Consumer medicine information

Tenaxil SR

Indapamide hemihydrate

BRAND INFORMATION

Brand name

Tenaxil SR

Active ingredient

Indapamide hemihydrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Tenaxil SR.

What is in this leaflet

This leaflet answers some common questions about TENAXIL SR. It does not contain all the available information about this medicine. Reading this leaflet 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 TENAXIL SR against the expected benefits 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 TENAXIL SR is

The name of your medicine is TENAXIL SR. The medicine releases the active ingredient indapamide progressively over 24 hours. Indapamide belongs to a group of medicines called chlorosulfamoyl diuretics (a type of "fluid" or "water" tablet).

What TENAXIL SR is used for

You have been prescribed TENAXIL SR for high blood pressure.

TENAXIL SR is available only with a doctor's prescription.

There is no evidence that TENAXIL SR is addictive.

Why TENAXIL SR is used for high blood pressure

Everyone has blood pressure. This pressure helps to circulate blood all around the body. Your blood pressure may be different at different times of the day, depending on how busy or stressed you are.

You have high blood pressure (also known as hypertension) which is when your blood pressure stays higher than is needed, even when you are calm and relaxed.

If high blood pressure is not treated it can lead to serious health problems. You may feel fine and have no symptoms, but eventually it can cause stroke, heart disease and kidney failure.

TENAXIL SR helps to lower your blood pressure.

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

Before you take TENAXIL SR

There are some people who should not take TENAXIL SR. Please read the lists below. If you think any of these situations apply to you, or you have any questions, please consult your doctor or pharmacist.

When you must not take TENAXIL SR

Do not take TENAXIL SR if:

  • You are allergic to indapamide, or any of the other ingredients of TENAXIL SR listed at the end of this leaflet.
  • You are allergic to sulfonamide (sulfa) antibiotics, or to thiazide diuretics (a type of "fluid" or "water" tablet).
  • You are pregnant or trying to become pregnant.
  • You are breastfeeding or plan to breast-feed.
  • You have severe kidney disease.
  • You have severe liver disease or suffer from a condition called hepatic encephalopathy (liver problems which affect the brain and central nervous system).
  • You have low potassium levels in your blood.
  • The packaging is torn or shows signs of tampering, or the tablets do not look quite right.
  • The expiry date (EXP) on the pack has passed.

Before you start to take it

Tell your doctor straight away if:

  • You have an intolerance to lactose.
  • You have or have had any other health problems, including:
    - High or low levels of potassium, sodium, or other problems with salt balance.
    - Gout.
    - Diabetes
    - Increased sensitivity to sunlight (photosensitivity reactions).
    - Systemic lupus erythematosus (a disease affecting the skin, joints and kidneys).
    - Heart rhythm problems.
    - Problems with your kidneys.
    - If you experience a decrease in vision or eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye or an increase of pressure in your eye and can happen within hours to a week of taking TENAXIL SR. This can lead to permanent vision loss, if not treated. If you earlier have had a penicillin or sulfonamide allergy, you can be at higher risk of developing this.
    - You have muscle disorders including muscle pain, tenderness, weakness or cramps.
    - A test to check how well your parathyroid gland is working.
  • Athletes should be aware that this medicine contains an active ingredient, which may give a positive reaction in doping tests.

Taking other medicines

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

Taking TENAXIL SR may change the effect of some medicines, and some medicines may affect how well TENAXIL SR works. You may need different amounts of your medication or to take different medicines.

You should not take TENAXIL SR with lithium medications (used to treat mood swings and some types of depression) due to the risk of increased levels of lithium in the blood.

The medicines that may interact with TENAXIL SR include the following:

  • Some steroid medicines.
  • Diuretics (sometimes called "fluid" or "water" tablets, e.g. amiloride, spironolactone, triamterene).
  • Medicines used for heart rhythm problems (e.g. disopyramide, amiodarone, sotalol, flecainide).
  • Some medications used to treat high blood pressure (e.g. angiotensin converting enzyme (ACE) inhibitors), a fast or irregular heartbeat and other heart conditions.
  • Medicines to treat mental illnesses such as some medicines for epilepsy, anxiety, schizophrenia and some other antidepressants (e.g. tricyclic antidepressants, antipsychotic drugs, neuroleptics such as: droperidol, haloperidol, chlorpromazine, trifluoperazine, amisulpride, sulpiride, psychoanaleptics).
  • Antiparasitic medicines used to treat certain types of malaria (e.g. chloroquine).
  • Pentamidine (a medicine used to treat certain types of pneumonia).
  • Antihistamines used to treat allergic reactions, such as hay fever.
  • Medicines used to treat nausea and vomiting (e.g ondansetron, domperidone)
  • Medicines used to treat cancer (e.g vandetanib, oxaliplatin).
  • Anagrelide (used to reduce elevated blood platelet counts).
  • Non-steroidal anti-inflammatory drugs for pain relief (e.g. ibuprofen) or high doses of aspirin.
  • Calcium supplements.
  • Stimulant laxatives.
  • Baclofen (a medicine used to treat muscle stiffness occurring in diseases such as multiple sclerosis).
  • Metformin (a medicine used to treat diabetes).
  • Cyclosporin, tacrolimus (medicines used to treat certain problems with the immune system).
  • Medicines used to treat fungal infections (e.g. Amphotericin B (amphotericin) by IV, fluconazole).
  • Medicines used during scans to see the images of your body.
  • Medicines used to treat gastro-intestinal problems (e.g. cisapride, papaverine).
  • Medicines used to treat bacterial infections (e.g. Moxifloxacin, ciprofloxacin, clarithromycin, erythromycin by IV ).
  • Allopurinol (a medicine used to treat gout).
  • Tetracosactide (tetracosactrin) (to treat Crohn’s disease).
  • Methadone (used to treat addiction).
  • Cilostazol (used to treat cramp-like pain in the legs when you walk).

Your doctor or pharmacist has more information on medicines to be careful with or avoid while taking TENAXIL SR.

For older people or children

  • Elderly people can generally use TENAXIL SR safely. However, some older people have reduced kidney function - in which case additional care may be required.
  • TENAXIL SR is not recommended for use in children.

How to take TENAXIL SR

Follow all directions given to you by your doctor and pharmacist carefully. If you do not understand the instructions on the label, ask your doctor or pharmacist for help.

Your doctor will select a dose when they prescribe TENAXIL SR for you. The usual dose is one tablet once daily.

Swallow your tablet with water, preferably in the morning. Do not crush or break them.

How long to take TENAXIL SR for

TENAXIL SR can help to control your blood pressure, but cannot cure it. TENAXIL SR treatment is usually for life - so you should keep taking the tablets regularly unless advised otherwise by your doctor.

If you forget to take TENAXIL SR

If your next usual dose is less than 6 hours away, just leave out the dose that you missed. Take the next dose at the usual time and continue as normal.

If your next dose is more than 6 hours away, take the dose you have missed as soon as you realise. Then take the next dose at the usual time and continue as normal.

Do not try to make up for missed doses by taking more than one dose at a time.

If you take too much TENAXIL SR

Taking too much TENAXIL SR (an overdose) may cause low blood pressure (also known as hypotension). Other effects like sickness, cramps, sleepiness, confusion, kidney problems, salt and water disturbances are possible. You may require urgent medical attention.

If you think that you or anyone else may have taken too much TENAXIL SR then act immediately

  • Telephone your doctor or the Poisons Information Centre (13 11 26 in Australia), or go to the Accident and Emergency department at your nearest hospital. Do this even if there are no signs of discomfort or poisoning.

While you are taking TENAXIL SR

Things you must do

Take TENAXIL SR exactly as your doctor has prescribed. Otherwise you may not get the benefits from treatment.

Tell all doctors, dentists and pharmacists who are involved with your treatment that you are taking TENAXIL SR.

Make sure you drink enough water during exercise and hot weather especially if you sweat a lot. This will help you avoid any dizziness or light-headedness caused by a sudden drop in blood pressure.

Tell your doctor straight away if you have excessive vomiting or diarrhoea while taking TENAXIL SR as these may affect how TENAXIL SR is processed by your body. If you experience any of the following symptoms, you may be dehydrated because you are losing too much water:

  • Dry mouth or thirst
  • Fainting
  • Weakness,
  • Tiredness or drowsiness
  • Muscle pain or cramps
  • Fast heartbeat
  • Passing less urine than normal.

Things you must not do

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

Do not use TENAXIL SR to treat any other complaints unless your doctor tells you to.

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

Things to be careful of

Be careful when driving or operating machinery until you know how TENAXIL SR affects you.

You may feel light-headed or dizzy when you begin to take TENAXIL SR. This is because your blood pressure is falling. Symptoms are likely to be made worse if you drink alcohol or take strong pain killers.

