1. Name of the medicinal product

Indapamide Tablets USP 1.5mg Taj Pharma
Indapamide Tablets USP 1.25mg Taj Pharma
Indapamide Tablets USP 2.5mg Taj Pharma

2. Qualitative and quantitative composition

a) Each tablet contains:
Indapamide USP? ? ?1.5mg
Excipients? ? ? ? ? ? ? ? ? q.s

b) Each tablet contains:
Indapamide USP? ? 1.25mg
Excipients? ? ? ? ? ? ? ? ?q.s

c) Each tablet contains:
Indapamide USP? ? 2.5mg
Excipients? ? ? ? ? ? ? ? ?q.s

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Film-coated tablet

Round, white, film-coated tablet.

4. Clinical particulars

4.1 Therapeutic indications

For the treatment of essential hypertension in adults.

4.2 Posology and method of administration

Posology

Adults

The dosage is one tablet, containing 2.5 mg indapamide hemihydrate, daily, to be taken in the morning.

The action of indapamide is progressive and the reduction in blood pressure may continue and not reach a maximum until several months after the start of therapy. A larger dose than 2.5 mg indapamide daily is not recommended as there is no appreciable additional antihypertensive effect but a diuretic effect may become apparent. If a single daily tablet of indapamide does not achieve a sufficient reduction in blood pressure, another antihypertensive agent may be added; those which have been used in combination with indapamide include beta-blockers, ACE inhibitors, methyldopa, clonidine and other adrenergic blocking agents. The co-administration of indapamide with diuretics which may cause hypokalaemia is not recommended.

There is no evidence of rebound hypertension on withdrawal of indapamide.

Special populations

Patients with renal impairment (see sections 4.3 and 4.4)

In severe renal failure (creatinine clearance below 30 ml/min), treatment is contraindicated.

Thiazide and related diuretics are fully effective only when renal function is normal or only minimally impaired.

Patients with hepatic impairment (see sections 4.3 and 4.4)

In severe hepatic impairment, treatment is contraindicated.

Elderly (see section 4.4)

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

Paediatric populations

Indapamide is not recommended for use in children and adolescents due to a lack of data on safety and efficacy.

Method of administration

Indapamide tablets are for oral administration only.

4.3 Contraindications

• Hypersensitivity to indapamide, to other sulfonamides or to any of the excipients listed in section 6.1.
• Severe renal failure.
• Hepatic encephalopathy or severe impairment of liver function.
• Hypokalaemia.

4.4 Special warnings and precautions for use

Special warnings

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

Photosensitivity

Cases of photosensitivity reactions have been reported with thiazides and thiazide-related diuretics (see section 4.8). If photosensitivity reaction occurs during treatment, it is recommended to stop the treatment. If a re-administration of the diuretic is deemed necessary, it is recommended to protect exposed areas to the sun or to artificial UVA.

Excipients

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Special precautions for use

Water and electrolyte balance

• Plasma sodium

This must be measured before starting treatment, then at regular intervals subsequently. The fall in plasma sodium may be asymptomatic initially and regular monitoring is therefore essential and should be even more frequent in the elderly and cirrhotic patients (see sections 4.8 and 4.9). Any diuretic treatment 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: the incidence and degree of this effect are slight.

• Plasma potassium

Potassium depletion with hypokalaemia is the major risk of thiazide and related diuretics. 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, coronary artery disease and cardiac failure patients. In this situation, hypokalaemia increases the cardiac toxicity of digitalis preparations and the risks of arrhythmias.

Individuals with a long QT interval are also at risk, whether the origin is congenital or iatrogenic. Hypokalaemia, as well as bradycardia, is then a predisposing factor to the onset of severe arrhythmias, in particular, potentially fatal?torsades de pointes.

More frequent monitoring of plasma potassium is required in all the situations indicated above. The first measurement of plasma potassium should be obtained during the first week following the start of treatment.

Detection of hypokalaemia requires its correction.

• Plasma calcium

Thiazide and related diuretics may decrease urinary calcium excretion and cause a slight and transitory rise in plasma calcium. Frank hypercalcaemia may be due to previously unrecognized hyperparathyroidism.

Treatment should be withdrawn before the investigation of parathyroid function.

Blood glucose

Monitoring of blood glucose is important in diabetics, in particular in the presence of hypokalaemia.

Uric acid

Tendency to gout attacks may be increased in hyperuricaemic patients.

Renal function and diuretics

Thiazide and related diuretics are fully effective only when renal function is normal or only minimally impaired (plasma creatinine below levels of the order of 25 mg/L, i.e. 220 ?mol/L in an adult). In the elderly, this plasma creatinine must be adjusted in relation to age, weight and gender.

Hypovolaemia, secondary to the loss of water and sodium induced by the diuretic at the start of treatment causes a reduction in glomerular filtration. This may lead to an increase in blood urea and plasma creatinine. This transitory functional renal insufficiency is of no consequence in individuals with normal renal function but may worsen pre-existing renal insufficiency.

Athletes

The attention of athletes is drawn to the fact that this medicinal product contains a drug substance, which may give a positive reaction in doping tests.

4.5 Interaction with other medicinal products and other forms of interaction

Combinations that are not recommended

Lithium

Increased plasma lithium with signs of overdosage, as with a salt-free diet (decreased urinary lithium excretion). However, if the use of diuretics is necessary, careful monitoring of plasma lithium and dose adjustment are required.

Combinations requiring precautions for use

Torsades de pointes-inducing drugs

• class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide),
• class III antiarrhythmics (amiodarone, sotalol, dofetilide, ibutilide),
• some antipsychotics :

– phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine),

– benzamides (amisulpride, sulpiride, sultopride, tiapride),

– butyrophenones (droperidol, haloperidol)

– others: bepridil, cisapride, diphemanil, erythromycin IV, halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, vincamine IV.

Increased risk of ventricular arrhythmias, particularly?torsades de pointes?(hypokalaemia is a risk factor).

Monitor for hypokalaemia and correct, if required, before introducing this combination. Clinical, plasma electrolytes and ECG monitoring.

Use substances which do not have the disadvantage of causing?torsades de pointes?in the presence of hypokalaemia.

N.S.A.I.Ds (systemic route) including COX-2 selective inhibitors, high dose salicylic acid (? 3 g/day)

Possible reduction in the antihypertensive effect of indapamide.

Risk of acute renal failure in dehydrated patients (decreased glomerular filtration). Hydrate the patient; monitor renal function at the start of treatment.

Angiotensin converting enzyme (ACE) inhibitors

Risk of sudden hypotension and/or acute renal failure when treatment with an ACE inhibitor is initiated in the presence of pre-existing sodium depletion (particularly in patients with renal artery stenosis).

In hypertension, when prior diuretic treatment may have caused sodium depletion, it is necessary:

• either to stop the diuretic 3 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 congestive heart failure, start with a very low dose of ACE inhibitor, possibly after a reduction in the dose of the concomitant hypokalaemic diuretic.

In all cases, monitor renal function (plasma creatinine) during the first weeks of treatment with an ACE inhibitor.

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

Increased risk of hypokalaemia (additive effect).

Monitoring of plasma potassium and correction if required. Must be particularly borne in mind in case of concomitant digitalis treatment. Use non-stimulant laxatives.

Baclofen

Increased antihypertensive effect.

Hydrate the patient; monitor renal function at the start of treatment.

Digitalis preparations

Hypokalaemia predisposing to the toxic effects of digitalis.

Monitoring of plasma potassium and ECG and, if necessary, adjust the treatment.

Combinations requiring special care

Allopurinol

Concomitant treatment with indapamide may increase the incidence of hypersensitivity reactions to allopurinol.

Combinations to be taken into consideration

Potassium-sparing diuretics (amiloride, spironolactone, triamterene)

Whilst rational combinations are useful in some patients, hypokalaemia or hyperkalaemia particularly in patients with renal failure or diabetes may still occur. Plasma potassium and ECG should be monitored and, if necessary, treatment reviewed.

Metformin

Increased risk of metformin induced lactic acidosis due to the possibility of functional renal failure associated with diuretics and more particularly with loop diuretics. Do not use metformin when plasma creatinine exceeds 15 mg/l (135 ?mol/L) in men and 12 mg/L (110 ?mol/L) in women.

Iodinated contrast media

In the presence of dehydration caused by diuretics, increased risk of acute renal failure, in particular when large doses of iodinated contrast media are used.

Rehydration before administration of the iodinated compound.

Imipramine-like antidepressants, neuroleptics

Antihypertensive effect and increased risk of orthostatic hypotension increased (additive effect).

Calcium (salts)

Risk of hypercalcaemia resulting from decreased urinary elimination of calcium.

Ciclosporin, tacrolimus

Risk of increased plasma creatinine without any change in circulating ciclosporin levels, even in the absence of water/sodium depletion.

Corticosteroids, tetracosactide (systemic route)

Decreased antihypertensive effect (water/sodium retention due to corticosteroids).

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of indapamide in pregnant women. Prolonged exposure to thiazide during the third trimester of pregnancy can reduce maternal plasma volume as well as uteroplacental blood flow, which may cause a foeto-placental ischaemia and growth retardation.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

As a precautionary measure, it is preferable to avoid the use of indapamide during pregnancy.

Breast-feeding

There is insufficient information on the excretion of indapamide/metabolites in human milk. Hypersensitivity to sulfonamide-derived medicines and hypokalaemia might occur. A risk to the newborns/infants cannot be excluded.

Indapamide is closely related to thiazide diuretics which have been associated, during breast-feeding, with decreased or even suppression of milk lactation.

Indapamide should not be used during breast-feeding.

Fertility

Reproductive toxicity studies showed no effect on fertility

4.7 Effects on ability to drive and use machines

Indapamide does not affect vigilance but different reactions in relation with the decrease in blood pressure may occur in individual cases, especially at the start of the treatment or when another antihypertensive agent is added.

As a result, the ability to drive vehicles or to operate machinery may be impaired.

4.8 Undesirable effects

Summary of safety profile

The most commonly reported adverse reactions are hypersensitivity reactions, mainly dermatological, in subjects with a predisposition to allergic and asthmatic reactions and maculopapular rashes.

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 4 to 6 weeks treatment. After 12 weeks treatment, the mean fall in plasma potassium was 0.41 mmol/l.

The majority of adverse reactions concerning clinical or laboratory parameters are dose-dependent.

Tabulated summary of adverse reactions

The following undesirable effects have been observed with indapamide during treatment ranked under the following frequency:

Very common (? 1/10); common (? 1/100, < 1/10); uncommon (? 1/1000, < 1/100); rare (? 1/10,000 to < 1/1000), very rare (?1/100,000 to < 1/10,000), not known (cannot be estimated from the available data).

MedDRA System Organ Class	Frequency	Undesirable Effects
Blood and the lymphatic system disorders	Very rare	Agranulocytosis, aplastic anaemia, haemolytic anaemia, leucopenia, thrombocytopenia
Metabolism and nutrition disorders	Very rare	Hypercalcaemia
	Not known	Potassium depletion with hypokalaemia, particularly serious in certain high risk populations (see section 4.4), hyponatraemia (see section (4.4)
Nervous system disorders	Rare	Vertigo, fatigue, headache, paraesthesia
	Not known	Syncope
Eye disorders	Not known	Myopia, blurred vision, visual impairment
Cardiac disorders	Very rare	Arrhythmia
	Now known	Torsade de pointes?(potentially fatal) (see sections 4.4 and 4.5)
Vascular disorders	Very rare	Hypotension
Gastrointestinal disorders	Uncommon	Vomiting
	Rare	Nausea, constipation, dry mouth
	Very rare	Pancreatitis
Hepatobiliary disorders	Very rare	Abnormal hepatic function
	Not known	Possibility of onset of hepatic encephalopathy in case of hepatic insufficiency (see sections 4.3 and 4.4), hepatitis
Skin and subcutaneous tissue disorders	Common	Hypersensitivity reactions, maculopapular rashes
	Uncommon	Purpura
	Very rare	Angioedema, urticaria, toxic epidermal necrolysis, Stevens-Johnson Syndrome
	Not known	Possible worsening of pre-existing acute disseminated lupus erythematosus, photosensitivity reactions (see section 4.4)
Renal and urinary disorders	Very rare	Renal failure
Investigations	Not known	Electrocardiogram QT prolonged (see sections 4.4 and 4.5), blood glucose increased (see section 4.4), blood uric acid increased (see section 4.4), elevated liver enzyme levels

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose

Symptoms

Indapamide has been found to be free of toxicity up to 40 mg, i.e. 16 times the therapeutic dose.

