Adult: Perindopril erbumine 4 mg and amlodipine 5 mg tab Perindopril erbumine 4 mg and amlodipine 10 mg tab Perindopril erbumine 8 mg and amlodipine 5 mg tab Perindopril erbumine 8 mg and amlodipine 10 mg tab Perindopril arginine 5 mg and amlodipine 5 mg tab Perindopril arginine 5 mg and amlodipine 10 mg tab Perindopril arginine 10 mg and amlodipine 5 mg tab Perindopril arginine 10 mg and amlodipine 10 mg tab
As substitute therapy in patients who are already maintained on separate doses of perindopril and amlodipine, given concurrently at the same dose level: 1 tab once daily, preferably in the morning. Available preparations and fixed-dose combinations may vary among individual products and between countries (refer to specific product guidelines).
What are the brands available for Perindopril + Amlodipine in Malaysia?
Individual dose titration with the monocomponents is recommended (refer to individual product guidelines).
Hepatic Impairment
Initiate at the lower end of dosing range.
Administration
Amlodipine + Perindopril Should be taken on an empty stomach.
Contraindications
Hereditary or idiopathic angioedema, history of angioedema associated with previous ACE inhibitor treatment; significant bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney; severe hypotension, shock (including cardiogenic shock), left ventricular outflow tract obstruction (e.g. high-grade aortic stenosis), haemodynamically unstable heart failure after acute MI. Extracorporeal treatment leading to contact of blood with negatively charged surfaces. Pregnancy. Concomitant use with aliskiren-containing drugs in patients with diabetes or renal impairment (GFR <60 mL/min/1.73 m2). Concomitant use or within 36 hours of switching to or from sacubitril/valsartan.
Special Precautions
Patient with history of angioedema unrelated to ACE inhibitor treatment, airway surgery; volume depletion, ischaemic heart disease, cerebrovascular disease, CHF, collagen vascular disease (e.g. SLE), hypertrophic cardiomyopathy, diabetes mellitus, primary hyperaldosteronism. Patients undergoing major surgery, desensitisation treatment (e.g. hymenoptera venom), LDL apheresis with dextran sulfate, or receiving anaesthesia that may produce hypotension. Black race. Perindopril and amlodipine fixed-dose combination is not recommended for initial treatment. Hepatic and renal impairment. Elderly. Lactation.
Adverse Reactions
Significant: Increased angina and/or MI; neutropenia, agranulocytosis, anaemia, thrombocytopenia; cough, hyperkalaemia, hypersensitivity reactions (e.g. anaphylaxis), symptomatic hypotension (with or without syncope). Rarely, angioedema of the face, extremities, lips, mucous membranes and intestine. Cardiac disorders: Palpitations. Ear and labyrinth disorders: Tinnitus, vertigo. Eye disorders: Visual impairment, diplopia. Gastrointestinal disorders: Abdominal pain, nausea, vomiting, dyspepsia, change of bowel habit, diarrhoea, constipation, dysgeusia. General disorders and administration site conditions: Fatigue, asthenia. Musculoskeletal and connective tissue disorders: Joint swelling, muscle cramps. Nervous system disorders: Somnolence, dizziness, headache, paraesthesia. Respiratory, thoracic and mediastinal disorders: Dyspnoea. Skin and subcutaneous tissue disorders: Pruritus, exanthema rash. Vascular disorders: Flushing. Potentially Fatal: Rarely, angioedema of the tongue, glottis or larynx; cholestatic jaundice which may lead to fulminant hepatic necrosis.
Patient Counseling Information
This drug may cause dizziness or weariness, if affected, do not drive or operate machinery.
Monitoring Parameters
Correct volume depletion prior to treatment initiation. Monitor blood pressure, renal function, and serum electrolytes (particularly serum K); CBC with differential (periodically, in patients with collagen vascular disease and renal impairment).
Overdosage
Symptoms: Amlodipine: Excessive peripheral vasodilation with marked and prolonged systemic hypotension. Rarely, non-cardiogenic pulmonary oedema. Perindopril: Hypotension, cough, dizziness, electrolyte disturbances, hyperventilation, tachycardia, palpitations, bradycardia, anxiety, renal failure, circulatory collapse. Management: Administer a vasoconstrictor to restore vascular tone and blood pressure. May give IV calcium gluconate to reverse the effects of Ca channel blockade. Administer IV infusion of NaCl 0.9% solution. In case of hypotension, place the patient in shock position. Administration of angiotensin II infusion and/or IV catecholamines may also be considered, if available. For treatment-resistant bradycardia, pacemaker therapy may be used. Continuously monitor vital signs, serum electrolytes, and creatinine levels.
Drug Interactions
Enhanced antihypertensive effect with baclofen, amifostine, TCAs, β-blockers, α-blockers (e.g. prazosin, alfuzosin, doxazosin, tamsulosin, terazosin), nitrates, and other antihypertensive agents.
