NEODOSE

INDICATIONS :

• Low Cardiac Output Post-Cardiac Surgery;Prophylaxis: In one double-blind, placebocontrolled study (n=238) in children after cardiac surgery, the relative risk reduction for the prevention of low cardiac output syndrome was 55% (p=0.023) with milrinone (75 mcg/kg bolus, followed by 0.75 mcg/kg/minute infusion) compared with placebo. The age range was 2 days to 6.9 years (median, 3 months). A transient increase in heart rate (149+/-13 to 163+/-12 beats/min) was observed in 10 neonates administered 50 mcg/kg loading dose over 15 minutes; no neonate experienced sustained supraventricular tachyarrhythmias or ventricular ectopy
• Low Systemic Blood Flow, Prevention: A randomized, placebo-controlled clinical trial demonstrated milrinone was no more effective than placebo in preventing low systemic blood flow in preterm neonates less than 30 weeks GA. Neonates received milrinone (started before 6 hours of age) 0.75 mcg/kg/minute for the first 3 hours followed by 0.20 mcg/kg/minute until 18 hours of age. There was no difference in superior vena cava flow between the milrinone and placebo groups. A heart rate of 160 beats/min or more occurred in 67% of the milrinone-treated group and 22% of the placebo-treated group (p=0.0001)
• Persistent Pulmonary Hypertension of the Newborn (PPHN): Low level evidence exists for the use of milrinone for PPHN. The use of IV milrinone for infants with PPHN and signs of left ventricular dysfunction may be considered. Typically, reserved for severe PPHN refractory to inhaled nitric oxide complicated by poor cardiac function on echocardiogram. In 5 observational studies, term neonates (n=47) with oxygen index (OI) greater than 20 despite inhaled nitric oxide received IV milrinone. Improvements observed were OI reduction, inhaled nitric oxide dose reduction, and indicators of myocardial performance increase. Transient nonsignificant decreases in systolic arterial pressure, as well as reductions in blood pressure requiring vasopressor inotropes have been observed. Dose ranges were 0.33 to 0.99 mcg/kg/min with or without a bolus dose of 50 mcg/kg over 60 minutes
• Severe Sepsis and Septic Shock: 

CONTRAINDICATIONS

• Allergy to cherries (Oral syrup).
• Acute narrow-angle glaucoma.
• Open-angle glaucoma, untreated.

PRECAUTIONS

• Cardiovasculer :
  • Hypotension is common when used in conjunction with narcotics, or following rapid bolus administration.
  • Rarely hypotensive episodes requiring treatment during or after diagnostic or surgical manipulations have been reported; increased risk in patients with hemodynamic instability or in those premedicated with a narcotic.
  • Serious cardiorespiratory events, including cardiac arrest resulting in death or permanent injury have been reported with use of milrinone.
• Endocrin & Metabolic: Use particular caution in uncompensated acute illness (eg, severe fluid or electrolyte disturbances).
• Respiratory:
  • Serious respiratory events including respiratory depression, airway obstruction, oxygen desaturation, apnea, respiratory arrest, sometimes resulting in death or permanent injury have been reported with use of milrinone; the risk is greatest in those with chronic obstructive pulmonary disease, chronic disease states, or decreased pulmonary reserve, and concomitant use of barbiturates, alcohol, or other CNS depressants.
  • Serious respiratory events including respiratory depression, airway obstruction, oxygen desaturation, apnea, respiratory arrest, sometimes resulting in death or permanent injury have been reported with use of milrinone; the risk is greatest in those with chronic obstructive pulmonary disease, chronic disease states, or decreased pulmonary reserve, and concomitant use of barbiturates, alcohol, or other CNS depressants
• Neurologic:
  • CNS depression may occur; increased risk with concomitant use of alcohol, other CNS depressants (eg, opioids), barbiturates, and moderate or strong CYP3A4 inhibitors
  • Partial or complete impairment of recall may exist for several hours following an administered dose.
  • Brain development in children may be affected by repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures, especially in children younger than 3 years or in fetuses of pregnant women during the third trimester; balance appropriate anesthesia use and timing of elective procedures that can be delayed against potential risks in children younger than 3 years and pregnant women, particularly with procedures that are longer than 3 hours or multiple procedures.
• Psychiatric :
  • Antiepileptic drugs, including milrinone, may increase the risk of suicidal thoughts or behavior; monitoring is recommended.
  • Agitation, involuntary movements (including tonic/clonic movements and muscle tremor), hyperactivity, and combativeness have been reported with milrinone when used for sedation; consider the possibility of cerebral hypoxia or true paradoxical reactions.
• Ophthalmic: May increase intraocular pressure in patients with glaucoma; may be used in patients with open-angle glaucoma only if they are receiving appropriate therapy; monitoring is recommended.
• Spacial Populations :Gasping syndrome or other severe or fatal adverse effects can occur in neonates and low birth weight infants, as formulation contains benzyl alcohol
  • Surgery: Risk of desaturation and hypoventilation from partial airway obstruction increased in pediatric patients undergoing procedures involving upper airway (eg, upper endoscopy, dental care); those with cardiac or respiratory compromise may be unusually sensitive. Dosage adjustment may be required in higher-risk patients
  • Withdrawal: Symptoms of withdrawal have occurred following discontinuation

ADVERSE EFFECTS

Assure adequate vascular volume prior to initiating therapy. Blood pressure will likely fall 5% to 9% after the loading dose, but should gradually return to baseline by 24 hours. Heart rate increases of 5% to 10% are also common. Thrombocytopenia was reported frequently in some studies and rarely in others. Arrhythmias occur occasionally.

ADMINISTRATION

Administer loading dose over 15 to 60 minutes. May give undiluted or further dilute in compatible diluent. For maintenance infusion, dilute in compatible solution to a maximum concentration of 200 mcg/mL, or use available premixed solution for injection (100-mL and 200-mL bags). May also be given by IO route if IV access unavailable. In premature infants less than 30 weeks gestational age, infuse loading dose over 3 hours.

MONITORING

Continuous monitoring of blood pressure, heart rate and rhythm. Assess signs of cardiac output. Carefully monitor fluid and electrolyte changes and renal function during therapy. Monitor platelet counts. For a full-term newborn, the target heart rate and perfusion pressure (mean arterial pressure minus central venous pressure) are 110 to 160 beats/min and 55 mm Hg, respectively.