Congestive Heart Failure
50 mcg/kg loading dose by IV push over 10 minutes, then 0.375-0.75 mcg/kg/min IV  

Maintenance: 1.13 mg/kg/day

Monitor electrolytes, renal function, blood pressure

Dosing Modifications
Renal impairment
CrCl <50 mL/min: 0.43 mcg/kg/min  
CrCl <40 mL/min/1.73m2: 0.38 mcg/kg/min
CrCl <30 mL/min/1.73m2: 0.33 mcg/kg/min
CrCl <20 mL/min/1.73m2: 0.28 mcg/kg/min
CrCl <10 mL/min/1.73m2: 0.23 mcg/kg/min
CrCl <5 mL/min/1.73m2: 0.2 mcg/kg/min
Right Heart Failure (Orphan)
Orphan designation for treatment of right heart failure (RHF) in left ventricular assist device (LVAD) patients

Sponsor
Cardiora Pty Ltd; Level 9, 278 Collins Street Melbourne Australia

Intercations:

Contraindicated (0)
Serious (2)
ozanimod
ponesimod
Monitor Closely (8)
anagrelide
cilostazol
dichlorphenamide
enoximone
inamrinone
landiolol
olprinone
riociguat
Minor (0)

Adverse Effects

>10%

• Ventricular arrhythmias

1-10%

• Supraventricular arrhythmia (4%)
• Headache (3%)
• Hypotension (3%)
• Angina/chest pain (1%)

<1%

• Abnormal liver function test results
• Anaphylaxis
• Atrial fibrillation
• Bronchospasm
• Hypokalemia
• Injection-site reaction
• Rash
• Thrombocytopenia
• Torsades de pointes
• Tremor
• Ventricular premature complex

Warnings
Contraindications
Hypersensitivity to milrinone and inamrinone

Cautions
Use caution in atrial fibrillation/flutter, hypertrophic subaortic stenosis, electrolyte abnormalities, hypotension, recent MI, severe aortic or pulmonic valvular disease, renal impairment

Severe aortic or pulmonic obstruction, acute phase after myocardial infarction (MI)

May increase risk of arrhythmias

Ensure that ventricular rate is controlled in atrial fibrillation/flutter before initiating therapy; may increase ventricular response rate

Concurrent use of disopyramide

Discontinue therapy if symptoms of hepatotoxicity (eg., increased LFTs) occur; monitor liver function

Monitor blood pressure/heart rate closely

Short-term use only

Pregnancy & Lactation
Pregnancy category: C

Lactation: Unknown whether drug is excreted into breast milk; use with caution; nursing is not priority in situations where milrinone is used

Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.

Pharmacology
Mechanism of Action
Phosphodiesterase inhibitor; positive inotrope with little chronotropic effect; direct vasodilator (decreases both preload and afterload)

Absorption
Onset: 5-15 min (IV)

Duration: 3-5 hr

Peak plasma time: 2 min

Therapeutic range: 100-300 ng/mL (hemodynamic effect)

Distribution
Protein bound: 70%

Vd: 0.38 L/kg (Injection); 0.45 L/kg (infusion)

Metabolism
Metabolized in liver (12%), mainly via glucuronidation

Metabolites: Milrinone O-glucuronide (activity unknown)

Elimination
Half-life: 2.5 hr

Clearance: 2.3 mL/kg/min

Excretion: Urine (95%; 83% as unchanged drug)

Administration
IV Incompatibilities
Additive: Procainamide

Syringe: Furosemide

Y-site: Furosemide, procainamide

IV Compatibilities
Solution: Most common solvents

Additive: Quinidine

Syringe: Atropine, calcium chloride, digoxin, epinephrine, lidocaine, morphine sulfate, propranolol, sodium bicarbonate, verapamil

Y-site (partial list): Acyclovir, amiodarone, calcium chloride, calcium gluconate, ciprofloxacin, digoxin, diltiazem, dobutamine, dopamine, epinephrine, fentanyl, heparin, lorazepam, magnersium sulfate, metronidazole, midazolam, morphine sulfate, nitroglycerin, norepinephrine, potassium chloride, propofol, propranolol, quinidine, sodium nitroprusside, vancomycin

IV Preparation
Injection: Dilute in NS, 1/2NS, or D5W to 10-20 mL

Infusion: Dilute in NS, 1/2NS, or D5W to 200 mcg/mL; use undiluted if giving 20 mg/100 mL in D5W

IV Administration
Injection: Administer slowly over 10 minutes; may use undiluted for initial direct IV injection

Infusion: Administer via calibrated electronic controlled-infusion device

Storage
Store intact vials at room temperature; protect from excess heat or freezing

Diluted solution may be stored for 72 hours