Olive Oil And Soybean Oil

FDA Drug Information • Also known as: Clinolipid

Brand Names: Clinolipid
Drug Class: Lipid Emulsion [EPC]
Route: INTRAVENOUS
Dosage Form: INJECTION, EMULSION
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION CLINOLIPID lipid injectable emulsion, USP is a sterile, non-pyrogenic, homogenous, white, milky lipid emulsion for intravenous infusion. The lipid content of CLINOLIPID is 0.2 g/mL and comprises a mixture of refined olive oil and refined soybean oil in an approximate ratio of 4:1 (olive:soy). The mean concentration 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). The phospholipids provide 470 milligrams or 15 mmol of phosphorus per liter. The total energy content, including fat, phospholipids and glycerin is 2000 kcal/L. Each 100 mL of CLINOLIPID 20% contains approximately 16 g of Olive Oil NF and 4 g of Soybean Oil USP, 1.2 g Egg Phospholipids NF, 2.25 g Glycerin USP, 0.03 g Sodium Oleate, and Water for Injection USP. Sodium Hydroxide NF for pH adjustment, pH: 6.0 to 9.0. The olive and soybean oils are refined natural products consisting of a mixture of neutral triglycerides of predominantly unsaturated fatty acids with the following structure: The major component fatty acids are linoleic (13.8 to 22.0%), oleic (44.3 to 79.5%), palmitic (7.6 to 19.3%), linolenic (0.5 to 4.2%), palmitoleic (0.0 to 3.2%) and stearic (0.7 to 5.0%). These fatty acids have the following chemical and structural formulas: CLINOLIPID has an osmolality of approximately 340 mOsmol/kg water (which represents an osmolarity of 260 mOsmol/liter of emulsion). CLINOLIPID contains no more than 25 mcg/L of aluminum. Structural Formula 1 Structural Formula 2

What Is Olive Oil And Soybean Oil Used For?

1 INDICATIONS AND USAGE CLINOLIPID is indicated in adults and pediatric patients, including term and preterm neonates, as a source of calories and essential fatty acids for parenteral nutrition (PN) when oral or enteral nutrition is not possible, insufficient, or contraindicated. CLINOLIPID is indicated in adults and pediatric patients, including term and preterm neonates, as a source of calories and essential fatty acids for parenteral nutrition (PN) when oral or enteral nutrition is not possible, insufficient, or contraindicated. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION

Use a 1.2 micron in-line filter when administering to a patient. ( 2.1 )

For infusion into a central or peripheral vein. ( 2.2 )

See full prescribing information for administration and admixing instructions. ( 2.2 , 2.3 )

CLINOLIPID Pharmacy Bulk Package is only indicated for use in pharmacy admixture programs for the preparation of three-in-one or total nutrition admixtures. ( 2.2 )

Protect the admixed parenteral solution from light. ( 2.3 )

Recommended dosage depends on age, energy expenditure, clinical status, body weight, tolerance, ability to metabolize and eliminate lipids, and consideration of additional energy given to the patient. ( 2.4 )

For information on the age-appropriate infusion rate, see the full prescribing information. ( 2.4 , 5.1 ) Age Initial Dose Maximum Dose Birth to 2 years of age (including preterm and term neonates) 0.5 to 1 g/kg/day 3 g/kg/day Pediatric patients 2 to less than 12 years of age 1 to 2 g/kg/day 3 g/kg/day Pediatric patients 12 to 17 years of age 1 g/kg/day 3 g/kg/day Adults 1 to 1.5 g/kg/day 2.5 g/kg/day 2.1 Use of an Inline Filter When Administering CLINOLIPID to a Patient Fragments of the administration port membrane could be dislodged into the bag after spiking. Use a 1.2 micron in-line filter during administration of CLINOLIPID (alone or as part of an admixture) to remove particulate matter or micro-precipitate contamination during administration of a lipid injection (alone or as part of an admixture). Particulate matter greater than 5 microns has the capability of obstructing blood flow through capillaries, which could lead to embolism and vascular occlusion. Do not use filters of less than 1.2 micron pore size with lipid emulsions. 2.2 Important Administration Instructions Before opening the overwrap, check the color of the oxygen indicator. Compare the color of the indicator to the reference color printed next to the OK symbol depicted in the printed area of the indicator label. Do not use the product if the color of the oxygen absorber/indicator does not correspond to the reference color printed next to the OK symbol. After opening the bag, use the contents immediately and discard unused portion. Visually inspect that the emulsion is a homogeneous liquid with a milky appearance. Inspect for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not exceed the recommended maximum infusion rate (0.75 mL/kg/hour for pediatric patients and 0.5 mL/kg/hour for adults) [see Dosage and Administration (2.4 ) and Warnings and Precautions (5.1) ] . When Administering CLINOLIPID to a Patient : Do not connect flexible bags in series to avoid air embolism due to possible residual gas contained in the primary bag. Air embolism can result if residual gas in the bag is not fully evacuated prior to administration if the flexible bag is pressurized to increase flow rates. Do not use vented administration sets with the vent in...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling:

