Milrinone is a parenteral positive inotrope and vasodilator with phosphodiesterase inhibitor activity indicated for the short-term treatment of patients with acute decompensated heart failure. It has minimal chronotropic activity. Milrinone is a preferred parenteral inotrope for patients with chronic heart failure, especially in the presence of significant right ventricular dysfunction, pulmonary hypertension, or concomitant beta-blocker therapy. Heart failure guidelines recommend inotropic support to maintain systemic perfusion and preserve end-organ performance until definitive therapy is initiated or the acute precipitating problem resolves. Short-term inotropic support may be reasonable in hospitalized patients presenting with documented severe systolic dysfunction with low blood pressure and significantly depressed cardiac output. Long-term palliative inotropic therapy may be considered for symptom control in patients with stage D heart failure refractory to optimal medical and device therapy who are awaiting mechanical circulatory support (MCS) or cardiac transplant or are not eligible for MCS or transplant. Milrinone may also be used to maintain hemodynamic stability postoperatively in heart transplant recipients. Dobutamine and milrinone have similar clinical effects in patients with severe heart failure. Both dobutamine and milrinone were used successfully as a pharmacologic bridge to heart transplantation (n = 36) with no significant differences in right heart hemodynamics, need for additional vasodilator/inotropic therapy, need for mechanical cardiac support, or death. In another study, there was no difference in mortality between chronic dobutamine or milrinone in patients with stage D heart failure being discharged from the hospital (n = 112). Inotropes can induce hypotension and arrhythmias. Milrinone is more likely to cause hypotension and less likely to cause tachyarrhythmias when compared to dobutamine and low-dose dopamine; however, milrinone may cause reflex tachycardia. Milrinone is primarily eliminated by the kidneys and requires dosage adjustment in patients with renal insufficiency.
General Administration Information
For storage information, see the specific product information within the How Supplied Section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Milrinone is a clear, colorless to pale yellow solution.
Intravenous Administration
Loading Dose
-Dilution of the 1 mg/mL solution is not necessary; however, diluting to a total volume of 10 to 20 mL may ease administration.
-Administer over 10 to 60 minutes.
-May divide loading dose into 5 equal aliquots and administer each aliquot over 10 minutes if blood pressure remains within an acceptable range.
Continuous IV Infusion
-Dilute to a final concentration of 200 mcg/mL using either 0.45% Sodium Chloride Injection, 0.9% Sodium Chloride Injection, or 5% Dextrose Injection.
-ASHP Recommended Standard Concentrations for Adult Continuous Infusions: 200 mcg/mL.
-Administer with a controlled infusion device.
-Titrate the infusion according to hemodynamic and clinical response.
-Observe the patient closely with appropriate electrocardiographic equipment. Immediate treatment for cardiac events, including life-threatening ventricular arrhythmias, must be available.
-Do not administer simultaneously with blood or furosemide. Furosemide is incompatible with milrinone; precipitation may occur if given together in the same line.
Other Injectable Administration
Intraosseous Administration
NOTE: Milrinone is not FDA-approved for intraosseous administration.
-The same milrinone dosage may be given via the intraosseous route when IV access is not available.
-After injection, flush with saline to promote medication entry into the central circulation.
Milrinone can cause hypotension (2.9%) and reflex sinus tachycardia due to its vasodilatory effects. Monitor blood pressure and heart rate during milrinone infusion; slow or stop the infusion in patients showing excessive decreases in blood pressure. Sustained hypotension requiring intervention occurred more frequently in patients receiving milrinone compared to placebo (10.7% vs. 3.2%) in an adult trial assessing clinical outcomes of patients hospitalized for acute exacerbation of chronic heart failure.
