Protein C Activity Monitoring

• Determine the patient's protein C plasma level before and during treatment with CEPROTIN by measuring protein C activity using a chromogenic assay.Certain clinical conditions, such as acute thrombosis, purpura fulminans, and skin necrosis, may shorten the half-life of CEPROTIN. See CLINICAL PHARMACOLOGY: Pharmacokinetics (12.3). In case of an acute thrombotic event, immediately measure protein C activity before the next injection until the patient is stable and monitor the protein C levels to maintain the trough protein C level above 25%.
• Patients treated during the acute phase of their disease may display much lower increases in protein C activity. In addition to protein C activity measurement, check the coagulation parameters also;however, data were insufficient to establish correlation between protein C activity levels and coagulation parameters in clinical trials.

Initiation of Vitamin K Antagonists

• In patients starting treatment with oral anticoagulants belonging to the class of vitamin K antagonists, a transient hypercoagulable state may arise before the desired anticoagulant effect becomes apparent. This transient effect may be because protein C, a vitamin K-dependent plasma protein, has a shorter half-life than most of the vitamin K-dependent proteins (i.e., Factor II, IX, and X).
• In the initial phase of treatment, the protein C activity is more rapidly suppressed than that of the procoagulant factors. For this reason, if the patient switched to oral anticoagulants, they must continue protein C replacement until stable anticoagulation is obtained. Although warfarin-induced skin necrosis can occur in any patient during the initiation of treatment with oral anticoagulant therapy, individuals with severe congenital protein C deficiency are particularly at risk.
• During the initiation of oral anticoagulant therapy, it is advisable to start with a low dose of the anticoagulant and adjust this incrementally, rather than use a standard loading dose of the anticoagulant.

Reconstitution: Use Aseptic Technique

1. Bring the CEPROTIN (powder) and Sterile Water for Injection, USP (diluent) to room temperature.
2. Remove caps from the CEPROTIN and diluent vials.
3. Cleanse stoppers with germicidal solution, and allow them to dry before use.
4. Remove protective covering from one end of the double-ended transfer needle and insert the exposed needle through the center of the diluent vial stopper.
5. Remove protective covering from the other end of the double-ended transfer needle. Invert diluent vial over the upright CEPROTIN vial; then rapidly insert the free end of the needle through the CEPROTIN vial stopper at its center. The vacuum in the vial will draw in the diluent. If there is no vacuum in the vial, do not use the product, and contact Takeda Pharmaceuticals Customer Service at 1-877-TAKEDA-7 (1-877-825-3327).
6. Disconnect the two vials by removing the needle from the diluent vial stopper. Then, remove the transfer needle from the CEPROTIN vial. Gently swirl the vial until all powder is dissolved. Be sure that CEPROTIN is completely dissolved; otherwise, active materials will be removed by the filter needle.

Administration: Use Aseptic Technique

Visually inspect CEPROTIN for particulate matter and discoloration before administration.

After reconstitution, the solution should be colorless to slightly yellowish and clear to slightly opalescent, and free of visible particles. Do not use the solution if it does not meet these criteria. Administer CEPROTIN at room temperature not more than 3 hours after reconstitution.

1. Attach the filter needle to a sterile, disposable syringe and draw back the plunger to admit air into the syringe.
2. Insert the filter needle into the vial of reconstituted CEPROTIN.
3. Inject air into the vial and then withdraw the reconstituted CEPROTIN into the syringe.
4. Remove and discard the filter needle in a hard-walled Sharps container for proper disposal. Use filter needles to filter the contents of a single vial of CEPROTIN only.
5. Attach a suitable needle or infusion set with winged adapter, and inject intravenously as instructed below under Administration by infusion.

Record the name and batch number of the product every time CEPROTIN is administered to a patient.

Administration by Infusion

Administer CEPROTIN at a maximum injection rate of 2 mL per minute except for children with a bodyweight of < 10 kg, where the injection rate should not exceed a rate of 0.2 mL/kg/minute.