ACE Inhibitors

Drug	Dosage	Remarks
Benazepril	Initial dose: 2.5 mg PO 24 hourly Adjust dose gradually according to response Max dose: 20 mg/day	Adverse Reactions CV effects (hypotension, palpitations); CNS effects (fatigue, headache, dizziness); GI effect (taste disturbances); Respiratory effects (persistent dry cough, upper respiratory tract symptoms); Dermatologic effects (skin rashes, erythema multiforme, toxic epidermal necrolysis, pruritus, angioedema, photosensitivity reaction); Renal effect (renal impairment); Other effects (electrolyte disturbances, eg hyperkalemia, hyponatremia; blood disorders) Special Instructions Patients with HF and those who may be salt or water depleted (taking diuretic or on dialysis) may experience hypotension during initial stages of ACE inhibitor therapy Start treatment only under close medical supervision; in these patients use a low dose and have the patient in a supine position Start with low dose and if lower doses have been tolerated, gradually increase dose every 2 weeks until maximum tolerated dose is achieved Avoid in patients with aortic stenosis, mitral stenosis, outflow tract obstruction, renovascular disease (eg renal artery stenosis, severe renal insufficiency) and hereditary or idiopathic angioedema Should not be given to patients if they have experienced life-threatening adverse reactions (angioedema or renal failure) with or without previous exposure to the drug, hypotensive patients who are at immediate risk of cardiogenic shock Check BP, renal function and electrolytes 1-2 weeks after each dose increment, at 3 months then every 6 months More frequent monitoring is necessary in patients with previous or existing renal dysfunction NSAIDs should be avoided since they can block the beneficial effects and increase adverse effects of ACE inhibitors and may synergistically compromise renal function
Captopril	Initial dose: 6.25-12.5 mg PO 8-12 hourly Adjust dose gradually according to response Maintenance dose: 25 mg PO 8-12 hourly or 50 mg PO 8 hourly Max dose: 150 mg/day
Cilazapril	Initial dose: 0.5 mg PO 24 hourly Maintenance dose: 1-2.5 mg PO 24 hourly Max dose: 5 mg/day
Enalapril	Initial dose: 2.5 mg PO 24 hourly Maintenance dose: 20 mg PO 24 hourly or divided 12 hourly Max dose: 40 mg/day
Fosinopril	Initial dose: 10 mg PO 24 hourly Adjust dose gradually according to response Max dose: 40 mg/day
Imidapril	Initial dose: 2.5-10 mg PO 24 hourly Adjust dose gradually according to patient’s age and response
Lisinopril	Initial dose: 2.5 mg PO 24 hourly Maintenance dose: 5-20 mg PO 24 hourly Max dose: 40 mg/day
Perindopril¹	Initial dose: 2-2.5 mg PO 24 hourly Maintenance dose: 4-5 mg PO 24 hourly
Quinapril	Initial dose: 5 mg PO 12-24 hourly Maintenance dose: 10-40 mg/day PO divided 12 hourly Max dose: 40 mg/day
Ramipril	Initial dose: 1.25 mg PO 24 hourly Adjust dose gradually according to response Doses ≥2.5 mg/day may be given 24 hourly or divided 12 hourly Max dose: 10 mg/day
Trandolapril	Initial dose: : 1 mg PO 24 hourly Adjust dose gradually according to response Max dose: 4 mg/day

¹Combination with Bisoprolol is available. Please see the latest MIMS for specific formulations and prescribing information.

Adrenergic Agonist

Drug

Dosage

Remarks

Dopamine

Initial dose: 2-5 mcg/kg/min IV infusion Gradually increase by 5-10 mcg/kg/min increments
Max dose: 20-50 mcg/kg/min

Adverse Reactions

CV effects (ectopic beats, tachycardia, palpitations, anginal pain, hypotension, vasoconstriction); Other effects (nausea/vomiting, headache, dyspnea)
Less common: CV effects (bradycardia, cardiac conduction abnormalities, hypertension may occur if overdosage); Other effects (piloerection, azotemia)

Special Instructions

Hypovolemia should be corrected prior to treatment
Avoid in patients with pheochromocytoma, hyperthyroidism and uncorrected tachyarrhythmias or ventricular fibrillation
Use with caution and in low dose in patients with shock secondary to MI, patients with history of peripheral vascular disease (PVD) who are at increased risk of ischemia of the extremities
Use with caution in patients with hypersensitivity to sodium metabisulfite
When discontinuing, it may be necessary to gradually decrease the dose while expanding blood volume with IV fluids to prevent hypotension

Angiotensin II Antagonists

Drug	Dosage	Remarks
Candesartan	Initial dose: 4 mg PO 24 hourly Increase dose at intervals of 2 weeks to reach the target dose Max dose: 32 mg/day	Adverse Reactions Usually mild and transient: CNS effects (dizziness, headache); CV effect (dose-related orthostatic hypotension which may occur particularly in patients with volume depletion) Special Instruction Patients with volume depletion (eg high-dose diuretic therapy) may experience hypotension and should be started on low dose Increase dose every 1-2 weeks until maximum tolerated or target dose is achieved Use with caution in patients with renal artery stenosis, renal impairment or hepatic impairment, aortic stenosis, mitral stenosis, obstructive hypertrophic cardiomyopathy, primary hyperaldosteronism Contraindicated in patients with severe renal or hepatic dysfunction and cholestasis Check BP, renal function and electrolytes 1-2 weeks after each dose increment, at 3 months then every 6 months More frequent monitoring is necessary in patients with previous or existing renal dysfunction
Losartan	Initial dose: 12.5 mg PO 24 hourly Titrated at weekly intervals to 12.5 mg, 25 mg, 50 mg, 100 mg PO 24 hourly up to Max dose: 150 mg/day
Valsartan	Initial dose: 40 mg PO 12 hourly May increase to 80-160 mg PO 12 hourly at least at 2-week interval Max dose: 320 mg/day
Angiotensin Receptor-Neprilysin Inhibitor (ARNI)
Sacubitril/Valsartan	100 mg PO 12 hourly doubled up to 200 mg PO 12 hourly every 2-4 weeks Patient not on ACE inhibitor or ARB Starting dose: 50 mg PO 12 hourly	Adverse Reactions GI effects (diarrhea, nausea, gastritis); CNS effects (dizziness, headache, syncope, asthenia); Metabolic effects (hyper- or hypokalemia, hypoglycemia); Other effects (hypotension, renal impairment, anemia, cough, fatigue) Special Instructions Not to be administered until 36 hours after last dose of ACE inhibitor Temporary down-titration/discontinue administration in case of symptomatic hypotension, hyperkalemia or renal dysfunction Treatment should not be initiated in patient with serum K level >5.4 mmol/L or SBP <100 mmHg; not recommended for end-stage renal disease Starting dose of 50 mg 12 hourly is recommended for patient with eGFR <30 mL/min/1.73 m² (use with caution) or moderate hepatic impairment (Child-Pugh Class B) or if patient is taking Enalapril ≤10 mg/day or equivalent or Valsartan ≤160 mg/day or equivalent Starting dose of 100 mg 12 hourly is recommended for patient taking Enalapril >10 mg/day or equivalent or Valsartan >160 mg/day or equivalent Caution is required in patient with renal artery stenosis and monitoring of renal function is recommended; caution when initiating in patient with NYHA Class IV Contraindicated in patients with known history of angioedema related to previous ACE inhibitor or ARB therapy, hereditary or idiopathic angioedema, concomitant use with ACE inhibitors or ARBs, Aliskiren-containing medicinal products in patients with DM or renal impairment, severe hepatic impairment, biliary cirrhosis and cholestasis Check BP, renal function and electrolytes after initiation and during dose titration

Anti-Anginal Drug

Drug

Dosage

Remarks

Ivabradine¹

Initial dose:
<75 years: 5 mg PO 12 hourly
≥75 years: 2.5 mg PO 12 hourly
Titrate dose after 2 weeks depending on patient’s heart rate:
>60 bpm: Increase by 2.5 mg PO 12 hourly until max dose of 7.5 mg PO 12 hourly
50-60 bpm: Maintain current dose
<50 bpm: Decrease to 2.5 mg PO 12 hourly or discontinue if already at 2.5 mg PO 12 hourly
Max dose: 7.5 mg PO 12 hourly

Adverse Reactions

Ophthalmologic effects (luminous phenomena [phosphenes], blurred vision); CV effects (bradycardia, AV block, ventricular extrasystoles, palpitation); CNS effects (headache, dizziness, syncope)

Special Instructions

Should be taken with food; avoid excessive consumption of grapefruit juice
Use with caution in patients with hypotension, arrhythmias, moderate hepatic impairment, congenital QT syndrome and patients taking QT-prolonging drugs, severe renal impairment
Contraindicated in patients with resting heart rate <70 bpm prior to treatment, BP <90/50 mmHg, sick sinus syndrome, SA block, unstable or AHF, pacemaker dependent, unstable angina, 3rd-degree AV block, cardiogenic shock, acute MI, severe hepatic impairment
Monitor heart rate, BP and cardiac rhythm
Discontinue if symptoms of bradycardia persist even after dose titration

¹Combination with Carvedilol is available. Please see the latest MIMS for specific formulations and prescribing information

