NEODOSE

INDICATIONS

• Place in Therapy: Multicomponent fish oil-containing lipid emulsions are recommended when long-term use of parental nutrition in children is anticipated. The optimal strategy (lipid reduction or source of lipid) for IV lipids in neonates and older children to prevent or treat liver complications is unknown. Long-term effects on fatty acid profile, growth, and neurodevelopment in children are unknown.

Omegaven: In 2 prospective open-label trials in 80pediatric patients (3 to 42 weeks of age, including preterm neonates with estimated gestationalage of more than 24 weeks at birth) with parenteral nutrition-associated cholestasis (PNAC),administration of fish oil triglyceride emulsion as part of a parenteral nutrition regimen wasassociated with a median decrease in direct bilirubin level from 3.8 mg/dL at baseline to 0.6 mgdL (interquartile range, 0.1 to 2.8 mg/dL). Historical control patients (n=41) who received asoybean oil-based lipid emulsion had similar age-appropriate growth; 63% of those receiving fishoil triglycerides and 59% of control patients achieved full enteral feeding by the end of thestudy.
Combination lipid emulsions vs Standard lipid emulsions: Combination lipid emulsions compared with standard lipid emulsions (soybean oil) were safe and well tolerated in 2 meta-analysis of infants younger than 12 months and neonates including preterm neonates. Different lipid emulsion formulations during short-term use did not change the rate of cholestasis (6 studies) or elevated bilirubin concentrations (5 studies) in preterm infants, neonates, and children in a meta-analysis. Another metaanalysis had similar findings. Prolonged parenteral fish oil-containing lipid emulsions in children with intestinal failure may decrease bilirubin concentrations. The mean changes in total bilirubin concentration from baseline to day 29 were significantly different between Smoflipid (-1.5 mcmol/L) and Intralipid (+2.3 mcmol/L) in a randomized, doubleblind study of 28 children (mean age 30.3 and 38.8 months, respectively) with short bowl syndrome, chronic intestinal pseudo-obstruction, or congenital disease of intestinal mucosa. Plasma α-tocopherol and ω-3 fatty acid (eicosapentaenoic acid and docosahexaenoic acid) increased significantly more with Smoflipid. Lipid peroxidation indices were not different between the 2 groups. No statistically significant differences in parenteral nutritionassociated liver disease and other clinical outcomes (death, growth, lung disease, infection, necrotizing enterocolitis (stage 2 or more), intraventricular hemorrhage (grade III to IV), difference in patent ductus arteriosus, or severe eye disease (retinopathy of prematurity stage 3 or more) in preterm neonates were demonstrated between Smoflipid and standard lipid emulsion in a meta-analysis of 7 studies (n=469).

FDA APPROVED INDICATION

• Nutrilipid®: Indicated as a source of calories and essential fatty acids for parenteral nutrition and as a source of essential fatty acids when a deficiency occurs when oral or enteral nutrition is not possible, insufficiency, or contraindicated.
• Omegaven®: Indicated as a source of calories and fatty acids in pediatric patients with parenteral nutrition-associated cholestasis (PNAC).
  Omegaven® not indicated for the prevention of PNAC. It has not been demonstrated that Omegaven prevents PNAC in parenteral nutrition-dependent patients.
  It has not been demonstrated that the clinical outcomes observed in patients treated with Omegaven are a result of the omega-6:omega-3 fatty acid ratio of the product.
• Smoflipid®: Safety and effectiveness of Smoflipid® have not been established in pediatric patients.

CONTRAINDICATIONS

• Severe hyperlipidemia (serum triglycerides greater than 1000 mg/dL) or severe disorders of lipid metabolism characterized by hypertriglyceridemia.
• Pathologic hyperlipemia, lipoid nephrosis, or acute pancreatitis if accompanied by hyperlipidemia.
• Nutrilipid
  • Hypersensitivity to egg or soybean proteins or to any of the ingredients, including excipients.
• Omegaven
  • Hypersensitivity to fish or egg protein or to any of the active ingredients or excipients.
• Smoflipid
  • Hypersensitivity to fish, egg, soybean, or peanut protein or to any of the active ingredients or excipients.

PRECAUTIONS

• General Information:
  • Use with caution in neonates and premature neonates with hyperbilirubinemia and cases with pulmonary hypertension.
• Aluminum toxicity:
  • Fat emulsions contains less than 25 mcg/mL of aluminum but may reach toxic levels with prolonged administration. Aluminum toxicity may occur, particularly in patients with impaired kidney function and in preterm infants.
• Endocrine and metabolic:
  • Fat overload syndrome has been reported with IV lipid formulations. Increased risk when lipid doses are exceeded, but also reported when administered as recommended; may be reversible upon discontinuation.
  • Refeeding syndrome, particularly in severely undernourished, may occur; thiamine deficiency and fluid retention may also develop. Slowly increase nutrient intake while avoiding overfeeding.
  • Parenteral nutrition associated liver disease (PNALD), (particularly in premature infants, or with prolonged administration, or with plant-derived lipid formulations) has been reported and may present as cholestasis or steatohepatitis. Dose reduction or discontinuation may be required.
  • Hypertriglyceridemia may occur. Dose reductions recommended. Increased risk of pancreatitis with serum triglyceride levels above 1000 mg/dL.
• Immunologic:
  • Hypersensitivity reaction may occur. If suspected, stop infusion immediately.
  • Cross reactions have been observed between soybean and peanut oil. Smoflipid contains soybean, fish oil, and egg phospholipids.
  • Infection and sepsis may occur. Increased risk associated with malnutrition and underlying disease state, poor catheter maintenance, use of immunosuppressive drugs or underlying immunosuppressive condition, or parenteral formulations.

ADVERSE EFFECTS

Nutrilipid
The most commonly reported adverse effects were hyperlipidemia, hypercoagulability, thrombophlebitis, and thrombocytopenia. Additional adverse effects reported in long-term use include hepatomegaly, jaundice, splenomegaly, thrombocytopenia, leukopenia, liver function test abnormalities, brown pigmentation of the liver, and overloading syndrome.
Omegaven
The most common adverse reaction with Omegaven-treated pediatric patients were vomiting (46%), agitation (35%), bradycardia (35%), apnea (20%), viral infection (16%), and erythema (12%).
Smoflipid
There was no difference in the incidence of infection between combination lipid emulsions (Smoflipid or Lipoplus) and standard lipid emulsions (soybean oil only) in a meta-analysis (6 trials) of neonates and infants younger than 12 months.

There were no differences observed between Smoflipid and Intralipid in acid-base status, platelet counts, and biochemical parameters (including triglycerides, bilirubin (total and direct), and alanine aminotransferase on postnatal days 2, 4, and 7 in a randomized trial of 96 very low birth infants. The potassium and aspartate aminotransferase concentrations were significantly higher, but within normal limits for preterm infants, in the Smoflipid group. There was no difference in the elevation of triglycerides in preterm neonates (n=60) between Smoflipid for a mean duration of 11 days and Intralipid for a mean duration of 10 days. The association between cholestasis and different lipid concentrations has not been established.

BLACK BOX WARNING

Deaths due to intravascular fat accumulation in the lungs of preterm infants after infusion of IV fat emulsion have been reported. Preterm infants and low birth weight infants have poor clearance of IV lipid emulsion and increased free fatty acid plasma levels following lipid emulsion infusion. Strict adherence to the recommended total daily dose is required; hourly infusion rate should be as slow as possible in each case and should not in any case exceed 1 g fat/kg in 4 hours. Consider administering less than the maximum recommended doses in premature and small for gestational age infants due reduce the likelihood of IV fat overload. The lipemia must clear between daily infusions.

ADMINISTRATION

• Administer via peripheral vein or by central venous infusion over a 12 to 24 hour period for Nutrilipid and 8 to 24 hours for Omegaven. Solutions with osmolarity of 900 mOsm/L or greater must be infused through a central vein.
• Admixture must be completely used within 24 hour after removal from refrigeration. Use a non-vented infusion set or close the air vent on a vented set. Use a dedicated line without any connections. Use filters with pore size of 1.2 microns. Use a vented infusion set when Omegaven is infused from the bottle.
• Do not use di(2-ethylhexyl phthalate (DEHP) containing administration sets or lines.
• Discard emulsion if frozen.
• Do not use and discard admixture if a yellowish streak or accumulation of yellowish droplets appear, which is evidence of separation of the emulsion. Discard if any particulates appear.
• May be infused into the same vein as carbohydrate/amino acid solutions by a Y-connector.

MONITORING

• • Laboratory Parameters
    Obtain serum triglyceride concentrations at baseline, with each dose adjustment, and regularly throughout treatment.
    Monitor fluid and electrolyte status, serum osmolarity, blood glucose, liver and kidneyfunction, blood count, and coagulation parameters throughout treatment. Monitor laboratory results that might indicate infection(including leukocytosis an hyperglycemia).
    Monitor platelet counts frequently in neonates.

• • Laboratory Interface:
    Omegaven may interfer with some laboratory blood tests(e.g.,hemoglobin, lactate dehydrogenase, bilirubin, and oxygen saturation) if blood is sampled before lipids have cleared from the bloodstream.Lipids are normally cleared after a period of 5 to 6 hours once the lipid infusion is stopped.

• Physical Findings
  Closely monitor fluid status in patients with pulmonary edema or heart failure
  Monitor for signs or symptoms of hypersensitivity.
  Carefully monitor for signs or symptoms of early infection
  .Carefully monitor for refeeding syndrome in severely undernourished patients.
  Frequently check for edema, redness, and/or discharge at the site of injection.
  Monitor for laboratory evidence of essential fatty acid deficiency.
  . Monitor for signs and symptoms of pleural or pericardial effusion.