ACE inhibitor + thiazide-like diuretic Pregnancy: Not recommended during the first trimester of pregnancy and contraindicated during the second and third trimesters. ACE inhibitor exposure in the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). Prolonged exposure to thiazide/indapamide in the third trimester can reduce maternal plasma volume and uteroplacental blood flow, which may cause foeto-placental ischaemia and growth retardation; as a precautionary measure it is preferable to avoid indapamide during pregnancy. Not recommended during lactation (eMC 4.6).

Perindopril arginine with indapamide

Brand names: Coversyl Arginine Plus

This is a fixed-dose oral combination of perindopril arginine, an ACE inhibitor, with indapamide, a thiazide-like diuretic, used for essential hypertension and, in selected patients, cardiovascular risk reduction.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: One film-coated tablet of perindopril arginine 5 mg / indapamide 1.25 mg (source SPC product: Coversyl Arginine Plus 5 mg/1.25 mg)

Route: Oral

Frequency: Once daily as a single dose, preferably to be taken in the morning and before a meal

eMC SPC 4.2. Where possible, individual dose titration with the components is recommended. The 5 mg/1.25 mg strength should be used when blood pressure is not adequately controlled on perindopril arginine/indapamide 2.5 mg/0.625 mg (where available); when clinically appropriate a direct change from monotherapy to the 5 mg/1.25 mg tablet may be considered. ELDERLY: treatment should be initiated after considering blood pressure response and renal function. RENAL IMPAIRMENT: treatment is contraindicated in severe renal impairment (creatinine clearance below 30 ml/min); in moderate renal impairment (creatinine clearance 30-60 ml/min) it is recommended to start treatment with the adequate dosage of the free combination; in patients with creatinine clearance greater than or equal to 60 ml/min no dose modification is required. Usual medical follow-up will include frequent monitoring of creatinine and potassium. HEPATIC IMPAIRMENT: contraindicated in severe hepatic impairment; no dose modification required in moderate hepatic impairment. PAEDIATRIC: the safety and efficacy of perindopril arginine/indapamide in the paediatric population have not yet been established and no data are available - the combination should not be used in children and adolescents; no paediatric dose is stated, refer to a children's formulary. NOTE: eMC 4.5 was not captured in this bundle - the interaction list below is drawn from SPC 4.3/4.4 only.

Dose adjustments

Renal

Contraindicated in severe renal impairment (creatinine clearance below 30 ml/min). In moderate renal impairment (creatinine clearance 30-60 ml/min) it is recommended to start treatment with the adequate dosage of the free combination. No dose modification is required in patients with creatinine clearance greater than or equal to 60 ml/min. Should not be used in dialysis patients. Usual follow-up includes frequent monitoring of creatinine and potassium (eMC 4.2, 4.3).

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Perindopril: hypersensitivity to the active substance or to any other ACE inhibitor; history of angioedema (Quincke's oedema) associated with previous ACE inhibitor therapy; hereditary/idiopathic angioedema
Perindopril: second and third trimesters of pregnancy
Perindopril: concomitant use with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m2)
Perindopril: concomitant use with sacubitril/valsartan therapy - must not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan
Perindopril: extracorporeal treatments leading to contact of blood with negatively charged surfaces; significant bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney
Indapamide: hypersensitivity to the active substance or to any other sulfonamide; severe renal impairment (creatinine clearance below 30 ml/min); hepatic encephalopathy; severe hepatic impairment; hypokalaemia
Hypersensitivity to any of the excipients. Due to the lack of sufficient therapeutic experience, should not be used in dialysis patients or in patients with untreated decompensated heart failure

Side effects

Hypokalaemia - 4% of patients on this combination experience a potassium level < 3.4 mmol/l (common with the indapamide component)
Dizziness, headache, paraesthesia, dysgeusia (common with perindopril)
Cough and dyspnoea (perindopril); hypotension (perindopril)
Vertigo, tinnitus and visual impairment (common with perindopril)
Gastrointestinal: abdominal pain, constipation, dyspepsia, diarrhoea, nausea, vomiting (common with perindopril)
Hypersensitivity reactions, mainly dermatological, in subjects with a predisposition to allergic and asthmatic reactions, and maculo-papular rashes (common with indapamide); hyponatraemia (uncommon)

Interactions

Lithium - the combination of lithium with perindopril and indapamide is usually not recommended (eMC 4.4)
ACE inhibitors, angiotensin II receptor blockers or aliskiren (dual blockade of the RAAS) - increased risk of hypotension, hyperkalaemia and decreased renal function including acute renal failure; not recommended, and ACE inhibitors and ARBs should not be used concomitantly in patients with diabetic nephropathy (eMC 4.4)
Potassium-sparing drugs, potassium supplements or potassium-containing salt substitutes - the combination with perindopril is usually not recommended (eMC 4.4)
Allopurinol, procainamide, immunosuppressant therapy (and collagen vascular disease) - use perindopril with extreme caution because of the risk of neutropenia/agranulocytosis, especially with pre-existing impaired renal function; periodic monitoring of white blood cell counts is advised (eMC 4.4)
Diuretic therapy with renal artery stenosis - treatment with diuretics may contribute to hypotension and renal insufficiency in renovascular hypertension (eMC 4.4)
NOTE: eMC 4.5 was not captured in this source bundle - the full interaction list must be checked against the SPC before publication.

Clinical monograph

How it works

Perindopril inhibits angiotensin-converting enzyme to reduce angiotensin-II formation and vasoconstriction, while indapamide promotes renal sodium and water loss and has a direct vasodilatory effect; together they lower blood pressure additively.

Prescribing in practice

Avoid in pregnancy because the ACE-inhibitor component is foetotoxic; counsel and review contraception in women of childbearing potential.
The combination can cause first-dose hypotension, hyperkalaemia and renal impairment, particularly with volume depletion, renal artery stenosis or concomitant NSAIDs; indapamide separately risks hyponatraemia and hypokalaemia.
ACE inhibitors can cause a persistent dry cough and, rarely, angioedema that may be life-threatening and warrants permanent discontinuation.

Monitoring

Monitor blood pressure, renal function and serum electrolytes including sodium and potassium at baseline, after initiation and after dose changes.

Counselling the patient

A persistent dry cough can occur; report it so an alternative can be considered.
Seek urgent help for any swelling of the face, lips, tongue or throat.
Tell your doctor immediately if you become pregnant.

Evidence & guidelines

Perindopril-indapamide reduced cardiovascular outcomes in trials such as ADVANCE in type-2 diabetes and HYVET in the very elderly, supporting its use beyond blood-pressure lowering alone.

Reference: NICE NG136; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways