Heart Failure - Acute 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 heart failure 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 (dose-related increases in heart rate and BP, ectopic beats, angina/chest pain, palpitations)
  • Reduce dose if the above occur or stop temporarily
• Other CV effects (rarely ventricular tachycardia, occasionally hypotension which may respond to decrease in dose); Other occasional effects (dyspnea, headache, nausea/vomiting, leg cramps, paresthesia)

• Hypovolemia should be corrected prior to treatment
• Avoid in patients with marked obstruction (eg idiopathic subaortic stenosis, severe valvular stenosis), atrial fibrillation, atrial flutter and hypersensitivity to sulfites
• Use with caution in patients with acute MI and in cardiogenic shock complicated by severe hypotension
• Tolerance may develop after 72 hours and higher dose may be needed
• Recommended to decrease dose slowly upon discontinuation

• 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 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 

• CV effects (palpitations, tachycardia, coldness of extremities, hypertension, vasodilation with flushing and hypotension); CNS effects (anxiety, restlessness, tremors, weakness, dizziness, headache); Other effects (sweating, hypersalivation)
• Overdosage or in susceptible subjects: Cardiac arrhythmias, sharp increase in BP

• Correction of hypovolemia, metabolic acidosis and hypoxia or hypercapnia should be carried out prior to administration or concomitantly
• Avoid in patients with pheochromocytoma, arrhythmia, tachycardia >140 bpm, severe hypertension and narrow-angle glaucoma
• Use with caution in patients with pre-existing arrhythmias or tachycardia, Prinzmetal’s angina, thromboembolic disorders, history of ischemic heart disease, history of occlusive vascular disease, hypertension, allergy to sodium metabisulfite, elderly and DM patients

• CV effects (hypertension, reflex bradycardia, peripheral ischemia which may be severe); CNS effects (headache, weakness, dizziness, tremor, restlessness, anxiety); Respiratory effects (respiratory difficulty, apnea); Other effects (pallor, intense sweating, vomiting)
• Severe local adverse effects may occur and extravasation must be avoided

• Correction of hypovolemia prior to administration is recommended
• Large vein should be used for IV infusion
• Avoid in the presence of hypertension and monitor BP closely
• Use with caution in patients with hypoxia or hypercapnia, cardiac arrhythmias are more likely in these patients
• Use with caution in hyperthyroidism
• When discontinuing, decrease dose slowly and observe patient for too rapid fall in BP
  • Additional IV fluids may be necessary

• Usually mild and transient: CNS effects (dizziness, headache); CV effect (dose-related orthostatic hypotension which may occur particularly in patients with volume depletion); renal impairment
• Rare other effects: Rash, angioedema, elevated liver function tests (LFTs); myalgia

• Patients with volume depletion (eg high-dose diuretic therapy) may experience hypotension and should be started on low dose
• 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

• 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)

• 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 heart failure 
• 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

• GU effects (urinary tract infection, genital mycotic infection); Other effects (volume depletion, diarrhea, hypoglycemia, dizziness)

• 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 (heart failure, 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
• During the titration period (increase or decrease in dose), monitor patient for heart failure 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 patients with severe bradycardia, 2nd- or 3rd-degree of AV block, SA block, sick sinus syndrome and severe, unstable LV failure or acute heart failure, hypotension, cardiogenic shock, severe asthma or COPD, 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, 1st-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

• Side effects are usually due to Digoxin toxicity or overdosage and Digoxin is usually well-tolerated at the recommended doses for chronic heart failure 
• 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); Visual disturbances (blurred vision, color disturbances); Toxic doses may cause serious CV effects (aggravation of heart failure, arrhythmias, conduction disturbances)
• Hypokalemia can predispose a person to Digoxin toxicity
• Rarely hypersensitivity reactions occur

• Dosage is individualized according to age, lean body weight and renal status; adjust dose based on toxicity, efficacy, and blood levels
• Low doses of Digoxin (62.5 mcg/day or 125 mcg every other day) should be used in the elderly, patients with impaired renal function or low lean body mass
• Avoid in patients with obstructive cardiomyopathy unless there is severe heart failure, in patients with Wolff-Parkinson-White (WPW) syndrome or evidence of accessory pathway
• Contraindicated in patients with ventricular tachycardia, intermittent complete heart block or 2nd-degree AV block
• Use with caution in partial heart block, sinus node disorders, acute myocarditis, acute MI, advanced heart failure, 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

• Effects seen during infusion: CV effect (hypotension); CNS effect (headache)
• Less commonly: CV effects (extrasystole, atrial fibrillation, tachycardia, palpitations, MI)
• Effects seen within 3 days after start of infusion: Hematologic effect (decreased Hb): Metabolic effect (hypokalemia); CNS effects (dizziness, headache); CV effects (hypotension, myocardial ischemia, extrasystoles, atrial fibrillation, tachycardia, ventricular tachycardia); GI effects (nausea/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, hypotension, tachycardia or atrial fibrillation with rapid ventricular response
• Monitor serum K levels and correct low K levels prior to therapy
• Correct hypovolemia before starting therapy
• Monitor heart rate for at least 3 days after the end of infusion or until the patient is clinically stable (5 days is recommended in those with mild-moderate hepatic impairment)

• Adverse effects are typically either due to hypotensive effects or from excessive cyanide accumulation (thiocyanate toxicity)
• These effects may be reduced with a decrease in infusion rate: GI effects (nausea/vomiting, abdominal pain); CNS effects (apprehension, headache, dizziness, restlessness); CV effects (retrosternal discomfort, palpitations); Other effects (perspiration, muscle twitching)
• Excessive cyanide may result in: Tachycardia, sweating, hyperventilation, arrhythmias and metabolic acidosis; methemoglobinemia may also occur
• Thiocyanate may cause: Tinnitus, miosis, hyperreflexia, confusion, hallucinations and convulsions have been reported

• BP, venous O₂ concentration and acid-base balance should be monitored closely
• Avoid extravasation
• Avoid in compensatory hypertension
• Use with caution or not at all in hepatic impairment and in patients with low plasma cobalamin concentration or Leber’s optic atrophy
• Use with caution in patients with impaired cerebrovascular circulation, hypothyroidism, renal impairment, ischemic heart disease and impaired pulmonary function
• If continued for longer than 72 hours, plasma concentrations of cyanide should be monitored
• When discontinuing, reduce dose slowly

• 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) 

• 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, 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)

Adverse Reactions

• CNS effects (paresthesia, drowsiness, confusion); Other effects (loss of appetite, hearing dysfunction, 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, respiratory acidosis, DM, history of renal calculi, potential urinary tract obstruction

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 imbalances: Headache, muscle cramps, dry mouth, hypotension, thirst, weakness, drowsiness, etc
• Less common other effects (blurred vision, dizziness, orthostatic hypotension, skin rashes and hypersensitivity reactions, tinnitus)

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 heart failure are more likely to suffer hyponatremia
• Monitor patient’s BP, renal function and electrolytes after initiation and during dose titration

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, muscle cramps, 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 1 week low dose and check serum K and Cr after 5-7 days of therapy and titrate dose as required
  • Continue to recheck serum K and Cr 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

Adverse Reactions

• CV effects (postural hypotension, venous thrombosis); Endocrine and metabolic effects (volume depletion, electrolyte imbalance, gout, hyperglycemia, altered lipid concentrations); CNS effects (lethargy, drowsiness, dizziness, syncope, vertigo, paresthesia); Dermatologic effects (hypersensitivity reactions, photosensitivity); GI effects (nausea/vomiting, dry mouth, diarrhea, constipation, pancreatitis, intrahepatic cholestasis); Hematologic effect (blood dyscrasia); GU effect (impotence); Musculoskeletal effects (muscle cramps, joint pain)

Special Instructions

• May cause hypokalemia, exacerbate SLE and aggravate DM and gout
• Use with caution in patients with hepatic and renal impairment, porphyria, existing electrolyte disturbance, hepatic cirrhosis, severe heart failure, hyperlipidemia, extrasystole
• Avoid in patients with severe renal and hepatic impairment, symptomatic hyperuricemia, sulfonamide allergy, Addison’s disease and refractory hypokalemia, hyponatremia, hypercalcemia
• Monitor 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

• IV administration (especially if given too rapidly): May cause CV effects (severe hypotension, retrosternal discomfort, palpitations, tachycardia, flushing); GI effects (nausea and retching, abdominal pain); CNS effects (apprehension, restlessness, muscle twitching, syncope, headache); Other effect (diaphoresis); prolonged administration has been associated with methemoglobinemia 

• 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, hypertrophic obstructive cardiomyopathy, cerebral hemorrhage or head trauma, low cardiac output secondary to hypovolemia, inferior MI with right ventricular involvement, raised intracranial pressure
• Use with caution in patients with severe renal or hepatic dysfunction, hypothyroidism, malnutrition, hypothermia, cerebrovascular disease, lung disease or cor pulmonale, mitral valve prolapse, cardiac tamponade, glaucoma
• Close monitoring of heart rate and BP is necessary during IV infusion
• Slow or temporarily stop infusion if mean arterial BP falls below 80 mmHg or SBP falls <90 mmHg
• Gradual withdrawal in patients who have received prolonged high-dose infusions
• Do not administer to patients who have taken phosphodiesterase inhibitors within the past 24 hours
• The plastic used for administration may absorb GTN and dosing may need to be adjusted for this

• 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 inhibitors (eg Sildenafil) is contraindicated within 24-hour interval after taking a nitrate preparation

• Instruct patient to sit down and use medication at first sign of angina attack
• Patient should be made aware that dose may be repeated in 5-10 minutes with max of 3 doses given
• Patient should seek emergency medical treatment if pain does not subside

• CV effects (hypotension, angina); CNS effects (dizziness, headache, anxiety, insomnia); GI effects (nausea/vomiting, abdominal pain)

• Contraindicated in patients with cardiogenic shock (when used as a primary therapy) and hypotension (SBP <90 mmHg)
• Not recommended in patients with known or suspected low cardiac filling pressures or in whom vasodilating agents are inappropriate (eg restrictive or obstructive cardiomyopathy, pericardial tamponade, significant valvular stenosis, constrictive pericarditis)
• Monitor BP closely during administration
• Stop or reduce dose if hypotension occurs during infusion

• CV effects (hypotension, supraventricular arrhythmia, ventricular arrhythmia, chest pain, vasculitis); CNS effects (headache, tremor); GI effects (nausea/vomiting); Metabolic effect (hypokalemia); Respiratory effect (bronchospasm); Other effects (fever, nail discoloration, hypersensitivity, myositis)
• Produces dose-dependent thrombocytopenia
• Long-term use may cause hepatotoxicity

• Monitor BP, heart rate, platelet count and liver function tests (LFTs)
• Maintain fluid and electrolyte balance
• Contraindicated in patients with heart valve stenosis and acute MI
• Use with caution in patients with severe obstructive aortic or pulmonary vascular disease, hypertrophic cardiomyopathy, atrial flutter or fibrillation