CYKLOKAPRON

Tranexamic acid is trans-4-(aminomethyl)cyclohexanecarboxylic acid, an antifibrinolytic agent. Tranexamic acid is a white crystalline powder. The structural formula is Empirical Formula: C 8 H 15 NO 2 Molecular Weight: 157.2 Each mL of the sterile solution for intravenous injection contains 100 mg tranexamic acid and Water for Injection to 1 mL. The aqueous solution for injection has a pH of 6.5 to 8.0. Chemical Structure

CYKLOKAPRON ® is indicated in patients with hemophilia for short-term use (2 to 8 days) to reduce or prevent hemorrhage and reduce the need for replacement therapy during and following tooth extraction. CYKLOKAPRON is an antifibrinolytic indicated in patients with hemophilia for short-term use (2 to 8 days) to reduce or prevent hemorrhage and reduce the need for replacement therapy during and following tooth extraction. ( 1 )

• Before Extraction: Administer 10 mg/kg actual body weight of CYKLOKAPRON intravenously with replacement therapy as a single‑dose. ( 2.1 ) • After Extraction: Administer 10 mg/kg actual body weight of CYKLOKAPRON intravenously 3 to 4 times daily for 2 to 8 days. ( 2.1 ) • Infuse undiluted solution no more than 1 mL/minute to avoid hypotension. ( 2.3 ) • Reduce the dosage for patients with renal impairment. ( 2.2 , 8.6 ) 2.1 Recommended Dosage The recommended dose of CYKLOKAPRON is 10 mg/kg actual body weight administered as a single intravenous dose immediately before tooth extractions . Following tooth extraction, CYKLOKAPRON may be administered at a dose of 10 mg/kg actual body weight intravenously 3 to 4 times daily for 2 to 8 days . 2.2 Recommended Dosage for Patients With Varying Degrees of Renal Impairment For patients with moderate to severe impaired renal function, the following dosages are recommended: Table 1. Recommended Dosage in Patients With Varying Degrees of Renal Impairment Dose reduction is recommended for all doses, both before and after tooth extraction. Serum Creatinine (mg/dL) CYKLOKAPRON Dosage 1.36 mg/dL to 2.83 mg/dL 10 mg/kg intravenously twice daily 2.83 mg/dL to 5.66 mg/dL 10 mg/kg intravenously daily >5.66 mg/dL 10 mg/kg intravenously every 48 hours or 5 mg/kg intravenously every 24 hours 2.3 Preparation and Administration CYKLOKAPRON is for intravenous administration only. CYKLOKAPRON can be administered undiluted or as a diluted solution. • Use aseptic technique to prepare CYKLOKAPRON. • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. CYKLOKAPRON is a clear and colorless solution. Discard the vial if particulate matter is observed. • Calculate the dose (mg) based on the patient’s actual body weight and the total volume (mL) of CYKLOKAPRON solution required. If diluting CYKLOKAPRON , follow the instructions below: • From the diluent infusion bag, withdraw a volume equal to the volume of the CYKLOKAPRON solution required for the patient’s dose. • Withdraw the required volume of CYKLOKAPRON solution from the vial and dilute with a compatible diluent (see below) to make a final concentration of 10 mg/mL or 20 mg/mL. Discard any unused portion left in the vial. o For intravenous infusion, CYKLOKAPRON Injection may be mixed with most solutions for infusion such as electrolyte solutions, carbohydrate solutions, amino acid solutions, and Dextran solutions. o Heparin may be added to CYKLOKAPRON Injection. o CYKLOKAPRON Injection should NOT be mixed with blood. o The drug is a synthetic amino acid and should NOT be mixed with solutions containing penicillin. • Gently invert the infusion bag to mix the diluted solution. DO NOT SHAKE. • If not used immediately, store the diluted CYKLOKAPRON infusion solution at room temperature 20ºC to 25°C (68ºF to 77°F) for up to 4 hours. Administration Infuse undiluted solution no more than 1 mL/minute to avoid hypotension [see Adverse Reactions (6.2) ]. Administer the undiluted and diluted solutions intravenously according to Table 2. Table 2. Administration Rates for Undiluted and Diluted Solutions Undiluted solution Diluted solution Final concentration 100 mg/mL 10 mg/mL 20 mg/mL Administration rate 0.5 mL/minute (no more than 1 mL/minute) 5 mL/minute 2.5 mL/minute

CYKLOKAPRON Injection is contraindicated: • As a neuraxial (i.e., intrathecal, epidural) injection [see Warnings and Precautions (5.1) ] . • In patients with subarachnoid hemorrhage. Anecdotal experience indicates that cerebral edema and cerebral infarction may be caused by CYKLOKAPRON in such patients. • In patients with active intravascular clotting [see Warnings and Precautions (5.2) ] . • In patients with hypersensitivity to tranexamic acid or any of the ingredients [see Warnings and Precautions (5.4) ] . • As a neuraxial (i.e., intrathecal, epidural) injection. ( 4 ) • In patients with subarachnoid hemorrhage, due to risk of cerebral edema and cerebral infarction. ( 4 ) • In patients with active intravascular clotting. ( 4 ) • In patients with severe hypersensitivity reactions to tranexamic acid or any of the ingredients. ( 4 )

The following clinically significant adverse reactions are described elsewhere in the labeling: • Risk of Medication Errors Due to Incorrect Route of Administration [see Warnings and Precautions (5.1) ] • Thromboembolic Risk [see Warnings and Precautions (5.2) ] • Seizures [see Warnings and Precautions (5.3) ] • Hypersensitivity Reactions [see Warnings and Precautions (5.4) ] • Visual Disturbances [see Warnings and Precautions (5.5) ] • Dizziness [see Warnings and Precautions (5.6) ] Most common adverse reactions are nausea, vomiting, diarrhea, allergic dermatitis, giddiness, hypotension, and thromboembolic events. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of tranexamic acid. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal disturbances (nausea, vomiting, diarrhea) may occur and may resolve with dose-reduction. Allergic dermatitis and giddiness have been reported. Hypotension has been reported when intravenous injection is too rapid. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, cerebral thrombosis, acute renal cortical necrosis, and central retinal artery, vein obstruction and cases associated with concomitant use of combination hormonal contraceptives) have been rarely reported in patients receiving tranexamic acid for indications other than hemorrhage prevention in patients with hemophilia. Convulsion, chromatopsia, and visual impairment have also been reported. Anaphylaxis or anaphylactoid reactions have been reported that are suggestive of a causal relationship.

Prothrombotic Medical Products: Avoid concomitant use, can further increase the risk of thromboembolic adverse reactions associated with tranexamic acid. ( 5.2 , 7.1 , 8.3 ) 7.1 Prothrombotic Medical Products Avoid concomitant use of CYKLOKAPRON with medical products that are prothrombotic because concomitant use can further increase the risk of thromboembolic adverse reactions associated with tranexamic acid [see Warnings and Precautions (5.2) , Use in Specific Populations (8.3) ] .