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Pronunciation
(eye NAM ri none)
Generic Available (U.S.)
Yes
Index Terms
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Short-term therapy in patients with intractable heart failure
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events have been observed in some animal reproduction studies.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to inamrinone, any component of the formulation, or bisulfites (contains sodium metabisulfite); patients with severe aortic or pulmonic valvular disease
Warnings/Precautions
Concerns related to adverse effects:
• Arrhythmias: Observe for arrhythmias in this very high-risk patient population. Ventricular or atrial arrhythmias may persist even after discontinuation of inamrinone, especially in patients with renal dysfunction. Ensure that ventricular rate is controlled in atrial fibrillation/flutter before initiating therapy; may increase ventricular response rate. In heart transplant candidates, institute appropriate measures to protect patient against risks of sudden cardiac death.
• Hepatic effects: Discontinue therapy if dose-related changes in LFTs and clinical symptoms of hepatotoxicity occur; monitor liver function.
• Hypotension: Monitor blood pressure and heart rate closely. Infusion may require reduction or temporary discontinuation if hypotension occurs. Hypotension may be prolonged especially in patients with renal dysfunction. Vigorous diuresis may contribute to hypotension; cautious administration of fluids may be required to prevent hypotension.
• Thrombocytopenia: Can cause thrombocytopenia (due to decreased platelet survival time). If platelet count falls below 150,000/mm3, may maintain therapy, decrease daily dose, or discontinue therapy based upon risk versus benefit. Monitor closely.
Disease-related concerns:
• Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to initiation of and throughout therapy.
• Idiopathic hypertrophic subaortic stenosis (IHSS)/hypertrophic obstructive cardiomyopathy (HOCM): May aggravate this condition.
• Myocardial infarction (MI): Not recommended in acute MI treatment.
Other warnings/precautions:
• Long-term therapy: According to the ACC/AHA 2009 heart failure guidelines, long-term, regularly-scheduled intermittent infusions are strongly discouraged.
• Monitoring: Monitor fluid status closely; patients may require adjustment of diuretic and electrolyte replacement therapy.
Adverse Reactions
1% to 10%:
Cardiovascular: Arrhythmias (3%; especially in high-risk patients), hypotension (1% to 2%; dose related)
Gastrointestinal: Nausea (1% to 2%), vomiting (1%)
Hematologic: Thrombocytopenia (~2%; dose related)
<1% (Limited to important or life-threatening): Abdominal pain, anorexia, chest pain, fever, hepatotoxicity, hyperbilirubinemia, hypersensitivity, injection site reactions, jaundice, liver enzymes increased
Metabolism/Transport Effects
None known.
Drug Interactions
There are no known significant interactions.
Storage
Store at 15°C to 30°C (59°F to 86°F). Protect from light. Store in carton until ready for use.
Reconstitution
For continuous infusion, dilute with 0.45% or 0.9% sodium chloride to final concentration of 1-3 mg/mL. Use within 24 hours. Do not directly dilute with dextrose-containing solutions; chemical interaction occurs. May be administered I.V. into running dextrose infusions.
Compatibility
Stable in NS, 1/2NS; incompatible in D5W.
Y-site administration: Compatible: Aminophylline, atropine, bivalirudin, calcium chloride, cimetidine, cisatracurium, dexmedetomidine, digoxin, dobutamine, dopamine, epinephrine, famotidine, fenoldopam, hetastarch in lactate electrolyte injection (Hextend®), hydrocortisone sodium succinate, isoproterenol, lidocaine, methylprednisolone sodium succinate, nesiritide, nitroglycerin, nitroprusside, norepinephrine, phenylephrine, potassium chloride, propofol, propranolol, remifentanil, verapamil. Incompatible: Furosemide, sodium bicarbonate. Variable (consult detailed reference): Procainamide.
Compatibility in syringe: Compatible: Atropine, calcium chloride, epinephrine, propranolol, sodium bicarbonate, verapamil.
Mechanism of Action
Inhibits myocardial cyclic adenosine monophosphate (cAMP) phosphodiesterase activity and increases cellular levels of cAMP resulting in a positive inotropic effect and increased cardiac output; also possesses systemic and pulmonary vasodilator effects resulting in pre- and afterload reduction; slightly increases atrioventricular conduction
Pharmacodynamics/Kinetics
Onset of action: I.V.: 2-5 minutes
Peak effect: ∼10 minutes
Duration (dose dependent): Low dose: ∼30 minutes; Higher doses: ∼2 hours
Half-life elimination, serum: Adults: Healthy volunteers: 3.6 hours, Congestive heart failure: 5.8 hours
Excretion: Urine (10% to 40% as parent drug)
Dosage
Dosage is based on clinical response (Note: Dose should not exceed 10 mg/kg/24 hours).
Infants (unlabeled population), Children (unlabeled population), and Adults: 0.75 mg/kg I.V. bolus over 2-3 minutes followed by maintenance infusion of 5-10 mcg/kg/minute; I.V. bolus may need to be repeated in 30 minutes.
Dosing adjustment in renal failure:
Infants and Children:
Clcr 30-50 mL/minute: Administer 100% of dose
Clcr10-29 mL/minute: Administer 50% of dose
Clcr <10 mL/minute: Administer 25% of dose
Intermittent hemodialysis or peritoneal dialysis: Administer 25% of dose
Adults:
Clcr ≥10 mL/minute: Administer 100% of dose
Clcr <10 mL/minute: Administer 50% to 75% of dose
Administration: I.V.
May be administered undiluted for I.V. bolus doses. Dilute for use as continuous infusion.
Monitoring Parameters
Platelet count, CBC, electrolytes (especially potassium and magnesium), liver function and renal function tests; ECG, CVP, SBP, DBP, heart rate; infusion site
If pulmonary artery catheter is in place, monitor cardiac index, stroke volume, systemic vascular resistance, pulmonary capillary wedge pressure and pulmonary vascular resistance.
Geriatric Considerations
While inamrinone is not specifically arrhythmogenic, the elderly may be at high risk for ventricular and particularly atrial arrhythmias due to high incidence of arrhythmias in this population. Also, the elderly are often hypovolemic due to dehydration; therefore, monitor fluid status carefully (CVP line) in order to have effective falling pressure for maximal response. Found to be as effective as dobutamine in the elderly with heart failure in one study despite the decline in beta-adrenergic response with age.
Cardiovascular Considerations
Although the phosphodiesterase inhibitor drugs may induce short-term improvement in clinical status in patients with intractable heart failure, longer-term studies of these drugs in heart failure have suggested that there is a net increase in mortality.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
May cause hypotension which may be exacerbated by psychotropics
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, solution: 5 mg/mL (20 mL [DSC])
References
Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007, p 45, 145.
Feldman AM, Bristow MR, Parmley WW, et al, “Effects of Vesnarinone on Morbidity and Mortality in Patients With Heart Failure. Vesnarinone Study Group,” N Engl J Med, 1993, 329(3):149-55.
Hunt SA, Abraham WT, Chin MH, et al, “2009 Focused Update Incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation,” J Am Coll Cardiol, 2009, 53(15):e1-e90.
Packer M, Carver JR, Rodeheffer RJ, et al, “Effect of Oral Milrinone on Mortality in Severe Chronic Heart Failure. The PROMISE Study Research Group,” N Engl J Med, 1991, 325(21):1468-75.
Packer M, Medina N, and Yushak M, “Hemodynamic and Clinical Limitations of Long-Term Inotropic Therapy With Amrinone in Patients With Severe Chronic Heart Failure,” Circulation, 1984, 70(6):1038-47.
International Brand Names
Lexi-Comp.com
Last full review/revision February 2012
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