If you have these symptoms when standing up or getting out of bed then getting up more slowly can help. This allows your body to get used to the change in position and blood pressure.

TENAXIL SR may cause your skin to become more sensitive to the sun. If this happens you should stop taking TENAXIL SR and contact your doctor.

If you have these symptoms and they don't get better in a short time then talk to your doctor.

Unwanted effects potentially due to treatment

If you do not feel well while you are taking TENAXIL SR then tell your doctor or pharmacist as soon as possible.

All medicines can have side effects. Most of the time they are not serious but sometimes they can be.

TENAXIL SR helps most people with high blood pressure, but it may sometimes have unwanted side effects. These can include:

  • Headache.
  • Feeling tired or as if you have less energy, difficulty sleeping.
  • Feeling faint, light-headed, or dizzy.
  • Feeling nervous or anxious.
  • Feeling sick or having an upset stomach, having an uncomfortable feeling after eating, vomiting or constipation.
  • Muscle weakness, pain, tenderness, cramp, tingling or numbness of the hands or feet (and particularly if at the same time you feel unwell or have a high temperature it may be caused by an abnormal muscle breakdown (not known)).
  • Skin rashes or other allergic reactions.
  • Gout.
  • Increased sensitivity to sunlight.
  • An increased risk of becoming dehydrated (in elderly patients and in patients with heart failure).
  • Kidney disease.
  • Inflammation of the pancreas.
  • Hepatic encephalopathy (liver problems which affect the brain and central nervous system).
  • Abnormal liver function.
  • If you suffer from systemic lupus erythematosus (a type of collagen disease), this might get worse.
  • Changes in blood cells, such as thrombocytopenia (a decrease in the number of platelets which causes easy bruising and nasal bleeding), leucopoenia (a decrease of white blood cells which may cause unexplained fever, soreness of the throat or other flu-like symptoms) and anaemia (a decrease in red blood cells).
  • Low blood pressure, unusual heartbeat.
  • High level of calcium in blood
  • Blurred or changed vision, short sightedness (myopia).
  • Decrease in vision or pain in your eyes due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye or acute angle-closure glaucoma).
  • Dry mouth.
  • Cystitis.
  • Erectile dysfunction.

Most of these side effects are mild when they occur. Do not be alarmed by this list of possible side effects. You may not experience any of them. However, if you do - or if you notice anything else that is making you feel unwell - you should consult your doctor or pharmacist.

Changes may occur in your laboratory parameters (blood tests) and your doctor may need to give you blood tests to check your condition. The following changes in laboratory tests may occur: low potassium, magnesium, chloride or sodium in the blood. Low sodium may lead to dehydration and low blood pressure. Increase in uric acid (a substance which may cause or worsen gout), increase in blood glucose levels in diabetic patients, increased levels of liver enzymes.

If any of the signs below occur then tell your doctor immediately or go to the Accident and Emergency department at your nearest hospital:

  • Swelling of your lips, face, mouth, tongue or throat.
  • Purple spots with occasional blisters on the front of your arms and legs and/or around your neck and ears (a rare condition known as Stevens-Johnson Syndrome).
  • Toxic epidermal necrolysis.
  • A fast and irregular heartbeat.
  • Severe blisters, skin rash, itching or other allergic reactions.

These side effects are extremely rare but can become serious.

After taking TENAXIL SR

Storage

Keep your tablets in the pack until it is time to take them. Keep them in a cool, dry place where it stays below 25°C. Keep them where children cannot reach them.

Disposal

If your doctor tells you to stop taking TENAXIL SR, or the tablets have passed their expiry date, return any leftover tablets to your pharmacist for disposal.

What TENAXIL SR looks like

TENAXIL SR tablets are white and round.

TENAXIL SR tablets come in a blister strip. Each box contains 90 tablets.

Ingredients

Each tablet of TENAXIL SR contains 1.5 mg of indapamide hemihydrate as the active ingredient and a number of inactive ingredients.

The inactive ingredients in TENAXIL SR tablets include colloidal anhydrous silica, glycerol, hypromellose, lactose monohydrate, macrogol 6000, magnesium stearate, povidone, and titanium dioxide.

The tablets are gluten free.