Milrinone has been associated with an increased frequency of ventricular and atrial arrhythmias. Monitor patients receiving milrinone closely with the use of continuous electrocardiographic monitoring to allow the prompt detection and management of ventricular arrhythmias. An increased risk of hospitalization and sudden death has been observed in patients on long-term oral milrinone therapy; there is no evidence that long-term continuous or intermittent infusion does not carry a similar risk. Ventricular arrhythmias (12.1%), premature ventricular contractions (PVCs) (8.5%), nonsustained ventricular tachycardia (2.8%), sustained ventricular tachycardia (1%), ventricular fibrillation (0.2%), supraventricular tachycardia (SVT) (3.8%), and angina/chest pain (unspecified) (1.2%) were reported in adult patients during clinical trials. Life-threatening arrhythmias were infrequent and usually associated with other precipitating factors. Torsade de pointes has been reported rarely with postmarketing use. New atrial arrhythmias occurred more frequently in patients receiving milrinone compared to placebo (4.6% vs. 1.5%) in an adult trial assessing clinical outcomes of patients hospitalized for acute exacerbation of chronic heart failure. Pediatric trials have reported a wide variance in the incidence of arrhythmia associated with milrinone. While some trials have reported no to rare occurrences of tachyarrhythmia (e.g., ventricular arrhythmia, supraventricular tachycardia), a study including 603 infants receiving milrinone postoperatively after congenital heart disease surgery reported that 50% experienced an arrhythmia. The most common arrhythmias were monomorphic ventricular tachycardia (12%), junctional ectopic tachycardia (10%), accelerated junctional rhythm (8%), and atrial tachyarrhythmias including atrial fibrillation, atrial flutter, and ectopic or chaotic atrial tachycardia (8%). After multivariate logistic regression analysis, milrinone use on admission to the cardiac intensive care unit remained independently associated with an increase in the odds of postoperative tachyarrhythmia resulting in an intervention (OR 2.8, 95% CI 1.3 to 6, p = 0.007).
Cases of injection site reaction have been reported with intravenous milrinone therapy. Carefully monitor the infusion site to avoid possible extravasation.
Milrinone is less likely to cause thrombocytopenia than inamrinone; in adult trials, thrombocytopenia was reported in 0.4% of patients but is not definitely related to the administration of milrinone. Pediatric trials have reported a wide variance in the incidence of thrombocytopenia associated with milrinone. Some trials including neonates, infants, and children have reported no new occurrence or progression (n = 12) or no difference in incidence when compared to placebo (n = 277). In another study of 19 infants and children who underwent open-heart surgery, 58% developed thrombocytopenia (defined as platelet count 100,000 cells/mm3 or less) during the postoperative milrinone infusion. The incidence of thrombocytopenia was 21% at 24 hours, 47% at 36 hours, and 42% at 48 hours of milrinone infusion. Platelet transfusion was required for 2 infants while receiving milrinone.
Headache, usually mild to moderate in severity, has been reported in 2.9% of patients receiving milrinone.
Tremor (0.4%) has been reported but is not definitely related to the administration of milrinone. Additionally, skin reactions, such as rash, and isolated spontaneous reports of bronchospasm and anaphylactic shock have been reported with postmarketing use. Nausea and vomiting may also occur.
Hypokalemia (0.6%) has been reported but is not definitely related to the administration of milrinone. Monitor fluid and electrolyte changes carefully during therapy with milrinone. Correct hypokalemia by potassium supplementation during use of milrinone. Additionally, elevated hepatic enzymes have been reported with postmarketing use.
Milrinone is contraindicated in patients with a milrinone hypersensitivity. Solutions containing dextrose may be contraindicated in those with a known corn hypersensitivity.
Do not use milrinone in patients with severe obstructive aortic or pulmonic valvular heart disease in lieu of surgical relief of the obstruction. Inotropes may aggravate outflow tract obstruction in patients with idiopathic hypertrophic subaortic stenosis.
Milrinone use has been associated with ventricular arrhythmias, including ventricular tachycardia. Milrinone produces a slight shortening of AV node conduction time, indicating a potential for an increased ventricular response rate in patients with atrial flutter or atrial fibrillation which is not controlled with digitalis therapy. Observe patients closely with continuous ECG monitoring to allow for prompt detection and management of ventricular arrhythmias. Correct hypovolemia and hypokalemia to minimize the potential of significant hypotension and/or arrhythmia. Milrinone has not been shown to be safe or effective when used for more than 48 hours in patients with heart failure. An increased risk of hospitalization and death has been observed in patients on long-term oral milrinone therapy; there is no evidence that long-term continuous or intermittent infusion does not carry a similar risk.
Milrinone use is not recommended during acute myocardial infarction. The effects of milrinone during the acute phase after myocardial infarction are unknown.