Perindopril: Increased risk of angioedema with estramustine, racecadotril, linagliptin, sitagliptin, vildagliptin, mTOR inhibitors (e.g. temsirolimus, sirolimus, everolimus). Increased risk of hyperkalaemia with trimethoprim/sulfamethoxazole, ciclosporin, heparin, K-sparing diuretics (e.g. spironolactone, amiloride), K supplements, and K-containing salt substitutes. May increase serum lithium concentration and enhance the risk of lithium toxicity. May increase the blood glucose-lowering effect of antidiabetic agents (e.g. insulin, oral hypoglycaemic agents). Increased risk of hypotension with diuretics. Nitritoid reactions (e.g. facial flushing, nausea, vomiting, hypotension) may occur when used concurrently with injectable gold (e.g. Na aurothiomalate). Increased risk of worsening renal function (e.g. acute renal failure) with NSAIDs (including COX-2 inhibitors) or ARBs.
Amlodipine: Increased serum concentration with moderate or strong CYP3A4 inhibitors (e.g. erythromycin, clarithromycin, verapamil, diltiazem). May increase the exposure of tacrolimus and simvastatin. Potentially Fatal: Perindopril: Increased risk of angioedema with sacubitril/valsartan. Concomitant use with aliskiren increases the risk of hyperkalaemia, worsening of renal function, and CV morbidity and mortality, particularly in patients with diabetes or renal impairment.
Food Interaction
Perindopril: Conversion to perindoprilat is reduced with food.
Amlodipine: May increase blood pressure-lowering effect with grapefruit juice.
Lab Interference
May give false-negative aldosterone/renin ratio (ARR).
Action
Description: Mechanism of Action: Perindopril, a prodrug of perindoprilat, is a competitive inhibitor of angiotensin-converting enzyme (ACE) which prevents the conversion of angiotensin I into angiotensin II (a potent vasoconstrictor). Reduction in angiotensin II leads to an increase in plasma renin activity and a decrease in aldosterone secretion.
Amlodipine is a dihydropyridine Ca channel blocker. It inhibits transmembrane influx of Ca ions into vascular smooth muscle and cardiac muscle resulting in vasodilation and relaxation, leading to the reduction of peripheral vascular resistance and blood pressure. Onset: Perindopril: 1-2 hours (peak effect).
Amlodipine: Antihypertensive effect: 24-48 hours. Duration: Amlodipine: Antihypertensive effect: At least 24 hours. Pharmacokinetics: Absorption: Perindopril: Rapidly absorbed from the gastrointestinal tract. Bioavailability: Perindopril: Approx 75%. Perindoprilat: Approx 25%; approx 16% with food. Time to peak plasma concentration: Approx 1 hour (perindopril); 3-7 hours (perindoprilat).
Amlodipine: Well absorbed from the gastrointestinal tract. Bioavailability: 64-90%. Time to peak plasma concentration: 6-12 hours. Distribution: Perindopril: Enters breast milk (perindopril and perindoprilat). Plasma protein binding: Approx 60% (perindopril); approx 10-20% (perindoprilat).
Amlodipine: Crosses the placenta and enters breast milk. Volume of distribution: 21 L/kg. Plasma protein binding: Approx 93%. Metabolism: Perindopril: Extensively metabolised in the liver via hydrolysis into perindoprilat (active metabolite) and other inactive metabolites, including glucuronides.
Amlodipine: Extensively metabolised in the liver into inactive metabolites. Excretion: Perindopril: Via urine (75%, 4-12% as unchanged drug). Elimination half-life: 1.5-3 hours (perindopril); 25-30 hours or longer (perindoprilat).
Amlodipine: Via urine (<10% as unchanged drug, 60% as metabolites). Terminal elimination half-life: 30-52 hours.
Chemical Structure
Perindopril Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 107807, Perindopril. https://pubchem.ncbi.nlm.nih.gov/compound/Perindopril. Accessed Apr. 29, 2025.
Amlodipine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 2162, Amlodipine. https://pubchem.ncbi.nlm.nih.gov/compound/Amlodipine. Accessed Feb. 25, 2025.
Storage
Store below 30°C. Protect from light and moisture.
C09BB04 - perindopril and amlodipine ; Belongs to the class of ACE inhibitors and calcium channel blockers. Used in the treatment of cardiovascular diseases.
References
Amlodipine. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 06/03/2025.Brayfield A, Cadart C (eds). Amlodipine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/03/2025.Brayfield A, Cadart C (eds). Perindopril. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/03/2025.Coveram 5 mg/5 mg, 5 mg/10 mg, 10 mg/5 mg, 10 mg/10 mg Tablets (Servier Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 06/03/2025.Joint Formulary Committee. Perindopril Erbumine with Amlodipine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/03/2025.Perindopril and Amlodipine. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 06/03/2025.Perindopril. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 06/03/2025.Perindopril/Amlodipine 4 mg/10 mg Tablets (KRKA, d.d., Novo Mesto). MHRA. https://products.mhra.gov.uk. Accessed 21/04/2025.Perindopril/Amlodipine 4 mg/5 mg Tablets (KRKA, d.d., Novo Mesto). MHRA. https://products.mhra.gov.uk. Accessed 06/03/2025.Perindopril/Amlodipine 8 mg/10 mg Tablets (KRKA, d.d., Novo Mesto). MHRA. https://products.mhra.gov.uk. Accessed 21/04/2025.Perindopril/Amlodipine 8 mg/5 mg Tablets (KRKA, d.d., Novo Mesto). MHRA. https://products.mhra.gov.uk. Accessed 10/03/2025.
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