Antidiabetic Agents

Sodium-Glucose Linked Transporter/Co-transporter 2 (SGLT2) Inhibitors
Drug	Dosage	Remarks
Dapagliflozin¹	10 mg PO 24 hourly	Adverse Reactions GU effects (polyuria, dysuria, vulvovaginitis, balanitis, increased susceptibility to infections); Renal effect (acute kidney injury); Hematologic effect (increased hematocrit); GI effects (nausea, constipation); CV effects (hypotension, decreased blood volume); Other effects (dyslipidemia, increased creatinine and urea levels, hypoglycemia, rash, hyperhidrosis, back pain, euglycemic diabetic ketoacidosis) Electrolyte disturbances (hyperphosphatemia, hypermagnesemia, hyperkalemia) Special Instruction Monitor kidney function prior to starting therapy and assess periodically during therapy Should not be given in patients with severe renal impairment Though current evidence suggests that CV and renal benefits appear to be maintained even at eGFR levels as low as 30 mL/min/1.73 m², physicians need to recognize that at a level of CKD stage 3b and lower, the glucose-lowering efficacy of SGLT2 inhibitors is weak Ensure Dapagliflozin eGFR is ≥25 mL/min/1.73 m² prior to treatment initiation; no lower bound cutoff for Empagliflozin Use with caution in patients taking diuretics, NSAIDs and those with decreased blood volume and congestive HF May need to lower doses of insulin, sulfonylurea, insulin secretagogues when used concomitantly with SGLT2 inhibitors Consider withholding SGLT2 inhibitors in events that may precipitate diabetic ketoacidosis, eg intercurrent illness, surgery (elective or emergency), trauma, severe carbohydrate restriction SGLT2 inhibitors are generally safe for diabetic patients during Ramadan but should be discontinued in select patients whose risk for adverse effects might be increased
Empagliflozin	10 mg PO 24 hourly
Sotagliflozin	200 mg PO 24 hourly May titrate to 400 mg PO 24 hourly as tolerated	Adverse Reactions GU effects (urinary tract infection, genital mycotic infection); Other effects (volume depletion, diarrhea, hypoglycemia, dizziness) Special Instructions Correct volume status before initiating treatment; in patients with decompensated HF, start dosing when they are hemodynamically stable Ensure eGFR is ≥25 mL/min/1.73 m² prior to treatment initiation Withhold treatment at least 3 days, if possible, before major surgery or procedures associated with prolonged fasting Use with caution in patients with type 1 DM and diabetic ketoacidosis, volume depletion, urosepsis, pyelonephritis, Fournier’s gangrene, genital mycotic infections May need to lower dose of insulin or insulin secretagogue when used concomitantly with Sotagliflozin

¹Combination with Metformin is available. Please see the latest MIMS for specific formulations and prescribing information.

Beta-Blockers

Drug	Dosage	Remarks
Bisoprolol¹	Initial dose: 1.25 mg PO 24 hourly x 1 week If tolerated, increase to 2.5 mg PO 24 hourly x 1 week If tolerated, increase to 3.75 mg PO 24 hourly x 1 week If tolerated, increase to 5 mg PO 24 hourly x 4 week If tolerated, increase to 7.5 mg PO 24 hourly x 4 weeks If tolerated, increase to: Max dose: 10 mg/day	Adverse Reactions CNS effects (fatigue, depression, dizziness, headache, confusion, sleep disturbances); CV effects (HF, heart block, coldness of extremities, male impotence); Respiratory effects (bronchospasm in susceptible patients and drugs with beta₁ selectivity should be used with caution in these patients); GI effects (nausea/vomiting, constipation, diarrhea); Metabolic effects (can produce hyper- or hypoglycemia, changes in serum cholesterol and triglycerides) Special Instructions Patients should be on optimal therapy with ACE inhibitors (unless contraindicated) and should be in stable condition without need of IV inotropic therapy and without signs of marked fluid retention Dose should be titrated individually every 2 weeks to maximum dose tolerated by the patient After initiation and during the titration period (increase or decrease in dose), monitor patient for HF symptoms, fluid retention, hypotension, bradycardia and adjust ACE inhibitors, diuretics and other drugs as necessary Patients need to be aware that clinical response to beta-blockers may take 2-3 months If improvement in symptoms does not occur, beta-blockers should still be continued to reduce risk of major clinical events Contraindicated in severe bradycardia, second- or third-degree AV block, SA block, sick sinus syndrome and severe, unstable LV failure or acute HF, hypotension, cardiogenic shock, severe asthma, late stages of peripheral arterial occlusive disease and Raynaud’s syndrome, untreated pheochromocytoma, metabolic acidosis Use with caution in patients with bronchospasm, asthma or obstructive airway diseases, first-degree AV block, Prinzmetal’s angina, depression, patients with PVD, renal or hepatic dysfunction, thyrotoxicosis, psoriasis and patients on Insulin Beta-blockers may mask the symptoms of hyperthyroidism and hypoglycemia and may aggravate psoriasis Patients on long-term treatment should not discontinue abruptly; should discontinue gradually over 1-2 weeks
Carvedilol²	Initial dose: 3.125 mg PO 12 hourly x 2 weeks If tolerated, increase to 6.25 mg PO 12 hourly x 2 weeks If tolerated, increase to 12.5 mg PO 12 hourly x 2 weeks If tolerated, increase to 25 mg PO 12 hourly Max dose in patients <85kg: 25 mg PO 12 hourly Max dose in patients ≥85kg: 50 mg PO 12 hourly or 10 mg PO 24 hourly x 2 weeks Increase dosage to 20 mg, 40 mg, and then 80 mg PO 24 hourly over intervals of at least 2 weeks as tolerated
Metoprolol	12.5-25 mg PO 24 hourly If tolerated, may titrate dose at intervals of 2 weeks up to: Max dose: 200 mg/day
Nebivolol	Initial dose: 1.25 mg PO 24 hourly May increase dose stepwise at 1-2 weekly intervals, depending on patient tolerability to 2.5 mg PO, 5 mg PO and 10 mg PO 24 hourly Max dose: 10 mg/day