Distributor

Arrotex Pharmaceuticals Pty Ltd
15-17 Chapel Street
Cremorne, 3121, Victoria

TENAXIL SR is registered on the Australian Register of Therapeutic Goods and has the Australian Register Number: AUST R 139607

This leaflet was last revised in July 2022

Published by MIMS September 2022

BRAND INFORMATION

Brand name

Tenaxil SR

Active ingredient

Indapamide hemihydrate

Schedule

S4

 

Notes

Distributed by Arrotex Pharmaceuticals Pty Ltd

1 Name of Medicine

Indapamide hemihydrate.

2 Qualitative and Quantitative Composition

Each Tenaxil SR tablet contains 1.5 mg of sustained release indapamide hemihydrate.

Excipient with known effect.

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

3 Pharmaceutical Form

Each Tenaxil SR tablet is a white, film coated biconvex tablet containing sustained release indapamide hemihydrate 1.5 mg.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of hypertension. It may be tried as a sole therapeutic agent in the treatment of hypertension. Normally, Tenaxil SR is used as the initial agent in multiple drug regimes.

4.2 Dose and Method of Administration

Adults.

One Tenaxil SR tablet daily to be taken, by oral route, in the morning. The tablet should be swallowed whole and must not be chewed or crushed. The action of Tenaxil SR is progressive and whilst the optimum reduction in blood pressure is usually seen after four weeks, a further small but useful reduction in blood pressure may be observed over the following four to six weeks. A larger dose than one tablet of Tenaxil SR daily is not recommended as there is little additional antihypertensive effect, whilst the diuretic effect becomes more pronounced.
A single daily tablet of Tenaxil SR may effectively be combined with the following antihypertensive medicines: beta-blockers, methyldopa sesquihydrate, clonidine, prazosin and ACE inhibitors.
Combination with a diuretic is not recommended as significant electrolyte disturbances may occur. Indapamide has a slight but significant carry-over hypotensive effect lasting up to one or two weeks after treatment is stopped.

4.3 Contraindications

Tenaxil SR is contraindicated in:
Severe renal failure, anuria, progressive and severe oliguria.
Hepatic coma, hepatic encephalopathy or severe impairment of liver function.
Known hypersensitivity to indapamide, other sulphonamide derivatives, or any of the excipients (see Section 6.1 List of Excipients).
Hypokalaemia.

4.4 Special Warnings and Precautions for Use

Electrolyte changes observed with indapamide hemihydrate become more pronounced at doses above 1.5 mg sustained release tablet/day. The daily maximum recommended dose of Tenaxil SR is one tablet/day, since doses above this increase the diuretic effect and electrolyte disturbances, without any further appreciable antihypertensive effect.
Hypokalaemia may occur at all doses. Symptoms of hypokalaemia include weakness, cramps, and cardiac dysrhythmias. Hypokalaemia is a particular hazard in patients treated with digoxin as dangerous or fatal arrhythmias may be precipitated. Although Tenaxil SR can be safely administered to hypertensive patients with renal impairment, caution should be observed when it is administered to patients with severe renal impairment. In this case the unchanged drug is excreted primarily by the renal route, and plasma concentrations are elevated (see Section 5.2 Pharmacokinetic Properties).

Precautions.

Hepatic encephalopathy.

When liver function is impaired, thiazide-related diuretics may cause, particularly in case of electrolyte imbalance, hepatic encephalopathy which can progress to hepatic coma. Administration of the diuretic must be stopped immediately if this occurs.

Uric acid.

Hyperuricaemia may occur during treatment with indapamide, and gout has been reported rarely. Tendency to gout attacks may be increased in patients with hyperuricaemia.

Lithium.

Diuretics should not be given with lithium because they reduce its renal clearance and add a high risk of lithium toxicity (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Photosensitivity.

Cases of photosensitivity reactions have been reported with thiazides and thiazide-related diuretics. It is recommended to stop treatment if a photosensitivity reaction occurs during treatment. If re-administration of the diuretic is deemed necessary, it is recommended that areas exposed to the sun or to artificial UVA are protected.

Lactose intolerance.

Tenaxil SR tablets contain lactose monohydrate.
Patients with an intolerance to lactose, rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Water and electrolyte balance.

Patients receiving indapamide should be monitored for signs and symptoms of fluid or electrolyte imbalance; namely hyponatraemia, hypochloraemia and hypokalaemia. Blood urea, nitrogen and uric acid should also be assessed during treatment. The signs of electrolyte imbalance are dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscle fatigue, hypotension, oliguria, gastrointestinal disturbances such as nausea and vomiting, tachycardia and ECG changes.

Plasma sodium.

