Milrinone

Milrinone is an intravenous medication used exclusively in the hospital setting for short-term treatment of heart failure emergencies.

• Milrinone Lactate Injection is approved for the short-term intravenous treatment of acute decompensated heart failure (a sudden, severe worsening of heart failure requiring urgent medical care)
• Milrinone Lactate in 5% Dextrose Injection is approved for the short-term intravenous treatment of acute decompensated heart failure
• Milrinone Lactate in Dextrose injection is approved for the short-term intravenous treatment of acute decompensated heart failure
• Most clinical experience is in patients who were also receiving digoxin and diuretics alongside milrinone
• There is no controlled trial experience with infusions lasting longer than 48 hours

Milrinone selectively blocks an enzyme called phosphodiesterase (specifically the peak III cAMP type) in heart muscle and blood vessel walls. Blocking this enzyme raises levels of a chemical messenger called cAMP inside cells. In the heart, higher cAMP increases calcium availability inside muscle cells, making contractions stronger. In blood vessels, it causes the vessel walls to relax, lowering the resistance the heart pumps against. The net effect: the heart pumps out more blood per beat, pressure backing up into the lungs drops, and blood vessels widen — all without increasing how much oxygen the heart muscle itself needs.

Milrinone works differently from digoxin (it does not block the sodium-potassium pump) and differently from adrenaline-type drugs (it is not a beta-agonist), making it a distinct option when those agents are already in use or not appropriate.

Milrinone is given only by intravenous infusion in a hospital, administered and managed entirely by your clinical care team. It is never taken by mouth or self-administered at home.

• Treatment typically begins with a loading dose given slowly over about 10 minutes, followed by a continuous maintenance infusion whose rate is adjusted to your response
• Milrinone Lactate in Dextrose flexible container products (200 mcg/mL) should NOT be used for the loading dose — the loading dose requires the 1 mg/mL vial formulation
• The infusion rate is adjusted based on your heart function and blood pressure; patients with kidney impairment generally need a lower infusion rate
• Duration depends on how you respond; controlled trial experience does not extend beyond 48 hours

The most common side effects seen in clinical trials include:

• Ventricular arrhythmias (dangerous irregular heartbeats from the lower heart chambers) — reported in more than 12% of patients; includes ventricular ectopic beats, and less commonly sustained fast rhythms or ventricular fibrillation
• Supraventricular arrhythmias (irregular rhythms from the upper chambers) — about 4% of patients
• Low blood pressure (hypotension) — about 3% of patients
• Headache (usually mild to moderate) — about 3% of patients
• Chest pain or angina — about 1% of patients
• Low potassium (hypokalemia), tremor, and low platelet count (thrombocytopenia) — less than 1% each
• Skin rash and liver enzyme abnormalities — reported after marketing
• Infusion site reactions at the IV site

Rarely, serious allergic reactions (anaphylactic shock) and bronchospasm (airway tightening) have been reported. A dangerous heart rhythm called torsades de pointes has also been reported rarely after marketing. Tell your care team immediately about any new or worsening symptoms.

• Serious heart rhythm problems: Milrinone can cause dangerous ventricular arrhythmias. Continuous heart-rhythm (ECG) monitoring and immediate treatment capability must be in place throughout therapy.
• Short-term use only: Milrinone is not proven safe or effective for treatment lasting more than 48 hours. Long-term oral milrinone increased risk of hospitalization and death — especially in patients with severe (Class IV) heart failure — and there is no evidence that long-term IV use is safer.
• Atrial flutter or fibrillation: Milrinone can speed up the ventricular response rate in patients with these rhythms. Digitalis should be considered before starting milrinone in these patients.
• Kidney impairment: Reduced kidney function significantly slows milrinone clearance; the infusion rate must be reduced to avoid drug accumulation.
• Hypotension risk: Milrinone can drop blood pressure. If this occurs, the infusion should be slowed or stopped until the patient stabilizes.

Your care team will review all your medications, but there are a few particularly important points to know about milrinone and other drugs:

• Furosemide (Lasix): Never inject furosemide into the same IV line as milrinone — they immediately form a solid precipitate (clump) that can block the line and prevent proper dosing of either drug
• Digoxin: Used together frequently without reported problems, but abnormally high digoxin levels can increase the risk of life-threatening arrhythmias alongside milrinone
• Diuretics (furosemide, hydrochlorothiazide, chlorthalidone, spironolactone): Commonly used together; however, low potassium caused by diuretics can raise the risk of dangerous heart rhythms with milrinone — potassium levels should be monitored
• Other heart medications (lidocaine, quinidine, hydralazine, prazosin, isosorbide dinitrate, nitroglycerin): Limited experience shows no major problems when used together with milrinone
• Blood thinners (heparin, warfarin): Used concurrently in some patients without reported adverse interactions in limited experience
• Potassium supplements: Often used alongside milrinone; maintaining normal potassium is important to reduce arrhythmia risk

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Tell your care team if you have ever had an allergic (hypersensitivity) reaction to milrinone
• If you are receiving a dextrose-containing formulation (Milrinone Lactate in 5% Dextrose or Milrinone Lactate in Dextrose), tell your team if you have a known allergy to corn or corn products, as dextrose solutions may be contraindicated
• Tell your team about any history of kidney disease — milrinone clears much more slowly when kidney function is reduced, and the dose will need adjustment
• Tell your team about any existing heart rhythm problems (arrhythmias), as milrinone can worsen some of them
• Tell your team if you have atrial flutter or atrial fibrillation — milrinone may increase the ventricular heart rate in these conditions
• Tell your team about all other medications you are taking, particularly digoxin and any diuretics
• Milrinone is for short-term hospital use only — long-term use carries serious risks and is not approved

Too much milrinone can cause a significant drop in blood pressure because of its blood-vessel-widening effect. If this happens, the infusion will be slowed or temporarily stopped by your care team until your condition stabilizes. There is no specific antidote, but general measures to support circulation will be used as needed.

In patients with heart failure caused by a weakened heart muscle, milrinone promptly increases cardiac output (the amount of blood the heart pumps per minute) and reduces pulmonary capillary wedge pressure (the backup pressure in the lungs) as well as systemic vascular resistance (the resistance in the blood vessels). Most patients see measurable improvements in heart function within 5 to 15 minutes of starting therapy. Mild to moderate increases in heart rate can also occur. Milrinone does not increase the heart muscle's demand for oxygen, which is an important advantage in patients with ischemic heart disease.

After intravenous administration, milrinone is approximately 70% bound to proteins in the blood. It has a mean elimination half-life of about 2.3 to 2.4 hours — meaning the body clears roughly half the drug in that time. Milrinone is primarily removed by the kidneys; about 60% is excreted in the urine within the first 2 hours and roughly 90% within 8 hours, reflecting active secretion by the kidneys. Because clearance depends heavily on kidney function, patients with significant kidney impairment will accumulate the drug more slowly and typically need a lower infusion rate.

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing.