Indapamide

Registered South African indications:

• Mild to moderate hypertension 

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to other sulphonamide derivatives
• Hepatic encephalopathy or severe impairment of hepatic function
• Severe renal failure
• Hypokalaemia
• Recent cerebrovascular accident (2.5mg tab)
• Pregnancy (2.5mg tab)
• Lactation (2.5mg tab)

Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to other sulphonamide derivatives
• Hepatic encephalopathy or severe impairment of hepatic function
• Severe renal failure
• Hypokalaemia

• Pregnancy (South African recommendations) (1.5mg SR tab)
• Pregnancy (Recommendations in other jurisdictions)
• Breastfeeding (South African recommendations) (1.5mg SR tab)
• Breastfeeding (Recommendations in other jurisdictions)
• Mild to moderate renal impairment (plasma creatinine below levels of the order of 25mg/l, i.e. 220µmol/l in an adult)
• Mild to moderate hepatic impairment
• Elderly
• Electrolyte disturbances
• Prolonged QT interval
• Diabetes mellitus
• Malnourished
• Athletes
• Coronary artery disease
• Cardiac failure
• Gout
• Galactose intolerance
• Lapp-lactase deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: fct, tab, sustained-release tablet (SR tab)

South African registered indications and dosages

Mild to moderate hypertension

• Oral (fct, tab): 2.5mg, daily in the morning

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May be used in conjunction with other agents for the management of hypertension if sufficient reduction in blood pressure is not achieved. These include beta-blockers, ACE inhibitors, methyldopa, clonidine, and other adrenergic blocking agents

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The coadministration of indapamide with diuretics which may cause hypokalaemia is not recommended

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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

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A larger dose than 2.5mg indapamide daily is not recommended as there is no appreciable additional antihypertensive effect, but a diuretic effect may become apparent 

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• Oral (SR tab): 1.5mg, daily preferably in the morning, swallowed whole with water, not chewed

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In more severe cases, indapamide can be combined with other categories of antihypertensive agents

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At higher doses, the antihypertensive action of indapamide is not enhanced, but the saluretic effect is increased

Not established for use in children below 18 years

Pregnancy

South African recommendations 

• 1.5mg SR tab: Caution; not recommended
• 2.5mg tab: Contraindicated
• The administration of indapamide sustained release tablets should be avoided in pregnant women and should never be used to treat physiological oedema of pregnancy. Diuretics can cause fetoplacental ischaemia, with a risk of impaired foetal growth

Recommendations in other jurisdictions

• Caution; not recommended
• 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
• As a precautionary measure, it is preferable to avoid the use of indapamide during pregnancy

Breastfeeding

South African recommendations

1.5mg SR tab

• Caution; not recommended
• Breastfeeding is not recommended while using indapamide as it is excreted in breast milk

2.5mg tab

• Contraindicated
• Indapamide should not be taken by breastfeeding mothers, as it is excreted in mother's milk and may cause electrolyte disturbance and create hypersensitivity to sulphonamide in the child
• The quantity of milk may be reduced

Recommendations in other jurisdictions

• Caution; not recommended
• 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 decrease or even suppression of milk lactation. Indapamide should not be used during breast-feeding

Fertility

South African recommendations

• No information available

Recommendations in other jurisdictions

• Reproductive toxicity studies showed no effect on fertility in female and male rats. No effects on human fertility are anticipated

Recommendations below are applicable to South Africa and other jurisdictions

• Mild to moderate (plasma creatinine below levels of the order of 25mg/l, i.e. 220µmol/l in an adult): Caution; no dose adjustment recommended
• Severe (CrCl<30ml/min): Contraindicated

Recommendations below are applicable to South Africa and other jurisdictions

• Mild to moderate: Caution; no dose adjustment recommended
  When liver function is impaired, thiazide-related diuretics may cause hepatic encephalopathy which can progress to hepatic coma, particularly in case of electrolyte imbalance. Administration of the diuretic must be stopped immediately if this occurs
• Severe: Contraindicated

Recommendations below are applicable to South Africa and other jurisdictions

• Caution; no dose adjustment recommended
  In the elderly, the plasma creatinine must be adjusted in relation to age, weight and gender. Elderly patients can be treated with indapamide sustained release tablets when renal function is normal or only minimally impaired
  The elimination time of indapamide tablets may be prolonged in the elderly, as they are more susceptible to electrolyte imbalance and fluid loss. It is advisable to monitor these patients frequently for evidence of such effects (South African recommendations)

Central Nervous System Disorders

• Vertigo
• Fatigue
• Headache
• Paraesthesia

Cardiovascular Disorders

• Arrhythmias
• Syncope
• Torsade de pointes 
• Hypotension

Gastrointestinal Disorders

• Nausea and vomiting
• Constipation
• Dry mouth
• Pancreatitis

Hepatobiliary Disorders

• Abnormal hepatic function
• Possibility of onset of hepatic encephalopathy in case of hepatic insufficiency 
• Hepatitis

Genitourinary Disorders

• Renal failure

Endocrine and Metabolic Disorders

• Hypercalcaemia
• Hypokalaemia
• Hyponatraemia 

Skin and Subcutaneous Tissue Disorders

• Hypersensitivity reactions
• Maculopapular rashes
• Purpura
• Angioedema
• Urticarial rash
• Toxic epidermal necrolysis
• Stevens-Johnson Syndrome
• Possible worsening of pre-existing acute disseminated lupus erythematosus
• Photosensitivity reactions 

Immune, Blood and Lymphatic System Disorders

• Agranulocytosis
• Aplastic anaemia
• Haemolytic anaemia
• Leucopenia
• Thrombocytopenia

Sensory Disorders

• Myopia
• Blurred vision
• Visual impairment

• Lithium
• Drugs that increase risk for Torsades de pointes
• Non-steroidal anti-inflammatory drugs
• Angiotensin-converting enzyme (ACE) inhibitors
• Baclofen
• Digitalis preparations
• Potassium-sparing diuretics
• Metformin
• Iodinated contrast media
• Imipramine-like antidepressants
• Imipramine-like neuroleptics
• Calcium salts
• Ciclosporin
• Tacrolimus
• Corticosteroids
• Tetracosactide

None routine. Specific cases may require

• Serum electrolytes
• Hepatic function
• Renal function
• Uric acid
• Blood glucose
• ECG

Indapamide is a sulphonamide derivative with an indole ring, pharmacologically related to thiazide diuretics, which acts by inhibiting the reabsorption of sodium in the distal convoluted tubule. It increases the urinary excretion of sodium and chlorides and, to a lesser extent, the excretion of potassium and magnesium, thereby increasing urine output and having an antihypertensive action.

Tablet sr 1.5mg

• Dyna Indapamide SR (Pharma Dynamics)
• Natrilix SR (Servier) originator

Tablet 2.5mg

• Adco-dapamax (Adcock)
• Catexan (Servier)
• Cipla Indapamide (Cipla Medpro)
• Daptril (F.D.C. SA)
• Hydro-less (Pharmacare)
• Mylan Indapamide (Mylan)
• Natrilix (Servier) originator
• Sandoz Indapamide (Sandoz)

COMBINATION PREPARATIONS

Perindopril/ Indapamide

Tablet 2mg/0.625mg

• Acesyl Co (Thebe)
• Preterax (Servier)
• Spec-Perindopril Plus (Specpharm)

Tablet 4mg/1.25mg

• Acesyl Co (Akacia)
• Ariprel Plus (Arrow)
• Ciplasyl Plus (Zydus)
• Circator Plus (Biogaran)
• Coversyl Plus (Servier) originator
• Pearinda Plus (Pharma Dynamics)
• Perincopril Co Unicorn (Servier)
• Prexum Plus (Biogaran)
• Spec-Perindopril Plus (Specpharm)
• Vectoryl Plus (Biogaran)

Tablet 5mg/1.25mg

• Coversyl Plus (Servier) originator
• Prexum Plus (Servier)

Tablet 10mg/2.5mg

• Bio Coversyl Plus (Servier) originator
• BioPrexum Plus (Servier)
• Prexum 2,5 Plus (Biogaran)

Perindopril/ Indapamide/ Amlodipine

Film-coated tablet 5mg/1.25mg/5mg

• Triplixam (Servier Laboratories SA)

Film-coated tablet 5mg/1.25mg/10mg

• Triplixam (Servier Laboratories SA)

Film-coated tablet 10mg/2.5mg/5mg

• Triplixam (Servier Laboratories SA)

Film-coated tablet 10mg/2.5mg/10mg

• Triplixam (Servier Laboratories SA)