This must be measured before starting treatment, then subsequently at regular intervals. The decrease in plasma sodium may initially be asymptomatic. Regular monitoring is therefore essential and should be more frequent in the elderly and in patients with cirrhosis (see Section 4.8 Adverse Effects (Undesirable Effects)). Treatment with any diuretic may cause hyponatraemia, sometimes with very serious consequences. Hyponatraemia with hypovolaemia may be responsible for dehydration and orthostatic hypotension. Concomitant loss of chloride ions may lead to secondary compensatory metabolic alkalosis.

Plasma potassium.

Potassium depletion with hypokalaemia is the major risk of thiazide and related diuretics. Hypokalaemia may cause muscle disorders. Cases of rhabdomyolysis have been reported, mainly in the context of severe hypokalaemia. The risk of onset of hypokalaemia (< 3.4 mmol/L) must be prevented in certain high risk populations, i.e. the elderly, malnourished and/or polymedicated, cirrhotic patients with oedema and ascites, and patients with coronary artery disease and/or heart failure. In these patients, hypokalaemia increases the cardiac toxicity of digitalis preparations and increases the risk of arrhythmias.
Hypokalaemia will be more common when combined with a steroid or adrenocorticotropic (ACTH) treatment and when electrolyte intake is inadequate.
Individuals with a long QT interval, whether the origin is congenital or iatrogenic, are also at increased risk as hypokalaemia and bradycardia are predisposing factors to the onset of severe arrhythmias, in particular potentially fatal torsades de pointes.
Plasma potassium should be measured in the first week of treatment. More frequent monitoring of plasma potassium is required in all the situations indicated above.
Hypokalaemia, if detected, should be corrected. Hypokalaemia found in association with low serum magnesium concentration can be refractory to treatment unless serum magnesium is corrected.

Plasma magnesium.

Thiazides and related diuretics have been shown to increase the urinary excretion of magnesium, which may result in hypomagnesaemia (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.8 Adverse Effects (Undesirable Effects)).

Plasma calcium.

Diuretic treatment should be withdrawn before the investigation of parathyroid function. Thiazide and related diuretics may decrease urinary calcium excretion and cause a slight and transitory rise in calcium. Frank hypercalcaemia may be due to previously unrecognised hyperparathyroidism.
Orthostatic hypotension may occur and may be potentiated by alcohol, barbiturates, narcotics or concurrent therapy with other antihypertensives.
When Tenaxil SR is combined with other non-diuretic antihypertensive medicines, the effects on blood pressure are additive.
Sulfonamide derivatives have been reported to exacerbate or activate systemic lupus erythematosus. Serious allergic skin reactions (such as Stevens-Johnson syndrome) have also occasionally been reported with sulfonamides. This should be considered when using indapamide.
Although a Tenaxil SR dose of one tablet/day can be used safely in patients with hypertension and renal impairment, treatment should be discontinued if there is an increase in azotaemia and oliguria.
A study in patients with impaired renal function demonstrated that patients with severe renal impairment (creatinine clearance 11-35 mL/min) had impaired clearance of indapamide and elevated plasma levels of the drug.

Blood glucose.

Monitoring of blood glucose is important in patients with diabetes, in particular in the presence of hypokalaemia.

Athletes.

Tenaxil SR contains indapamide which may give a positive reaction in doping tests.

Choroidal effusion, acute myopia and secondary angle-closure glaucoma.

Sulfonamide, or sulfonamide derivative drugs can cause an idiosyncratic reaction resulting in choroidal effusion with visual field defect, transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue drug intake as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

Use in the elderly.

In the elderly, the plasma creatinine must be adjusted in relation to age, weight and gender. Elderly patients can be treated with Tenaxil SR when renal function is normal or only minimally impaired.

Paediatric use.

Safety and effectiveness have not been established.

Effects on laboratory tests.

Hyperuricaemia (0.4%). Hyperglycaemia (0.4%) (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interactions have been reported between indapamide and anticoagulants, or between indapamide and uricosuric medicines. It is recommended that Tenaxil SR not be used in combination with a diuretic since the combination may cause hypokalaemia and hyperuricaemia.

Combined use which is not recommended.

Lithium.

The combined use of Tenaxil SR and lithium may result in increased plasma lithium levels and symptoms of overdose (due to decreased urinary lithium excretion). If diuretics are necessary, careful monitoring of plasma lithium and dose adjustment are required.

Combined use which require special care.

Torsades de pointes-inducing drugs.

The combined use of Tenaxil SR and torsades de pointes-inducing drugs, including the following, is not recommended due to the increased risk of ventricular arrhythmias, particularly torsades de pointes (hypokalaemia is a risk factor). Medicines which induce torsades de pointes include (but are not limited to):
class Ia antiarrhythmic agents (e.g. disopyramide) and class Ic antiarrhythmic agents (e.g. flecainide);
class III antiarrhythmic agents (e.g. amiodarone, sotalol);
some antipsychotics: phenothiazines (e.g. chlorpromazine, trifluoperazine), benzamides (e.g. amisulpride, sulpiride), butyrophenones (e.g. droperidol, haloperidol) and other antipsychotics;
psychoanaleptic (e.g. donepezil);
some antidepressants (e.g. citalopram, escitalopram);
antimicrobial agents: fluoroquinolones (e.g. moxifloxacin, ciprofloxacin), macrolides (e.g. erythromycin IV, clarithromycin), azole antifungals (e.g. fluconazole);
antiparasitics (e.g. chloroquine, pentamidine);
antihistamines;
antiemetics (e.g. ondansetron, domperidone);
antineoplastic and immunomodulating agents (e.g. vandetanib, oxaliplatin, anagrelide);
anaesthetics (e.g. propofol, sevoflurane);
others: diphemanil, methadone, papaverine, cilostazol.
This list is indicative and not exhaustive.
Monitor (using plasma electrolytes and ECG) for hypokalaemia and correct, if required, before using Tenaxil SR and a torsades de pointes-inducing drug in combination.

NSAIDs (systemic route) including COX-2 selective inhibitors, high dose acetylsalicylic acid (≥ 3 g/day).

Due to the risk of acute renal failure in patients with dehydration as a result of decreased glomerular filtration, it is recommended that hydration and renal function be monitored at the start of treatment. Combined use with NSAIDs may also result in a reduction in the antihypertensive effect of Tenaxil SR.

Angiotensin converting enzyme (ACE) inhibitors.

Combined use with ACE inhibitors in the presence of pre-existing sodium depletion (particularly in patients with renal artery stenosis) may increase the risk of sudden hypotension and/or acute renal failure.
In patients with hypertension when prior diuretic treatment may have caused sodium depletion, it is necessary to either:
stop the diuretic three days before starting treatment with the ACE inhibitor, and restart a hypokalaemic diuretic if necessary; or
give low initial doses of the ACE inhibitor and increase the dose gradually.
In patients with congestive heart failure, initiation with a very low dose of ACE inhibitor, possibly after a reduction in the dose of the hypokalaemic diuretic, is recommended.
The monitoring of renal function (plasma creatinine) during the first weeks of treatment with an ACE inhibitor is recommended in all patients.

Other compounds causing hypokalaemia: amphotericin B (amphotericin) (IV), gluco- and mineralo-corticoids (systemic route), stimulant laxatives.

Due to the increased risk of hypokalaemia (additive effect):
monitoring, and correction if required, of plasma potassium (especially during treatment with digoxin) is recommended;
the use of non-stimulant laxatives is recommended.

Baclofen.

Due to the increased risk of antihypertensive effects, it is recommended that hydration and renal function be monitored at the start of treatment.

Digitalis preparations.

Monitoring of plasma potassium, plasma magnesium and ECG is recommended during treatment with digitalis, and if necessary, adjust the treatment as hypokalaemia and/or hypomagnesaemia predispose to the toxic effects of digitalis.

Allopurinol.

Combined use with indapamide may increase the incidence of hypersensitivity reactions to allopurinol.

Combinations to be taken into consideration.

Potassium-sparing diuretics (amiloride, spironolactone, triamterene).

Due to the increased risk of either hyperkalaemia or hypokalaemia (particularly in patients with renal failure or diabetes), care should be taken when co-administering potassium-sparing diuretics. Plasma potassium and ECG should be monitored and, if necessary, treatment reviewed.

Metformin.

Do not co-administer with metformin when plasma creatinine exceeds 15 mg/L (135 micromol/L) in men and 12 mg/L (110 micromol/L) in women due to the increased risk of metformin induced lactic acidosis as a result of the possibility of functional renal failure associated with diuretics and more particularly with loop diuretics.

Iodinated contrast media.

Adequate hydration before administration of the iodinated compound is recommended due to an increased risk of acute renal failure resulting from dehydration, particularly when large doses of iodinated contrast media are used.

Imipramine-like antidepressants, neuroleptics.

Caution is recommended with these combinations due to an increased antihypertensive effect and increased risk of orthostatic hypotension.

Calcium (salts).

Caution is recommended with this combination due to the risk of hypercalcaemia resulting from decreased urinary elimination of calcium.

Cyclosporin, tacrolimus.

Caution is recommended with this combination due to the risk of increased plasma creatinine without any change in circulating cyclosporin levels, even in the absence of water/sodium depletion.

Corticosteroids, tetracosactide (tetracosactrin) (systemic route).

Caution is recommended with this combination due to the risk of decreased antihypertensive effect (water/sodium retention due to corticosteroids).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

A reproductive toxicity study in rats showed no impairment of male or female fertility at oral indapamide doses up to 25 mg/kg/day, however, the number of implantation sites was reduced at the highest dose.
(Category C)
Indapamide should be avoided in pregnant women and should not be used to treat oedema in pregnancy. There are limited data with the use of indapamide in pregnant women. Prolonged exposure to thiazides during the third trimester of pregnancy can reduce maternal plasma volume as well as uteroplacental blood flow, which may cause foetal-placental ischaemia and growth retardation.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.
Thiazides, related diuretics and loop diuretics enter the foetal circulation and may cause electrolyte disturbances. Neonatal thrombocytopaenia has been reported with thiazides and related diuretics. Loop diuretics like furosemide (frusemide) and bumetanide are probably also associated with this risk. During the latter part of pregnancy, medicines of this type should be used with caution and at the lowest effective dose.
Indapamide should not be used during breast-feeding. Indapamide is excreted in human breast milk and the possible effect on the newborn is unknown and cannot be excluded. Indapamide is closely related to thiazide diuretics which have associated with a decrease in, or even suppression of, lactation.
Hypersensitivity to sulfonamide-derived medicines and hypokalaemia might occur.

4.7 Effects on Ability to Drive and Use Machines

Indapamide does not affect vigilance but different reactions related to a decrease in blood pressure may occur in individual cases, especially at the start of treatment or when another antihypertensive agent is added. Treatment with any blood pressure lowering agent may, therefore, affect the ability to drive, cross the road safely or operate machinery.

4.8 Adverse Effects (Undesirable Effects)

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.
In general, most adverse effects are mild and transient. The most frequently reported are: hypokalaemia, hypersensitivity reactions, mainly dermatological (in subjects with a predisposition to allergic and asthmatic reactions and maculopapular rashes), asthenia, dizziness, headache, fatigue, muscle cramps and gastrointestinal disturbances. These usually occur within the first month of treatment.
During clinical trials, hypokalaemia (plasma potassium < 3.4 mmol/L) was seen in 25% of patients and < 3.2 mmol/L in 10% of patients after four to six weeks treatment. After 12 weeks treatment, the mean fall in plasma potassium was 0.41 mmol/L. Hypochloraemia 9.4%; hyponatraemia 3.1%.
The majority of adverse reactions concerning clinical or laboratory parameters are dose-dependent.
Other adverse reactions have been non-specific. Cutaneous rash and impotence have been occasionally reported. Percentages shown below indicate the incidence in clinical trials.
The following adverse effects have been observed with indapamide during treatment ranked according to the following frequencies: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000); very rare (< 1/10,000); not known (cannot be estimated from the available data). See Table 1.
Other adverse reactions, reported in clinical studies with the immediate release formulation of indapamide, and not seen in the Tenaxil SR studies, include the following:

Central nervous system.

Lethargy.

Gastrointestinal.

Anorexia, gastralgia, diarrhoea.

Metabolism and nutrition disorders.

Hypochloraemia, hyponatraemia.

Musculoskeletal.

Joint pain, back pain, weakness of legs.

Cardiac disorders.

Tachycardia, ECG changes (nonspecific ST-T changes, U waves, left ventricular strain).

Urogenital.

Modification of libido, polyuria.

Vascular disorders.

Orthostatic hypotension.

Endocrine.

Gout.

Other.

Tinnitus, malaise/fainting, sweat.

Laboratory abnormalities.

BUN increase, blood creatinine increase.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
Signs of acute poisoning at higher doses take the form of water/electrolyte disturbances (hyponatraemia, hypokalaemia) and may include the possibility of nausea, vomiting, hypotension, cramps, vertigo, drowsiness, confusion, polyuria or oliguria possibly to the point of anuria (by hypovolaemia). In patients with cirrhosis, an overdose might precipitate hepatic coma.

Treatment.