Clinical Decompensation with Rapid Infusion of Intravenous Lipid Emulsion in Neonates and Infants [see Warnings and Precautions (5.1) ]

Parenteral Nutrition-Associated Liver Disease and Other Hepatobiliary Disorders [see Warnings and Precautions (5.2)]

Hypersensitivity reactions [see Warnings and Precautions (5.3) ]

Infections [see Warnings and Precautions (5.4) ]

Fat overload syndrome [see Warnings and Precautions (5.5) ]

Refeeding syndrome [see Warnings and Precautions (5.6) ]

Hypertriglyceridemia [see Warnings and Precautions (5.7) ]

Aluminum toxicity [see Warnings and Precautions (5.8) ]

Essential Fatty Acid Deficiency [see Warnings and Precautions (5.9) ] Most common (≥5%) adverse drug reactions from clinical trials in adults were nausea and vomiting, hyperlipidemia, hyperglycemia, hypoproteinemia, and abnormal liver function tests. Most common (≥5%) adverse reactions from clinical trials in pediatric patients were hyperbilirubinemia, patent ductus arteriosus, anemia, gastroesophageal reflux disease, bradycardia, feeding intolerance, neonatal intraventricular hemorrhage, increased alkaline phosphatase, atrial septal defect, hyponatremia, sepsis, and infantile apnea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare at 1-866-888-2472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The CLINOLIPID trials had small sample sizes and patients had a variety of underlying medical conditions both between different trials and within the individual trials. Patients had gastrointestinal diseases/dysfunction or were recovering from gastrointestinal or other surgeries, trauma, burns, or were afflicted by other chronic illness. Adult Trials Commonly observed adverse reactions in 261 adult patients who received CLINOLIPID were nausea and vomiting, hyperlipidemia, hyperglycemia, hypoproteinemia, and abnormal liver function tests and occurred in 2 to 10 % of patients. The largest clinical trial in adult patients (Study 1) enrolled 48 subjects with different underlying diagnoses. Study 2 was a randomized, open label multicenter study that enrolled 22 subjects, aged 32-81 years, who required long-term parenteral nutrition. The most common adverse reactions in Study 1 and Study 2 were infectious complications (urinary tract infection, septicemia, and fever of unknown origin), treatment emergent abnormalities on liver/gallbladder ultrasound and abnormalities of serum chemistries, principally, hepatic function tests. Adverse reactions reported with other intravenous lipid emulsions include hyperlipidemia, hypercoagulability, thrombophlebitis, and thrombocytopenia. Adverse reactions reported in long-term use with other intravenous lipid emulsions include hepatomegaly, jaundice due to central lobular cholestasis, splenomegaly, thrombocytopenia, leukopenia, abnormalities in liver function tests, brown pigmentation of the liver and overloading syndrome (focal seizures, fever, leukocytosis, hepatomegaly, splenomegaly, and shock). Pediatric Trials The safety of CLINOLIPID in pediatric patients was evaluated in Studies 3, 4, 5, and 6 [see Clinical Studies (14.2) ] . In Study 3, EFAD was defined by calculating the Holman index (the triene [Mead acid] to tetraene [arachidonic acid] ratio; T:T ratio > 0.4). Although no patient developed EFAD, one CLINOLIPID-treated patient who had a T:T ratio that increased from < 0.2 at baseline to > 0.2 at end of study treatment was considered at risk for EFAD. This patient’s arachidonic and linoleic acid levels remained within the normal range. No soybean oil lipid...

Drug Interactions

7 DRUG INTERACTIONS No drug interaction studies have been performed with CLINOLIPID. Olive and soybean oils have a natural content of Vitamin K 1 that may counteract the anticoagulant activity of coumadin derivatives, including warfarin. The anticoagulant activity of coumarin derivatives, including warfarin, may be counteracted. ( 7 )

Contraindications

4 CONTRAINDICATIONS The use of CLINOLIPID is contraindicated in patients with the following:

Known hypersensitivity to egg, soybean, peanut or to any of the active or inactive ingredients in CLINOLIPID [see Warnings and Precautions (5.3) ] .

Severe disorders of lipid metabolism characterized by hypertriglyceridemia (serum triglyceride >1,000 mg/dL) [see Warnings and Precautions (5.7) ] .

Known hypersensitivity to egg, soybean, peanut, or any of the active or inactive ingredients. ( 4 )

Severe disorders of lipid metabolism characterized by hypertriglyceridemia (serum triglycerides >1,000 mg/dL). ( 4 , 5.7 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Administration of the recommended dose of CLINOLIPID is not expected to cause major defects, miscarriage, or other adverse maternal or fetal outcomes. No animal reproduction studies have been conducted with lipid injectable emulsion. There are clinical considerations if CLINOLIPID is used in pregnant women [see Clinical Considerations ] . The estimated background risk of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations 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 woman’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 developing fetus.

Overdosage

10 OVERDOSAGE In the event of overdose, serious adverse reactions may result [see Warnings and Precautions (5.1 , 5.5 )] . Stop the infusion to allow lipids to clear from serum. The effects are usually reversible after the lipid infusion is stopped. If medically appropriate, further intervention may be indicated. The lipid administered and fatty acids produced are not dialyzable.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING CLINOLIPID is a sterile, white, milky homogenous lipid injectable emulsion supplied in CLARITY polyolefin Flexible Containers as follows: Strengths Container Size Product Code NDC Number (1 Bag) NDC Number (Shelf Pack) 20% (20 g/100 mL) (0.2 g/mL) 100 mL EADB9520 0338-9540-01 (single-dose Flexible Container) 0338-9540-05 (15 pack) 20% (50 g/250 mL) (0.2 g/mL) 250 mL EADB9521 0338-9540-02 (single-dose Flexible Container) 0338-9540-06 (10 pack) 20% (100 g/500 mL) (0.2 g/mL) 500 mL EADB9523 0338-9540-03 (single-dose Flexible Container) 0338-9540-07 (12 pack) 20% (200 g/1,000 mL) (0.2 g/mL) 1,000 mL EADB9524 0338-9540-04 (Pharmacy Bulk Package bag) 0338-9540-08 (6 pack) The CLARITY Container is a lipid-compatible plastic container (PL 2401-1). The bag is packaged in an oxygen barrier overpouch, which contains an oxygen absorber / oxygen indicator sachet. CLINOLIPID should be stored at 20°C to 25°C (68°F to 77°F). Excursion permitted between 15°C to 30 °C (59°F to 86°F). See USP Controlled Room Temperature. Protect from freezing. Avoid excessive heat. Store in overpouch until ready to use. CLINOLIPID 100 mL, 250 mL and 500 mL single-dose Flexible Containers : After removing the overpouch, infuse immediately. If not used immediately, the product should be stored for no longer than 24 hours at not more than 25°C (77°F) [ See Dosage and Administration (2.2) ]. CLINOLIPID 1,000 mL Pharmacy Bulk Package : Use the pharmacy bulk package immediately for admixing after removal from overpouch. If not used immediately, the product should be stored for no longer than 24 hours at not more than 25°C (77°F) [ see Dosage and Administration (2.2) ].

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.