2 DOSAGE AND ADMINISTRATION •Use a 1.2 micron in-line filter when administering to a patient (2.1) •See full prescribing information for administration and admixing instructions (2.2, 2.3) •CLINOLIPID is intended for intravenous infusion. (2.4) •The recommended dose depends on energy expenditure, clinical status, body weight, tolerance, ability to metabolize and consideration of additional energy given to the patient. The usual daily lipid dosage in adults is 1 to 1.5 g/kg/day and should not exceed 2.5 g/kg/day. (2.4) 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 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. 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 the open position. This can result in air embolism. If CLINOLIPID is mixed with dextrose and/or amino acid solutions, check the compatibility before administration by inspecting the mixture closely for the presence of precipitates. Formation of precipitates could result in vascular occlusion. When infused alone, CLINOLIPID can be administered via central or peripheral vein. When administered with dextrose and amino acids, the choice of a central or peripheral venous route should depending on the osmolarity of the final infusate. Do not use administration sets and lines that contain di-2-ehtylhexyl phthalate (DEHP). Use only a 1.2 micron pore size in-line filter to administer CLINOLIPID. DO NOT use any size less than 1.2 micron pore size in-line filter [see Dosage and Administration (2.1)]. 2.3 Admixing Guidelines When Admixing CLINOLIPID in the Pharmacy: Prepare the admixture using strict aseptic techniques to avoid microbial contamination. Do not add additives directly to CLINOLIPID. Do not add CLINOLIPID to the total parenteral nutrition container first; destabilization of the lipid may occur from such an admixture. Do not use the EXACTAMIX Inlet REF 173 (H938173) with an EXACTAMIX compounder to transfer CLINOLIPID. This inlet spike has been associated with dislodgement of the administration port membrane into the CLINOLIPID bag. Use of EXACTAMIX Inlet REF 174 (H938174) is recommended. The following proper mixing sequence must be followed to minimize pH related problems by ensuring that typically acidic Dextrose Injections are not mixed with lipid emulsions alone: 1.Transfer Dextrose Injection to the Total Parenteral Nutrition Admixture Container 2.Transfer Amino Acid Injection 3.Transfer Lipid Emulsion Amino Acid Injection, Dextrose Injection and Lipid Emulsions may be simultaneously transferred to the admixture container. Use gentle agitation during admixing to minimize localized concentration effects; shake bags gently after each addition. The prime destabilizers of emulsions are excessive acidity (such as a pH below 5) and inappropriate electrolyte content. Give careful consideration to additions of divalent cations (Ca++ and Mg++), which have been shown to cause emulsion instability. Amino acid solutions exert buffering effects that protect the emulsion. Inspect the admixture closely for separation of the emulsion. This can be visibly identified by a yellowish streaking or the accumulation of yellowish droplets in the admixed emulsion. The admixture should also be examined for particulates. Discard the admixture if any of the above is observed. 2.4 Dosing Considerations The dosing of CLINOLIPID depends on energy expenditure, the patient’s clinical status, body weight, tolerance, and ability to metabolize CLINOLIPID, as well as additional energy given orally/enterally to the patient. For complete parenteral nutrition, concomitant supplementation with amino acids, carbohydrates, electrolytes, vitamins, and trace elements is necessary. Prior to administration of CLINOLIPID, correct severe water and electrolyte disorders, severe fluid overload states, and severe metabolic disorders. Before starting the infusion, obtain serum triglyceride levels to establish the baseline value. In patients with elevated triglyceride levels, initiate CLINOLIPID injection at a lower dose, and advance in smaller increments, checking the triglyceride levels prior to each adjustment. Adjust the administration flow rate by taking into account the dose being administered, the daily volume intake, and the duration of the infusion [see Overdosage (10)]. The recommended duration of infusion for a parenteral nutrition bag is between 12 and 24 hours, depending on the clinical situation. Treatment with parenteral nutrition may be continued for as long as is required by the patient’s condition. The maximum daily dose of CLINOLIPID should be based on individual total nutritional requirements and patient tolerance. The usual lipid dosage is 1 to 1.5 g/kg/day (equal to 5 to 7.5 mL/kg/day of CLINOLIPID 20%) 1. The daily dose should not exceed 2.5 g/kg/day. The initial infusion rate should not exceed 0.1 g (equal to 0.5 mL) per minute for the first 15 to 30 minutes. If tolerated, gradually increase until reaching the required rate after 30 minutes.