Severe renal impairment significantly increases the half-life of milrinone. Infusion rate reductions are recommended for patients with renal impairment or renal failure (CrCl 50 mL/minute or less). Monitor renal function during milrinone infusion.
Use milrinone during pregnancy only if the potential benefit justifies the potential risk for the fetus. There are no adequate and well-controlled studies of milrinone use in pregnant women. No evidence of teratogenicity was observed when milrinone was administered intravenously at doses up to 2.5 times the maximum recommended clinical dose to pregnant rats and rabbits during organogenesis, although an increased resorption rate was seen in rabbits.
Use caution when administering milrinone to a breast-feeding woman. It is unknown if milrinone is excreted into human breast milk.
For the short-term treatment of acute heart failure and other low cardiac output states (e.g., cardiogenic shock*, low cardiac output syndrome (LCOS)* after cardiac surgery):
Continuous Intravenous Infusion dosage:
Adults: 50 mcg/kg IV loading dose, then 0.125 to 0.75 mcg/kg/minute continuous IV infusion. Heart failure guidelines do not recommend an initial bolus. Inotropic support is recommended to maintain systemic perfusion and preserve end-organ performance until definitive therapy is initiated or the acute precipitating problem resolves. Short-term inotropic support may be reasonable in hospitalized patients presenting with documented severe systolic dysfunction with low blood pressure and significantly depressed cardiac output. Consider long-term inotropic support as palliative therapy for symptom control in patients with stage D heart failure refractory to optimal medical and device therapy who are awaiting mechanical circulatory support (MCS) or cardiac transplant or are not eligible for MCS or transplant.
Infants*, Children*, and Adolescents*: 50 mcg/kg IV loading dose, then 0.25 to 1 mcg/kg/minute continuous IV infusion.
Neonates*: 50 mcg/kg IV loading dose, then 0.25 to 1 mcg/kg/minute continuous IV infusion.
Premature Neonates*: 0.75 mcg/kg/minute continuous IV infusion for 3 hours, then 0.2 mcg/kg/minute for 18 hours.
For the treatment of cerebral vasospasm* after aneurysmal subarachnoid hemorrhage:
Intra-Arterial dosage:
Adults: 4 mg intra-arterially over 30 minutes (0.25 mg/minute) to the main artery dedicated to the vasospastic territory. Repeat doses up to 15 mg in the same territory or up to 24 mg including a different territory. May follow with continuous IV infusion for up to 14 days after initial bleeding.
Continuous Intravenous Infusion dosage:
Adults: 0.5 mcg/kg/minute continuous IV infusion after initial intra-arterial milrinone and for up to 14 days after initial bleeding. If well tolerated, may titrate up to 1.5 mcg/kg/minute; stop titration if heart rate more than 100 beats per minute or blood pressure reduction more than 20% occurs.
For the short-term treatment of low cardiac output during septic shock* or postresuscitation stabilization*:
Continuous Intravenous or Intraosseous Infusion dosage:
Infants, Children, and Adolescents: 50 mcg/kg IV/IO load, then 0.25 to 1 mcg/kg/minute continuous IV/IO infusion. Some experts choose not to bolus milrinone in patients with septic shock to decrease the risk of hypotension.
Neonates: 50 mcg/kg IV/IO load, then 0.25 to 1 mcg/kg/minute continuous IV/IO infusion. Some experts choose not to bolus milrinone in patients with septic shock to decrease the risk of hypotension.
For the treatment of persistent pulmonary hypertension of the newborn (PPHN)* in patients with poor response to nitric oxide:
Continuous Intravenous Infusion dosage:
Neonates: 50 mcg/kg IV load, then 0.33 to 0.5 mcg/kg/minute continuous IV infusion, initially. Titrate by 0.33 mcg/kg/minute every 2 hours until clinical response is attained. Max: 1 mcg/kg/minute. Avoid loading dose to minimize the risk of hypotension.
Maximum Dosage Limits:
-Adults
0.75 mcg/kg/minute continuous IV infusion.
-Geriatric
0.75 mcg/kg/minute continuous IV infusion.
-Adolescents
Safety and efficacy have not been established; however, up to 1 mcg/kg/minute continuous IV infusion has been used.
