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.

Injection: 1,000 mg/10 mL (100 mg/mL) clear and colorless solution in single-dose ampules Injection: 1,000 mg/10 mL (100 mg/mL) clear and colorless solution in single-dose vials • Injection: 1,000 mg/10 mL (100 mg/mL) in single-dose ampules • Injection: 1,000 mg/10 mL (100 mg/mL) in single-dose vials

• Before Extraction: Administer 10 mg/kg actual body weight of CYKLOKAPRON intravenously with replacement therapy as a single‑dose. • After Extraction: Administer 10 mg/kg actual body weight of CYKLOKAPRON intravenously 3 to 4 times daily for 2 to 8 days. • Infuse undiluted solution no more than 1 mL/minute to avoid hypotension. • Reduce the dosage for patients with renal impairment

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

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 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 . 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

• Risk of Thrombosis with Concomitant Use of Factor IX: Avoid concomitant use. • Seizures: Inadvertent injection into neuraxial system may result in seizures. • Hypersensitivity Reactions: In case of severe reaction, discontinue use and seek immediate medical attention. • Visual Disturbances: Visual or ocular adverse effects may occur. Discontinue use if visual or ocular symptoms occur. • Dizziness: Advise patients not to drive if dizziness occurs. 5.1 Risk of Medication Errors Due to Incorrect Route of Administration CYKLOKAPRON is for intravenous use only. Serious , including fatal , adverse reactions including seizures and cardiac arrythmias have occurred when CYKLOKAPRON was inadvertently administered via the neuraxial route . Confirm the correct route of administration for CYKLOKAPRON and avoid confusion with other injectable solutions that might be administered at the same time as CYKLOKAPRON. Clearly label syringes containing CYKLOKAPRON with the intravenous route of administration

Thromboembolic Risk CYKLOKAPRON is contraindicated in patients with active intravascular clotting. Tranexamic acid is an antifibrinolytic and may increase the risk of thromboembolic events. Venous and arterial thrombosis or thromboembolism has been reported in patients treated with CYKLOKAPRON. Avoid concomitant use of CYKLOKAPRON and medical products that are pro-thrombotic, as the risk of thrombosis may be increased. These medications include but are not limited to, Factor IX Complex concentrates, Anti-inhibitor Coagulant concentrates, and hormonal contraceptives

Seizures CYKLOKAPRON may cause seizures, including focal and generalized seizures. The most common setting for tranexamic acid-induced seizures has been during cardiovascular surgery (a setting in which CYKLOKAPRON is not FDA‑approved and which uses doses of up to 10‑fold higher than the recommended human dose and in patients inadvertently given tranexamic acid via the neuraxial route ). CYKLOKAPRON is contraindicated for neuraxial administration (i.e., epidural, intrathecal) . Consider dose reduction during surgery and dose adjustments for patients with clinical conditions such as renal dysfunction. Closely monitor the patient during surgery. Consider electroencephalogram (EEG) monitoring for patients with history of seizures or who experience myoclonic movements, twitching, or show evidence of focal seizures. Discontinue CYKLOKAPRON if seizures occur

Hypersensitivity Reactions Cases of hypersensitivity reactions, including anaphylactic reactions, have occurred with use of intravenous tranexamic acid. Discontinue treatment with CYKLOKAPRON if serious reaction occurs, provide appropriate medical management, and do not restart treatment. CYKLOKAPRON is contraindicated in patients with a history of hypersensitivity to tranexamic acid

Visual Disturbances Although not seen in humans, focal areas of retinal degeneration have been observed in cats and dogs following oral or intravenous tranexamic acid at doses between 250 to 1600 mg/kg/day (1.6 to 22 times the recommended usual human dose based on body surface area) from 6 days to 1 year. No retinal changes have been observed in eye examinations of patients treated with tranexamic acid for up to 8 years. Patients expected to be treated for greater than 3 months may consider ophthalmic monitoring including visual acuity and optical coherence tomography at regular intervals. Discontinue CYKLOKAPRON if changes in ophthalmological examination occurs

Dizziness CYKLOKAPRON may cause dizziness. Concomitant use of other drugs that may also cause dizziness may worsen this effect. Advise patients to avoid driving or using machines until they know how CYKLOKAPRON affects them.

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 .