Consumer medicine information

Kaluril

Amiloride hydrochloride

BRAND INFORMATION

Brand name

Kaluril

Active ingredient

Amiloride hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Kaluril.

What is in this leaflet

This leaflet answers some common questions about Kaluril.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking Kaluril against the benefits expected for you.

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

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

What Kaluril is used for

Kaluril is used to:

  • decrease swelling (oedema) of the ankles, feet or legs due to certain heart problems
  • reduce build-up of fluid in the abdomen (ascites) due to liver disease
  • lower high blood pressure (hypertension)

Kaluril is a fluid tablet or diuretic. It reduces the amount of excess fluid in the body by increasing the amount of urine produced. Kaluril helps reduce oedema, fluid build-up and high blood pressure by making your kidneys pass more water and salt.

Kaluril may be taken alone or in combination with other medicines to treat your condition.

It is especially useful when taken together with certain other diuretics, which cause loss of potassium from the body. Unlike these other diuretics, Kaluril retains potassium and is able to maintain a normal potassium level in the blood.

Ask your doctor if you have any questions about why Kaluril has been prescribed for you. Your doctor may have prescribed Kaluril for another reason.

Kaluril is available only with a doctor's prescription.

There is no evidence that Kaluril is addictive.

Before you take Kaluril

When you must not take it

Do not take Kaluril if you have had an allergic reaction to:

  • medicines containing amiloride (e.g. Amizide, Midamor, Moduretic)
  • any of the ingredients listed at the end of this leaflet

Some of the symptoms of an allergic reaction may include skin rash, itching or hives; swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing; wheezing or shortness of breath.

Do not take Kaluril if you:

  • have severe kidney disease
  • are not producing or passing any urine
  • have high potassium levels in your blood (hyperkalaemia)
  • are following a high potassium diet, or taking potassium tablets or other potassium-conserving medicines

Check with your doctor or pharmacist if you are not sure about any of the above.

Do not take Kaluril if you are pregnant or intend to become pregnant. Like most diuretic medicines, Kaluril is not recommended for use during pregnancy.

Do not take Kaluril if you are breastfeeding or plan to breastfeed. It is not known whether Kaluril passes into breast milk. However, because of the potential harm to the baby, Kaluril is not recommended for use during breast-feeding.

Do not give Kaluril to children. The safety of Kaluril in children has not been established.

Do not take Kaluril if the expiry date (EXP) printed on the pack has passed. If you take this medicine after the expiry date, it may not work as well.

Do not take Kaluril if the packaging shows signs of tampering or the tablets do not look quite right.

Before you start to take it

Tell your doctor if you are allergic to any other medicines, foods, dyes or preservatives.

Tell your doctor if you have, or have had, any medical conditions, especially the following:

  • diabetes
  • kidney problems
  • liver problems
  • heart and lung problems.

Your doctor may want to take special care if you have any of these conditions.

Tell your doctor if you are following a potassium-rich diet (i.e. eating foods which are high in potassium such as bananas or oranges) or are taking potassium supplements. Your blood potassium levels may increase too much.

If you have not told your doctor about any of the above, tell him/her before you start taking Kaluril.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines may be affected by Kaluril, or may affect how well it works. These include:

  • tablets or supplements containing potassium (e.g. Slow-K, Span-K, KSR)
  • salt-substitutes which contain potassium
  • multivitamin preparations containing potassium
  • certain other fluid tablets or diuretics such as spironolactone (Aldactone, Spiractin)
  • angiotensin converting enzyme (ACE) inhibitors (e.g. Renitec, Alphapril, Zestril, Prinivil and Lisodur) and angiotensin II receptor antagonists (e.g. Atacand, Cozaar), medicines used to treat high blood pressure and certain heart or kidney conditions
  • ciclosporin (e.g. Neoral, Sandimmun) and tacrolimus (Prograf), medicines used to help prevent organ transplant rejection or to treat certain problems with the immune system
  • lithium, a medicine used to treat mood swings and some types of depression
  • non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (e.g. Nurofen, Rafen) and diclofenac (e.g. Voltaren, Fenac), medicines used to relieve pain, swelling and other symptoms of inflammation including arthritis
  • digoxin (Lanoxin), a medicine used to treat heart failure.

