Perindopril Tert-butylamine

Registered South African indications:

• Hypertension - mild to moderate
• Congestive heart failure
  - Not adequately controlled by conventional therapy with diuretics and digitalis and in whom vasodilatation is indicated
•  Reduction of risk of cardiac events in patients with stable coronary artery disease and without heart failure

South African registered contraindications

• Hypersensitivity to perindopril or to any of the excipients
• History of angioedema related to previous therapy with ACE inhibitor therapy, angiotensin receptor blockers (ARBs) or renin inhibitors. These patients must never again be given these medicines
• Hereditary or idiopathic angioedema
• Hypertrophic obstructive cardiomyopathy (HOCM)
• Severe renal function impairment (creatinine clearance less than 30ml/min)
• Bilateral renal artery stenosis
• Renal artery stenosis in patients with a single kidney
• Aortic stenosis
• Porphyria
• Coadministration with lithium
• Pregnancy
• Lactation
• Concomitant therapy with potassium sparing diuretics such as spironolactone, triamterene, amiloride
• Coadministration with renin inhibitors such as aliskiren
• Coadministration with fluoroquinolones in patients with moderate to severe renal impairment (creatinine clearance≤30ml/min) and in elderly patients
• Coadministration with sacubitril/valsartan
• Extracorporeal treatments leading to contact of blood with negatively charged surfaces

Contraindications registered in other jurisdictions

• Hypersensitivity to active substance or to any of the excipients
• Hypersensitivity to any other ACE inhibitor
• History of angioedema associated with previous ACE inhibitor therapy
• Hereditary or idiopathic angioedema
• Second and third trimesters of pregnancy
• Coadministration with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR<60ml/min/1.73m²)
• Coadministration with sacubitril/valsartan therapy
  - Perindopril must not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan
• 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

South African recommendations

Women of childbearing potential

• Prompt discontinuation and switch of medication upon pregnancy detection

Renal impairment

• In renal impairment, dose adjustment is necessary and routine monitoring of potassium and creatinine is required
• Risk of acute renal failure in patients with symptomatic heart failure if hypotension occurs after initiating therapy
• Potential for increases in blood urea and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney
• Consideration for dosage reduction or discontinuation in hypertensive patients with no pre-existing renal vascular disease (especially when given concomitantly with a diuretic) but show increases in blood urea and serum creatinine

Haemodialysis patients

• A change in dialysis membrane or antihypertensive medication class may be necessary

Recent kidney transplantation

• There is no experience regarding the administration of perindopril in patients with a recent kidney transplant

Hepatic failure

• Syndrome involving progression from cholestatic jaundice to fulminant hepatic necrosis (sometimes death) associated with ACE inhibitors; patients developing jaundice or marked elevations of hepatic enzymes should discontinue treatment and receive appropriate medical follow-up

Elderly

• Test renal function and potassium levels before starting treatment with perindopril. Adjust the initial dose according to blood pressure response, particularly in cases of water and electrolyte depletion, to avoid sudden onset of hypotension

Concomitant use with fluoroquinolones

• Use perindopril cautiously when co-administered with fluoroquinolones. Monitor renal function before and during treatment

Stable coronary artery disease

• Re-evaluation of benefit/risk balance if an unstable angina episode occurs during the first month of perindopril treatment

Cerebrovascular disease or ischaemic heart disease

• Reduction in blood pressure could aggravate cerebrovascular disease (such as atherosclerosis) or ischaemic heart disease and may result in myocardial infarction and cerebrovascular accidents

Hypotension

• Patients at a high risk of symptomatic hypotension e.g. patients with salt or volume depletion with or without hyponatraemia should have these conditions corrected before therapy with perindopril
• Treatment with perindopril must not be initiated in acute myocardial infarction patients who are at risk of further serious haemodynamic deterioration after treatment with a vasodilator. These include patients with systolic blood pressure of 100mmHg or lower or cardiogenic shock
• Hypotension is more likely in volume depleted patients (e.g. by diuretic therapy, dietary salt restriction, dialysis, diarrhoea or vomiting or who have severe renin-dependent hypertension), although it may occur in normo-volaemic patients

Aortic and mitral valve stenosis/ hypertrophic cardiomyopathy

• Mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy

Hypersensitivity/ angioedema

• Risk of angioedema involving face, extremities, lips, mucous membranes, tongue, glottis and/or larynx during therapy; emergency treatment and discontinuation of therapy required if airway obstruction is likely
• Increased risk of angioedema in patients with a history of angioedema unrelated to ACE inhibitor therapy
• Intestinal angioedema, presenting as abdominal pain with or without nausea or vomiting, should be considered in patients presenting with abdominal pain

Anaphylactoid reactions during low-density lipoproteins LDL apheresis

• Possible life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during LDL apheresis with dextran sulphate; these reactions can be avoided by temporarily withholding ACE inhibitor therapy prior to each apheresis

Anaphylactic reactions during desensitisation

• Anaphylactoid reactions can occur in patients receiving ACE inhibitors like perindopril during desensitisation treatments (e.g. hymenoptera venom); reactions can be avoided by temporarily suspending the ACE inhibitor, but may reappear upon rechallenge

Neutropenia/ agranulocytosis/ thrombocytopenia/ anaemia

• Neutropenia/agranulocytosis, thrombocytopenia and anaemia reported in patients using perindopril, especially those with complicating factors like collagen vascular disease, immunosuppressant therapy, allopurinol or procainamide treatment, or impaired renal function

Race

• Higher rate of angioedema and potentially less effective blood pressure lowering in black patients

Cough

• Non-productive, persistent cough, which typically resolves after discontinuation of therapy, reported with the use of perindopril

Surgery/ anaesthesia

• Perindopril may induce hypotension during major surgery or anaesthesia, requiring discontinuation a day prior to surgery

Hyperkalaemia

• Risk of elevated serum potassium levels, particularly in patients with uncontrolled diabetes mellitus, renal insufficiency, worsening of renal function, age (>70 years), diabetes mellitus, inter-current events, in particular dehydration, acute cardiac decompensation, metabolic acidosis those using concomitant potassium supplements, potassium-sparing diuretics or potassium-containing salt substitutes; or those patients on other medicines associated with increases in serum potassium (e.g. heparin)

Diabetic patients

• Close monitoring of glycaemic control needed in diabetic patients previously treated with oral antidiabetic medicines or insulin during the first month of perindopril treatment

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

• Concurrent use of ACE inhibitors and angiotensin II receptor blockers may increase risk of hypotension, hyperkalaemia, and renal function impairment

Concomitant use of other NEP inhibitors

• Concurrent use of NEP inhibitors like racecadotril and ACE inhibitors may increase the risk of angioedema. A careful benefit-risk assessment is needed before starting treatment with NEP inhibitors in patients on perindopril

Concomitant use of mTOR inhibitors

• Patients on mTOR inhibitors (e.g., sirolimus, everolimus, temsirolimus) may face an increased risk of angioedema (airway or tongue swelling, potentially with respiratory impairment)

Potassium supplements or potassium-containing salt substitutes

• Combination of perindopril with potassium supplements, or potassium-containing salt substitutes is generally discouraged as these medications may lead to severe hyperkalaemia

Primary aldosteronism

• Perindopril is typically ineffective for patients with primary hyperaldosteronism and is therefore not recommended

Excipients

• May contain lactose monohydrate. Patients with rare hereditary conditions like galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine. Furthermore, the lactose in perindopril could affect the glycaemic control of patients with diabetes mellitus

Recommendations in other jurisdictions

Pregnancy and lactation (detail)

• ACE inhibitors should not be initiated during pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and if appropriate, alternative therapy should be started

Renal impairment (detailed)

• In patients with renal impairment (creatinine clearance <60ml/min), the initial perindopril dosage should be adjusted based on the patient's creatinine clearance and then as a function of the patient's response to treatment. Patients with symptomatic heart failure may experience further renal function impairment due to hypotension following the initiation of therapy with ACE inhibitors. Patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney treated with ACE inhibitors may see increases in blood urea and serum creatinine

Haemodialysis patients

• Anaphylactoid reactions have been reported in patients dialysed with high flux membranes and treated concomitantly with an ACE inhibitor. For these patients, it may be necessary to consider using a different type of dialysis membrane or a different class of antihypertensive agent

Kidney transplantation

• There is no experience with the administration of perindopril in patients who have recently had a kidney transplant

Hepatic failure

• ACE inhibitors have rarely been associated with a syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and sometimes death. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up

Elderly

• Elimination of perindoprilat is decreased in the elderly, and also in patients with heart or renal failure

Stable coronary artery disease

• If an episode of unstable angina pectoris, major or not, occurs during the first month of perindopril treatment, a thorough evaluation of the benefit/risk should be performed before treatment continuation

Hypotension

• ACE inhibitors like perindopril can cause a drop in blood pressure. If hypotension occurs, the patient should be laid flat, and if necessary, receive an intravenous infusion of normal saline. A brief hypotensive response is not a contraindication to further doses. If hypotension becomes symptomatic, a dose reduction or discontinuation of perindopril may be necessary

Aortic and mitral valve stenosis/ hypertrophic cardiomyopathy

• Perindopril should be administered with caution to patients with mitral valve stenosis and obstruction in the left ventricle outflow, such as aortic stenosis or hypertrophic cardiomyopathy

Renovascular hypertension

• Patients with bilateral renal artery stenosis or stenosis of the artery to a solitary functioning kidney are at increased risk of hypotension and renal insufficiency when treated with ACE inhibitors like perindopril. Loss of renal function can occur with only minor changes in serum creatinine, even in patients with unilateral renal artery stenosis

Hypersensitivity/ angioedema

• Angioedema of various parts of the body, including the face, extremities, and lips, has been reported rarely in patients treated with ACE inhibitors like perindopril. In cases where there's involvement of the tongue, glottis, or larynx that may cause airway obstruction, emergency therapy should be administered promptly. Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor

Intestinal angioedema

• Intestinal angioedema has been reported rarely in patients treated with ACE inhibitors, presenting with abdominal pain, with or without nausea or vomiting. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain

Concomitant use with other drugs

• The concomitant use of ACE inhibitors with racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus), and vildagliptin can lead to an increased risk of angioedema. Caution should be used when starting these drugs in a patient already taking an ACE inhibitor

Anaphylactoid reactions during low-density lipoproteins (LDL) apheresis

• Patients receiving ACE inhibitors during LDL apheresis with dextran sulfate have rarely experienced life-threatening anaphylactoid reactions. Temporarily discontinuing the ACE inhibitor before each apheresis can avoid these reactions

Anaphylactic reactions during desensitization

• Patients receiving ACE inhibitors during desensitization treatment (e.g. hymenoptera venom) have experienced anaphylactoid reactions. These reactions can be avoided if the ACE inhibitor is temporarily discontinued, but they do reappear upon inadvertent rechallenge

Neutropenia/ agranulocytosis/ thrombocytopenia/ anaemia

• ACE inhibitors like perindopril may cause neutropenia/agranulocytosis, thrombocytopenia, and anaemia. Use caution with patients with collagen vascular disease, immunosuppressant therapy, treatment with allopurinol or procainamide, or a combination of these complicating factors, especially if there is pre-existing impaired renal function. In such patients, periodic monitoring of white blood cell counts is advised and patients should be instructed to report any sign of infection

Race

• ACE inhibitors may cause a higher rate of angioedema in black patients than in non-black patients. Perindopril may be less effective in lowering blood pressure in black people, possibly due to a higher prevalence of low-renin states in the black hypertensive population

Cough

• Cough has been reported with the use of ACE inhibitors, typically non-productive, persistent, and resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough

Surgery/ anaesthesia

• Perindopril may block angiotensin II formation secondary to compensatory renin release in patients undergoing major surgery or during anaesthesia with agents that produce hypotension. Treatment should be discontinued one day prior to the surgery.  If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion

Serum potassium

• ACE inhibitors can cause hyperkalemia because they inhibit the release of aldosterone. This effect is usually not significant in patients with normal renal function. However, in patients with impaired renal function and/or taking potassium supplements, hyperkalemia can occur

Diabetic patients

• In diabetic patients treated with oral antidiabetic agents or insulin, glycaemic control should be closely monitored during the first month of treatment with an ACE inhibitor

Lithium

• The combination of lithium and perindopril is generally not recommended

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

• The concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is not recommended due to increased risk of hypotension, hyperkalemia, and decreased renal function. If dual blockade therapy is considered absolutely necessary, it should only occur under specialist supervision

Primary aldosteronism

• Patients with primary hyperaldosteronism generally will not respond to anti-hypertensive drugs acting through inhibition of the renin-angiotensin system. Therefore, the use of perindopril is not recommended

Excipient

• Perindopril tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine

Forms avail. in SA and covered in this monograph: tab

South African registered indications and dosages

Hypertension - mild to moderate

• Oral (tab): Initial: 4mg daily before breakfast; Increase to 8mg daily after one month of treatment, if necessary

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Insulin and non-insulin dependent diabetics can be treated with the usual doses

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Patients with renovascular hypertension, salt and/or volume depletion, cardiac decompensation or severe hypertension may experience an excessive drop in blood pressure following the initial dose. It is recommended that initiation of treatment should take place under medical supervision, using a starting dose of 2mg in such patients

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Congestive heart failure
- Not adequately controlled by conventional therapy with diuretics and digitalis and in whom vasodilatation is indicated

• Oral (tab): Initial: 2mg daily in the morning; Maintenance: Can be increased to 4mg daily once blood pressure acceptability has been demonstrated

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Treatment initiation should be under close medical supervision

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Reduction of risk of cardiac events in patients with stable coronary artery disease and without heart failure

• Oral (tab): Initial: 4mg daily for 2 weeks; Titration: Can be increased to 8mg daily depending on renal function

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Missed dose (all indications): Patients should be advised to take a dose as soon as possible and then continue with the normal dose. They should not take a double dose to compensate for the missed dose

Not established for use in children

Pregnancy

South African recommendations

• Contraindicated
• The use of perindopril is contraindicated during pregnancy
• Pregnant women should be informed of the potential hazards to the foetus and must not take perindopril during pregnancy
• Patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy
• When pregnancy is diagnosed, treatment with perindopril should be stopped immediately and if appropriate, alternative therapy should be started
• Foetal exposure to ACE inhibitors during the first trimester of pregnancy has been reported to be associated with an increased risk of malformations of the cardiovascular (atrial and/or ventricular septal defect, pulmonic stenosis, patent ductus arteriosus) and central nervous system (microcephaly spina bifida) and of kidney malformations
• Perindopril passes through the placenta and can be presumed to cause disturbance in foetal blood pressure regulatory mechanisms
• Oligohydramnios as well as hypotension, oliguria and anuria in newborns, have been reported after administration of perindopril during the second and third trimester
• Cases of defective skull ossification have been observed
• Prematurity and low birth mass can occur

Recommendations in other jurisdictions

• Second and third trimester: Contraindicated
• First trimester: Caution; not recommended
• The use of ACE inhibitors is not recommended during the first trimester of pregnancy. The use of ACE inhibitors is contraindicated during the 2nd and 3rd trimester of pregnancy
• Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however, a small increase in risk cannot be excluded. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy
• When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started
• Exposure to ACE inhibitor/ therapy during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia)
• Should exposure to ACE inhibitor have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Infants whose mothers have taken ACE inhibitors should be closely observed for hypotension

Breastfeeding

South African recommendations

• Contraindicated
• Safety in lactation has not been established

Recommendations in other jurisdictions

• Caution; not recommended
• Because no information is available regarding the use of perindopril during breastfeeding, perindopril is not recommended and alternative treatments with better established safety profiles during breastfeeding are preferable, especially while breastfeeding a newborn or preterm infant

Fertility

South African recommendations

• No information available

Recommendations in other jurisdictions

• There was no effect on reproductive performance or fertility

South African recommendations

• Mild to moderate: Caution: dose adjustment recommended
  Between 30-60ml/min: 2mg, daily
  The mean dialysis clearance of perindopril is 52ml/min and that of perindoprilat 67.2 ml/min, therefore the dose should be taken after the dialysis
• Moderate to severe (when coadministered with fluoroquinolones): Contraindicated
• Severe (CrCl<30ml/min): Contraindicated

Recommendations in other jurisdictions

• Caution; dose adjustment recommended

CrCl (ml/min)	Recommended Dose
≥60	4mg/day
30-<60	2mg/day
15-<30	2mg every other day
<15	2mg on dialysis days
Haemodialysis patients	Dialysis clearance of perindoprilat is 70ml/min For patients on haemodialysis, the dose should be taken after dialysis

• GFR<60ml/min/1.73m² (when coadministered with aliskiren-containing products): Contraindicated

South African recommendations

• No dose adjustment recommended

Recommendations in other jurisdictions

• No dose adjustment recommended

South African recommendations

• Caution; dose adjustment recommended
  Recommended adjustment: 2mg once daily for 1 week; Then: 4mg once daily the next week, before increasing the dose up to 8mg once daily depending on renal function
• When co-administered with fluoroquinolones: Contraindicated

Recommendations in other jurisdictions

• Caution; dose adjustment recommended
  Hypertension: Treatment should be initiated at 2mg which may be progressively increased to 4mg after 1 month; Then to 8 mg if necessary depending on renal function
  Stable coronary artery disease: Recommended adjustment: 2mg once daily for 1 week; Then: 4mg once daily the next week, before increasing the dose up to 8 mg once daily depending on renal function
  The dose should be increased only if the previous lower dose is well tolerated

Central Nervous System Disorders

• Mood disturbances
• Sleep disorder
• Depression
• Dizziness
• Headache
• Paraesthesia
• Vertigo
• Somnolence
• Syncope
• Confusion
• Asthenia
• Malaise

Cardiovascular Disorders

• Palpitations
• Tachycardia
• Angina pectoris
• Arrhythmia
• Myocardial infarction (possibly secondary to excessive hypotension in high-risk patients)
• Hypotension
• Vasculitis
• Flushing
• Stroke (possibly secondary to excessive hypotension in high-risk patients)
• Raynaud's phenomenon
• Chest pain

Respiratory Disorders

• Cough
• Dyspnoea
• Bronchospasm
• Eosinophilic pneumonia
• Rhinitis
• Sinusitis

Gastrointestinal Disorders

• Abdominal pain
• Constipation
• Diarrhoea
• Dysgeusia
• Dyspepsia
• Nausea and vomiting
• Dry mouth
• Pancreatitis

Hepatobiliary Disorders

• Hepatitis (either cytolitic or cholestatic)
• Increased serum bilirubin 
• Increased serum hepatic enzymes
• Jaundice

Genitourinary Disorders

• Renal insufficiency
• Acute renal failure
• Oliguria
• Anuria
• Proteinuria
• Increased blood urea 
• Increased blood creatinine
• Erectile dysfunction

Endocrine and Metabolic Disorders

• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• Hypoglycaemia
• Hyperkalaemia
• Hyponatraemia

Musculoskeletal Disorders

• Muscle cramps
• Arthralgia
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Pruritis
• Rash
• Urticaria
• Photosensitivity 
• Pemphigoid
• Hyperhidrosis
• Erythema multiforme
• Psoriasis aggravation
• Diaphoresis
• Alopecia
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
• Eosinophilia
• Agranulocytosis
• Pancytopenia
• Decreased haemoglobin 
• Decreased haematocrit 
• Leucopenia
• Neutropenia
• Anaemia
• Haemolytic anaemia (in patients with a congenital deficiency of G-6PDH)
• Aplastic anaemia (sometimes fatal)
• Thrombocytopenia
• Pyrexia
• Peripheral oedema
• Angioedema of face, extremities, lips, mucous membranes, tongue, glottis and/or larynx
• Bone marrow depression
• Intestinal angioedema, a symptom complex has been reported which may include
  - Fever
  - Vasculitis
  - Myalgia
  - Arthritis/arthralgia
  - Positive antinuclear antibodies (ANA)
  - Elevated erythrocyte sedimentation rate
  - Eosinophilia
  - Leucocytosis

