"Potential drug treatments are tested on paper, in laboratories and eventually in thousands of people. But every drug that goes through this cycle â€“ every drug that FDA approves â€“ carries some risk. One of the first lines of defense against "...
Death in Preterm Infants
The safe and effective use of CLINOLIPID injection in pediatric patients, including preterm infants, has not been established. CLINOLIPID injection 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 chills.
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 formulations.
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 device.
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 injection 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 instructions.
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 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 preventing EFAD.
In CLINOLIPID injection, the mean composition of linoleic acid (an omega-6 essential fatty acid) is 35.8 mg/mL (range 27.6 - 44.0 mg/mL) and a-linolenic acid (an omega-3 essential fatty acid) is 4.7 mg/mL (range 1.0 - 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
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 injection contains no more than 25 mcg/L of aluminum.
The aluminum contained in CLINOLIPID injection 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 steatohepatitis1. 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 injection treated patients develop liver test abnormalities consider discontinuation or dose reduction.
Reduce dose of CLINOLIPID injection 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 pancreatitis.
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 Suppl)
Carcinogenesis, Mutagenesis, Impairment of Fertility.
Studies with CLINOLIPID injection have not been performed to evaluate the carcinogenic potential, mutagenic potential, or effects on fertility.
Animal Toxicology and/or Pharmacology
CLINOLIPID injection was evaluated in toxicity studies conducted in rats and dogs for up to 3 months. The principle signs of toxicity noted in the 3-month studies were:
- Slight hemolytic anemia at 12 g/kg/day in rats and at 6 g/kg/day in dogs. These doses in rats and dogs are 4.8 and 2.4 times higher, respectively, than the recommended adult dose (2.5 g/kg/day) of CLINOLIPID injection.
- Dose-dependent decrease in urea levels in rats at 6 and 12 g/kg/day dose levels and in dogs at 3, 4.5 and 6 g/kg/day dose levels associated with decreased feed consumption.
- Hypercholesterolemia in dogs at 3, 4.5 and 6 g/kg/day dose levels.
- Hepatic pathology of lipid and pigmentary overload in male and female rats at 3, 6 and 12 g/kg/day dose levels and brownish-yellow pigmentation in vacuolated Kupffer cells in male and female dogs at 3, 4.5 and 6 g/kg/day dose levels with hepatocyte vacuolation in male dogs at 6 g/kg/day and female dogs at 4.5 and 6 g/kg/day dose levels.
- Splenic pigmentation and vacuolization in rats at 3, 6 and 12 g/kg/day dose levels, and dogs in 4.5 and 6 g/kg/day dose levels.
At doses of 3 g/kg/day, slight lipid and pigmentary overload of the liver and vacuolization of Kupffer cells were observed in rats and dogs. At a dose of 12 g/kg/day in rats, hepatocellular vacuolation, granulomatous inflammation of the liver, hepatocellular necrosis and hemosiderosis of the liver and lipid deposits and splenic hemosiderosis, were observed. In dogs, at a dose of 6 g/kg/day, brownish-yellow pigmentation in the Kupffer cells of liver and spleen, hyperplasia of vacuolated Kupffer cells, hepatocyte vacuolization, a slight increase in the number of lipid storage cells (Ito cells) in the liver and macrophage vacuolization of the spleen were observed.
Use In Specific Populations
Pregnancy Category C
There are no adequate and/or well-controlled studies with CLINOLIPID injection in pregnant women. Animal reproduction studies have not been conducted with CLINOLIPID injection. It is also not known whether CLINOLIPID injection can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. CLINOLIPID injection should be given to a pregnant woman only if clearly needed. It is not known whether the administration of CLINOLIPID injection 20% to pregnant women provides adequate essential fatty acids to the developing fetus.
It is not known whether CLINOLIPID injection is present in human milk. Because many drugs are present in human milk, exercise caution when CLINOLIPID injection is administered to a nursing woman.
The safety and effectiveness of CLINOLIPID injection have not been established in pediatric patients. LINOLIPID injection is not indicated for use in pediatric patients. Pediatric studies did not establish that
CLINOLIPID injection 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 provided.
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 ( < 1%).
Of the total number of subjects in clinical studies of CLINOLIPID injection, 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 patients.
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.
Last reviewed on RxList: 10/18/2013
This monograph has been modified to include the generic and brand name in many instances.
Additional Clinolipid Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.