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Milrinone information from DrugsUpdate  

See Available Brands of Milrinone in India

P - Caution when used during pregnancy
L - Caution when used during lactation

Milrinone (Primacor) is a phosphodiesterase III inhibitor. It potentiates the effect of cyclic adenosine monophosphate (cAMP).

Milrinone also enhances relaxation of the left ventricle by increasing Ca2+-ATPase activity on the cardiac sarcoplasmic reticulum. This increases calcium ion uptake.

It has positive inotropic, vasodilating and minimal chronotropic effects. It is used in the management of heart failure only when conventional treatment with vasodilators and diuretics has proven insufficient. This is due to the potentially fatal adverse effects of milrinone, including ventricular arrhythmias.

Whereas beneficial hemodynamic effects are shown (at least short-term), several studies have shown no or a negative effect on mortality rates of hospitalized patients receiving milrinone.

One negative side to the use of milrinone is the prolonged half-life (1 to 2 hours). This can result in a prolonged weaning and possible adverse outcomes from stopping this medication rapidly.

Pharmacodynamics

Pharmacokinetics

Milrinone is a selective phosphodiesterase III inhibitor with positive inotropic and vasodilator activity. It selectively inhibits cyclic adenosine monophosphate (cAMP) phosphodiesterase activity in cardiac and vascular muscles resulting in increased intracellular concentrations of cAMP. It also acts directly on vascular smooth muscle.

Onset
IV: 5-15 minutes.

Distribution
Protein binding: About 70%. Volume of distribution at steady-state: 0.32-0.45 L/kg.

Metabolism

About 12% metabolised hepatically.

Excretion

Eliminated via urine (85% as unchanged drug). Elimination half life: About 2.5 hours.

Milrinone Indications / Milrinone Uses

Information Not Available

Milrinone Adverse Reactions / Milrinone Side Effects

Angina-like chest pain, headache, hypokalaemia, tremor, thrombocytopenia, bronchospasm.

Potentially Fatal: Supraventricular and ventricular arrhythmias; hypotension.

Precautions

Milrinone should not be used in patients with severe obstructive aortic or pulmonic valvular disease in lieu of surgical relief of the obstruction. Like other inotropic agents, it may aggravate outflow tract obstruction in hypertrophic subaortic stenosis.

Supraventricular and ventricular arrhythmias have been observed in the high-risk population treated. In some patients, injections of Milrinone and oral Milrinone have been shown to increase ventricular ectopy, including nonsustained ventricular tachycardia. The potential for arrhythmia, present in congestive heart failure itself, may be increased by many drugs or combinations of drugs. Patients receiving Milrinone should be closely monitored during infusion.

Milrinone produces a slight shortening of AV node conduction time, indicating a potential for an increased ventricular response rate in patients with atrial flutter/fibrillation which is not controlled with digitalis therapy.

During therapy with Milrinone, blood pressure and heart rate should be monitored and the rate of infusion slowed or stopped in patients showing excessive decreases in blood pressure.

If prior vigorous diuretic therapy is suspected to have caused significant decreases in cardiac filling pressure, Milrinone should be cautiously administered with monitoring of blood pressure, heart rate, and clinical symptomatology.

There is no experience in controlled trials with infusions of Milrinone for periods exceeding 48 hours. Cases of infusion sitereaction have been reported with intravenous Milrinone therapy. Consequently, careful monitoring of the infusion site should be maintained to avoid possible extravasation.

Use in acute myocardial infarction
No clinical studies have been conducted in patients in the acute phase of post myocardial infarction. Until further clinical experience with this class of drugs is gained, Milrinone is not recommended in these patients.

Special Precautions

Severe obstructive aortic or pulmonary valvular disease, hypertrophic cardiomyopathy, atrial flutter or fibrillation. Monitor blood pressure, heart rate, ECG, fluid and electrolyte balance. Pregnancy and lactation. Use for >48 hours.

Other Drug Interactions

Information Not Available

Other Interactions

Information Not Available

Dosage

Intravenous
Short-term management of severe heart failure, Acutely decompensated heart failure
Adult: Initially, a loading dose of 50 mcg/kg by slow IV injection over 10 min then continuous maintenance infusion of 0.375-0.75 mcg/kg/min. Adjust according to haemodynamics and clinical response. Max dose 1.13 mcg/kg/day.
Child: Initial loading dose of 75 mcg/kg by IV injection over 10-60 minutes followed by continuous infusion of 0.5-0.75 mcg/kg/min.
CrCl (ml/min)    Dosage Recommendation
50                    0.43 mcg/kg/min
40                    0.38 mcg/kg/min
30                    0.33 mcg/kg/min
20                    0.28 mcg/kg/min
10                    0.23 mcg/kg/min
5                      0.20 mcg/kg/min


Reconstitution
Use 0.45% sodium chloride, 0.9% sodium chloride or 5% dextrose injection as diluents.

Incompatibility
Y-site incompatibility: Imipenem-cilastin, furosemide, procainamide. Syringe incompatibility: Furosemide. Admixture incompatibility: Furosemide, procainamide, bumetanide.

Food(before/after)

Information Not Available

List of Contraindications

Milrinone and Pregnancy

Caution when used during pregnancy

Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Milrinone and Lactation

Caution when used during lactation

Milrinone and Children

Safety and effectiveness in pediatric patients have not been established.

Milrinone and Geriatic

There are no special dosage recommendations for the elderly patient. Ninety percent of all patients administered Milrinone in clinical studies were within the age range of 45 to 70 years, with a mean age of 61 years. Patients in all age groups demonstrated clinically and statistically significant responses. No age-related effects on the incidence of adverse reactions have been observed. Controlled pharmacokinetic studies have not disclosed any age-related effects on the distribution and elimination of Milrinone.

Milrinone and Other Contraindications

Heart valve stenosis, acute myocardial infarction.

Storage

Intravenous
Store at 15-30°C.

Lab interference

Intravenous
Store at 15-30°C.

Milrinone brands in India:

Milicor Milron Milzucia Myolong Primacor-IV

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