Sensory Disorders

• Visual disturbances
• Tinnitus

Others

• Fall

• Renin inhibitors
• Aliskiren
• Angiotensin II receptor blockers
• Fluoroquinolones
• Sacubitril/valsartan
• Potassium-sparing diuretics
• Spironolactone
• Eplerenone
• Triamterene
• Amiloride
• Lithium
• Estramustine
• Racecadotril
• mTOR inhibitors
• Sirolimus
• Everolimus
• Temsirolimus
• Potassium supplements
• Potassium-containing salt substitutes
• Agents that increase serum potassium
• Trimethoprim/sulfamethoxazole
• Antidiabetic agents
• Insulins
• Oral hypoglycaemic agents
• Baclofen
• Non-potassium-sparing diuretics
• Non-steroidal anti-inflammatory drugs
• Aspirin ≥3g/day
• Ciclosporin
• Heparin
• Antihypertensive agents
• Vasodilators
• Nitroglycerin and other nitrates
• Gliptins
• Linagliptin
• Saxagliptin
• Sitagliptin
• Vildagliptin
• Anaesthetic agents
• Tricyclic antidepressants
• Antipsychotics
• Immunosuppressant agents
• Tacrolimus
• Sympathomimetics
• Angiotensin-converting enzyme inhibitors
• Digoxin
• Epoetins
• Interleukin-3

Other interactions

• Gold
• Extracorporeal treatments

• Blood pressure
• Blood urea nitrogen (BUN)
• Serum creatinine levels
• Electrolytes
  - With particular attention to potassium (especially for patients on concomitant potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts)

Specific cases may require

• Full blood count (FBC) with differential
  - In patients with collagen vascular disease and/or kidney impairment, conduct periodic monitoring

Observations

• If angioedema is suspected, assess the risk of airway obstruction
  - Consider factors such as involvement of the tongue, glottis, or larynx, and any history of airway surgery

Diuretic-treated patients

• Caution is advised in patients on current diuretic treatment. The effects of perindopril may be potentiated in a situation where hypovolaemia may occur
• Patients taking diuretics should therefore have the diuretic withdrawn 2-3 days before beginning therapy with perindopril, and resumed later if required. If this is not possible, an initial dose of 2mg may be given
• In patients where diuretic therapy cannot be discontinued, it is recommended that a potassium salt or a potassium sparing agent not be prescribed

Perindopril is an inhibitor of the enzyme that converts angiotensin I into angiotensin II (angiotensin converting enzyme (ACE)). The converting enzyme, or kinase, is an exopeptidase that allows conversion of angiotensin I into the vasoconstrictor angiotensin II as well as causing the degradation of the vasodilator bradykinin into an inactive heptapeptide. Inhibition of ACE results in a reduction of angiotensin II in the plasma, which leads to increased plasma renin activity (by inhibition of the negative feedback of renin release) and reduced secretion of aldosterone. Since ACE inactivates bradykinin, inhibition of ACE also results in an increased activity of circulating and local kallikrein-kinin systems (and thus also activation of the prostaglandin system). It is possible that this mechanism contributes to the blood pressure-lowering action of ACE inhibitors and is partially responsible for certain of their side effects (e.g. cough).

Perindopril acts through its active metabolite, perindoprilat. The other metabolites show no inhibition of ACE activity in vitro.

Tablet 4mg

• Acesyl (Akacia)
• Acti-Prex (Activo)
• Auro Perindopril (Aurobindo)
• Bindace (Novagen)
• Cipla-Perindopril (Cipla Medpro)
• Ciplasyl (Cipla Medpro)
• Circator (Biogaran)
• Coversyl (Servier) originator
• Pearinda (Pharma Dynamics)
• Perindopril Unicorn (Biogaran)
• Peristar (Adcock)
• Prexum (Biogaran)
• Ran-Perindopril (Ranbaxy)
• Reprex (Aurobindo)
• Spec-Perindopril (Specpharm)
• Zydus Perindopril (Zydus)
• Vectoryl (Biogaran)

Tablet 8mg

• Auro Perindopril (Aurobindo)
• Bindace (Novagen)
• Cipla-Perindopril (Cipla Medpro)
• Ciplasyl (Cipla Medpro)
• Circator (Biogaran)
• Pearinda (Pharma Dynamics)
• Perindopril Unicorn (Biogaran)
• Peristar (Adcock)
• Prexum Plus (Biogaran)
• Reprex (Aurobindo)
• Spec-Perindopril (Specpharm)
• Vectoryl (Biogaran)