Signs of acute poisoning take the form above all of water/electrolyte disturbances (hyponatraemia, hypokalaemia). Clinically, there is a possibility of nausea, vomiting, hypotension, cramps, vertigo, drowsiness, confusion, polyuria or oligouria possibly to the point of anuria (by hypovolaemia).

Management

Initial measures involve the rapid elimination of the ingested substance(s) by gastric washout and/or administration of activated charcoal, followed by restoration of water/electrolyte balance to normal in a specialized centre.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: sulfonamides, plain;

Mechanism of action

Indapamide is a non-thiazide sulphonamide with an indole ring, belonging to the diuretic family. At the dose of 2.5 mg per day indapamide exerts a prolonged antihypertensive activity in hypertensive human subjects.

Pharmacodynamic effects

Dose-effect studies have demonstrated that, at the dose of 2.5 mg per day, the antihypertensive effect is maximal and the diuretic effect is of mild intensity.

At this antihypertensive dose of 2.5 mg per day, indapamide reduces vascular hyperactivity to noradrenaline in hypertensive patients and decreases total peripheral resistance and arteriolar resistance.

The implication of an extrarenal mechanism of action in the antihypertensive effect is demonstrated by maintenance of its antihypertensive efficacy in functionally anephric hypertensive patients.

The vascular mechanism of action of indapamide involves:

• a reduction in the contractility of vascular smooth muscle due to a modification of transmembrane ion exchanges, essentially calcium;
• vasodilation due to stimulation of the synthesis of prostaglandin PGE₂and the vasodilator and platelet antiaggregant prostacyclin PGI_2;
• potentiation of the vasodilator action of bradykinin.

It has also been demonstrated that in the short-, medium- and long-term, in hypertensive patients, indapamide:

• reduces left ventricular hypertrophy;
• does not appear to alter lipid metabolism: triglycerides, LDL-cholesterol and HDL-cholesterol;
• does not appear to alter glucose metabolism, even in diabetic hypertensive patients. Normalization of blood pressure and significant reduction in microalbuminuria have been observed after prolonged administration of indapamide in diabetic hypertensive subjects.

Lastly, the co-prescription of indapamide with other antihypertensives (beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors) results in an improved control of hypertension with an increased percentage of responders compared to that observed with single-agent therapy.

5.2 Pharmacokinetic properties

Absorption

Indapamide is rapidly and completely absorbed after oral administration. Peak blood levels are obtained after 1-2 hours.

Distribution

Indapamide is concentrated in the erythrocytes and is 79% bound to plasma protein and to erythrocytes. It is taken up by the vascular wall in smooth vascular muscle according to its high lipid solubility.

Metabolism

70% of a single oral dose is eliminated by the kidneys and 23% by the gastrointestinal tract. Indapamide is metabolized to a marked degree with 7% of the unchanged product found in the urine during the 48 hours following administration. Elimination half-life (? phase) of indapamide is approximately 15 – 18 hours.

5.3 Preclinical safety data

Indapamide has been tested negative concerning mutagenic and carcinogenic properties.

The highest doses administered orally to different animal species (40 to 8000 times the therapeutic dose) have shown an exacerbation of the diuretic properties of indapamide. The major symptoms of poisoning during acute toxicity studies with indapamide administered intravenously or intraperitoneally were related to the pharmacological action of indapamide, i.e. bradypnoea and peripheral vasodilation.

Reproductive toxicity studies have not shown embryotoxicity and teratogenicity.

Fertility was not impaired either in male or in female rats.

6. Pharmaceutical particulars

6.1 List of excipients

Tablet: Spray dried lactose, Microcrystalline cellulose, Magnesium stearate, Croscarmellose sodium

Film Coat: ?Hypromellose, Macrogol, Titanium dioxide.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

None.

6.5 Nature and contents of container

White, opaque PVC/aluminium foil blister packs.

Pack sizes: 7, 14, 28, 30, 50, 90, 100 and 500 tablets.

Not All Packs May be Marketed.

6.6 Special precautions for disposal and other handling

7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of ?Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail:?tajgroup@tajpharma.com

Indapamide Tablets USP 1.5mg/1.25mg/2.5mg
(Indapamide)

PATIENT INFORMATION LEAFLET

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. (See section 4).
• Your doctor may have given you this medicine before from another company. It may have looked slightly different. However, either brand will have the same effect.

What is in this leaflet:

1. What indapamide is and what it is used for
   2. What you need to know before you take indapamide
   3. How to take indapamide
   4. Possible side effects
   5. How to store indapamide
   6. Contents of the pack and other information

 

1. What indapamide is and what it is used for

The name of your medicine is Indapamide 2.5mg Tablets (called indapamide throughout this leaflet). It belongs to a group of medicines called diuretics (water tablets).

Indapamide can be used for treating:

• High blood pressure (hypertension). It may be used on its own or in combination with other medicine for high blood pressure.

Most diuretics increase the amount of urine produced by the kidneys. However, indapamide is different from other diuretics, as it only causes a slight increase in the amount of urine produced. In addition, indapamide widens blood vessels so that blood passes through more easily. This helps lower blood pressure.

2. What you need to know before you take indapamide

Do not take indapamide if:

• if you are allergic (hypersensitive) to indapamide, any other sulfonamide or to any of the other ingredients of this medicine (listed in section 6).
• if you have severe kidney disease
• if you have severe liver disease or suffer from a condition called hepatic encephalopathy (liver problems which affect your brain and central nervous system)
• if you have low levels of potassium in your blood (hypokalaemia)

Do not take the medicine if any of the above applies to you. If you are not sure, talk to your doctor or pharmacist before taking indapamide.

Warnings and precautions

Talk to your doctor or pharmacist before taking indapamide:

• if you suffer from gout or have diabetes
• if you have kidney problems
• if you have an overactive thyroid gland (hyperparathyroidism)
• if you have heart rhythm problems
• if you have liver problems

You should tell your doctor if you have had photosensitivity reactions.

Your doctor may give you blood tests to check for low sodium or potassium levels or high calcium levels.

Athletes should be aware that this medicine contains an active ingredient, which may give a positive reaction in doping tests.

If you think any of these situations may apply to you or you have any questions or doubts about taking your medicines, you should consult your doctor or pharmacist.

Other medicines and indapamide

Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes medicines you buy without a prescription, including herbal medicines. This is because indapamide can affect the way some medicines work. Also some medicines can affect the way indapamide works.

In particular, tell your doctor if you are taking any of the following as special care may be required:

• lithium (used to treat depression). You should not take indapamide with lithium due to the risk of increased levels of lithium in the blood
• medicines for heart rhythm problems such as quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, ibutilide, dofetilide or digitalis
• bepridil (used to treat angina pectoris, a condition causing chest pain)
• stimulant laxatives
• medicines used to treat mental disorders such as depression, anxiety or schizophrenia (for example tricyclic antidepressants, antipsychotic drugs, neuroleptics)
• sparfloxacin, moxifloxacin, erythromycin by injection (antibiotics used to treat infections)
• vincamine by injection (used to treat symptomatic cognitive disorders in elderly including memory loss)
• pentamidine (used to treat certain types of pneumonia)
• halofantrine (antiparasitic drug used to treat certain types of malaria)
• mizolastine (used to treat allergic reactions, such as hay fever)
• non-steroidal anti-inflammatory drugs for pain relief (e.g. ibuprofen) or high doses of acetylsalicylic acid (aspirin)
• angiotensin converting enzyme (ACE) inhibitors (used to treat high blood pressure and heart failure)
• amphotericin B by injection (anti-fungal medicines)
• oral corticosteroids used to treat various conditions including severe asthma and rheumatoid arthritis
• allopurinol (for the treatment of gout)
• baclofen (to treat muscle stiffness occurring in diseases such as multiple sclerosis)
• potassium-sparing diuretics (amiloride, spironolactone, triamterene)
• metformin (to treat diabetes)
• iodinated contrast media (used for tests involving X-rays)
• calcium tablets or other calcium supplements
• ciclosporin, tacrolimus or other medicines to depress the immune system after organ transplantation, to treat autoimmune diseases, or severe rheumatic or dermatological diseases,
• tetracosactide (to treat Crohn?s disease)
• cisapride (used to treat reduced movement of the gullet and stomach)
• diphemanil (used to treat gastro-intestinal problems such as ulcers, too much acid, overactive digestive system)

