Adult: Dose is individualised based on patient’s clinical response, tolerability and target blood pressure. As monotherapy or in combination with other antihypertensives: Initially, 2.5 mg once daily, 1st dose preferably given at bedtime; may be doubled at intervals of 2-4 weeks if needed. Maintenance: 2.5-5 mg once daily. Max: 10 mg daily given as single or in 2 divided doses. In patients at risk of profound hypotension or on diuretics: Initially, 1.25 mg daily then adjust according to response; if possible, may also discontinue diuretics 2-3 days before initiating ramipril therapy. Elderly: Initiate at lower doses then adjust gradually according to response.
Adult: Initially, 1.25 mg once daily; may be doubled at intervals of 2 weeks. Maintenance: 5 mg once daily. Adjust dose based on patient’s clinical response and tolerability. Elderly: Initiate at lower doses then adjust gradually according to response.
Oral Prophylaxis of cardiovascular events in high-risk patients
Adult: In patients ≥55 years who have CV disease, stroke or peripheral vascular disease or with diabetes mellitus and at least 1 CV risk: Initially, 2.5 mg once daily for 1-2 weeks, may increase to 5 mg once daily for the next 2-3 weeks. Maintenance: 10 mg once daily. Adjust dose based on patient’s clinical response and tolerability. Elderly: Initiate at lower doses then adjust gradually according to response.
Oral Congestive heart failure
Adult: Patients on diuretics: Initially, 1.25 mg once daily; may be doubled every 1-2 weeks. Maintenance: 10 mg daily in 2 divided doses. Adjust dose based on patient’s clinical response and tolerability. Elderly: Initiate at lower doses then adjust gradually according to response.
Oral Heart failure post myocardial infarction
Adult: In clinically and haemodynamically stable patients (within 24-48 hours post-MI): Initially 2.5 mg bid for 3 days; if not tolerated, start at 1.25 mg bid for 2 days, then increase to 2.5 mg bid. May double the doses at intervals of 1-3 days. Maintenance dose: 5 mg bid. Adjust dose based on patient’s clinical response and tolerability. Elderly: Initiate at lower doses then adjust gradually according to response.
Patients on haemodialysis: Initially, 1.25 mg daily. Max: 5 mg daily. Doses to be given few hours post-haemodialysis.
Initially, 1.25 mg daily. Max: 5 mg daily.
Usual initial dose. Max: 5 mg daily.
Usual initial dose. Max: 10 mg daily.
Max: 2.5 mg daily.
May be taken with or without food.
History of angioedema (e.g. hereditary, idiopathic, due to previous angioedema with ACE inhibitors or angiotensin II receptor antagonists [AIIRAs]); extracorporeal treatments resulting to contact of blood with negatively charged surfaces (e.g. dialysis or haemofiltration with certain high-flux membranes [e.g. polyacrylonitril membranes] and low-density lipoprotein apheresis with dextran); haemodynamically relevant bilateral renal artery stenosis or unilateral in the single kidney; hypotensive or haemodynamically unstable states. Concurrent use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment (GFR <60 mL/min/1.73 m2); concurrent use or within 36 hours of shifting to or from sacubitril/valsartan. Pregnancy and lactation.
Patients with severe hypertension, decompensated CHF; relevant left ventricular inflow or outflow impediment (e.g. aortic or mitral valve stenosis), hypertrophic cardiomyopathy with outflow tract obstruction, unstented unilateral or bilateral renal artery stenosis, volume or salt depletion, liver cirrhosis and/or ascites; transient or persistent heart failure post-MI, ischaemic heart disease or cerebrovascular disease, uncontrolled diabetes mellitus, hypoaldosteronism, acute cardiac decompensation, metabolic acidosis, collagen disease (e.g. SLE or scleroderma); history of airway surgery. Dehydrated patients. Patient undergoing major surgery or during anaesthetics. Desensitisation treatment (e.g. hymenoptera venom). Black race. Renal and hepatic impairment. Elderly.
Significant: Angioedema (e.g. head and neck angioedema, intestinal angioedema), hyperkalaemia, hypotension (with or without syncope, orthostatic), cholestatic jaundice, syndrome of inappropriate antidiuretic hormone (SIADH), hyponatraemia; rarely, haematologic effects (e.g. neutropenia or agranulocytosis, thrombocytopenia, anaemia); cough, renal impairment and/or increase in serum creatinine, anaphylactoid/anaphylactic reactions. Cardiac disorders: Chest pain, arrhythmia. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, dry mouth, gastrointestinal inflammation, digestive disturbances, abdominal discomfort, dyspepsia, constipation, dysgeusia. General disorders and administration site conditions: Asthenia, fatigue. Musculoskeletal and connective tissue disorders: Myalgia, muscle spasm. Nervous system disorders: Headache, dizziness, paraesthesia, vertigo. Respiratory, thoracic and mediastinal disorders: Bronchitis, sinusitis, dyspnoea. Skin and subcutaneous tissue disorders: Maculopapular rash, alopecia. Potentially Fatal: Rarely, pancreatitis, airway obstruction (due to angioedema of the tongue, glottis or larynx), fulminant hepatic necrosis, Stevens-Johnson syndrome, toxic epidermal necrolysis.
This drug may cause dizziness, if affected, do not drive or operate machinery.
Evaluate renal function and electrolytes before and during treatment. Monitor blood pressure, BUN, serum creatinine, K levels and Na levels; CBC with differentials. Monitor for signs of angioedema. Assess pregnancy status prior to therapy.
Symptoms: Excessive peripheral vasodilation (e.g. marked hypotension, shock), bradycardia, electrolyte disturbance, renal failure. Management: Symptomatic and supportive treatment. May perform gastric lavage or administer adsorbents; give α1- adrenergic agonists or angiotensin II (angiotensinamide) to restore haemodynamic stability.
May increase risk for angioedema with mammalian target of rapamycin (mTOR) inhibitors (e.g. everolimus, sirolimus, temsirolimus), dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. vildagliptin), neutral endopeptidase (NEP) inhibitor (e.g. racecadotril). May increase risk for hyperkalaemia with K salts, K-sparring diuretics, other drugs that increase K levels (e.g. heparin, trimethoprim/sulfamethoxazole, tacrolimus, ciclosporin). May increase risk of hypotension with other antihypertensive drugs (e.g. diuretics), other drugs that decrease blood pressure (e.g. anaesthetic, alfuzosin, baclofen, doxazosin, nitrates, prazosin, TCAs, tamsulosin, terazosin). May have decreased antihypertensive effect with vasopressor sympathomimetics and other drugs (e.g. dobutamine, dopamine, epinephrine, isoproterenol). May increase risk for haematologic reactions with allopurinol, cytostatics, corticosteroids, immunosuppressants, procainamide, other drugs that alter blood cell count. May increase serum levels and toxicity of lithium. May increase risk for hypoglycaemia with antidiabetic drugs (e.g. insulin). Reduced antihypertensive effect, increased risk of worsening renal function and increased serum K levels with NSAIDs. Potentially Fatal: Increased risk of hypotension, hyperkalaemia and impaired renal function (e.g. acute renal failure) with aliskiren. Increased risk of angioedema with concomitant sacubitril/valsartan therapy. May cause severe anaphylactic reactions with dextran sulfate in LDL apheresis. Increased risk for toxicity with angiotensin II receptor blockers in patients with diabetic nephropathy.
May increase risk of hypotension with acute alcohol intake.
May cause false-positive urine test for acetone determination using Na nitroprusside reagent. May result in false-negative aldosterone/renin ratio (ARR). May cause a positive direct Coombs’ test.
Description: Ramipril, an ACE inhibitor, is a prodrug of ramiprilat. After administration, ramipril metabolises in the liver via saponification by esterases into its active metabolite, ramiprilat. Ramiprilat competitively and reversibly binds to ACE thus inhibiting the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor) and the breakdown of bradykinin (vasodilator) which results in vasodilation and also reduced aldosterone secretion. Onset: 1-2 hours. Duration: 24 hours. Pharmacokinetics: Absorption: Rapidly absorbed from the gastrointestinal tract. Bioavailability: 28% (ramipril); 45% (ramiprilat). Time to peak plasma concentration: Within 1 hour (ramipril); 2-4 hours (ramiprilat). Distribution: Crosses the placenta. Plasma protein binding: 73% (ramipril); approx 56% (ramiprilat). Metabolism: Almost completely metabolised in the liver via saponification by esterases into ramiprilat (active metabolite). Excretion: Mainly via urine (60%) and the remainder via faeces (40%) as parent drug and metabolites. Elimination half-life: 13-17 hours (effective); >50 hours (terminal).