There is no specific antidote. Treatment is symptomatic and supportive. Discontinue drug; induce emesis or perform gastric lavage and/or 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), correct dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Indapamide is an oral antihypertensive medicine. The mechanism whereby indapamide exerts its antihypertensive action has not been completely elucidated; both vascular and renal actions have been implicated.
The possible beneficial pharmacological effects of indapamide in the treatment of hypertension include a reduction in cardiac hypertrophy and a reduction in the thickening of arterial walls, a prevention of the accumulation of the embryonic isoform of fibronectin in coronary vessels, free radical scavenging leading to stimulation of vasodilator eicosanoid formation, and interaction with renal carbonic anhydrase.
The renal effects of Tenaxil SR (sustained release film-coated tablet containing 1.5 mg of indapamide hemihydrate) are minimal and the antihypertensive effect of indapamide has been attributed to a reduction in vascular reactivity to pressor amines. The finding that indapamide retains its antihypertensive activity in patients who are functionally anephric lends support to this hypothesis.
The renal site of action of indapamide is the proximal segment of the distal tubule. Indapamide appears to have natriuretic properties (sodium and chloride being excreted in equivalent amounts) with less effect on kaliuresis or uric acid excretion. Only at doses greater than 1.5 mg indapamide hemihydrate sustained release tablet/day is an appreciable increase in urinary volume observed in man. No significant changes in plasma sodium levels have been observed in clinical studies. Significant hypokalaemia (plasma potassium < 3.2 mmol/L) has been reported in 4% of patients.
Tenaxil SR (one tablet daily) does not adversely affect serum triglycerides, LDL cholesterol, the LDL-HDL cholesterol ratio, or glucose tolerance.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

The fraction of indapamide released is rapidly and totally absorbed via the gastrointestinal digestive tract. Ingestion with food slightly increases the rate and extent of absorption. These changes are unlikely to be clinically significant. Peak serum level following a single dose occurs about 12 hours after ingestion, repeated administration reduces the variation in serum levels between two doses.

Distribution.

Indapamide is widely distributed throughout the body, with extensive binding to specific sites. In blood, it is highly bound to red blood cells (80%) and, more specifically, to carbonic acid anhydrase (98%) without having any significant inhibiting activity on this enzyme.
Binding of indapamide to plasma proteins is 79%. The plasma elimination half-life is 14 to 24 hours (mean 18 hours). The drug has a volume of distribution of approximately 60 L. Steady state is achieved after 7 days. Repeated administration does not lead to accumulation.

Metabolism.

The drug is extensively metabolised in the liver, with only 5 to 7% of the dose excreted in the urine as unchanged drug. Elimination is essentially urinary (70% of the dose) and faecal (22%) in the form of inactive metabolites.

High risk individuals.

In patients with severe renal impairment, plasma concentrations sometimes increase significantly.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

Carcinogenicity studies in mice and rats showed no evidence of tumourigenicity when indapamide was administered in the diet at levels up to 100 mg/kg/day.

Mutagenicity.

Indapamide was negative in mutagenicity tests in bacteria, and bone marrow micronucleus tests in mice. There was a decrease in weight gain of the F1 generation from rats treated orally at 2.5 mg/kg/day. Galactopoiesis was affected in the F1 generation from rats treated orally at 0.5 mg/kg/day and this led to increased mortality of the F2 generation during the first 48 hours of life. No embryo-foetal toxicity or teratogenic potential were seen in rats (up to 150 mg/kg/day) and in rabbits (up to 180 mg/kg/day).

6 Pharmaceutical Particulars

6.1 List of Excipients

Colloidal anhydrous silica, glycerol, hypromellose, lactose monohydrate, macrogol 6000, magnesium stearate, povidone, titanium dioxide.

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 in a dry place below 25°C.

6.5 Nature and Contents of Container

Tenaxil SR is supplied in boxes containing 10#, 30 or 90 tablets. Tablets are in blister platforms of 30.
# The 10 tablet pack is not supplied in Australia.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Indapamide hemihydrate (4-chloro-N(2-methyl-1-indolinyl)-3-sulfamoyl benzamide hemihydrate) is a non-thiazide indole derivative of chlorosulfonamide. The active ingredient is a racemic mixture. Indapamide is a white crystalline lipophilic powder, soluble in methanol, ethanol, acetic acid and ethyl acetate, very slightly soluble in ether, chloroform and benzene and practically insoluble in water.

Chemical structure.


CAS number.

26 807-65-8.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes