 mg/kg/day, 100 mg/kg/day and 150 mg/kg/day of spironolactone, the range of proliferative effects observed was consistent with earlier studies. There were statistically significant increases at the higher doses in hepatocellular adenomas and testicular interstitial cell tumours in males, and in thyroid follicular cell adenomas and carcinomas in both sexes. There was also a statistically significant increase in benign uterine endometrial polyps in females. There was an increase in hepatocellular carcinomas in males at 150 mg/kg but this was not statistically significant. There was no significant increase in the incidence of mammary tumours.
The significance of these findings with respect to clinical use is not known.
Spironolactone was not mutagenic in the Ames test using five strains of Salmonella typhimurium with or without metabolic activation.
A dose related (above 20 mg/kg/day) incidence of myelocytic leukaemia was observed in rats fed daily doses of potassium canrenoate for a period of 1 year. Canrenone and canrenoic acid are the major metabolites of potassium canrenoate. Spironolactone is also metabolised to canrenone. In long-term (2 year) oral carcinogenicity studies of potassium canrenoate in rats, myelocytic leukaemia and hepatic, thyroid, testicular and mammary tumours were observed. Potassium canrenoate did not produce a mutagenic effect in tests using bacteria or yeast. It did produce a positive mutagenic effect in several in vitro tests in mammalian cells following metabolic activation. In an in vivo mammalian system, potassium canrenoate was not mutagenic. An increased incidence of leukaemia was not observed in chronic rat toxicity or carcinogenicity studies conducted with spironolactone at doses up to 500 mg/kg/day. The recommended human dose of spironolactone is 1.4 mg/kg/day to 5.7 mg/kg/day.

4 Clinical Particulars

4.1 Therapeutic Indications

Essential hypertension.

Aldactone, when used alone, is effective in lowering both systolic and diastolic blood pressure. Aldactone improves the hypotensive action of thiazide diuretics, while at the time reducing or preventing potassium loss due to the thiazide. Aldactone enhances the effectiveness of other antihypertensive agents such as beta-blockers, vasodilators, etc.
As adjunctive therapy in malignant hypertension.
In diuretic induced hypokalaemia when other measures are considered inappropriate or inadequate.
Prophylaxis of hypokalaemia in patients taking digitalis when other measures are considered inadequate or inappropriate.

Oedematous disorders, such as oedema and ascites of congestive cardiac failure, cirrhosis of the liver, nephrotic syndrome.

Congestive cardiac failure.

Aldactone, when used alone, is effective in the management of oedema and sodium retention associated with congestive cardiac failure. Aldactone may be used in combination with a thiazide or other conventional diuretics for achieving diuresis in patients whose oedema is resistant to a thiazide or other conventional diuretics. Unlike conventional diuretics, Aldactone does not produce hypokalaemia. When administered with a thiazide or other conventional diuretics, Aldactone offsets hypokalaemia induced by these diuretics. The prevention of potassium loss is particularly important in the treatment of digitalised patients since digitalis intoxication may be precipitated if hypokalaemia is induced by conventional diuretic therapy.

Hepatic cirrhosis with ascites and oedema.

Aldactone, when used alone, is frequently adequate for the relief of ascites and oedema associated with hepatic cirrhosis. Aldactone provides a mild and even diuresis and prevents excessive potassium excretion caused by thiazide diuretics, thus avoiding possible precipitation of hepatic coma.

Nephrotic syndrome.

Although glucocorticoids, whose anti-inflammatory activity appears to benefit the primary pathologic process in the renal glomerulus, should probably be employed first, Aldactone either alone or in combination with a conventional diuretic is useful for inducing diuresis.

Diagnosis and treatment of primary hyperaldosteronism.

Aldactone may be used to establish the diagnosis of primary hyperaldosteronism by therapeutic trial. Aldactone may also be used for the short-term pre-operative treatment of patients with primary hyperaldosteronism, long-term maintenance therapy for patients with discrete aldosterone producing adrenal adenomas who are judged to be poor operative risks (or who decline surgery), and the long-term maintenance therapy for patients with bilateral micro or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism).

Hirsutism.

Aldactone is effective in the treatment of females with hirsutism, an androgen related increase in facial and body hair. A reduction in hair growth, hair shaft diameter and hair pigmentation are seen.
Use of Aldactone should be considered only after all other alternatives of non-drug therapy has been explored. For women of childbearing age, see Section 4.3 Contraindications; Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy.

4.3 Contraindications

Acute renal insufficiency, significant impairment of renal function, anuria.
Addison's disease or other conditions associated with hyperkalaemia (see Section 4.4 Special Warnings and Precautions for Use).
Hyperkalaemia.
Pregnancy.
Hypersensitivity to spironolactone.
Concomitant use of eplerenone.

4.4 Special Warnings and Precautions for Use

Concomitant use of spironolactone with angiotensin converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs, angiotensin II antagonists, aldosterone blockers, heparin, low molecular weight heparin, other drugs or conditions known to cause hyperkalaemia, potassium supplements, a diet rich in potassium, including salt substitutes containing potassium, or other potassium sparing agents is not recommended as it may lead to severe hyperkalaemia.
Hyperkalaemia may be fatal in patients with severe heart failure (New York Heart Association [NYHA] class III-IV). Potassium and creatinine levels should be closely monitored 1 week after initiation or monthly for the first 3 months, then quarterly for a year, and then every 6 months when increasing the dose of spironolactone. Concomitant use of spironolactone and other potassium sparing diuretics in patients with severe heart failure should be avoided. If serum potassium is > 3.5 mEq/L, oral potassium supplements should be avoided. Treatment with spironolactone should be discontinued or interrupted in patients with serum potassium > 5 mEq/L or with serum creatinine > 4 mg/dL.
Periodic estimation of serum electrolytes is desirable due to the possibility of hyperkalaemia, hyponatraemia and possible transient blood urea nitrogen (BUN) elevation especially in the elderly and/or patients with pre-existing impaired renal or hepatic function, in whom the risk/ benefit ratio should always be weighed.
Reversible hyperchloraemic metabolic acidosis, usually in association with hyperkalaemia, has been reported to occur in some patients with decompensated hepatic cirrhosis, even in the presence of normal renal function.
The safety of Aldactone for the treatment of hirsutism in women of childbearing age has not been established by specific long-term clinical trials. Epidemiological studies are also inadequate to establish the safety of long-term use in this population.

Use in hepatic impairment.

See Section 4.4 Special Warnings and Precautions for Use.

Use in renal impairment.

See Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use.

Use in the elderly.

See Section 4.4 Special Warnings and Precautions for Use.

Paediatric use.

No data available.

Effects on laboratory tests.

Spironolactone can interfere with assays for plasma digoxin concentrations.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Concomitant use of drugs known to cause hyperkalaemia with spironolactone may result in severe hyperkalaemia (see Section 4.4 Special Warnings and Precautions for Use).
Hyperkalaemia has been associated with the use of indomethacin or ACE inhibitors in combination with potassium sparing diuretics.
Spironolactone reduces the vascular responsiveness to noradrenaline. Therefore caution should be exercised in the management of patients subjected to regional or general anaesthesia while they are being treated with Aldactone.
As carbenoxolone may cause sodium retention and thus decrease the effectiveness of spironolactone, concurrent use of the two agents should be avoided.
Spironolactone has been shown to increase the half-life of digoxin. This may result in increased serum digoxin levels and subsequent digitalis toxicity. It may be necessary to reduce the digoxin dose when spironolactone is administered, and the patient should be carefully monitored to avoid over- or under-digitalisation.
Spironolactone may have an additive effect when given concomitantly with other diuretics and antihypertensive agents. The dose of such drugs may need to be reduced when spironolactone is added to the treatment regimen.
Nonsteroidal anti-inflammatory drugs such as aspirin, indomethacin, and mefenamic acid may attenuate the natriuretic efficacy of diuretics due to inhibition of intrarenal synthesis of prostaglandins and have been shown to attenuate the diuretic effect of spironolactone.
Spironolactone enhances the metabolism of antipyrine.
Hyperkalaemic metabolic acidosis has been reported in patients given spironolactone concurrently with ammonium chloride or cholestyramine.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In animal studies, spironolactone was devoid of teratogenic effects in mice and rabbits at oral doses up to 20 mg/kg/day, and in rats at dietary doses up to 50 mg/kg/day. However, increased resorption rate was seen at 20 mg/kg/day in rabbits, and the incidence of stillbirths was increased in rats dosed at 50 mg/kg/day. Subcutaneous administration of spironolactone (approximately 50 mg/kg/day to 100 mg/kg/day) to rats during late pregnancy caused endocrine dysfunction in both sexes of offspring 70-80 days after birth (hypoprolactinaemia and decreased ventral prostate and seminal vesicle weights in males; increased luteinizing hormone secretion and ovarian and uterine weights in females). Feminisation of the external genitalia of male fetuses was reported in another study in rats at oral doses of approximately 200 mg/kg/day. Subcutaneous administration of spironolactone to neonatal female mice caused histological changes in the cervicovaginal epithelium that were similar to those caused by diethylstilboestrol (a drug which causes vaginal neoplasia in adulthood following in utero exposure).
The risk of demasculinisation of the male fetus will only occur from about 6 weeks postconception onwards, hence if inadvertent spironolactone administration is stopped at an early stage, the risk to the male fetus is small.
(Category B3)
Experimentally, passive transfer of potassium sparing diuretics across the human placenta has been demonstrated. Maternal treatment during pregnancy may result in electrolyte disturbances in the fetus. Spironolactone should not be used in pregnancy (see Section 4.3 Contraindications). Women of childbearing potential should employ adequate contraception (i.e. oral contraceptives or IUDs) during administration of spironolactone, and the drug should be stopped if pregnancy occurs or is suspected.
Canrenone, an active metabolite of spironolactone, appears in breast milk. If use of the drug is deemed essential, an alternative method of infant feeding should be instituted.

4.8 Adverse Effects (Undesirable Effects)

Gynaecomastia may develop in association with the use of spironolactone, and physicians should be alert to its possible onset. The development of gynaecomastia appears to be related to both dosage level and duration of therapy and is normally reversible when Aldactone is discontinued. In rare instances some breast enlargement may persist.
Other adverse reactions that have been reported in association with Aldactone are: gastrointestinal symptoms, including cramping, diarrhoea, nausea, vomiting, gastric bleeding, ulceration and gastritis; drowsiness, lethargy, headache, maculopapular or erythematous cutaneous eruptions, urticaria, mental confusion, drug fever, ataxia, inability to achieve or maintain erection, irregular menses or amenorrhoea, postmenopausal bleeding, malaise, benign breast neoplasm, breast pain, leucopenia (including agranulocytosis), thrombocytopenia, abnormal hepatic function, electrolyte disturbances, hyperkalaemia, leg cramps, dizziness, changes in libido, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), alopecia, hypertrichosis, pruritus, rash and acute renal failure.
Carcinoma of the breast has been reported in patients taking spironolactone, but a cause and effect relationship has not been established.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Dosage.

Adults.

Essential hypertension.

50 mg/day to 100 mg/day which may be given either in divided doses or as a single daily dose.
Dosage should be adjusted according to response, but it should be noted that maximum effect of Aldactone therapy may not occur for up to 2 weeks after starting treatment.
Aldactone may potentiate the action of diuretics or other antihypertensive drugs, and their dosage should first be reduced by at least 50% when Aldactone is added to the regimen, and then adjusted as necessary.

Oedematous disorders.

The daily dose may be given either in divided doses or as a single daily dose.

Congestive cardiac failure.

Initial dose: 100 mg/day. In difficult or severe cases the dosage may be gradually increased up to 200 mg/day. When oedema is controlled, the usual maintenance level is 25 mg/day to 200 mg/day.

Cirrhosis.

If urinary Na+/K+ ratio is greater than 1 (one), the recommended dose is 100 mg/day. If the ratio is less than 1 (one), the recommended dose is 200 mg/day to 400 mg/day. Maintenance dosage should be individually determined.

Nephrotic syndrome.

Usually 100 mg/day to 200 mg/day. Spironolactone is not anti-inflammatory, has not been shown to affect the basic pathological process, and its use is only advised when treatment of the underlying disease, restriction of fluid intake and sodium intake, and the use of other diuretics do not provide an adequate response.

Diagnosis and treatment of primary aldosteronism.

Aldactone may be employed as an initial diagnostic measure to provide presumptive evidence of primary hyperaldosteronism while patients are on normal diets.

Long test.

Aldactone is administered at a daily dosage of 400 mg for 3 to 4 weeks. Correction of hypokalaemia and hypertension provides presumptive evidence for the diagnosis of primary hyperaldosteronism.

Short test.

Aldactone is administered at a daily dosage of 400 mg for 4 days. If serum potassium increases during Aldactone administration but drops when Aldactone is discontinued, a presumptive diagnosis of primary hyperaldosteronism should be considered.
After the diagnosis of hyperaldosteronism has been established by more definitive testing procedures, Aldactone may be administered in doses of 100 mg to 400 mg daily in preparation for surgery. For patients who are considered unsuitable for surgery, Aldactone may be employed for long-term maintenance therapy at the lowest effective dosage determined for the individual patient.

Malignant hypertension.

Aldactone should be used as adjunctive therapy only, where there is an excessive secretion of aldosterone, hypokalaemia and metabolic alkalosis. Initial dosage: 100 mg/day increased as necessary in two weekly intervals to 400 mg/day. Initial therapy should include a combination of other antihypertensive drugs and spironolactone. Do not automatically reduce the dose of other treatments as is recommended for essential hypertension.

Hypokalaemia.

Aldactone may be useful in treating diuretic induced hypokalaemia when oral potassium supplements are considered inappropriate. In treating hypokalaemia, the lowest dose should be used and titrated upwards. A daily dose exceeding 100 mg is not recommended.

Female hirsutism.

100 mg/day to 200 mg/day in divided doses is usual, however 50 mg/day has also been shown to be effective.
Clinical improvement is usually shown within 3 to 6 months and an initial course of treatment should continue for 12 months.
Aldactone may be administered continuously or as a cyclical dosage for approximately 3 weeks out of every 4 weeks. Dosing from Day 5 to Day 21 of the menstrual cycle, with a drug free interval during menstruation, has been effective.
Cyclical dosing may reduce menstrual irregularities in women with previously regular cycles.
Combined use with oestrogen-progestogen oral contraceptives may also be considered to provide both regular menstrual cycles and adequate contraception (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).

Children and adolescents.

Oedema.

The initial daily dosage should provide approximately 3.3 mg/kg. For small children, Aldactone tablets may be pulverised and administered as a suspension in cherry syrup. When refrigerated, such a suspension is stable for 1 month.

4.7 Effects on Ability to Drive and Use Machines

Somnolence and dizziness have been reported to occur in some patients. Caution is advised when driving or operating machinery until the response to initial treatment has been determined.

4.9 Overdose

Symptoms.

Overdosage may be manifested by nausea and vomiting, dizziness and (more rarely) by drowsiness, mental confusion, maculopapular or erythematous rash or diarrhoea. Electrolyte imbalances and dehydration may occur. Hyperkalaemia may be produced; symptoms include paraesthesia, weakness, flaccid paralysis and tetany. The earliest signs are characteristic electrocardiographic abnormalities including tall "tent shaped" T waves, decreased amplitude of the P waves and widening of the QRS complex. Delayed onset of hyperkalaemia has been reported after acute ingestion of spironolactone (peak levels at 24 hours and 32 hours).

Treatments.

Symptomatic and supportive measures should be employed. There is no specific antidote. Support respiratory and cardiac functions. Treat fluid depletion, electrolyte imbalances and hypotension by established procedures.
Severity of intoxication should be based on clinical findings and serial determination of serum potassium levels. Monitoring plasma levels of spironolactone is not clinically useful.
Hyperkalaemia can be treated promptly by the rapid intravenous administration of glucose (20% to 50%) and regular insulin, using 0.25 to 0.5 units of insulin per gram of glucose. Potassium excreting diuretics and ion exchange resins may also be administered, repeating as required.
Aldactone should be discontinued and potassium intake (including dietary potassium) restricted.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Calcium sulfate dihydrate, maize starch, povidone, magnesium stearate, hypromellose, macrogol 400, Felcofix peppermint flavour 961149/701213, Opaspray yellow M-1-6032B.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

The 25 mg and 100 mg tablets are available as blister packs of 100 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes