Consumer medicine information

HYGROTON [10901]

Chlortalidone

BRAND INFORMATION

Brand name

Hygroton 25 Tablets

Active ingredient

Chlortalidone

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using HYGROTON [10901].

What is in this leaflet

This leaflet answers some common questions about Hygroton 25 tablets. It does not contain all 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 Hygroton 25 against the benefits they expect it will have for you.

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

Keep this leaflet.

You may need to read it again.

What Hygroton 25 is used for

This medicine contains chlortalidone. It is used to treat high blood pressure (also called hypertension) and fluid build-up.

Everyone has blood pressure. This pressure helps to move your blood around your body. Your blood pressure may be different at various times of the day, and can be affected by how busy you are.

You have high blood pressure (hypertension) when your blood pressure stays higher than is needed even when you are calm and relaxed. There may be no symptoms of high blood pressure so you need to have it checked regularly. If high blood pressure is not treated, it can lead to serious health problems. Hygroton 25 helps to lower your blood pressure.

Hygroton 25 is also used to treat fluid build-up caused by heart or liver problems.

This medicine belongs to a group of medicines called diuretics (commonly called fluid or water tablets). These medicines help to reduce the amount of salt and water in the body by acting on the kidneys to increase the flow of urine.

Hygroton 25 can be used alone or in combination with other medicines to treat your condition.

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

Your doctor may have prescribed it for another reason.

This medicine is not addictive.

It is available only with a doctor's prescription.

Before you take Hygroton 25

When you must not take it

Do not take Hygroton 25 if you have an allergy to:

  • any medicine containing chlortalidone
  • any of the ingredients listed at the end of this leaflet
  • any other medicines with a similar structure (e.g. thiazide diuretics or sulfur drugs).

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

Do not take Hygroton 25 if you have any of the following health conditions:

  • severe kidney or liver failure
  • too little potassium or sodium in your blood
  • too much calcium in your blood
  • gout or if you have had gout in the past
  • high blood pressure during pregnancy
  • adrenal glands not working properly.

If you are not sure whether any of the above medical conditions apply to you, ask your doctor or pharmacist.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

If it has expired or is damaged, return it to your pharmacist for disposal.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

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

  • any form of kidney or liver trouble
  • a problem with your heart
  • unusual amount of salt in your body
  • diabetes
  • high cholesterol.

Your doctor may want to take special precautions if you have any of the above conditions.

Tell your doctor if you are pregnant or plan to become pregnant or are breastfeeding.

Hygroton 25 may affect your baby during pregnancy and at birth.

The active ingredient in Hygroton 25 passes into breast milk and there is a possibility that your baby could be affected.

Your doctor can discuss the risks and benefits involved.

Tell your doctor if you are lactose intolerant.

This medicine contains lactose.

If you have not told your doctor about any of the above, tell him/her before you start taking Hygroton 25.

Taking other medicines

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

Some medicines and Hygroton 25 may interfere with each other. These include:

  • some medicines used to treat high blood pressure or heart problems (e.g. ACE inhibitors, digitalis)
  • medicines used to relax muscles
  • insulin or other medicines for diabetes
  • medicines for arthritis, pain or inflammation, such as non- steroidal anti-inflammatory drugs (called NSAIDs)
  • asthma relievers
  • amphotericin B, a medicine used to treat fungal infections
  • carbenoxolone, a medicine for stomach ulcer
  • ACTH, a medicine for increasing steroid levels in the body
  • steroid medicines, such as cortisone or prednisone
  • lithium, a medicine used for mood swings and some types of depression
  • colestyramine, a medicine used to lower high cholesterol
  • allopurinol, a medicine for gout
  • vitamin D or calcium supplements
  • ciclosporin, a medicine used to prevent organ transplant rejection or to treat certain problems with the immune system
  • medicines for Parkinson's disease (e.g. amantadine, biperiden)
  • atropine, a medicine used in some eye drops or products to manage diarrhoea
  • some medicines used to treat cancer or to treat joint pain and swelling (e.g. cyclophosphamide monohydrate, methotrexate).