¹Combination with Perindopril is available. Please see the latest MIMS for specific formulations and prescribing information.
²Combination with Ivabradine is available. Please see the latest MIMS for specific formulations and prescribing information.

Calcium Antagonists

Drug	Dosage	Remarks
Dihydropyridines		Adverse Reactions CV effects (depression of cardiac function, hypotension, worsening HF, edema, flushing, tachycardia, palpitations, ischemic chest pain); GI effects (nausea, dyspepsia, dry mouth, constipation, abdominal pain, abnormal LFTs, gingival hyperplasia); CNS effects (headache, dizziness, tremor, insomnia, paresthesia); Hematologic effect (thrombocytopenia); Dermatologic effect (rashes) Short-acting dihydropyridine agents should be avoided because they have the potential to enhance risk of adverse cardiac events Special Instructions Contraindicated in patients with overt decompensated HF, though vasoselective dihydropyridines (eg Amlodipine, Felodipine) are tolerated in patients with a decreased LVEF Avoid in patients with cardiogenic shock, recent MI or acute unstable angina, severe aortic stenosis Use with caution in patients with acute cerebral infarction or hemorrhage, pheochromocytoma, hepatic impairment or decreased hepatic blood flow, portal hypertension, renal impairment and CHF Sudden withdrawal may exacerbate angina
Amlodipine	Initial dose: 5 mg PO 24 hourly Max dose: 10 mg/day
Benidipine	Initial dose: 2-4 mg PO 24 hourly Max dose: 8 mg/day
Felodipine	Initial dose: 5 mg PO 24 hourly Max dose: 10 mg/day
Isradipine	Initial dose: 1.25 mg PO 12 hourly or 2.5 mg PO 24 hourly
Nicardipine	Initial dose: 20 mg PO 8 hourly May increase at intervals of at least 3 days until required effect is achieved Maintenance dose: 30 mg PO 8 hourly or 60-120 mg/day PO in divided doses

Nisoldipine	Initial dose: 10 mg PO 24 hourly Maintenance dose: 20-40 mg PO 24 hourly

Cardiac Drugs

Drug

Dosage

Remarks

Amino Acid Derivative

L-carnitine

650-990 mg PO 8 hourly

Special Instructions

Should be taken with food
Contraindicated in patients with hypersensitivity to L-carnitine

