Heart Failure - Chronic Drug Summary

• 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)

• 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

• 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)

• 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

• 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

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; no washout period needed for patient already on ARB
• 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 1 week after initiation and during dose titration

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

• 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

• 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

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

• 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)

• 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

• GI effects (nausea, abdominal pain); CNS effects (headache, somnolence, dizziness); Other effects (edema, flushing, fatigue, palpitations)

• Contraindicated in patients with severe hypotension, shock, LV outflow obstruction, hemodynamically unstable HF after acute MI
• Use with caution in patients with hepatic impairment, during pregnancy and lactation

Special Instructions

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

• 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

• 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

• Metabolic effects (hyperkalemia, hyponatremia); GI effects (nausea/vomiting); CNS effects (headache, dizziness); Other effects (pruritus, hypotension)

• Prior to initiation of therapy, verify that eGFR ≥30 mL/min/1.73 m² (Finerenone eGFR ≥25 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
  • Discontinue if K ≥6 mmol/L in a non-hemolyzed sample
• Contraindicated in patients with hyperkalemia, severe renal impairment; concomitant use with strong CYP3A4 inhibitors
• Use with caution in patients with moderate hepatic impairment

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

• 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

• 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

• 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)

• 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

• 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

• 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

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

• CNS effects (headache, lightheadedness, dizziness, syncope); rarely CV effects (bradycardia, hypotension); GI effects (nausea/vomiting, bowel incontinence, xerostomia)
• Topical preparations: Contact dermatitis, local irritation and erythema

• 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 type 5 inhibitors (eg Sildenafil, Vardenafil, Tadalafil) is contraindicated

• CNS effects (headache, lightheadedness, dizziness, syncope, vertigo, restlessness, confusion); rarely CV effects (tachycardia, hypotension, flushing, palpitation); GI effects (nausea and vomiting, bowel incontinence, xerostomia)

• 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 type 5 inhibitors (eg Sildenafil, Vardenafil, Tadalafil) is contraindicated

• 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)

• 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

• 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

• 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

• CV effect (hypotension); CNS effects (syncope, headache); GI effects (nausea/vomiting, dyspepsia, GERD); Other effect (anemia)

• 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

• 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)

• 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

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

• Monitor INR if taken concomitantly with Warfarin

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

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