These medicines may be affected by Hygroton 25 or may affect how well it works. You may need different amounts of your medicines or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to take Hygroton 25

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 label, ask your doctor or pharmacist for help.

How much to take

You will usually be started on a low dose of Hygroton 25 and, if necessary, your doctor will increase the dose gradually.

For an adult, the usual dose ranges from 12.5 mg to 50 mg (half a tablet to two tablets), taken each day or sometimes every other day. For a child, the dose needed will depend on how much the child weighs.

How to take it

Take the tablets during a meal with a full glass of water.

If you take only one dose of Hygroton 25 each day, take it in the morning unless your doctor tells you otherwise.

If you take more than one dose each day, take the last dose no later than 6 pm if possible.

Diuretic medicines tend to increase the amount of urine you pass. It is best to take the last dose of medicine no later than 6 pm so that you will not have to get up during the night to urinate.

How long to take it

Continue taking your medicine for as long as your doctor tells you to.

This medicine helps to control your condition, but it does not cure it. It is important to keep taking your medicine even if you feel well. Your doctor will check your progress to make sure the medicine is working and will discuss with you how long your treatment should continue.

If you forget to take it

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 it as soon as you remember, and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose that 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.

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 the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at your nearest hospital, if you think that you or anyone else may have taken too much Hygroton 25. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

Some of the symptoms of an overdose may include nausea (feeling sick), dizziness, sleepiness, muscle spasms, low blood pressure and irregular heartbeat.

While you are taking Hygroton 25

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking Hygroton 25.

Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.

If you are going to have surgery, tell your surgeon or anaesthetist that you are taking Hygroton 25.

This will help to prevent unwanted side effects such as a sudden drop in blood pressure. Hygroton 25 may affect other medicines used during surgery.

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

If you are about to have any blood tests, tell your doctor that you are taking this medicine.

It may interfere with the results of some tests.

Keep all of your doctor's appointments so that your progress can be checked.

Your doctor will want to check your heart and blood pressure and do regular blood tests to make sure the treatment is working and to prevent unwanted side effects.

Follow any instructions that your doctor gives you to maintain the correct level of a salt (called potassium) in your blood.

Hygroton 25 may sometimes cause your body to lose too much potassium. To help prevent this from happening, your doctor may ask you to:

  • eat foods that have high potassium content (such as vegetables, fruit, fresh fruit juices, nuts, legumes and wholegrain cereals)
  • take a potassium supplement
  • take another medicine to help prevent the loss of potassium.

It is important not to add potassium to your diet without your doctor's advice. Extra potassium may not be needed and, in some cases, could be harmful.

If you are sick and have severe or continuing vomiting or diarrhoea, tell your doctor.

Vomiting and diarrhoea may cause your body to lose too much salt and water, causing unwanted side effects.

If you are being treated for diabetes, monitor your blood sugar carefully and report any problems to your doctor.

Hygroton 25 may increase your blood sugar levels and affect how well your diabetes is controlled. The dose of your medicines for diabetes may have to be changed.

Things you must not do

Do not take Hygroton 25 to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you or if their condition seems similar to yours.

Do not stop taking your medicine or lower the dosage without checking with your doctor.

If you stop taking it suddenly, your condition may worsen.

Things to be careful of

Be careful driving, operating machinery or doing jobs that require you to be alert until you know how Hygroton 25 affects you.

This medicine may cause dizziness, light-headedness or blurred vision in some people. If you have any of these symptoms, do not drive or do anything else that could be dangerous.

Be careful when drinking alcohol while you are taking this medicine.

If you drink alcohol, it can cause a sudden drop in your blood pressure and dizziness or light-headedness may be worse.

If you feel light-headed, dizzy or faint when getting up from a sitting or lying position, get up slowly.

These symptoms may be due to a sudden fall in your blood pressure. If this problem gets worse or doesn't go away, talk to your doctor.

