TRISODIUM: 137 Adverse Event Reports & Safety Profile

SODIUM CITRATE 4% W/V ANTICOAGULANT SOLUTION USP is designed to be metered by an apheresis device in apheresis procedures, to prevent platelet activation and coagulation as blood moves throughout the extracorporeal unit (tubing set) in an apheresis procedure. The solution is sterile and non-pyrogenic, and it contains no bacteriostatic or antimicrobial agents. Sterilized with steam. The formulas of the active ingredients are provided in Table 1.

Table

1: Active Ingredients Ingredients Molecular Formula Molecular Weight Sodium Citrate Dihydrate C 6 H 9 Na 3 O 9

294.10 Water for Injection H 2 O

18.00 Each 100 mL of SODIUM CITRATE 4% W/V ANTICOAGULANT SOLUTION USP contains: Sodium Citrate (dihydrate) 4.0 g; and Water for Injection to 100 mL (pH adjusted with citric acid). Approximate millimoles of sodium citrate: 13.8. The polyolefin bag is not made with natural rubber latex. The bag contains materials that have been tested to demonstrate the suitability of the container for storing pharmaceutical solutions. The bag is nontoxic and biologically inert. The bag-solution unit is a closed system and is not dependent upon entry of external air during administration. The bag is overwrapped to provide protection from the physical environment and to provide an additional moisture barrier when necessary.

INDICATIONS AND USAGE triCitrasol ® Anticoagulant Sodium Citrate Concentrate, 46.7% Trisodium Citrate, is an anticoagulant used in granulocytapheresis procedures (granulocyte collection by apheresis). Just prior to performing granulocytapheresis, aseptically add 30 mL of triCitrasol ® to 500 mL of the 6% solution of Hydroxyethyl Starch (HES), e.g. Hespan ® 2-8 . Agitate the resultant solution for 1 minute to assure a uniform concentration of anticoagulant. The resultant solution of triCitrasol ® and 6% solution of HES contains the following concentration depending upon the volume used: Volume of triCitrasol ® Volume of HES Total Volume Final Concentration of triCitrasol ® 30 mL 500 mL (measured from HES bag) 530 mL 2.6% 30 mL 558 mL (injected directly into HES bag) 588 mL 2.4% The triCitrasol ® /HES solution is stable for up to 24 hours at room temperature after mixing. Refer to the manufacturer's Operator's Manual of the apheresis medical device for the directions to perform the granulocytapheresis procedure.

AND ADMINISTRATION SODIUM CITRATE 4% W/V ANTICOAGULANT SOLUTION USP is added to tubing sets during apheresis procedures. ( 2 ) SODIUM CITRATE 4% W/V ANTICOAGULANT SOLUTION USP may only be used with apheresis devices. For instructions on the use of the solution see the apheresis device operator's manual. ( 2.1 ) Follow the directions for connecting the SODIUM CITRATE 4% W/V ANTICOAGULANT SOLUTION USP bag to the apheresis system. ( 2.2 )

2.1 General Dosing Information SODIUM CITRATE 4% W/V ANTICOAGULANT SOLUTION USP is added to tubing sets during apheresis procedures. The solution bag is connected to the tubing set in an apheresis collection. The recommended dose is determined by the apheresis device and metered into the tubing set by the apheresis device. It is not intended for direct intravenous infusion. For instructions on the use of the solution with the apheresis device and tubing set, see the device operator's manual.