Cardiac Glycosides

Drug	Dosage	Remarks
Digoxin	62.5-250 mcg PO 24 hourly Elderly, patients with impaired renal function or low lean body mass: 62.5 mcg/day PO or 125 mcg PO every other day	Adverse Reactions Side effects usually due to Digoxin toxicity or overdosage & Digoxin is usually well-tolerated at the recommended doses for CHF Digoxin toxicity: GI effects (nausea/vomiting, anorexia, diarrhea, abdominal pain) are usually the first signs of Digoxin toxicity; Other signs of toxicity: CNS effects (headache, fatigue, facial pain, weakness, dizziness, mental confusion); Ophthalmologic effects (blurred vision, color disturbances); Toxic doses may cause serious CV effects (aggravation of HF, arrhythmias, conduction disturbances) Hypokalemia can predispose a person to Digoxin toxicity Special Instructions Loading doses are not necessary in CHF patients Dosage is individualized according to age, lean body weight and renal status; adjust dose based on toxicity, efficacy, and blood levels Avoid in patients with obstructive cardiomyopathy unless there is severe HF, in patients with Wolff-Parkinson-White (WPW) syndrome or evidence of accessory pathway Contraindicated in patients with ventricular tachycardia, intermittent complete heart block or second-degree AV block Use with caution in partial heart block, sinus node disorders, acute myocarditis, acute MI, advanced HF, severe pulmonary disease, thyroid dysfunction, in patients undergoing electrocardioversion (withhold Digoxin for 24 hours prior to procedure) and with other drugs that can depress the sinus or AV nodal function (eg Amiodarone or beta-blocker) Hypokalemia, hypercalcemia, hypomagnesemia, hypoxia and hypothyroidism may affect the sensitivity to Digoxin Monitoring of Digoxin levels is only necessary if there is suspected toxicity
Metildigoxin (Methyl digoxin)	100-600 mcg PO 24 hourly

Diuretics

Drug	Dosage	Remarks
Aldosterone Antagonists
Eplerenone	Initial dose: 25 mg PO 24 hourly May increase dose to 50 mg PO 24 hourly within 4 weeks Max dose: 50 mg/day	Adverse Reactions CNS effects (headache, dizziness, drowsiness, ataxia, mental confusion); GI effects (cramps, diarrhea, abdominal pain, elevated liver enzymes); CV effect (angina); Endocrine and metabolic effects (gynecomastia, hirsutism, menstrual irregularities, impotence, mild acidosis, hyponatremia, hyperkalemia, increased uric acid, and transient increases in BUN); Respiratory effect (cough); Dermatologic effects (rash, angioneurotic edema) Special Instructions Prior to initiation of therapy, verify that eGFR ≥30 mL/min/1.73 m², creatinine ≤2.5 mg/dL (men) or ≤2 mg/dL (women) and serum K ≤5 mEq/L Closely monitor serum K and renal function 3 days after initiating therapy, at 1 week after initiation/titration, at least monthly for the first 3 months of treatment, then every 3 months thereafter Avoid in patients with hyperkalemia, severe renal impairment or Addison’s disease Use with caution in patients at increased risk of developing hyperkalemia (eg DM, elderly, patients with renal or hepatic impairment)
Spironolactone¹	Initial dose: 12.5-25 mg PO 24 hourly If after 1 month patient is still symptomatic but normokalemic, increase dose to 50 mg PO 24 hourly
Carbonic Anhydrase Inhibitor
Acetazolamide	250-375 mg PO 24 hourly in the morning	Adverse Reactions CNS effects (paresthesia, drowsiness, confusion); Other effects (loss of appetite, hearing dysfunction, taste alteration, GI disturbances, polyuria, acidosis, transient myopia) Special Instructions Avoid in patients with depressed Na and/or K blood serum levels, marked kidney or liver disease, hyperchloremic acidosis, cirrhosis Use with caution in patients with pulmonary obstruction or emphysema; rapid ascent to high altitude
Loop Diuretics
Bumetanide	Initial dose: 0.5-1 mg PO 24 hourly Give 2nd dose 6-8 hours later if necessary High doses may be given 8-12 hourly Max dose: 10 mg/day	Adverse Reactions Endocrine and metabolic effects (hypomagnesemia, hyponatremia, hypokalemia and hypochloremic alkalosis especially after large doses or prolonged administration, hyperglycemia, glycosuria, hyperuricemia and may precipitate gout) Signs of electrolyte imbalance: Headache, hypotension, muscle cramps, dry mouth, drowsiness, thirst, weakness Special Instructions Avoid in patients with anuria or in renal insufficiency caused by nephrotoxic or hepatotoxic drugs or caused by hepatic coma Contraindicated in patients with severe electrolyte depletion, hypersensitivity to sulfonamides and Furosemide, Addison’s disease Use with caution in patients with existing or at a risk of fluid and electrolyte imbalances, prostatic hyperplasia, impairment of micturition and gout Patients with hepatic cirrhosis are more likely to develop hypokalemia and patients with severe HF are more likely to suffer hyponatremia Monitor patient’s BP, renal function and electrolytes after initiation and during dose titration
Furosemide (Frusemide)²	Initial dose: 20-80 mg PO 12-24 hourly Max dose: 600 mg/day
Torasemide (Torsemide)	10-20 mg PO 24 hourly Max dose: 200 mg/day
Potassium-Sparing Diuretics
Amiloride³	Patient on ACE inhibitor Initial dose: 2.5 mg PO 24 hourly Max dose: 20 mg/day Patient not on ACE inhibitor Initial dose: 5-10 mg PO 24 hourly Max dose: 20 mg/day	Adverse Reactions Endocrine and metabolic effects (hyperkalemia especially in the elderly, patients with DM and patients with impaired renal function, hyponatremia has occurred in patients receiving combination diuretic therapy); GI effects (nausea/vomiting, abdominal pain, diarrhea, constipation, thirst); CNS effects (headache, dizziness, weakness, paresthesia); CV effect (orthostatic hypotension); Dermatologic effects (rash, pruritus) Special Instructions Use only if hypokalemia persists after the start of ACE inhibitors and other diuretics Avoid in patients with hyperkalemia or severe renal impairment Use with caution in patients at increased risk of developing hyperkalemia (eg DM, elderly, patients with renal or hepatic impairment) Use low dose for 1 week, then check serum K and creatinine after 5-7 days of therapy and titrate dose as required Continue to recheck serum K and creatinine every 5-7 days until K values are stable Monitor serum electrolytes regularly Discontinue for at least 3 days before glucose tolerance tests are done
Triamterene	Patient on ACE inhibitor Initial dose: 25 mg PO 24 hourly Max dose: 100 mg/day Patient not on ACE inhibitor Initial dose: 100 mg PO 12 hourly Max dose: 300 mg/day
Thiazides & Related Diuretics
Bendroflumethiazide	Initial dose: 5-10 mg PO 24 hourly or on alternate days Maintenance dose: 5-30 mg PO weekly in divided doses Max dose: 20 mg/day	Adverse Reactions CV effects (postural hypotension, venous thrombosis); Endocrine and metabolic effects (hyperuricemia and may precipitate gout in some patients, hypochloremic alkalosis, hyponatremia, hypokalemia, hyponatremia, hypomagnesemia, hyperglycemia and glucosuria in DM or other susceptible patients, altered lipid concentrations); GI effects (GI irritation, nausea/vomiting, constipation, anorexia, diarrhea, pancreatitis, intrahepatic cholestasis); CNS effects (headache, dizziness, lethargy, syncope, vertigo, paresthesia); Dermatologic effects (hypersensitivity reactions, photosensitivity); GU effect (impotence) Signs of electrolyte imbalances: Headache, muscle cramps, dry mouth, hypotension, thirst, weakness, drowsiness Special Instructions Do not use thiazides if GFR <30 mL/min unless used synergistically with loop diuretics Avoid in patients with severe hepatic impairment if encephalopathy may be precipitated, in patients with severe renal impairment or anuria, in patients with preexisting hypercalcemia, symptomatic hyperuricemia, sulfonamide allergy, Addison’s disease and refractory hypokalemia, hyponatremia Use with caution in patients with existing or at risk of fluid and electrolyte imbalances (eg elderly), patients with hepatic cirrhosis are more likely to develop hypokalemia and patients with severe HF are more likely to suffer hyponatremia Use with caution in patients with hepatic and renal impairment, porphyria, hyperlipidemia and extrasystole May exacerbate SLE and aggravate DM and gout Monitor patient for signs of fluid and electrolyte imbalance
Chlortalidone (Chlorthalidone)	Initial dose: 25-50 mg PO 24 hourly May increase to 100-200 mg PO 24 hourly in severe cases Maintenance dose: 25-50 mg PO 24 hourly or on alternate days Max dose: 200 mg/day
Cyclopenthiazide	Initial dose: 0.25-0.5 mg PO 24 hourly Reduce to lowest effective dose for maintenance Max dose: 1 mg/day

