Included as part of the PRECAUTIONS section.
Death In Preterm Infants
Deaths in preterm infants after infusion of intravenous
lipid emulsions have been reported1. Autopsy findings included
intravascular lipid accumulation in the lungs.
Preterm and small for gestational age infants have poor
clearance of intravenous lipid emulsion and increased free fatty acid plasma
levels following lipid emulsion infusion.
The safe and effective use of CLINOLIPID in pediatric
patients, including preterm infants, has not been established. CLINOLIPID is
not indicated for and not recommended for use in pediatric patients.
Stop infusion immediately and treat patient accordingly
if signs or symptoms of a hypersensitivity or allergic reaction develop. Signs
or symptoms may include: tachypnea, dyspnea, hypoxia, bronchospasm,
tachycardia, hypotension, cyanosis, vomiting, nausea, headache, sweating,
dizziness, altered mentation, flushing, rash, urticaria, erythema, pyrexia and
Patients who require parenteral nutrition are at high
risk of infections due to malnutrition and their underlying disease state.
Infection and sepsis may occur as a result of the use of
intravenous catheters to administer parenteral nutrition, poor maintenance of
catheters, or immunosuppressive effects of illness, drugs, and parenteral
Decrease the risk of septic complications with heightened
emphasis on aseptic technique in catheter placement and maintenance, as well as
aseptic technique in the preparation of the nutritional formula.
Carefully monitor for signs and symptoms (including fever
and chills) of early infections, including laboratory test results (including
leukocytosis and hyperglycemia) and frequent checks of the parenteral access
Fat Overload Syndrome
Fat overload syndrome is a rare condition that has been
reported with intravenous lipid formulations. A reduced or limited ability to
metabolize the lipids contained in CLINOLIPID accompanied by prolonged
plasma clearance may result in a syndrome characterized
by a sudden deterioration in the patient's condition accompanied by fever,
anemia, leukopenia, thrombocytopenia, coagulation disorders, hyperlipidemia,
liver fatty infiltration (hepatomegaly), deteriorating liver function, and
central nervous system manifestations (e.g., coma). The cause of the fat
overload syndrome is unclear. The syndrome is usually reversible when the
infusion of the lipid emulsion is stopped. Although it has been most frequently
observed when the recommended lipid dose was exceeded, cases have also been
described where the lipid formulation was administered according to
Refeeding severely undernourished patients with
parenteral nutrition may result in the refeeding syndrome, characterized by the
intracellular shift of potassium, phosphorus, and magnesium as the patient
becomes anabolic. Thiamine deficiency and fluid retention may also develop.
Carefully monitor severely undernourished patients and slowly increase their
nutrient intakes, while avoiding overfeeding, to prevent these complications.
Monitor fluid status closely in patients with pulmonary
edema or heart failure.
Monitor serum triglycerides, fluid and electrolyte
status, serum osmolarity, blood glucose, liver and kidney function, and blood
count, including platelets and coagulation parameters, throughout treatment.
Essential Fatty Acids
Monitoring patients for signs and symptoms of essential
fatty acid deficiency (EFAD) is recommended. Laboratory tests are available to
determine serum fatty acids levels. Reference values should be consulted to
help determine adequacy of essential fatty acid status. Increasing essential
fatty acid intake (enterally or parenterally) is effective in treating and
In CLINOLIPID injection, the mean composition of linoleic
acid (an omega-6 essential fatty acid) is 35.8 mg/mL (range 27.6 to 44.0 mg/mL)
and α-linolenic acid (an omega-3 essential fatty acid) is 4.7 mg/mL (range
1.0 to 8.4 mg/mL). There are insufficient long-term data to determine whether
CLINOLIPID 20% can supply essential fatty acids in adequate amounts in patients
who may have increased requirements.
Interference With Laboratory Tests
Content of Vitamin K may counteract anticoagulant
activity [see DRUG INTERACTIONS].
The lipids contained in this emulsion may interfere with
the results of certain laboratory tests if the blood sample is taken before the
lipids are eliminated from the serum (these are generally eliminated after a
period of 5 to 6 hours without receiving lipids).
CLINOLIPID contains no more than 25 mcg/L of aluminum.
The aluminum contained in CLINOLIPID may reach toxic
levels with prolonged administration in patients with impaired kidney function.
Preterm infants are at greater risk because their kidneys are immature, and
they require large amounts of calcium and phosphate solutions that contain
aluminum. Patients with impaired kidney function, including preterm infants,
who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day,
accumulate aluminum at levels associated with central nervous system and bone
toxicity. Tissue loading may occur at even lower rates of administration of
total parenteral nutrition products.