2.2 Administration Ensure solution is the SODIUM CITRATE 4% W/V ANTICOAGULANT SOLUTION USP and is within the expiration date. Inspect the bag. Do not use if the container is damaged, leaking or if there is any visible sign of deterioration. Use only if solution is clear and free of particulate matter. Protect from sharp objects. Directions for connecting the SODIUM CITRATE 4% W/V ANTICOAGULANT SOLUTION USP bag to the apheresis device. At the prompt to connect anticoagulant to the apheresis device tubing set: Remove the overwrap by pulling down at the notch, and remove the SODIUM CITRATE 4% W/V ANTICOAGULANT SOLUTION USP bag. Before use, perform the following checks <span class="opacity-50 text-xs">[see Warnings and Precautions (5) ]</span> : Check for leaks by gently squeezing the bag. If leaks are found, discard the bag. Ensure that the solution is the SODIUM CITRATE 4% W/V ANTICOAGULANT SOLUTION USP and is within the expiration date. Inspect the solution in good light. Bags showing cloudiness, haze, or particulate matter should not be used. Remove the protective cap from the port on the bag. Connect the bag to the apheresis device tubing set using aseptic technique and hang the solution. Proceed according to the apheresis device operator&apos;s manual. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever the solution and container permit.

4. CONTRAINDICATIONS DO NOT INFUSE ANTICOAGULANT SODIUM CITRATE 4% W/V SOLUTION USP DIRECTLY TO THE DONOR. DO NOT INFUSE ANTICOAGULANT SODIUM CITRATE 4% W/V SOLUTION USP DIRECTLY TO THE DONOR. ( 4 )

REACTIONS Citrate reactions or toxicity may occur with the infusion of blood products to patients and return of blood containing citrate anticoagulant to donors. The recipient of the blood containing citrate should be monitored for the signs and symptoms of citrate toxicity. The signs and symptoms of citrate toxicity begin with paresthesia, a "tingling" sensation around the mouth or in the extremities, followed by severe reactions that are characterized by hypotension and possible cardiac arrhythmia. Citrate toxicity may occur more frequently in patients who are hypothermic, have impaired liver or renal function, or have low calcium levels because of an underlying disease. Citrate reactions or toxicity may occur with the infusion and return of blood containing citrate anticoagulant. The recipient of the blood containing citrate should be monitored for the signs and symptoms of citrate toxicity. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Terumo BCT, Inc. at 1-877-339-4228 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Warnings Do not use if you

• have Hereditary Fructose Intolerance (HFI). This product contains fructose. Ask a doctor before use if you
• have diabetes because this product contains sugar
• are on a sodium-restricted diet Ask a doctor or pharmacist before use if you
• are taking any other medications. This product may interact with certain prescription drugs. When using this product,
• do not take more than 24 tablets in a 24-hour period. Stop use and ask a doctor if
• nausea lasts more than two weeks or recurs frequently. If pregnant or breast-feeding,
• ask a health professional before use. Keep out of reach of children In case of overdose, get medical help or contact a Poison Control Center right away at 1-800-222-1222.

PRECAUTIONS General Aseptic technique must be maintained at all times. triCitrasol ® Anticoagulant Sodium Citrate Concentrate is a clear/colorless solution. If the product shows any cloudiness or turbidity, the concentrate should be discarded. The cap/stopper system provides a biological barrier and should be intact – discard product if system is comprised. Information for Patients None.

Laboratory Tests

There are no laboratory tests for the drug product at this time.

Drug Interactions

There are no adverse reactions for the addition of the product to the rouleaux agent. Carcinogenesis, mutagenesis, impairment of fertility Long-term studies in animals have not been performed to evaluate the carcinogenic potential of triCitrasol ® .

Pregnancy

Long-term studies in animals have not been performed to evaluate the effects of triCitrasol ® on pregnant women.

Pediatric Use

The safety and effectiveness of triCitrasol ® in children have not been established.

Drug Interactions There are no adverse reactions for the addition of the product to the rouleaux agent.

Active ingredient (in each chewable tablet) Sodium citrate dehydrate USP 230 mg

Inactive ingredients Acacia, D&C Yellow No. 10 Lake, Dextrose, Flavors (natural and artificial), Fructose, Ginger root, Hydroxypropylcellulose, Magnesium stearate, Malic acid, Maltodextrin, Povidone, Silicon dioxide, Stearic acid, Stevia extract, Sucralose, Sucrose.