Your doctor can tell you what to do if you are taking any of these medicines.

If you are not sure whether you are taking any of these medicines, check with your doctor or pharmacist. Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking Kaluril.

How to take Kaluril

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

If you do not understand the instructions on the bottle, ask your doctor or pharmacist.

How much to take

The usual starting dose is one or two tablets (5 mg or 10 mg) each day.

Your doctor may adjust the dose depending on how well you respond to Kaluril and whether or not you are taking any other medicines.

The maximum dose is four tablets (20 mg) a day.

How to take Kaluril

Swallow the tablets with a glass of water.

When to take Kaluril

Take Kaluril every day at about the same time each day, unless your doctor tells you otherwise. Taking your tablets at the same time each day will have the best effect on your blood pressure. It will also help you to remember when to take the tablets.

Kaluril can be taken with or without food.

If you are taking Kaluril once a day, take it in the morning, for example, at breakfast time. Kaluril takes about two hours to start working.

If you are taking more than one dose a day, take the last dose no later than 6 pm, unless your doctor tells you otherwise. Kaluril may increase the amount of water (urine) you pass and also the number of times you go to the toilet. By taking the last dose no later than 6 pm there may be less chance of your sleep being disturbed.

If you forget to take Kaluril

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take the missed dose as soon as you remember, and then go back to taking your tablets as you would normally.

Do not take a double dose to make up for the dose you missed. This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

How long to take Kaluril for

Keep taking Kaluril for as long as your doctor recommends. Kaluril helps to control your condition but does not cure it. Most people will need to take Kaluril on a long-term basis.

If you take too much Kaluril (overdose)

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

If you take too much Kaluril, you may feel weak, thirsty, tired, confused, dizzy, nauseated (feeling sick). You may also vomit, have muscle cramps or an irregular heart beat.

While you are taking Kaluril

Things you must do

Before starting any new medicine, tell your doctor or pharmacist that you are taking Kaluril.

Tell all the doctors, dentists and pharmacists who are treating you that you are taking Kaluril.

If you become pregnant while taking Kaluril, tell your doctor immediately.

Tell your doctor if you have any of the following symptoms:

  • excessive vomiting or diarrhoea
  • dry mouth, thirst
  • weakness, tiredness, drowsiness
  • muscle pain or cramps
  • irregular heart beat
  • passing less urine than normal.

If you experience any of the above symptoms, you may be dehydrated from losing too much water.

Make sure you drink enough water during exercise and hot weather when you are taking Kaluril, especially if you sweat a lot. If you do not drink enough water while taking Kaluril, you may feel faint, lightheaded or sick. This is because your blood pressure is dropping suddenly. If you continue to feel unwell, tell your doctor.

If you plan to have surgery, including dental surgery, which needs a general anaesthetic, tell your doctor or dentist that you are taking Kaluril. Your doctor or dentist may advise you to temporarily stop taking Kaluril before surgery to avoid a sudden drop in your blood pressure during the procedure.

If you have to have any blood tests, tell your doctor that you are taking Kaluril.

Visit your doctor regularly so they can check on your progress. Your doctor may want to check your blood pressure and perform blood tests to check your levels of potassium and other minerals to make sure Kaluril is working properly.

Keep a continuous supply of medicine so you don't run out, especially over weekends or on holidays.

Things you must not do

Do not use salt-substitutes, which commonly contain potassium, in your cooking or at the table. Your potassium levels may increase too much.

Do not stop taking Kaluril, or change the dose, without checking with your doctor.

Do not use Kaluril to treat any other conditions unless your doctor tells you to.

Do not give Kaluril to anyone else, even if they have the same condition as you.

Things to be careful of

Be careful driving or operating machinery until you know how Kaluril affects you. Kaluril may cause drowsiness, dizziness or lightheadedness in some people. If any of these occur, do not drive, operate machinery or do anything else that could be dangerous.

Be careful getting up from a sitting or lying position. Dizziness, lightheadedness or fainting may occur, especially when you get up quickly. Getting up slowly may help. If this problem continues or gets worse, talk to your doctor.

Be careful when drinking alcohol or while taking Kaluril. Combining Kaluril with alcohol can make you more dizzy or lightheaded.

Be aware of foods, drinks or supplements that have a high potassium content. Kaluril helps to maintain a normal potassium level in your body. However, if you eat foods or have drinks that are high in potassium this may lead to an increase of potassium in your body, which can be harmful. Your doctor and pharmacist have more information on potassium-rich foods.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Kaluril. Kaluril is usually well tolerated but it may have unwanted side effects in some people. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

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

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

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

  • dizziness or lightheadedness
  • drowsiness or sleeping problems
  • headache
  • lack of energy, weakness
  • nausea (feeling sick), vomiting, loss of appetite
  • diarrhoea or constipation
  • heartburn, stomach discomfort or pain
  • passing wind
  • visual disturbances, nasal congestion
  • impotence.

The side effects listed above are usually mild.

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

  • very dry mouth or unusual thirst
  • muscle cramps, joint pain
  • numbness or tingling in the hands or feet
  • tremor or shaking
  • mental confusion
  • pain when passing urine
  • signs of frequent infections such as fever, severe chills, sore throat or mouth ulcers
  • bruising or bleeding more easily than normal.

The above list includes serious side effects. You may need urgent medical attention.

Tell your doctor immediately or go to Accident and Emergency at the nearest hospital if you notice any of the following:

  • chest pain or a feeling of tightness in the chest
  • an irregular heart beat or palpitations
  • vomiting blood or material that looks like coffee grounds
  • bleeding from the back passage, black, sticky bowel motions (stools) or bloody diarrhoea
  • rash, itching or hives
  • swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are rare.

Tell your doctor if you notice anything that is making you feel unwell.

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

After taking Kaluril

Storage

Keep Kaluril 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.

Keep your tablets in the bottle until it is time to take them. If you take the tablets out of the bottle they may not keep well.

Keep your tablets in a cool dry place where the temperature stays below 25°C.

Do not store Kaluril or any other medicine in the bathroom or near a sink.

Do not leave Kaluril in the car or on window sills. Heat and dampness can destroy some medicines.

Disposal

If your doctor tells you to stop taking Kaluril, or your tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

Kaluril is a round, pale yellow tablet marked "AR" over a line over "5" on one side and "G" on the other.

Each bottle contains 50 tablets.

Ingredients

The active ingredient in Kaluril is amiloride hydrochloride dihydrate. Each tablet contains 5 mg of amiloride hydrochloride dihyrate.

The tablets also contain:

  • lactose monohydrate
  • maize starch
  • microcrystalline cellulose
  • povidone
  • magnesium stearate.

The tablets are gluten free.

Supplier

Kaluril is supplied in Australia by:

Alphapharm Pty Limited
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.mylan.com.au

Australian registration number:

AUST R 17652

This leaflet was prepared in July 2019.

Kaluril_cmi\Jul19/00

Published by MIMS September 2019

BRAND INFORMATION

Brand name

Kaluril

Active ingredient

Amiloride hydrochloride

Schedule

S4

 

1 Name of Medicine

Amiloride hydrochloride dihydrate.

6.7 Physicochemical Properties

The chemical name for amiloride hydrochloride dihydrate is N-amidino- 3,5-diamino- 6-chloropyrazine- 2-carboxamide hydrochloride dihydrate.
Molecular formula: C6H9Cl2N7O,2H2O.
Molecular weight: 302.12.
Amiloride hydrochloride dihydrate is a pale yellow to greenish yellow powder, odourless or almost odourless.

Chemical structure.

Its structural formula is:

CAS number.

CAS registry number: 17440-83-4.

2 Qualitative and Quantitative Composition

The active ingredient of Kaluril tablets is amiloride hydrochloride dihydrate. Each Kaluril tablet contains 5 mg of amiloride hydrochloride dihydrate.
Kaluril also contains lactose monohydrate. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

5 mg tablet: pale yellow, flat bevelled edge, scored on one side, marked AR/5 on one side, G on reverse.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Kaluril is a potassium conserving (antikaliuretic) drug which possesses mild natriuretic, diuretic, and antihypertensive activity (compared with thiazide diuretics). These actions may be additive to the effects of thiazides or other saluretic antihypertensive agents. Amiloride hydrochloride dihydrate has potassium conserving activity in patients receiving kaliuretic diuretic agents; its principal use is to conserve potassium in patients receiving diuretic agents in whom excessive potassium losses occur or are expected.
Kaluril interferes with the mechanism involved in the exchange of sodium for potassium in the distal convoluted tubule of the nephron. An increase in sodium and a decrease in potassium and hydrogen ion excretion are induced in the presence or absence of aldosterone, thereby suggesting a direct tubular action of the drug. Sodium excretion increases moderately, while chloride excretion may remain unchanged or increase slowly with continued therapy. This effect may diminish the risk of hypochloraemic alkalosis encountered with some saluretic agents. The positive effect of Kaluril on potassium balance is usually beneficial; however, potassium retention to the point of hyperkalaemia may be avoided by keeping the dosage of amiloride hydrochloride dihydrate below 20 mg/day.
Amiloride hydrochloride dihydrate, when administered with hydrochlorothiazide, has been shown to result in less excretion of magnesium than thiazide or loop diuretics used alone.
Amiloride hydrochloride dihydrate is not an aldosterone antagonist and its effects are seen even in the absence of aldosterone.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Kaluril usually begins to act within 2 hours after an oral dose. Its effect on electrolyte excretion reaches a peak between 6 and 10 hours and lasts about 24 hours. Peak plasma levels are obtained in 3 to 4 hours and the plasma half-life varies from 6 to 9 hours. Effects on electrolytes increase with single doses of amiloride hydrochloride dihydrate up to approximately 15 mg.

Metabolism and excretion.

Amiloride hydrochloride dihydrate is not metabolised by the liver but is excreted unchanged by the kidneys. About 50% of a 20 mg dose of amiloride hydrochloride dihydrate is excreted in the urine and 40% in the stool within 72 hours. Amiloride hydrochloride dihydrate has little effect on glomerular filtration rate or renal blood flow. Because amiloride hydrochloride dihydrate is not metabolised by the liver, drug accumulation is not anticipated in patients with hepatic dysfunction, but accumulation can occur if the hepatorenal syndrome develops.

5.3 Preclinical Safety Data

Genotoxicity.

Amiloride hydrochloride dihydrate was devoid of mutagenic activity in Salmonella typhimurium with or without a mammalian liver microsomal activation system (Ames test).The potential to cause chromosomal damage has not been investigated.

Carcinogenicity.

There was no evidence of a tumorigenic effect when amiloride hydrochloride dihydrate was administered for 92 weeks to mice at doses up to 10 mg/kg/day (3 times the maximum daily human dose, based on body surface area). Amiloride hydrochloride dihydrate has also been administered for 104 weeks to male and female rats at doses up to 6 and 8 mg/kg/day (3.2 and 4.3 times the maximum daily dose for humans, based on body surface area, respectively) and showed no evidence of carcinogenicity.

4 Clinical Particulars

4.1 Therapeutic Indications

Kaluril's main indication is as concomitant therapy with diuretics to conserve potassium during periods of vigorous diuresis and during long-term maintenance therapy with thiazides or other more potent diuretics. Kaluril, when used alone, has mild diuretic and antihypertensive activity.

Oedema of cardiac origin.

Although Kaluril alone may provide adequate diuresis for some patients with oedema of cardiac origin, it is primarily indicated for concomitant use in patients receiving thiazides or more potent saluretic diuretic agents. In these patients it may provide increased sodium, chloride and water excretion and decreased potassium excretion. The positive effect of Kaluril on potassium balance may be especially important for digitalised cardiac patients, in whom potassium depletion sensitises or exaggerates the response of the heart to the toxic effects of digitalis (e.g. increased ventricular irritability), which may precipitate digitalis intoxication with potentially serious cardiac arrhythmias.

Hypertension.

Kaluril is used as an adjunctive agent for the prevention of potassium depletion in patients receiving thiazides or other oral saluretic antihypertensive therapy over a prolonged period. When combined with hydrochlorothiazide, Kaluril produces an additive antihypertensive effect.

Hepatic cirrhosis with ascites and oedema.

Kaluril, when used alone, usually provides adequate diuresis with diminished potassium loss and with a reduced risk of metabolic alkalosis. Kaluril may also be used with other more potent saluretic diuretic agents where greater diuresis is needed while maintaining a more balanced serum electrolyte pattern.
As with all therapy for the ascites of hepatic cirrhosis, gradual weight loss and avoidance of electrolyte imbalance are the chief objectives (see Section 4.4 Special Warnings and Precautions for Use).

4.3 Contraindications

Hyperkalaemia.

Amiloride hydrochloride dihydrate should not be used in the presence of elevated serum potassium levels (interpreted as over 5.5 mmol/L).

Antikaliuretic therapy or potassium supplementation.

Kaluril should not be given to patients receiving other potassium conserving agents, such as spironolactone or triamterene. Potassium supplementation in the form of medication or a potassium rich diet should not be used with Kaluril except in severe and/or refractory cases of hypokalaemia. Such concomitant therapy can be associated with rapid increases in serum potassium levels. If potassium supplementation is used, careful monitoring of the serum potassium level is necessary.

Impaired renal function.

Anuria, acute renal failure, severe progressive renal disease, and diabetic nephropathy are contraindications to use of amiloride hydrochloride dihydrate. Patients with increases in BUN over 30 mg/100 mL (10.7 mmol/L), in serum creatinine levels over 1.5 mg/100 mL (0.13 mmol/L), or in whole blood urea values over 60 mg/100 mL (10 mmol/L), should not receive the drug without careful, frequent monitoring of serum electrolytes and BUN levels. Potassium retention in the presence of renal impairment is accentuated by the addition of an antikaliuretic agent and may result in the rapid development of hyperkalaemia.

Known sensitivity to the drug.

As with all drugs, prior sensitisation is a contraindication to the use of the compound.

4.4 Special Warnings and Precautions for Use

Diabetes mellitus.

In diabetic patients, hyperkalaemia has commonly occurred during therapy with amiloride hydrochloride dihydrate, particularly if chronic renal disease or prerenal azotaemia is present. The status of renal function should therefore be known before starting therapy in diabetic or suspected diabetic patients.
One patient with poorly controlled diabetes mellitus, who became severely hyperkalaemic while on amiloride hydrochloride dihydrate, died following 2 repeated intravenous glucose tolerance tests. Therefore, therapy should be discontinued for at least 3 days in any suspected diabetic patient on Kaluril who requires glucose tolerance testing.

Metabolic or respiratory acidosis.

In severely ill patients in whom respiratory or metabolic acidosis may occur, such as patients with cardiopulmonary disease and patients with decompensated diabetes, antikaliuretic therapy should be instituted only with caution. Shifts in acid-base balance alter the balance of extracellular/ intracellular potassium, and the development of acidosis may be associated with rapid increases in serum potassium levels.

Effects related to diuresis in cirrhotic patients.

Oral diuretic therapy is more frequently accompanied by adverse reactions in patients with hepatic cirrhosis and ascites, because these patients are intolerant of acute shifts in electrolyte balance and because they often have pre-existing hypokalaemia as a result of associated aldosteronism.
Hepatic encephalopathy, manifested by tremors, confusion and coma, has been reported.
In cirrhotic patients, jaundice associated with the underlying disease process has deepened in a few instances but the relationship to the drug is uncertain.

Hyperkalaemia.

Hyperkalaemia, defined as serum potassium levels over 5.5 mmol/L, has been observed in patients who received amiloride hydrochloride dihydrate, either alone or in combination with other diuretic drugs. This has been noted particularly in aged patients and in hospitalised patients with hepatic cirrhosis or cardiac oedema who have known renal involvement, are seriously ill, or are undergoing vigorous diuretic therapy. These patients should be monitored carefully for clinical, laboratory and electrocardiographic evidence of hyperkalaemia. Some deaths have been reported in this group of patients.
Paraesthesias, muscular weakness, fatigue, flaccid paralysis of the extremities, bradycardia, shock and serum potassium and ECG abnormalities are warning signs of hyperkalaemia. As hyperkalaemia is not always associated with an abnormal electrocardiogram, careful monitoring of the serum potassium level is important. When abnormal, the ECG in hyperkalaemia is characterised primarily by tall, peaked T waves or elevations from previous tracings. There may also be lowering of the R wave and increased depth of the S wave, widening and even disappearance of the P wave, progressive widening of the QRS complex, and prolongation of the PR interval and ST depression.
In the event of hyperkalaemia occurring in patients taking Kaluril, the drug should be discontinued immediately and, if necessary, active measures taken to reduce the plasma potassium level. Discontinuation of antikaliuretic therapy should be followed by intravenous administration of molar sodium lactate or oral or parenteral glucose with a rapid acting insulin. If needed, a cation exchange resin such as sodium polystyrene sulfonate may be given orally or by enema. Patients with persistent hyperkalaemia may require dialysis.

Electrolyte imbalance and reversible BUN increases.

Hyponatraemia and hypochloraemia may occur when amiloride hydrochloride dihydrate is used with other diuretics, and increases in BUN levels have been reported. These increases usually have accompanied vigorous fluid elimination, especially when diuretic therapy was used in seriously ill patients, such as those who had hepatic cirrhosis with ascites and metabolic alkalosis, or those with resistant oedema. Therefore, careful monitoring of serum electrolytes and BUN levels is important when Kaluril is given with other diuretics to such patients. In patients with pre-existing severe liver disease, hepatic encephalopathy, manifested by tremors, confusion, and coma, and increased jaundice, have been reported in association with diuretics, including amiloride hydrochloride dihydrate.

Use in the elderly.

No data available.

Paediatric use.

Kaluril is not recommended in the paediatric age group as the safety for use of amiloride hydrochloride dihydrate in children has not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Lithium generally should not be given with diuretics because they reduce its renal clearance and add a high risk of lithium toxicity. Read circulars for lithium preparations before use of such concomitant therapy.
When amiloride hydrochloride dihydrate is administered concomitantly with an angiotensin converting enzyme (ACE) inhibitor, an angiotensin II receptor antagonist, ciclosporin or tacrolimus, the risk of hyperkalaemia may be increased. Therefore, if concomitant use of these agents is indicated because of demonstrated hypokalaemia, they should be used with caution and with frequent monitoring of serum potassium.
Concomitant administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and potassium sparing agents, including amiloride hydrochloride dihydrate, may cause hyperkalaemia and renal failure, particularly in elderly patients. Therefore, when amiloride hydrochloride dihydrate is concomitantly used with NSAIDs, renal function and serum potassium levels should be carefully monitored.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Reproduction studies in rats at four times the expected maximum daily dose for humans based on body surface area showed no evidence of impaired fertility.
(Category C)
Passive transfer of potassium sparing diuretics across the human placenta has been demonstrated. Maternal treatment during pregnancy may result in electrolyte disturbances in the foetus.
Teratogenicity studies with amiloride hydrochloride dihydrate in rabbits and mice given doses of 8 and 10 mg/kg respectively (six and three times the maximum human dose, based on body surface area) revealed no evidence of harm to the foetus. At approximately three or more times the expected maximum daily dose for humans, based on body surface area, some toxicity was seen in adult rats and rabbits and a decrease in rat pup growth and survival occurred.
There are, however, no adequate and well controlled studies in pregnant women.
Kaluril is not recommended for use during pregnancy. The potential benefits of the drug must be weighed against possible hazards to the fetus if it is administered to a woman of childbearing age.
 Studies in rats have shown that amiloride is excreted in milk in concentrations higher than that found in blood. It is not known whether Kaluril is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from amiloride hydrochloride dihydrate, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

4.8 Adverse Effects (Undesirable Effects)

Kaluril is usually well tolerated and, except for hyperkalaemia (serum potassium levels greater than 5.5 mmol/L, see Section 4.4 Special Precautions and Warnings for Use), significant adverse effects have been reported infrequently. Minor adverse reactions were reported relatively frequently (about 20%) but the relationship of many of the reports to amiloride hydrochloride dihydrate is uncertain and the overall frequency was similar in hydrochlorothiazide treated groups. Nausea, anorexia, abdominal pain, flatulence and mild skin rash have been reported and probably are related to amiloride. Other adverse experiences that have been reported with amiloride are generally those known to be associated with diuresis, or with the underlying disease being treated.

Body as a whole.

Headache, weakness, fatiguability, back pain, chest pain, neck/ shoulder ache, pain in extremities.

Cardiovascular.

Angina pectoris, orthostatic hypotension, arrhythmia, palpitation; one patient with a partial heart block developed complete heart block.

Gastrointestinal.

Anorexia, nausea, vomiting, diarrhoea, constipation, abdominal pain, GI bleeding, jaundice, thirst, dyspepsia, heartburn, flatulence.

Metabolic.