-Children
Safety and efficacy have not been established; however, up to 1 mcg/kg/minute continuous IV infusion has been used.
-Infants
Safety and efficacy have not been established; however, up to 1 mcg/kg/minute continuous IV infusion has been used.
-Neonates
Safety and efficacy have not been established; however, up to 1 mcg/kg/minute continuous IV infusion has been used.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
For adult patients, initiate the maintenance IV infusion rate as follows and titrate until clinical response is attained:
CrCl more than 50 mL/minute: No dosage adjustment needed.
CrCl 41 to 50 mL/minute: 0.43 mcg/kg/minute continuous IV infusion.
CrCl 31 to 40 mL/minute: 0.38 mcg/kg/minute continuous IV infusion.
CrCl 21 to 30 mL/minute: 0.33 mcg/kg/minute continuous IV infusion.
CrCl 11 to 20 mL/minute: 0.28 mcg/kg/minute continuous IV infusion.
CrCl 6 to 10 mL/minute: 0.23 mcg/kg/minute continuous IV infusion.
CrCl 5 mL/minute or less: 0.2 mcg/kg/minute continuous IV infusion.
For pediatric patients, initiate the maintenance IV infusion rate as follows and titrate until clinical response is attained:
CrCl more than 50 mL/minute: No dosage adjustment needed.
CrCl 30 to 50 mL/minute: 0.33 to 0.43 mcg/kg/minute continuous IV infusion.
CrCl 10 to 29 mL/minute: 0.23 to 0.33 mcg/kg/minute continuous IV infusion.
CrCl less than 10 mL/minute: 0.2 mcg/kg/minute continuous IV infusion.
Intermittent hemodialysis
It is not known whether milrinone is removed by hemodialysis.
*non-FDA-approved indication
Acebutolol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Alpha-blockers: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Amiloride: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response. (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Amlodipine: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Amlodipine; Atorvastatin: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Amlodipine; Benazepril: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response. (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Amlodipine; Celecoxib: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Amlodipine; Olmesartan: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response. (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Amlodipine; Valsartan: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response. (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response. (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Anagrelide: (Moderate) Anagrelide is an inhibitor of cAMP phosphodiesterase III. The effects of milrinone, which is an inhibitor of cAMP phosphodiesterase isozyme in cardiac and vascular muscle, may be increased if coadministered with anagrelide.
Angiotensin II receptor antagonists: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Angiotensin-converting enzyme inhibitors: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Atenolol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Atenolol; Chlorthalidone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response. (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Azilsartan: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Azilsartan; Chlorthalidone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Benazepril: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Beta-blockers: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Betaxolol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Bisoprolol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response. (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Brimonidine; Timolol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Bumetanide: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Calcium-channel blockers: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Candesartan: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Captopril: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Carteolol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Carvedilol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Central-acting adrenergic agents: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Chlorothiazide: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Chlorthalidone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Clevidipine: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Clonidine: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Diazoxide: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Diltiazem: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Dorzolamide; Timolol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Doxazosin: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Enalapril, Enalaprilat: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Eplerenone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Epoprostenol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Eprosartan: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Esmolol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Ethacrynic Acid: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Felodipine: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Fenoldopam: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Fosinopril: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Furosemide: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Ginger, Zingiber officinale: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of inotropic agents, however, no clinical data are available.
Guanfacine: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Hydralazine: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Iloprost: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Irbesartan: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Isradipine: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Labetalol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Levamlodipine: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Levobunolol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Lisinopril: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Loop diuretics: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Losartan: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Mecamylamine: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Methyldopa: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Metolazone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Metoprolol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response. (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Minoxidil: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Moexipril: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Nadolol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Nebivolol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Nebivolol; Valsartan: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response. (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Nicardipine: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
NIFEdipine: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Nimodipine: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Nisoldipine: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Nitroprusside: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Olmesartan: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response. (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Perindopril: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Perindopril; Amlodipine: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response. (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Phenoxybenzamine: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Phentolamine: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Pindolol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Potassium-sparing diuretics: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Prazosin: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Propranolol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Quinapril: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Ramipril: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Riociguat: (Moderate) Coadministration of riociguat and phosphodiesterase inhibitors, including specific phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil) and nonspecific phosphodiesterase inhibitors (dipyridamole or theophylline, aminophylline) is contraindicated due to the risk of hypotension. Clinical experience with other phosphodidesterase inhibitors (e.g., milrinone, cilostazol, and roflumilast) is limited. The addition of riociguat to a stable sildenafil regimen (20 mg three times a day) resulted in additive hemodynamic effects in an exploratory interaction study in 7 patients with pulmonary arterial hypertension (PAH). Among patients with PAH on stable sildenafil treatment and riociguat there was one death, possibly related to the combination of these drugs, and a high rate of discontinuation for hypotension.
Sacubitril; Valsartan: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Sotalol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Spironolactone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response. (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Telmisartan: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Telmisartan; Amlodipine: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response. (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Terazosin: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Thiazide diuretics: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Timolol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Torsemide: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Trandolapril: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Trandolapril; Verapamil: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response. (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Treprostinil: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Triamterene: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response. (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Valsartan: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Vasodilators: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Verapamil: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Milrinone is a positive inotrope and vasodilator with little chronotropic activity. Milrinone selectively inhibits phosphodiesterase III, preventing breakdown of cyclic adenosine monophosphate (cAMP) in cardiac and vascular muscle cells. This results in increased myocardial contractility and vasodilation. Milrinone also improves diastolic relaxation (lusitropy), thus reducing preload, afterload, and systemic vascular resistance.
Milrinone is administered by intravenous infusion. Milrinone has a Vd of about 0.45 L/kg, a mean elimination half-life of 2.4 hours, and a clearance of 0.14 L/kg/hour after continuous infusion in adult patients with congestive heart failure. Milrinone is approximately 70% bound to human plasma protein. It is primarily eliminated via the urine, with 83% excreted as the parent drug and 12% as its O-glucuronide metabolite. Elimination is rapid; approximately 60% is recovered in the urine within 2 hours of dosing and 90% is recovered within 8 hours. The mean renal clearance of milrinone is approximately 0.3 L/minute, indicating active secretion.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Intravenous Route
Onset of action occurs in 2 to minutes, peaking around 10 minutes, with a variable duration ranging from 1.5 to 5 hours. Inotropic and vasodilatory effects of milrinone have been observed over the therapeutic range of 100 to 300 ng/mL.
-Special Populations
Renal Impairment
Renal impairment (CrCl 30 mL/minute or less) significantly increases the half-life of milrinone.
Pediatrics
Children and Adolescents
Compared to adults, children have a larger Vd, faster clearance, and similar half-life of milrinone. Although Vd is similar, clearance is significantly faster in children compared to infants. Vd was 0.7 +/- 0.2 L/kg, clearance was 5.9 +/- 2 mL/kg/minute, and half-life was 1.86 +/- 2 hours in a prospective, open-label study in children after open-heart surgery (n = 7, age: 1 to 13 years). In pediatric patients with septic shock (n = 11, age: 8 months to 15 years), Vd was 1.47 +/- 1.03 L/kg, mean clearance was 11 +/- 9.6 mL/kg/minute, and median half-life was 1.47 hours (0.62 to 10.85 hours).
Infants
Compared to adults, infants have a larger Vd, faster clearance, and prolonged half-life of milrinone. Although Vd is similar, clearance is significantly faster in children compared to infants. Vd was 0.9 +/- 0.4 L/kg, clearance was 3.8 +/- 1 mL/kg/minute, and half-life was 3.15 +/- 2 hours in a prospective, open-label study in infants after open-heart surgery (n = 12). In pediatric patients with septic shock (n = 11, age: 8 months to 15 years), Vd was 1.47 +/- 1.03 L/kg, mean clearance was 11 +/- 9.6 mL/kg/minute, and median half-life was 1.47 hours (0.62 to 10.85 hours).
Premature Neonates
Estimated half-life is approximately 5-times longer in premature neonates compared to children or adults. In a prospective, open-label pilot study in 29 very preterm neonates (gestational age younger than 29 weeks, postnatal age younger than 12 hours), the population mean (95% CI) clearance estimate was 0.64 mL/kg/minute, the population mean Vd was 0.576 L/kg, and the half-life estimate was 10.3 hours.