Risk Of Parenteral Nutrition Associated Liver Disease
Parenteral Nutrition Associated Liver Disease (PNALD) has
been reported in patients who receive parenteral nutrition for extended periods
of time, especially preterm infants, and can present as cholestasis or
steatohepatitis. The exact etiology is unknown and is likely multifactorial.
Intravenously administered phytosterols (plant sterols) contained in
plant-derived lipid formulations have been associated with development of PNALD
although a causal relationship has not been clearly established. If CLINOLIPID
treated patients develop liver test abnormalities consider discontinuation or
Reduce dose of CLINOLIPID and monitor serum triglyceride
levels in patients with serum triglyceride concentrations above 400 mg/dL to
avoid the clinical consequences associated with hypertriglyceridemia. Serum triglyceride
levels above 1000 mg/dL have been associated with an increased risk of
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Studies with CLINOLIPID have not been performed to
evaluate the carcinogenic potential, mutagenic potential, or effects on
Use In Specific Populations
The limited available data on the use of CLINOLIPID in
pregnant women are not sufficient to inform a drug-associated risk. However,
there are clinical considerations if CLINOLIPID is used in pregnant women [see
Clinical Considerations]. Animal reproduction studies have not been conducted
with lipid injectable emulsion.
The estimated background risk of major birth defects and
miscarriage for the indicated population are unknown. In the U.S. general
population, the estimated background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2 to 4% and15 to 20%,
Disease-Associated Maternal and/or Embryo-Fetal Risk
Severe malnutrition in a pregnant woman is associated
with preterm delivery, low birth weight, intrauterine growth restriction,
congenital malformations and perinatal mortality. Parenteral nutrition should
be considered if a pregnant womanÃ¢â¬™s nutritional requirements cannot be
fulfilled by oral or enteral intake. It is not known whether the administration
of CLINOLIPID to pregnant women provides adequate essential fatty acids to the
There are no data available to assess the presence of
CLINOLIPID and/or its active metabolite(s) in human milk, the effects on the
breastfed child or the effects on milk production The developmental and health
benefits of breastfeeding should be considered along with the motherÃ¢â¬™s clinical
need for CLINOLIPID and any potential adverse effects on the breastfed child
from CLINOLIPID or from the underlying maternal condition.
The safety and effectiveness of CLINOLIPID have not been
established in pediatric patients. CLINOLIPID is not indicated for use in
pediatric patients. Pediatric studies did not establish that CLINOLIPID
provides sufficient amounts of essential fatty acids (EFA) in pediatric
patients. Pediatric patients may be particularly vulnerable to neurologic
complications due to EFA deficiency if adequate amounts of EFA are not
Deaths in preterm infants after infusion of intravenous
lipid emulsion have been reported [see WARNINGS AND PRECAUTIONS].
Patients, particularly preterm infants, are at risk for aluminum toxicity [see
WARNINGS AND PRECAUTIONS]. Patients, including pediatric patients, may be
at risk for PNALD [see WARNINGS AND PRECAUTIONS]. In clinical trials of
a pure soybean oil based intravenous lipid emulsion product, thrombocytopenia
in neonates occurred (less than 1%).
Of the total number of subjects in clinical studies of
CLINOLIPID, 21% were 65 and over, while 10% were 75 and over. No overall
differences in safety or effectiveness were observed between these subjects and
younger subjects, and other reported clinical experience has not identified
differences in responses between the elderly and younger patients, but greater
sensitivity of some older individuals cannot be ruled out.
Parenteral nutrition should be used with caution in
patients with hepatic impairment. Hepatobiliary disorders are known to develop
in some patients without preexisting liver disease who receive parenteral
nutrition, including cholestasis, hepatic steatosis, fibrosis and cirrhosis
(parenteral nutrition associated liver disease), possibly leading to hepatic
failure. Cholecystitis and cholelithiasis have also been observed. The etiology
of these disorders is thought to be multifactorial and may differ between
Monitor liver function parameters closely. Patients
developing signs of hepatobiliary disorders should be assessed early by a
clinician knowledgeable in liver diseases in order to identify causative and
contributory factors, and possible therapeutic and prophylactic interventions.
1. Mirtallo J, Canada T, Johnson D, Kumpf V, Petersen C,
Sacks G, et al. Task Force for the Revision of Safe Practices for Parenteral
Nutrition, Special Report: safe practices for parenteral nutrition. JPEN J
Parenter Enteral Nutr 2004, 28(6):S39-70