Elevated serum potassium levels (> 5.5 mmol/L); hyponatraemia.

Integumentary.

Pruritus, rash, dryness of mouth, alopecia.

Musculoskeletal.

Muscle cramps, joint pain.

Nervous.

Dizziness, vertigo, paraesthesia, tremors, encephalopathy.

Psychiatric.

Nervousness, mental confusion, insomnia, decreased libido, depression, somnolence.

Respiratory.

Cough, dyspnoea.

Special senses.

Nasal congestion, visual disturbances, increased intraocular pressure, tinnitus.

Urogenital.

Impotence, polyuria, dysuria, bladder spasms, frequency of micturition.

Causal relationship unknown.

Other reactions have been reported but occurred under circumstances where a causal relationship could not be established. However, in these rarely reported events, that possibility cannot be excluded. Therefore, these observations are listed to serve as alerting information to physicians.
Activation of probably pre-existing peptic ulcer; aplastic anaemia; neutropenia; abnormalities of liver function tests.

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

General considerations.

Kaluril usually begins to act within 2 hours following oral administration. Its effect upon electrolyte excretion reaches a peak between 6 and 10 hours and lasts for approximately 24 hours. Most patients respond during the first day of treatment; however, maximum therapeutic effect may not be seen for several days.
The rate of weight loss and serum electrolyte levels should determine the dose. After initiating diuresis, the most satisfactory rate of weight loss is generally about 0.5 to 1.0 kg daily.

Kaluril alone.

The initial dosage should be 10 mg (as a single dose or 5 mg twice daily). Dosage may be increased, depending upon the need for effective potassium sparing action, but must not exceed 20 mg daily. Once diuresis has been achieved, the dosage may be reduced by 5 mg increments to the least amount required.

Kaluril plus other diuretic therapy.

Oedema of cardiac origin.

Kaluril, 5 or 10 mg daily, may be employed with the usual doses of other saluretic diuretic agents. If diuresis is not achieved with minimal doses of both agents, the dosage of both drugs may be gradually increased. The dosage of Kaluril should not exceed 20 mg/day. Once diuresis is achieved, reduction in dosage of both agents may be attempted. The dosage of both drugs is determined by the diuretic response and the serum potassium level.

Hypertension.

5 or 10 mg daily, given with the usual antihypertensive doses of thiazides. The dosage may be adjusted if necessary. It is not usually necessary to exceed 10 mg of Kaluril daily; in any event, no more than 20 mg daily should be administered.

Hepatic cirrhosis with ascites.

Treatment should be initiated with a small dose of Kaluril, i.e. 5 mg, plus low doses of any other saluretic diuretic agent that may be employed. If necessary, dosages of both drugs may be increased gradually until there is effective diuresis. The dosage of Kaluril should not exceed 20 mg daily. Maintenance doses may be lower than those required to initiate diuresis; therefore, reduction in the daily dose should be attempted when the patient's weight is stabilised. Gradual weight reduction in cirrhotic patients is especially desirable to reduce the likelihood of untoward reactions.

4.7 Effects on Ability to Drive and Use Machines

No specific studies have been conducted to assess the direct effect of Kaluril on the ability to drive and use machines. However, adverse effects of Kaluril include dizziness and mental confusion which could affect the ability to drive or use machines. See Section 4.8 Adverse Effects (Undesirable Effects).

4.9 Overdose

No data are available with regard to overdosage in humans. The oral LD50 of amiloride hydrochloride dihydrate (calculated as the base) is 56 mg/kg in mice and 36 to 85 mg/kg in rats, depending on the strain.

Symptoms.

The most likely signs and symptoms to be expected with overdosage are dehydration and electrolyte imbalance. These can be treated by established procedures.

Treatment.

Therapy with Kaluril should be discontinued and the patient observed closely. There is no specific antidote. Emesis should be induced or gastric lavage performed. Treatment is symptomatic and supportive. If hyperkalaemia occurs, active measures should be taken to reduce the serum potassium levels.
It is not known whether this drug is dialysable.
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

The tablets also contain lactose monohydrate, maize starch, microcrystalline cellulose, povidone and magnesium stearate.

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 25ºC.

6.5 Nature and Contents of Container

Packed in bottles (HDPE) of 50 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking it to your local pharmacy.

Summary Table of Changes