Adult: In patients without volume or salt depletion: Initially, 15 mg once daily, titrate upwards to achieve optimal blood pressure control at intervals of 4-weeks. Usual dose: 30 mg once daily. Max: 60 mg once daily as a single dose or in 2 divided doses. In patients suspected of volume or salt depletion: Initially, 15 mg once daily. Correct salt/volume deficiencies, discontinue diuretics for 2-3 days prior to initiation of treatment. If not possible, initiate at 7.5 mg once daily.
Oral Acute myocardial infarction
Adult: Initiate therapy within 24 hours after the onset of symptoms. Initially, 7.5 mg 12 hourly on days 1 and 2, then 15 mg 12 hourly on days 3 and 4, then 30 mg 12 hourly on day 5 onwards up to 6 weeks. Re-evaluate according to patient’s response after 6 weeks. Dosing interruption or discontinuation may be required according to patient’s systolic blood pressure (refer to detailed product guideline).
Patient on haemodialysis: Reduce daily dose by 75%.
Reduce daily dose by 50%.
Mild to moderate: Reduce daily dose by 50%. Severe:
May be taken with or without food.
History of angioneurotic oedema related to previous ACE inhibitor treatment, hereditary or idiopathic angioedema, bilateral or unilateral renal artery stenosis in cases of a solitary single kidney. Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (GFR<60 mL/min/1.73 m2). Severe hepatic impairment. Pregnancy (2nd-3rd trimester).
Patient with electrolyte or volume depletion, dietary salt restriction, angina pectoris, heart failure with or without associated renal insufficiency, cerebrovascular disease, renovascular hypertension, pre-existing bilateral renal artery stenosis, aortic or mitral valve stenosis, hypertrophic cardiomyopathy, diabetes mellitus, primary aldosteronism, hypoaldosteronism, history of angioedema, collagen vascular disease (e.g. SLE, scleroderma), psoriasis. Patients undergoing major surgery or during anaesthesia; LDL apheresis with dextran sulfate or desensitisation treatment. Black race. Renal and mild to moderate hepatic impairment. Elderly (MI patient). Pregnancy (1st trimester) and lactation.
Significant: 1st-dose hypotension, symptomatic hypotension, increased blood urea and creatinine concentration, hyperkalaemia, cholestatic jaundice, cough, neutropenia, agranulocytosis, thrombocytopenia, anaemia, proteinuria, marked elevation of liver enzymes. Cardiac disorders: Tachycardia, palpitations, arrhythmia, angina pectoris. Ear and labyrinth disorders: Tinnitus. Eye disorders: Blurred vision. Gastrointestinal disorders: Nausea, vomiting, abdominal pain, diarrhoea, dry mouth. General disorders and admin site conditions: Fatigue, asthenia, peripheral oedema. Hepatobiliary disorders: Jaundice, hepatitis. Investigations: Increased BUN, elevated serum creatinine. Metabolism and nutrition disorders: Hypoglycaemia. Musculoskeletal and connective tissue disorders: Muscle cramp, myalgia. Nervous system disorders: Headache, dizziness, paraesthesia, dysgeusia. Psychiatric disorders: Depression, sleep disorders, confusion. Reproductive system and breast disorders: Erectile dysfunction. Respiratory, thoracic and mediastinal disorders: Dyspnoea, rhinitis, sinusitis. Skin and subcutaneous tissue disorders: Rash, pruritus, alopecia, hyperhidrosis. Vascular disorders: Flushing. Potentially Fatal: Anaphylactoid reactions in patient undergoing desensitisation treatment. Angioedema. Rarely, fulminant hepatic necrosis.
Patient Counseling Information
This drug may cause dizziness, drowsiness or weariness, if affected, do not drive or operate machinery.
Monitor blood pressure, LFT, CBC with differential, serum K, serum creatinine, BUN, and urinary protein test (dip-stick) prior to treatment initiation, during therapy and periodically thereafter.
Symptoms: Severe hypotension, shock, stupor, electrolyte disturbances, bradycardia and renal failure. Management: Perform gastric lavage and administer adsorbents and Na sulfate for recent ingestion. Place the patient in shock position and administer volume expanders or angiotensin II treatment for hypotension. Administer atropine for bradycardia or extensive vagal reactions.
Increased risk of hypotension with cimetidine, thiazide or loop diuretics. Increased risk of angioedema with mammalian target of rapamycin (mTOR) inhibitors (e.g. temsirolimus, sirolimus, everolimus). May potentiate hypoglycaemic effects of insulin and sulfonylureas. Increased risk of hyperkalaemia with heparin, sulfamethoxazole/trimethoprim, K-sparing diuretics (e.g. spironolactone, amiloride, triamterene), K supplements or K-containing salts. May increase risk of leucopoenia with allopurinol, procainamide, systemic corticosteroids, cytostatic and immunosuppressive agents. May increase serum levels and toxicity of lithium. May cause nitritoid reaction characterised by flushing, nausea, vomiting, and hypotension with parenteral gold (e.g. Na aurothiomalate). May enhance hypotensive effect of some anaesthetics. Increased risk of renal dysfunction with ciclosporin. Reduced bioavailability with antacids. Diminished antihypertensive effect with NSAIDs and aspirin. Reduced antihypertensive effects with sympathomimetics. Potentially Fatal: Increased risk of hypotension, hyperkalaemia, and decreased renal function with aliskiren. May cause anaphylactoid reactions with dextran sulfate in LDL apheresis.
Food may reduce rate of absorption.
Description: Zofenopril, a prodrug of zofenoprilat, an ACE inhibitor which acts primarily on the suppression of the plasma renin-angiotensin aldosterone system thus decreasing plasma angiotensin II concentration, leading to decreased vasopressor activity and reduced aldosterone secretion. Pharmacokinetics: Absorption: Rapidly and completely absorbed from the gastrointestinal tract. Food decreases rate of absorption. Time to peak plasma concentration: Approx 1.5 hours. Distribution: Volume of distribution: 96 L. Plasma protein binding: Approx 88%. Metabolism: Undergoes nearly complete metabolism in the liver via thio-ester hydrolysis to its active metabolite, zofenoprilat. Excretion: Via urine (69% as metabolites); faeces (26%). Elimination half-life: 5.5 hours.