To avoid symptoms of low blood pressure, here are some hints that may help:

  • stand up slowly to help your body get used to the change in position and blood pressure
  • if you feel dizzy, sit or lie down until you feel better
  • if you feel faint, breathe deeply, sit down, bend forward and put your head between your knees
  • avoid alcohol or medicines to help you sleep as they may make your blood pressure fall even more
  • take extra care when exercising, driving or standing for long periods, especially in hot weather. Drink plenty of fluids, especially if you sweat a lot.

Be careful to stay out of direct sunlight as much as possible until you find out if your skin is more sensitive to the sun than usual. Wear protective clothing and use a sunscreen. Do not use a sunlamp.

In rare cases, this medicine can make the skin more sensitive to sunlight than usual.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Hygroton 25.

This medicine helps most people with high blood pressure, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, but most of the time they are not. You may need medical attention if you get some of the side effects.

If you are over 65 years of age, you may have an increased chance of getting side effects.

Do not be alarmed by the following lists of 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 side effects and they worry you:

  • dizziness or light-headedness, especially on standing up
  • loss of appetite, stomach upset, nausea (feeling sick) or vomiting
  • diarrhoea or constipation
  • headache
  • skin rash
  • problems with sexual function.

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

  • unusual tiredness, lack of energy or weakness, sometimes with nausea and a feeling of disorientation
  • difficulty breathing
  • constant "flu-like" symptoms (chills, fever, sore throat, aching joints, swollen glands)
  • unusual bleeding or bruising, reddish or purplish blotches under the skin
  • pain in the abdomen with nausea, vomiting and fever
  • yellowing of the skin or eyes
  • irregular heart beat
  • burning, numbness or pain in arms and legs
  • symptoms of gout such as pain and swelling of the joints, often in the big toe
  • difficulty urinating, sometimes with pain or fever
  • blurred or changed vision
  • symptoms of sunburn (redness, itching, swelling, blistering) that happen much more quickly than normal.

The above list includes serious side effects that may require medical attention. Serious side effects are rare.

Tell your doctor immediately, or go to Accident and Emergency at your nearest hospital, if you notice:

  • serious allergic reaction (shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin).

This is a very serious side effect. You may need urgent medical attention or hospitalisation. This side effect is very rare.

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

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

Some of these side effects (e.g. raised cholesterol levels) can only be found when your doctor does tests from time to time to check your progress.

After taking Hygroton 25

Storage

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

Do not store Hygroton 25 or any other medicine in the bathroom, near a sink. Do not leave it on a window sill or in the car.

Heat and dampness can destroy some medicines.

Keep it 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 Hygroton 25 or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Hygroton 25 tablets are pale orange, speckled, round flat tablets with bevelled edges. One side bears the imprint "CW" with a score line and there is nothing on the other side. Each bottle contains 50 tablets.

Ingredients

Hygroton 25 contains 25 mg of chlortalidone as the active ingredient.

It also contains:

  • colloidal anhydrous silica
  • lactose monohydrate
  • magnesium stearate
  • maize starch
  • purified talc
  • iron oxide yellow
  • iron oxide red

This medicine does not contain sucrose, gluten, preservatives, tartrazine or any other azo dyes.

Sponsor

Distributed in Australia by:

Amdipharm Mercury (Australia) Pty Ltd
Level 9, 76 Berry Street
North Sydney NSW 2060

Date of preparation:
31 January 2017

Australian Registration Number:
AUST R 11035

Amdipharm Mercury (Australia) Pty Ltd is licensed to use the trademark Hygroton.

BRAND INFORMATION

Brand name

Hygroton 25 Tablets

Active ingredient

Chlortalidone

Schedule

S4

 

1 Name of Medicine

Chlortalidone.

6.7 Physicochemical Properties

Chemical formula: 2-chloro-5-(1-hydroxy-3-oxo-1,2- dihydroisoindol-1-yl)- benzenesulfonamide. Molecular formula: C14H11ClN2O4S. Molecular weight: 338.767.
Chlortalidone is a white or creamy-white odourless, or almost odourless, tasteless crystalline powder. Melting point is about 220°C with decomposition. Chlortalidone is practically insoluble in water; soluble 1 in 150 parts of alcohol, 1 in 650 parts of chloroform, and 1 in 25 parts of methyl alcohol; slightly soluble in ether; soluble in solutions of alkali hydroxides.

Chemical structure.


CAS number.

77-36-1.

2 Qualitative and Quantitative Composition

Each Hygroton tablet contains 25 mg of chlortalidone as the active ingredient.

Excipients with known effect.

Lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Hygroton tablets are pale orange, speckled, round flat tablets with bevelled edges. One side bears the imprint "CW" and a score line, nothing on the other side.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Chlortalidone, the active substance of Hygroton 25 is a sulfonamide-derived benzothiadiazine (thiazide)-related diuretic with a long duration of action.
Thiazide and thiazide-like diuretics act primarily on the distal renal tubule (early convoluted part), inhibiting NaCl reabsorption (by antagonising the Na+-Cl- cotransporter), and promoting Ca++ reabsorption (by an unknown mechanism). The enhanced delivery of Na+ and water to the cortical collecting tubule and/or the increased flow rate leads to increased secretion and excretion of K+ and H+.
In persons with normal renal function, diuresis is induced after the administration of as little as 12.5 mg Hygroton 25. The resulting increase in urinary excretion of sodium and chloride and the less prominent increase in urinary potassium are dose-dependent and occur both in normal and in oedematous patients. The diuretic effect sets in after 2 to 3 hours, reaches its maximum after 4 to 24 hours and may persist for 2 to 3 days.
Thiazide-induced diuresis initially leads to decreases in plasma volume, cardiac output and systemic blood pressure. The renin-angiotensin-aldosterone system may possibly become activated, blunting antihypertensive efficacy.
In hypertensive individuals, chlortalidone gently reduces blood pressure. On continued administration, the hypotensive effect is maintained, probably due to the fall in peripheral resistance; cardiac output returns to pretreatment values, plasma volume remains slightly below normal and plasma renin activity may be elevated.
On chronic administration, the antihypertensive effect of Hygroton 25 is dose-dependent between 12.5 and 50 mg/day. Raising the dose above 50 mg increases metabolic complications and is rarely of therapeutic benefit.
As with other diuretics, when Hygroton 25 is given as monotherapy, blood pressure control is achieved in about half of patients with mild to moderate hypertension. In general, elderly and black patients are found to respond especially well to diuretics as primary therapy.
Combined treatment with other antihypertensives potentiates the blood pressure lowering effects. In a large proportion of patients failing to respond adequately to monotherapy, a further decrease in blood pressure can thus be achieved.
Because thiazide diuretics including chlortalidone reduce Ca++ excretion, they have been used to prevent the formation of recurrent renal calcium oxalate stones.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

The bioavailability of an oral dose of 50 mg Hygroton 25 is approximately 64%, peak blood concentrations being attained after 8 to 12 hours. For doses of 25 and 50 mg, Cmax values average 1.5 microgram/mL (4.4 micromol/L) and 3.2 microgram/mL (9.4 micromol/L) respectively. For doses up to 100 mg there is a proportional increase in AUC. On repeated daily doses of 50 mg, steady-state blood concentrations, measured at the end of the 24-hour dosage interval, averaging 7.2 microgram/mL (21.2 micromol/L) are reached after 1 to 2 weeks.

Distribution.

In blood, only a small fraction of chlortalidone is free, due to extensive accumulation in erythrocytes and binding to plasma proteins. Owing to the large degree of high-affinity binding to the carbonic anhydrase of erythrocytes, only some 1.4% of the total amount of chlortalidone in whole blood was found in plasma at steady state during treatment with 50 mg doses. In vitro, plasma protein binding of chlortalidone is about 76%, and the major binding protein is albumin.
Chlortalidone crosses the placental barrier and passes into breast milk. In mothers treated with 50 mg chlortalidone daily before and after delivery, chlortalidone levels in foetal whole blood are about 15% of those found in maternal blood. Chlortalidone concentrations in amniotic fluid and in the maternal milk are approximately 4% of the corresponding maternal blood level.