Hydrochlorothiazide⁴ (Dihydrochlorothiazide)	Initial dose: 25 mg PO 24 hourly Maintenance dose: 25-100 mg PO 24 hourly Max dose: 200 mg/day
Indapamide	Initial dose: 1.5-2.5 mg PO 24 hourly May increase to 5 mg PO 24 hourly after 1 week if necessary Max dose: 5 mg/day
Metolazone	Initial dose: 2.5 mg PO 24 hourly May increase to 20 mg PO 24 hourly Max dose: 80 mg/day
Vasopressin Antagonist
Tolvaptan	Usual dose: 15 mg PO 24 hourly May increase to 30 mg PO 24 hourly after at least 24 hours For patients with serum Na <125 mEq/L or for whom rapid volume decrease is considered inappropriate: Start with 7.5 mg PO 24 hourly Max dose: 60 mg/day Max duration of therapy: 30 days	Adverse Reactions GI effects (dry mouth, constipation, hepatotoxicity); Endocrine effects (thirst, polyuria, hyperglycemia) Special Instructions Assess serum Na concentration and neurologic status especially during initiation and after titration Carefully monitor patient’s fluid intake, urine volume, serum Na level and for occurrence of clinical symptoms (eg thirst, dehydration) Contraindicated in cases of urgent need to raise serum Na acutely, in hypernatremia, in patients unable to autoregulate fluid balance Discontinue treatment if serum Na is increased above normal range, if significant signs and symptoms of dehydration and hypovolemia are present Use with caution in hyperkalemia or drugs that increase serum K, co-administration with hypertonic saline solutions

¹Combinations of Spironolactone and Hydroflumethiazide, and Spironolactone and Furosemide are available. Please see the latest MIMS for specific formulations and prescribing information.
²Combination with Spironolactone is available. Please see the latest MIMS for specific formulations and prescribing information.
³Combination with Hydrochlorthiazide is available. Please see the latest MIMS for specific formulations and specific prescribing information.
⁴Combination with Amiloride or Candesartan is available. Please see the latest MIMS for specific formulations and specific prescribing information.

Nitrates (Oral)

Drug	Available Strength	Dosage	Remarks
Glyceryl trinitrate (Nitroglycerin, GTN, NTG)	400, 500, 600 mcg sublingual (SL) tab	400-600 mcg SL every 5 minutes until cessation of pain or side effects occur Max dose: 3 doses within 15 minutes	Adverse Reactions CNS effects (headache, lightheadedness, dizziness, syncope, vertigo, restlessness, confusion); rarely CV effects (tachycardia, hypotension, flushing, palpitation); GI effects (nausea and vomiting, bowel incontinence, xerostomia) Special Instructions Nitrate-free interval is recommended in patients on long-term therapy with nitrates to decrease the risk of nitrate tolerance Avoid in patients with severe hypotension, hypovolemia, marked anemia, heart failure due to obstruction or raised intracranial pressure due to head trauma or hemorrhage Use with caution in patients with severe renal or hepatic dysfunction, hypothyroidism, malnutrition, mitral valve prolapse, arterial hypoxemia, glaucoma or hypothermia Co-administration with phosphodiesterase inhibitors (eg Sildenafil) is contraindicated within 24-hour interval after taking a nitrate preparation
Glyceryl trinitrate (Nitroglycerin, GTN, NTG)	400 mcg/dose SL spray	1-2 sprays (400-800 mcg) SL, closing the mouth after spraying Max dose: 3 doses within 15 minutes
Isosorbide dinitrate	5 mg, 10 mg SL tab	5-10 mg SL every 2-3 hours until cessation of pain or side effect occurs
	10 mg tab	30-160 mg/day PO in divided doses Max dose: 240 mg/day
	20 mg retard tab	20 mg PO 12 hourly
	40 mg retard tab	40 mg PO 12 hourly
	1.25 mg/dose buccal spray	1-3 sprays (1.25-3.75 mg) into the buccal cavity, waiting 30 seconds between sprays Do not inhale medication
Isosorbide 5-mononitrate (Isosorbide mononitrate)	20 mg/tab	20 mg PO 12 hourly Max dose: 120 mg/day
	50 mg/cap	50 mg PO 24 hourly May increase to 100 mg PO simultaneously
	60 mg/tab	30-60 mg PO 24 hourly Max dose: 120 mg/day

Vasodilators Used in Cardiac Diseases

Drug	Dosage	Remarks
Hydralazine¹	In combination w/ Isosorbide dinitrate: Initial dose: 25 mg PO 6-8 hourly May increase every ≥1-2 weeks if needed Maintenance dose: 50-75 mg PO 6 hourly	Adverse Reactions Typically subside with continued therapy: CV effects (tachycardia, palpitations, angina, flushing); GI effects (anorexia, nausea/vomiting, diarrhea); Other effects (dizziness, nasal congestion) Other CV effects (postural hypotension, fluid retention, edema); Other effects (weight gain, tremor, conjunctivitis, muscle cramps, lacrimation) Special Instructions Avoid in patients with severe tachycardia, HF with high cardiac output, dissecting aortic aneurysm, cor pulmonale or myocardial insufficiency due to mechanical obstruction (eg aortic stenosis, mitral stenosis, constrictive pericarditis), idiopathic SLE and related disorders Use with caution in patients with ischemic heart disease, recent MI, cerebrovascular disorders, impaired renal or hepatic function CBC, antinuclear antibody determinations and urinalysis should be done periodically during long-term therapy Monitor BP and heart rate after initiation and during dose titration
Isosorbide dinitrate¹	Use in combination with Hydralazine: Initial dose: 20 mg PO 8 hourly x 2-4 weeks If tolerated, increase dose to Maintenance dose: 40 mg PO 8 hourly Max dose: 120 mg/day	Adverse Reactions CNS effects (headache which usually decreases with long-term administration, lightheadedness, dizziness, syncope, confusion, weakness, restlessness, vertigo); rarely CV effects (palpitations, tachycardia, hypotension, flushing); GI effects (nausea/vomiting, abdominal pain, bowel incontinence, xerostomia) Nitrate tolerance usually develops with long-term use and dosing with adequate nitrate-free interval is recommended Special Instructions Avoid in patients with severe hypotension, hypovolemia, marked anemia, HF due to obstruction or raised intracranial pressure due to head trauma or hemorrhage Use with caution in patients with severe renal or hepatic dysfunction, hypothyroidism, malnutrition or hypothermia Co-administration with phosphodiesterase inhibitors (eg Sildenafil) are contraindicated Monitor BP and heart rate after initiation and during dose titration
Soluble Guanylate Cyclase Stimulator
Vericiguat	2.5 mg PO 24 hourly May double the dose every 2 weeks to up to Maintenance dose: 10 mg PO 24 hourly	Adverse Reactions CV effect (hypotension); CNS effects (syncope, headache); GI effects (nausea/vomiting, dyspepsia, GERD); Other effect (anemia) Special Instructions Contraindicated in pregnancy, patients with concomitant use of other soluble guanylate cyclase stimulators Breastfeeding or concomitant use of PDE-5 inhibitors is not recommended Monitor BP and CBC for anemia