Driving and using machines:

This medicine can cause side effects such as tiredness or dizziness due to lowering of the blood pressure (see section 4). These side effects are more likely to occur after the initiation of the treatment and after dose increases. If this occurs, you should refrain from driving and other activities requiring alertness. However, under good control, these side effects are unlikely to occur.

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking indapamide.

Pregnancy and breast-feeding

Indapamide is not recommended during pregnancy. When a pregnancy is planned or confirmed, the switch to an alternative treatment should be initiated as soon as possible.

• Talk to your doctor before taking this medicine if you are pregnant, might become pregnant, think you may be pregnant or wish to become pregnant.
• Do not use this medicine if you are breast-feeding or planning to breast-feed. The active ingredient is excreted in milk.

Indapamide contains lactose.

If you have been told by your doctor that you cannot digest or tolerate some sugars, talk to your doctor before taking this medicine.

3. How to take indapamide

Always take indapamide exactly as your doctor or pharmacist has told you. You should check with your doctor or pharmacist if you are not sure.

Taking this medicine

• Keep taking this medicine until your doctor tells you to stop. It may take several months before this medicine shows its full effect.
• Tablets can be taken with or without food
• Swallow the tablets whole with a drink of water

Adults and Elderly

The usual dose is one tablet, once a day, taken in the morning

If you take more indapamide than you should

If you take more tablets than you should, tell your doctor or go to your nearest hospital casualty department immediately.

Take the carton and any indapamide tablets left with you so that the doctors know what you have taken.

Taking too much indapamide may make you feel or be sick (nausea or vomiting), cause low blood pressure, cramps, dizziness, drowsiness, confusion and changes in the amount of urine produced by the kidneys due to severe dehydration.

If you forget to take indapamide

Do not take a double dose to make up for a forgotten tablet. Miss it out and take the next dose at the usual time.

If you stop taking indapamide

Keep taking indapamide until your doctor tells you to stop taking it. Treatment for high blood pressure is usually life-long.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, indapamide can cause side effects, although not everybody gets them.

Stop taking indapamide and see your doctor immediately or go to a hospital straight away if you experience any of the following side effects:

• Angioedema and/or urticaria. Angioedema is characterised by swelling of the skin around the eyes, lips, tongue, hands or feet. It may cause swelling of the throat, tongue or airways resulting in shortness of breath or difficulty in swallowing. If this occurs, contact your doctor immediately;
• Severe skins reactions including intense skin rash, reddening of the skin over your whole body, severe itching, blistering, peeling and swelling of the skin, inflammation of mucous membranes (Stevens-Johnson Syndrome), flu-like symptoms and fever or other allergic reactions;
• You get an irregular heartbeat (Torsade de pointes), which could be life-threatening;
• Severe stomach pain which may reach through to your back. This could be a sign of pancreatitis;
• Abnormal liver function (with symptoms such as tiredness, loss of appetite, feeling or being sick, swollen extremities, yellow skin);
• In cases of liver failure, there is a possibility of getting hepatic encephalopathy (liver problems which affect the brain and central nervous system).

Tell your doctor as soon as possible if you have any of the following side-effects:

• You feel tired, weak, confused and have muscles that ache, are stiff or do not work well. This may be due to low sodium levels in your blood (hyponatraemia)
• You feel irritable and your muscles twitch. This may be due to an imbalance in your blood called metabolic alkalosis
• Itchy, lumpy rash. You may also have a high temperature, sore throat, headache or diarrhoea
• You get more infections than usual or bruise more easily. This could be caused by problems with your blood.
• You get increased thirst, hunger and weight loss. These could be signs of diabetes

Tell your doctor or pharmacist if any of the following side effects get serious or lasts longer than a few days. Also tell them if you notice any side effects not listed in this leaflet.

Common (may affect up to 1 in 10 people):

• Red raised skin rash;
• Allergic reactions, mainly dermatological, such as skin rashes in patients with a predisposition to allergic and asthmatic reactions.

Uncommon (may affect less than 1 in 100 people):

• Being sick (vomiting);
• Red pinpoints on skin (purpura).

Rare (may affect less than 1 in 1000 people):

• Feeling of tiredness, headache, pins and needles (paresthesia), vertigo;
• Gastro-intestinal disorders such as nausea (feeling sick) or constipation, dry mouth;

Very rare (may affect less than 1 in 10,000 people):

• Heart rhythm irregularities (causing palpitations, feeling of the heart pounding), low blood pressure;
• Kidney disease (causing symptoms of tiredness, increased need to urinate, itchy skin, feeling sick, swollen extremities);
• Changes in blood cells, such as thrombocytopenia (decrease in the number of platelets which causes easy bruising and nasal bleeding), leucopenia (decrease of white blood cells which may cause unexplained fever, soreness of the throat or other flu-like symptoms ? if this occurs, contact your doctor) and anaemia (decrease in red blood cells);
• High level of calcium in the blood.
• Abnormal hepatic function.

Not known:

• Fainting;
• Visual impairment such as short sightedness (myopia) and blurred vision;
• Dizziness, lightheadedness, fainting when you stand or sit up quickly (due to low blood pressure) loss of appetite (anorexia), indigestion;
• Abnormal ECG heart trace;
• Hepatitis;
• Low potassium in the blood, which may cause muscle weakness;
• The following changes in your blood test results may occur:
  • increase in uric acid, a substance which may cause or worsen gout (painful joints especially in the feet)
  • increased levels of liver enzymes

If you suffer from systemic lupus erythematosus (a disorder of the immune system leading to inflammation and damage to the joints, tendons and organs with symptoms including skin rashes, tiredness, loss of appetite, weight gain and joint pain), this might get worse.

Cases of photosensitivity reactions (change in skin appearance) after exposure to the sun or artificial UVA have also been reported.

Some changes may occur in your blood and your doctor may need to give you blood tests to check your condition. The following changes in your blood test results may occur:

• low potassium in the blood,
• low sodium in the blood that may lead to dehydration and low blood pressure, increase in uric acid, a substance which may cause or worsen gout (painful joint(s) especially in the feet),
• increase in blood glucose levels in diabetic patients,
• increase of calcium in blood.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

5. How to store indapamide

Keep out of the reach and sight of children.

• Do not use indapamide after the expiry date which is stated on the carton. The expiry date refers to the last day of that month.
• Do not use indapamide if you notice that the tablets are crumbling, broken or discoloured.
• Indapamide tablets do not need any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Contents of the pack and other information

What Indapamide Tablets contain

a) Each tablet contains:
Indapamide USP? ? ?1.5mg
Excipients? ? ? ? ? ? ? ? ? q.s

b) Each tablet contains:
Indapamide USP? ? 1.25mg
Excipients? ? ? ? ? ? ? ? ?q.s

c) Each tablet contains:
Indapamide USP? ? 2.5mg
Excipients? ? ? ? ? ? ? ? ?q.s

The other ingredients are microcrystalline cellulose, magnesium stearate, lactose, croscarmellose sodium, hypromellose, macrogol and titanium dioxide.

What Indapamide 2.5mg Tablets look like and contents of the pack

Round, white, film-coated tablet.

White, opaque PVC/aluminium foil blister packs.

Pack sizes: 7, 14, 28, 30, 50, 90, 100 and 500 tablets.

Not All Packs May be Marketed.

7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of ?Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail:?tajgroup@tajpharma.com