Metabolism and excretion.

Chlortalidone is eliminated from whole blood and plasma with an elimination half-life averaging 50 hours. The elimination half-life is unaltered after chronic administration. The major part of an absorbed dose of chlortalidone is excreted by the kidneys, with a mean renal plasma clearance of 60 mL/min. Metabolism and hepatic excretion into bile constitute a minor pathway of elimination. Within 120 hours, about 70% of the dose is excreted in the urine and in the faeces, mainly in unchanged form.

Special patient groups.

Renal dysfunction does not seem to alter the pharmacokinetics of chlortalidone, the rate limiting factor in the elimination of the medicine from blood or plasma being most probably the affinity of the medicine to the carbonic anhydrase of erythrocytes.
In elderly patients, the elimination of chlortalidone is slower than in healthy young adults, although absorption is the same. Therefore, close medical observation is indicated when treating patients of advanced age with Hygroton 25.

5.3 Preclinical Safety Data

Genotoxicity.

Tests for induction of gene mutations in bacteria or cultured mammalian cells were negative. At high cytotoxic doses, chromosome aberrations were induced in Chinese hamster ovary (CHO) cells. However, a test for unscheduled DNA synthesis in rat hepatocytes showed no evidence for the ability to induce DNA damage, and in vivo tests for micronuclei in mouse bone marrow and rat liver revealed no evidence for the induction of chromosome damage. Thus, the results in the CHO cell assay are considered an artefact arising from cytotoxicity, rather than a reflection of genotoxicity. It is concluded that chlortalidone does not present a risk of mutagenicity to humans.

Carcinogenicity.

Long-term carcinogenicity studies have not been performed with chlortalidone.

4 Clinical Particulars

4.1 Therapeutic Indications

Essential arterial hypertension, as long as creatinine clearance is > 30 mL/min; as primary therapy or in combination with other antihypertensive agents.
Stable, chronic heart failure of mild to moderate degree (functional class II, III), as long as creatinine clearance is > 30 mL/min.
Ascites due to cirrhosis of the liver in stable patients under close control.

4.3 Contraindications

Anuria, severe renal failure (creatinine clearance lower than 30 mL/min) and hepatic failure.
Hypersensitivity to chlortalidone and other sulfonamide derivatives or to any of the excipients in Hygroton 25.
Refractory hypokalaemia, hyponatraemia and hypercalcaemia.
Symptomatic hyperuricaemia (history of gout or uric acid calculi).
Hypertension during pregnancy.
Conditions involving enhanced potassium loss, e.g. salt-losing nephropathies and prerenal (cardiogenic) impairment of kidney function.
Untreated Addison's disease.

4.4 Special Warnings and Precautions for Use

Renal and hepatic impairment.

Hygroton 25 should be used with caution in patients with renal disease or with impaired hepatic function (see Section 4.3 Contraindications).
Thiazides may precipitate azotaemia in patients with severe renal disease, and the effects of repeated administration may be cumulative.
Hygroton 25 and other thiazide diuretics lose their diuretic effect when the creatinine clearance is < 30 mL/min. In these cases loop diuretics are indicated.
In patients with impaired hepatic function or progressive liver disease, especially in patients with liver cirrhosis, minor changes in the fluid and electrolyte balance due to thiazide diuretics may precipitate hepatic coma.

Electrolytes.

Treatment with thiazide diuretics has been associated with electrolyte disturbance such as hypokalaemia, hypomagnesaemia, hypercalcaemia and hyponatraemia. Hypokalaemia can sensitise the heart or exaggerate its response to the toxic effects of digitalis.
As with all thiazide diuretics, kaluresis induced by Hygroton 25 is dose-dependent and varies in extent from one subject to another. With 25 mg/day, the decrease in serum potassium concentrations averages 0.7 mmol/L. For chronic treatment, serum potassium concentrations should be checked initially and then after 3 to 4 weeks. Thereafter, if the potassium balance is not disturbed by additional factors (e.g. vomiting, diarrhoea, change in renal function, etc.), checks should be carried out every 4 to 6 months.
Titrated co-administration of an oral potassium salt (e.g. KCl) may be considered in patients receiving digitalis; in patients exhibiting signs of coronary heart disease, unless they are also receiving an Angiotensin Converting Enzyme (ACE) inhibitor; in patients on high doses of a beta-adrenergic agonist; and in all cases where plasma potassium concentrations are < 3.0 mmol/L. If oral potassium preparations are not tolerated, Hygroton 25 may be combined with a potassium-sparing diuretic (e.g. triamterene).
In all cases of combined treatment, maintenance or normalisation of the potassium balance should be checked closely. If hypokalaemia is accompanied by clinical signs (e.g. muscular weakness, paresis and ECG alteration), Hygroton 25 should be discontinued.
Combined treatment consisting of Hygroton 25 and a potassium salt or a potassium-sparing diuretic must be avoided in patients also receiving ACE inhibitors or angiotensin II inhibitors (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Hyponatraemia, accompanied by neurological symptoms (nausea, debility, progressive disorientation, apathy), has been observed in isolated cases.
Monitoring of serum electrolytes is particularly indicated in the elderly, in patients with ascites due to liver cirrhosis, and in patients with oedema due to nephrotic syndrome. For the latter condition, Hygroton 25 should be used only under close control in normokalaemic patients with no signs of volume depletion or severe hypoalbuminaemia.

Metabolic effects.

Chlortalidone may raise the serum uric acid level, but attacks of gout are rarely observed during chronic treatment.
Although glucose tolerance may be adversely affected, diabetes mellitus very seldom occurs under treatment.
Small and partly reversible increases in plasma concentrations of total cholesterol, triglycerides, or low-density lipoprotein cholesterol were reported in patients during long-term treatments with thiazides and thiazide-like diuretics. The clinical relevance of these findings is not clear.
Hygroton 25 should not be used as a first-line medicine for long-term treatment in patients with overt diabetes mellitus or in subjects receiving therapy for hypercholesterolaemia (diet or combined).

Combination with an ACE inhibitor or angiotensin II inhibitor.

The antihypertensive effect of ACE inhibitors or angiotensin II inhibitors is potentiated by agents that increase plasma renin activity (diuretics). A cautious dosage schedule should therefore be adopted when an ACE inhibitor or angiotensin II inhibitor is added to a diuretic agent. It is recommended that the diuretic be reduced in dosage or withdrawn for 2-3 days and that a low initial dose of the ACE inhibitor or angiotensin II inhibitor be used.

Use in the elderly.

Elimination is slower in elderly patients than in young, healthy adults, although absorption is the same. Consequently, close medical observation including monitoring of serum electrolytes is essential when treating elderly patients with Hygroton 25 (see Section 5.2 Pharmacokinetic Properties; Section 4.4 Special Warnings and Precautions for Use, Electrolytes).

Paediatric use.

No data available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Lithium.

Since diuretics raise blood lithium levels, the latter must be monitored in patients under lithium therapy who are taking Hygroton 25 at the same time. Where lithium has induced polyuria, diuretics may exert a paradoxical antidiuretic effect.

Non-depolarising relaxants, curare derivatives and antihypertensive medicines.

Diuretics potentiate the action of non-depolarising relaxants, curare derivatives and antihypertensive medicines (e.g. guanethidine, methyldopa sesquihydrate, beta-blockers, vasodilators, calcium antagonists, ACE inhibitors or angiotensin II inhibitors).

Corticosteroids, ACTH, beta-2 agonists, amphotericin B (amphotericin), and carbenoxolone.

The hypokalaemic effect of diuretics, with risk of heart and/or muscle disorders may be increased by corticosteroids, ACTH, beta-2 agonists, amphotericin B (amphotericin), and carbenoxolone.

Insulin and oral antidiabetic agents.

It may prove necessary to adjust the dosage of insulin and of oral antidiabetic agents (see Section 4.4 Special Warnings and Precautions for Use, Metabolic effects).

Digitalis.

Thiazide induced hypokalaemia or hypomagnesaemia may favour the occurrence of digitalis-induced cardiac arrhythmias (see Section 4.4 Special Warnings and Precautions for Use).

Non-steroidal anti-inflammatory drugs.

Concomitant administration of certain non-steroidal anti-inflammatory drugs (e.g. indometacin) may weaken the diuretic and antihypertensive activity of diuretics, and there have been isolated reports of a deterioration in renal function in predisposed patients.

Allopurinol.

Co-administration of thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol.

Amantadine.

Co-administration of thiazide diuretics may increase the risk of adverse effects from amantadine.

Antineoplastic agents (e.g. cyclophosphamide monohydrate, methotrexate).

Concomitant use of thiazide diuretics may reduce renal excretion of cytotoxic agents and enhance the myelosuppressive effects.

Anticholinergics (e.g. atropine, biperiden).

The bioavailability of thiazide-type diuretics may be increased by anticholinergic agents, apparently due to a decrease in gastrointestinal motility and stomach emptying rate.

Anion exchange resins (e.g. colestyramine).

Absorption of thiazide diuretics is decreased by anion exchange resins e.g. colestyramine. A decrease of the pharmacological effect may be expected.

Vitamin D.

Use of thiazide diuretics may decrease urinary excretion of calcium, and co-administration of vitamin D may potentiate the increase in serum calcium.

Ciclosporin.

Concomitant treatment with diuretics may increase the risk of hyperuricaemia and gout-type complications.

Calcium salts.

Concomitant use of thiazide-type diuretics may cause hypercalcaemia by increasing tubular calcium reabsorption. The resulting hypercalcaemia may persist and be symptomatic in patients with hyperparathyroidism (weakness, fatigue, anorexia).

Diazoxide.

Thiazide diuretics may enhance the hyperglycaemic effect of diazoxide.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Category C: "Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible."
Hygroton 25, like other diuretics, can cause placental hypoperfusion. Since they do not prevent or alter the course of EPH (edema, proteinuria, hypertension) gestosis (pre-eclampsia), these medicines must not be used to treat hypertension in pregnant women. The use of Hygroton 25 for other indications (e.g. heart disease) in pregnancy should be avoided unless there are no safer alternatives.
Thiazides, related diuretics and loop diuretics enter the foetal circulation and may cause electrolyte disturbances. Neonatal thrombocytopenia, foetal bone marrow depression and foetal and neonatal jaundice have been reported with thiazides and related diuretics. During the latter part of pregnancy, products of this type should therefore only be given on sound indications, and then in the lowest effective dose.
Teratogenicity studies in rats and rabbits revealed no teratogenic potential at oral doses up to 1000 and 300 mg/kg/day, respectively.
Chlortalidone passes into breast milk. For safety reasons, avoid use in nursing mothers.

4.8 Adverse Effects (Undesirable Effects)

The following adverse drug reactions which have been derived from multiple sources, including post-marketing experience with Hygroton 25 are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first.
Frequency estimate: very rare < 1/10,000; rare ≥ 1/10,000 to < 1/1000; uncommon ≥ 1/1000 to < 1/100; common ≥ 1/100 to < 1/10; very common ≥ 1/10.

Blood, and lymphatic system disorders.

Rare: thrombocytopaenia, leucopaenia, agranulocytosis, eosinophilia.

Immune system disorders.

Hypersensitivity.

Metabolism and nutritional disorders.

Very common: (mainly at higher doses) hypokalaemia, hyperuricaemia, hyperlipidemia. Common: hyponatraemia, hypomagnesaemia, hyperglycaemia, decreased appetite. Rare: hypercalcaemia, diabetes mellitus inadequate control, gout. Very rare: hypochloraemic alkalosis.

Nervous system disorders.

Common: dizziness. Rare: paraesthesia, headache.

Ear and labyrinth disorders.

Vertigo.

Eye disorders.

Rare: visual impairment.

Respiratory, thoracic and mediastinal disorders.

Very rare: noncardiogenic pulmonary oedema.

Gastrointestinal disorders.

Common: abdominal discomfort. Rare: mild nausea and vomiting, abdominal pain upper, constipation, diarrhoea. Very rare: pancreatitis.

Hepatobiliary disorders.

Rare: intrahepatic cholestasis, jaundice.

Skin and subcutaneous disorders.

Common: urticarial, other forms of skin rash. Rare: photosensitivity reaction.

Musculoskeletal and connective tissue disorders.

Common: muscular weakness.

Renal and urinary disorders.

Rare: glycosuria. Very rare: tubulointerstitial nephritis.

Cardiac disorders.

Rare: arrhythmia.

Vascular disorders.

Common: orthostatic hypotension which may be aggravated by alcohol, anaesthetics or sedatives. Very rare: vasculitis.

Reproductive system and breast disorders.

Common: erectile dysfunction.

Investigations.

Very rare: blood cholesterol increased.

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

As with all diuretics, therapy should be initiated with the lowest possible dose. This dose should be titrated according to the individual patient's response to gain maximum therapeutic benefit while keeping side effects to a minimum.
A single dose daily or every other day given in the morning with food is recommended.

Hypertension.

Adults.

The range of clinically useful doses is 12.5 to 50 mg/day. Recommended starting doses are either 12.5 or 25 mg/day, the latter being sufficient to produce the maximum hypotensive effect in most patients. For a given dose, the full effect is reached after 3 to 4 weeks. If the decrease in blood pressure proves inadequate with 25 or 50 mg/day, combined treatment with other antihypertensive medicines (such as beta-blockers, ACE inhibitors or angiotensin II inhibitors) is recommended. When adding an ACE inhibitor or angiotensin II inhibitors, Hygroton 25 should be reduced or discontinued (see Section 4.4 Special Warnings and Precautions for Use).

Stable, chronic heart failure (functional class II/III).

Adults.

The recommended starting doses are 25 to 50 mg/day. In patients with severe chronic heart failure (grade IV) not tolerating loop diuretics, initial doses of two 50 mg tablets of Hygroton 25 may be given every other day. For maintenance, use the lowest effective dose: 12.5 to 50 mg/day or 25 to 50 mg every other day. If the response proves inadequate, a positive inotropic medicine (e.g. digitalis), possibly combined with an ACE inhibitor, may be added. In the latter case, Hygroton 25 is to be reduced or discontinued (see Section 4.4 Special Warnings and Precautions for Use).

Oedema of specific origin (see Section 4.1 Therapeutic Indications).

Adults.

The lowest effective dose is to be identified by titration and administered over limited periods only. Doses should not exceed 50 mg/day.

Children.

The lowest effective dose should also be used in children. For example, an initial dose of 0.5 to 1 mg/kg/48 hours and a maximum dose of 1.7 mg/kg/48 hours have been used.

4.7 Effects on Ability to Drive and Use Machines

Hygroton 25, especially at the start of treatment, may impair the patient's reactions, e.g. when driving or operating machines.

4.9 Overdose

Signs and symptoms.

In poisoning due to an overdosage the following signs and symptoms may occur: dizziness, nausea, somnolence, hypovolaemia, hypotension, and electrolyte disturbances associated with cardiac arrhythmias and muscle spasms.

Management.

Induction of vomiting or gastric lavage and administration of activated charcoal. Activated charcoal may reduce absorption of the medicine if given within one or two hours after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected. Intravenous fluid and electrolyte replacement may be indicated.
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

Hygroton contains colloidal anhydrous silica, lactose monohydrate, magnesium stearate, maize starch, purified talc, iron oxide yellow and iron oxide red.

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

Hygroton is supplied in glass bottles of 50 tablets.

6.6 Special Precautions for Disposal

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

Summary Table of Changes