¹The combination of Hydralazine and Isosorbide dinitrate should not be used for the treatment of HF in patients who have no prior use of ACE inhibitor and should not be substituted for ACE inhibitor in patients who are tolerating ACE inhibitors without difficulty.

Other Cardiovascular Drugs

Drug

Dosage

Remarks

Levosimendan

Individualize dosage
Initial dose:
6-12 mcg/kg IV over 10 minutes followed by
Continuous infusion:
0.1 mcg/kg/min IV for 24 hours If tolerated and an increased hemodynamic effect is required, may increase to 0.2 mcg/kg/min
Rate of infusion may be decreased to 0.05 mcg/kg/min or discontinued if the response is deemed excessive

Adverse Reactions

Hematologic effect (decreased Hb): Metabolic effect (hypokalemia); CNS effects (dizziness, headache); CV effects (hypotension, myocardial ischemia, extrasystoles, AF, tachycardia, ventricular tachycardia); GI effects (nausea and vomiting)

Special Instructions

Contraindicated in patients with severe renal or hepatic impairment, significant mechanical obstructions affecting ventricular filling or outflow or both, severe hypotension and tachycardia, history of torsades de pointes
Use with caution in patients with mild to moderate renal or hepatic impairment, ischemic CV disease and concurrent anemia, tachycardia or AF with rapid ventricular response, ongoing coronary ischemia, acute HF related to a recent onset of a non-cardiac condition, serious deterioration of HF after surgery and severe HF awaiting heart transplantation; concomitant use with other inotropic agents (except Digoxin) or QTc-prolonging drugs
Monitor serum K levels, changes in BP or heart rate

Ubidecarenone
(Coenzyme Q10, Ubiquinone-10)

Adjunctive therapy:
30-200 mg PO 24 hourly

Adverse Reactions

GI effects (nausea, epigastric pain, heartburn, diarrhea); Other effects (appetite suppression, rash, sleep disturbances)

Special Instructions

Monitor INR if taken concomitantly with Warfarin

Other Drugs Acting on The Genito-Urinary System

Drug

Dosage

Remarks

Sambong leaf (Blumea balsamifera L.)

500 mg PO 8 hourly

Adverse Reactions

GI effects (epigastric pain, constipation, flatulence); Dermatologic effects (itching, skin irritation)

Special Instructions

Use with caution in patients with excretory urogram showing signs of renal obstruction; pregnancy and lactation

Disclaimer

All dosage recommendations are for non-pregnant and non-breastfeeding women and non-elderly adults with normal renal and hepatic function unless otherwise stated.
Not all products are available or approved for above use in all countries.
Products listed in the Drug Summary are based on indications stated in the locally approved product monographs.
Please refer to local product monographs in Related MIMS Drugs for country-specific prescribing information.

Heart Failure - Chronic Drug Summary

ACE Inhibitors

Adrenergic Agonist

Angiotensin II Antagonists

Anti-Anginal Drug

Antidiabetic Agents

Beta-Blockers

Calcium Antagonists

Cardiac Drugs

Cardiac Glycosides

Diuretics

Nitrates (Oral)

Vasodilators Used in Cardiac Diseases

Other Cardiovascular Drugs

Other Drugs Acting on The Genito-Urinary System

Disclaimer

Related MIMS Drugs