Primacor

Positive Inotropic Agents

For storage information, see the specific product information within the How Supplied Section.

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.

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.

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.

ventricular tachycardia / Early / 0-12.0
atrial flutter / Early / 0-8.0
atrial fibrillation / Early / 0-8.0
atrial tachycardia / Early / 0-8.0
torsade de pointes / Rapid / 0-1.0
ventricular fibrillation / Early / 0.2-0.2
bronchospasm / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known

thrombocytopenia / Delayed / 0-58.0
hypotension / Rapid / 2.9-10.7
premature ventricular contractions (PVCs) / Early / 8.5-8.5
supraventricular tachycardia (SVT) / Early / 3.8-3.8
chest pain (unspecified) / Early / 1.2-1.2
angina / Early / 1.2-1.2
hypokalemia / Delayed / 0.6-0.6
sinus tachycardia / Rapid / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known

headache / Early / 2.9-2.9
tremor / Early / 0.4-0.4
injection site reaction / Rapid / Incidence not known
nausea / Early / Incidence not known
vomiting / Early / Incidence not known
rash / Early / Incidence not known

Primacor

Rx

Parenteral positive inotrope and vasodilator with phosphodiesterase inhibitor activity
Used for short-term treatment of acute heart failure
Minimal chronotropic activity

50 mcg/kg IV loading dose, then 0.125 to 0.75 mcg/kg/minute continuous IV infusion.[30865] [57101] [62661] 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.[57101] [62661]

50 mcg/kg IV loading dose, then 0.25 to 1 mcg/kg/minute continuous IV infusion.

50 mcg/kg IV loading dose, then 0.25 to 1 mcg/kg/minute continuous IV infusion.

0.75 mcg/kg/minute continuous IV infusion for 3 hours, then 0.2 mcg/kg/minute for 18 hours.

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.

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.

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.

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.

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.

†Indicates off-label use

Specific guidelines for dosage adjustments are not available; it appears that no dosage adjustments are needed.

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.

Acebutolol: (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.
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.
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.
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.
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.
Dorzolamide; Timolol: (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.
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.
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.
Iloprost: (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.
Levobunolol: (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.
Mecamylamine: (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.
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.
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.
Propranolol: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Propranolol; Hydrochlorothiazide, HCTZ: (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.
Sotalol: (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.
Treprostinil: (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.

Milrinone Lactate/Milrinone Lactate, Dextrose/Primacor Intravenous Inj Sol: 1mg, 1mL, 20-5%

0.75 mcg/kg/minute continuous IV infusion.

0.75 mcg/kg/minute continuous IV infusion.

Safety and efficacy have not been established; however, up to 1 mcg/kg/minute continuous IV infusion has been used.

Safety and efficacy have not been established; however, up to 1 mcg/kg/minute continuous IV infusion has been used.

Safety and efficacy have not been established; however, up to 1 mcg/kg/minute continuous IV infusion has been used.

Safety and efficacy have not been established; however, up to 1 mcg/kg/minute continuous IV infusion has been used.

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.[30865] [54335]

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

Onset of action occurs in 2 to minutes, peaking around 10 minutes, with a variable duration ranging from 1.5 to 5 hours.[64934] Inotropic and vasodilatory effects of milrinone have been observed over the therapeutic range of 100 to 300 ng/mL.

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.