Perindopril


Thông tin thuốc gốc
Chỉ định và Liều dùng
Oral
Hypertension
Adult: As perindopril erbumine: Initially, 4 mg once daily, may be titrated according to clinical response. Max: 8 mg daily. As perindopril arginine: Initially, 5 mg once daily, may be titrated according to clinical response. Max: 10 mg daily. Patient with renovascular hypertension, volume depletion, severe hypertension or patient on diuretics: As perindopril erbumine: Initially, 2 mg once daily; As perindopril arginine: 2.5 mg once daily.
Elderly: As perindopril erbumine: Initially, 2 mg once daily, may increase dose to 4 mg if necessary. Max: 8 mg daily. As perindopril arginine: 2.5 mg once daily, may increase dose to 5 mg if necessary. Max: 10 mg daily.

Oral
Heart failure
Adult: As perindopril erbumine: Initially, 2 mg once daily, preferably in the morning, may adjust according to clinical response. Usual maintenance dose: 4 mg once daily. As perindopril arginine: Initially, 2.5 mg once daily, preferably in the morning, may adjust dose according to clinical response. Usual maintenance dose: 5 mg once daily.

Oral
Stable coronary artery disease
Adult: As perindopril erbumine: Initially, 4 mg once daily for 2 weeks, may be titrated according to clinical response. Max dose: 8 mg daily. As perindopril arginine: Initially, 5 mg once daily for 2 weeks, may be titrated according to clinical response. Max dose: 10 mg daily.
Elderly: As perindopril erbumine: Initially, 2 mg once daily for 1 week, then may increase dose to 4 mg once daily, may further titrate to 8 mg once daily according to clinical response. As perindopril arginine: Initially, 2.5 mg once daily for 1 week, then may increase dose to 5 mg once daily, may further titrate to 10 mg once daily according to clinical response.
Renal Impairment
CrCl (mL/min) Dosage
<15 2 mg (as perindopril erbumine) or 2.5 mg (as perindopril arginine) on dialysis days.
15-30 2 mg (as perindopril erbumine) or 2.5 mg (as perindopril arginine) every other day.
30-60 2 mg (as perindopril erbumine) or 2.5 mg (as  perindopril arginine) once daily.
Cách dùng
Should be taken on an empty stomach.
Chống chỉ định
History of angioedema related to previous ACE inhibitor treatment, hereditary or idiopathic angioedema, bilateral or unilateral renal stenosis, patients with extracorporeal treatments leading to contract of blooding with negatively charged surfaces. Concomitant use with aliskiren especially in patient with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73 m2). Concomitant use with sacubitril/valsartan. Pregnancy and lactation.
Thận trọng
Patient with hypertrophic cardiomyopathy with outflow tract obstruction, salt or volume depletion, collagen vascular disease (e.g. SLE, scleroderma), severe mitral valve and aortic stenosis, ascites due to cirrhosis, refractory ascites, diabetes, primary aldosteronism, CV disease (e.g. ischaemic heart disease). Patients undergoing major surgery or during anaesthesia. Black race. Desensitisation treatment (e.g. hymenoptera venom). Renal and hepatic impairment. Elderly.
Phản ứng phụ
Significant: Cholestatic jaundice, hypotension, syncope, hyperkalaemia, cough, neutropenia, agranulocytosis, anaemia, thrombocytopenia.
Cardiac disorders: Palpitations, tachycardia.
Ear and labyrinth disorders: Tinnitus.
Eye disorders: Visual disturbance.
Gastrointestinal disorders: Nausea, constipation, diarrhoea, dyspepsia, vomiting, abdominal pain.
General disorders and admin site conditions: Asthenia, peripheral oedema.
Immune system disorders: Urticaria.
Investigations: Elevated BUN, increased serum creatinine, increased serum bilirubin.
Musculoskeletal and connective tissue disorders: Muscle cramps.
Nervous system disorders: Headache, paresthesia, vertigo, dysgeusia, dizziness.
Psychiatric disorders: Mood disturbances, sleep disorders.
Renal and urinary disorders: Renal insufficiency, proteinuria.
Reproductive system and breast disorders: Erectile dysfunction.
Respiratory, thoracic and mediastinal disorders: Dyspnoea, bronchospasm.
Skin and subcutaneous tissue disorders: Pruritus, rash.
Vascular disorders: Vasculitis, flushing, impaired peripheral circulation, epistaxis, Raynaud’s phenomenon.
Potentially Fatal: Angioedema, arrhythmia. Rarely, fulminant hepatic necrosis.
Thông tin tư vấn bệnh nhân
May impair ability to drive or operate machinery.
MonitoringParameters
Monitor BP, BUN, serum K and creatinine levels, renal function, CBC with differential. Monitor for signs of angioedema and assess pregnancy status.
Quá liều
Symptoms: Hypotension, bradycardia, circulatory shock, renal failure, hyperventilation, electrolyte disturbances, tachycardia, palpitations, dizziness, anxiety, and cough. Management: Administer IV infusion of NaCl 0.9%. If hypotension occurs, place the patient in shock position. May also consider administration of angiotensin II infusion and/or IV catecholamines. Haemodialysis may be beneficial.
Tương tác
Increased hypotensive effect with antihypertensive agents, diuretics, nitrates and baclofen. Increased risk of hyperkalaemia with K-sparing diuretics (e.g. spironolactone, eplerenone), K supplements, or other agents affecting serum K concentrations (e.g. trimethoprim, ciclosporin, heparin). May increase hypoglycaemic effect with insulin and oral hypoglycaemics agents. Increased risk of angioedema with mammalian target of rapamycin (mTOR) inhibitors (e.g. temsirolimus, sirolimus, everolimus), neutral endopeptidase (NEP) inhibitors (e.g. racecadotril), and dipeptidyl peptidase-IV (DPP-IV) inhibitors (e.g. sitagliptin, linagliptin). Concomitant use with NSAIDs including selective COX-2 inhibitors may result to renal function deterioration and reduced antihypertensive effect. May increase serum levels and toxicity of lithium. Coadministration with parenteral gold (e.g. Na aurothiomalate) may cause nitritoid reaction characterized by facial flushing, nausea, vomiting, and hypotension.
Potentially Fatal: Increased risk of hypotension, hyperkalaemia, and changes in renal function with aliskiren. Increased risk of angioedema with sacubitril/valsartan. May cause anaphylactoid reactions with dextran sulfate in LDL apheresis.
Food Interaction
May reduce hepatic biotransformation with food.
Lab Interference
May result to false-negative aldosterone/renin ratio (ARR).
Tác dụng
Description: Perindopril, a prodrug of perindoprilat, is an ACE inhibitor which prevents conversion of angiotensin I to angiotensin II, thereby increasing plasma renin activity and decreasing vasoconstriction and aldosterone secretion.
Onset: 1-2 hours.
Pharmacokinetics:
Absorption: Rapidly absorbed from the gastrointestinal tract. Slightly reduced absorption with food. Bioavailability: Approx 65-75% (perindopril); approx 25% (perindoprilat). Time to peak plasma concentration: Approx 1 hour (perindopril); 3-4 hours (perindoprilat).
Distribution: Volume of distribution: Approx 0.2 L/kg (perindoprilat). Plasma protein binding: Approx 60% (perindopril); 10-20% (perindoprilat).
Metabolism: Extensively metabolised in the liver via hydrolysis to by hepatic esterases to perindoprilat (as active form) and inactive metabolites including glucuronides.
Excretion: Via urine (75%, 4-12% as unchanged drug). Terminal elimination half-life: 25-30 hours or longer (perindoprilat).
Đặc tính

Chemical Structure Image
Perindopril

Source: National Center for Biotechnology Information. PubChem Database. Perindopril, CID=107807, https://pubchem.ncbi.nlm.nih.gov/compound/Perindopril (accessed on Jan. 22, 2020)

Bảo quản
Store between 20-25°C. Protect from light and moisture.
Phân loại ATC
C09AA04 - perindopril ; Belongs to the class of ACE inhibitors. Used in the treatment of cardiovascular disease.
References
Aceon Tablets. U.S. FDA. https://www.fda.gov/. Accessed 20/11/2013.

Anon. Perindopril. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 20/11/2013.

Anon. Perindopril. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 20/11/2013.

Apotex NZ Ltd. Apo Perindopril 2 mg, 4 mg, and 8 mg tablets data sheet 28 August 2018. Medsafe. http://www.medsafe.govt.nz/. Accessed 01/03/2019.

Buckingham R (ed). Perindopril. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/11/2013.

Perindopril 2mg, 4mg, 8mg Tablets. MHRA. https://products.mhra.gov.uk/. Accessed 20/11/2013.

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