These Highlights Do Not Include All The Information Needed To Use Cyklokapron Safely And Effectively. See Full Prescribing Information For Cyklokapron.

Risk Summary

Available data from published studies, case series and case reports with tranexamic acid use in pregnant women in the second and third trimester and at the time of delivery have not clarified whether there is a drug-associated risk of miscarriage or adverse maternal or fetal outcomes. There are 2 (0.02%) infant cases with structural abnormalities that resulted in death when tranexamic acid was used during conception or the first trimester of pregnancy; however, due to other confounding factors the risk of major birth defects with use of tranexamic acid during pregnancy is not clear. Tranexamic acid is known to pass the placenta and appears in cord blood at concentrations approximately equal to maternal concentration (see Data).

Reproduction studies performed in mice, rats, and rabbits have not revealed any adverse effects on the fetus due to tranexamic acid administered during organogenesis. Doses examined were multiples of up to 3 times (mouse), 6 times (rat), and 3 times (rabbit) the maximum human dose based on body surface area in the mouse, rat, and rabbit, respectively (see Data).

The estimated background risk for major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2–4% and 15–20%, respectively.

It is not known whether tranexamic acid use in pregnant women may cause a drug-associated risk of miscarriage or adverse maternal or fetal outcomes. For decisions regarding the use of CYKLOKAPRON during pregnancy, the potential risk of CYKLOKAPRON administration on the fetus should always be considered along with the mother's clinical need for CYKLOKAPRON; an accurate risk-benefit evaluation should drive the treating physician's decision.

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.

Cases of overdosage of CYKLOKAPRON have been reported. Based on these reports, symptoms of overdosage may be gastrointestinal, e.g., nausea, vomiting, diarrhea; hypotensive, e.g., orthostatic symptoms; thromboembolic, e.g., arterial, venous, embolic; neurologic, e.g., visual impairment, convulsions, headache, mental status changes; myoclonus; and rash.

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.

Tranexamic acid is trans-4-(aminomethyl)cyclohexanecarboxylic acid, an antifibrinolytic agent. Tranexamic acid is a white crystalline powder. The structural formula is

Empirical Formula: C₈H₁₅NO₂                         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.

There are limited data concerning the use of CYKLOKAPRON in pediatric patients with hemophilia who are undergoing tooth extraction. The limited data suggest that there are no significant pharmacokinetic differences between adults and pediatric patients.

Clinical studies of CYKLOKAPRON did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].

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)].

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)]

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)

Reduce the dosage of CYKLOKAPRON in patients with renal impairment, based on the patient's serum creatinine [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].

Tranexamic acid, in concentrations of 1 mg/mL and 10 mg/mL prolongs the thrombin time. An antifibrinolytic concentration of tranexamic acid remains in different tissues for about 17 hours, and in the serum, up to 7 or 8 hours.

Tranexamic acid in concentrations up to 10 mg/mL blood has no influence on the platelet count, the coagulation time or various coagulation factors in whole blood or citrated blood from healthy subjects.

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.

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 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 [see Drug Interactions (7.1), Use in Specific Populations (8.3)].

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.

Tranexamic acid is a synthetic lysine amino acid derivative, which diminishes the dissolution of hemostatic fibrin by plasmin. In the presence of tranexamic acid, the lysine receptor binding sites of plasmin for fibrin are occupied, preventing binding to fibrin monomers, thus preserving and stabilizing fibrin's matrix structure.

The antifibrinolytic effects of tranexamic acid are mediated by reversible interactions at multiple binding sites within plasminogen. Native human plasminogen contains 4 to 5 lysine binding sites with low affinity for tranexamic acid (Kd = 750 μmol/L) and 1 with high affinity (Kd = 1.1 μmol/L). The high affinity lysine site of plasminogen is involved in its binding to fibrin. Saturation of the high affinity binding site with tranexamic acid displaces plasminogen from the surface of fibrin. Although plasmin may be formed by conformational changes in plasminogen, binding to and dissolution of the fibrin matrix is inhibited.

• •
  Risk of Thrombosis with Concomitant Use of Factor IX: Avoid concomitant use. (5.2)
• •
  Seizures: Inadvertent injection into neuraxial system may result in seizures. (5.3)
• •
  Hypersensitivity Reactions: In case of severe reaction, discontinue use and seek immediate medical attention. (5.4)
• •
  Visual Disturbances: Visual or ocular adverse effects may occur. Discontinue use if visual or ocular symptoms occur. (5.5)
• •
  Dizziness: Advise patients not to drive if dizziness occurs. (5.6)

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

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.

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.

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.

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)].

CYKLOKAPRON Injection is a clear and colorless solution supplied in the following presentations:

Store at 20ºC to 25°C (68ºF to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

NDC 0013-1114-21

Contains 10 of NDC 0013-1114-20

Rx only

10 x 10 mL Vials

Cyklokapron^®

(tranexamic acid injection)

1,000 mg/10 mL (100 mg/mL)

Intravenous Use Only

Single-Dose Vial

Discard Unused Portion

Pfizer

Hospital

TEAR HERE

Nonclinical studies have shown a retinal toxicity associated with tranexamic acid. Toxicity is characterized by retinal atrophy commencing with changes to the retinal pigmented epithelium and progressing to retinal detachment in cats. The toxicity appears to be dose related, and changes are partially reversible at lower doses. Effects were observed in dogs at oral doses of 800 mg/kg/day and higher (multiple of 11 times the maximum human dose based on body surface area), and in cats at 250 mg/kg/day for 14 days (multiple of 1.6 times the maximum human dose based on body surface area). Some fully reversible changes in pigmentation were observed in cats at doses of 125 mg/kg/day (multiple of 0.8 times the maximum human dose based on body surface area). Studies suggest that the underlying mechanism may be related to a transient retinal ischemia at high exposures, linked to the known sympathomimetic effect of high plasma exposures of tranexamic acid.

NDC 0013-1114-20

10 mL Vial

Cyklokapron^®

(tranexamic acid injection)

1,000 mg/10 mL

(100 mg/mL)

Intravenous Use Only

Pfizer

NDC 0013-1114-01

10 mL ampule

Cyklokapron^®

(tranexamic acid injection)

1,000 mg/10 mL

(100 mg/mL)

Intravenous Use Only

Single-Dose Ampule

Discard Unused Portion

PAA221603

NDC 0013-1114-10

Contains 10 of NDC 0013-1114-01

10 x 10 mL ampules

Cyklokapron^®

tranexamic acid injection

1000 mg/10 mL

(100 mg/mL)

Solution for intravenous injection

Single-Dose ONLY

Discard any remaining

portion after single use

Rx only

Tranexamic acid was not carcinogenic in a 2-year study in rats and mice at oral doses up to 3 and 5.3 g/kg/day, which are approximately 12 and 11 times the maximum recommended human dose based on body surface area, respectively.

Tranexamic acid was not genotoxic in the reverse mutation bacterial (Ames) test, and in vitro and in vivo cytogenetic test.

In a fertility and early embryonic development study, tranexamic acid was administered to male rats as 0.3% and 1% of drug in diet (average doses of 222 and 856 mg/kg/day) or to female rats at dose levels of 0.3% and 1.2% of drug in diet. Tranexamic acid had no effect on fertility or reproductive function of male or female rats at dose multiples of 4 or 5 times the maximum recommended human dose based on body surface area, respectively.

NDC 0013-1114-01

Contains 1 Ampule 10 mL

Cyklokapron^®

tranexamic acid injection

1000 mg/10 mL

(100 mg/mL)

Solution for intravenous injection

Single-Dose ONLY

Discard any remaining portion

after single use

Rx only

Pfizer Injectables

NDC 0013-1114-15

Contains 1 Ampule 10 mL

Cyklokapron^®

(tranexamic acid injection)

1,000 mg/10 mL

(100 mg/mL)

Intravenous Use Only

Single-Dose Ampule

Discard Unused Portion

Rx only

Pfizer

Hospital

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.

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 [see Warnings and Precautions (5.1)].

For patients with moderate to severe impaired renal function, the following dosages are recommended:

Risk Summary

Available data from published studies, case series and case reports with tranexamic acid use in pregnant women in the second and third trimester and at the time of delivery have not clarified whether there is a drug-associated risk of miscarriage or adverse maternal or fetal outcomes. There are 2 (0.02%) infant cases with structural abnormalities that resulted in death when tranexamic acid was used during conception or the first trimester of pregnancy; however, due to other confounding factors the risk of major birth defects with use of tranexamic acid during pregnancy is not clear. Tranexamic acid is known to pass the placenta and appears in cord blood at concentrations approximately equal to maternal concentration (see Data).

Reproduction studies performed in mice, rats, and rabbits have not revealed any adverse effects on the fetus due to tranexamic acid administered during organogenesis. Doses examined were multiples of up to 3 times (mouse), 6 times (rat), and 3 times (rabbit) the maximum human dose based on body surface area in the mouse, rat, and rabbit, respectively (see Data).

The estimated background risk for major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2–4% and 15–20%, respectively.

It is not known whether tranexamic acid use in pregnant women may cause a drug-associated risk of miscarriage or adverse maternal or fetal outcomes. For decisions regarding the use of CYKLOKAPRON during pregnancy, the potential risk of CYKLOKAPRON administration on the fetus should always be considered along with the mother's clinical need for CYKLOKAPRON; an accurate risk-benefit evaluation should drive the treating physician's decision.

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.

Cases of overdosage of CYKLOKAPRON have been reported. Based on these reports, symptoms of overdosage may be gastrointestinal, e.g., nausea, vomiting, diarrhea; hypotensive, e.g., orthostatic symptoms; thromboembolic, e.g., arterial, venous, embolic; neurologic, e.g., visual impairment, convulsions, headache, mental status changes; myoclonus; and rash.

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.

Tranexamic acid is trans-4-(aminomethyl)cyclohexanecarboxylic acid, an antifibrinolytic agent. Tranexamic acid is a white crystalline powder. The structural formula is

Empirical Formula: C₈H₁₅NO₂                         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.

There are limited data concerning the use of CYKLOKAPRON in pediatric patients with hemophilia who are undergoing tooth extraction. The limited data suggest that there are no significant pharmacokinetic differences between adults and pediatric patients.

Clinical studies of CYKLOKAPRON did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].

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)].

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)]

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)

Reduce the dosage of CYKLOKAPRON in patients with renal impairment, based on the patient's serum creatinine [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].

Tranexamic acid, in concentrations of 1 mg/mL and 10 mg/mL prolongs the thrombin time. An antifibrinolytic concentration of tranexamic acid remains in different tissues for about 17 hours, and in the serum, up to 7 or 8 hours.

Tranexamic acid in concentrations up to 10 mg/mL blood has no influence on the platelet count, the coagulation time or various coagulation factors in whole blood or citrated blood from healthy subjects.

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.

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 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 [see Drug Interactions (7.1), Use in Specific Populations (8.3)].

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.

Tranexamic acid is a synthetic lysine amino acid derivative, which diminishes the dissolution of hemostatic fibrin by plasmin. In the presence of tranexamic acid, the lysine receptor binding sites of plasmin for fibrin are occupied, preventing binding to fibrin monomers, thus preserving and stabilizing fibrin's matrix structure.

The antifibrinolytic effects of tranexamic acid are mediated by reversible interactions at multiple binding sites within plasminogen. Native human plasminogen contains 4 to 5 lysine binding sites with low affinity for tranexamic acid (Kd = 750 μmol/L) and 1 with high affinity (Kd = 1.1 μmol/L). The high affinity lysine site of plasminogen is involved in its binding to fibrin. Saturation of the high affinity binding site with tranexamic acid displaces plasminogen from the surface of fibrin. Although plasmin may be formed by conformational changes in plasminogen, binding to and dissolution of the fibrin matrix is inhibited.

• •
  Risk of Thrombosis with Concomitant Use of Factor IX: Avoid concomitant use. (5.2)
• •
  Seizures: Inadvertent injection into neuraxial system may result in seizures. (5.3)
• •
  Hypersensitivity Reactions: In case of severe reaction, discontinue use and seek immediate medical attention. (5.4)
• •
  Visual Disturbances: Visual or ocular adverse effects may occur. Discontinue use if visual or ocular symptoms occur. (5.5)
• •
  Dizziness: Advise patients not to drive if dizziness occurs. (5.6)

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

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.

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.

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.

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)].

CYKLOKAPRON Injection is a clear and colorless solution supplied in the following presentations:

Store at 20ºC to 25°C (68ºF to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

NDC 0013-1114-21

Contains 10 of NDC 0013-1114-20

Rx only

10 x 10 mL Vials

Cyklokapron^®

(tranexamic acid injection)

1,000 mg/10 mL (100 mg/mL)

Intravenous Use Only

Single-Dose Vial

Discard Unused Portion

Pfizer

Hospital

TEAR HERE

Nonclinical studies have shown a retinal toxicity associated with tranexamic acid. Toxicity is characterized by retinal atrophy commencing with changes to the retinal pigmented epithelium and progressing to retinal detachment in cats. The toxicity appears to be dose related, and changes are partially reversible at lower doses. Effects were observed in dogs at oral doses of 800 mg/kg/day and higher (multiple of 11 times the maximum human dose based on body surface area), and in cats at 250 mg/kg/day for 14 days (multiple of 1.6 times the maximum human dose based on body surface area). Some fully reversible changes in pigmentation were observed in cats at doses of 125 mg/kg/day (multiple of 0.8 times the maximum human dose based on body surface area). Studies suggest that the underlying mechanism may be related to a transient retinal ischemia at high exposures, linked to the known sympathomimetic effect of high plasma exposures of tranexamic acid.

NDC 0013-1114-20

10 mL Vial

Cyklokapron^®

(tranexamic acid injection)

1,000 mg/10 mL

(100 mg/mL)

Intravenous Use Only

Pfizer

NDC 0013-1114-01

10 mL ampule

Cyklokapron^®

(tranexamic acid injection)

1,000 mg/10 mL

(100 mg/mL)

Intravenous Use Only

Single-Dose Ampule

Discard Unused Portion

PAA221603

NDC 0013-1114-10

Contains 10 of NDC 0013-1114-01

10 x 10 mL ampules

Cyklokapron^®

tranexamic acid injection

1000 mg/10 mL

(100 mg/mL)

Solution for intravenous injection

Single-Dose ONLY

Discard any remaining

portion after single use

Rx only

Tranexamic acid was not carcinogenic in a 2-year study in rats and mice at oral doses up to 3 and 5.3 g/kg/day, which are approximately 12 and 11 times the maximum recommended human dose based on body surface area, respectively.

Tranexamic acid was not genotoxic in the reverse mutation bacterial (Ames) test, and in vitro and in vivo cytogenetic test.

In a fertility and early embryonic development study, tranexamic acid was administered to male rats as 0.3% and 1% of drug in diet (average doses of 222 and 856 mg/kg/day) or to female rats at dose levels of 0.3% and 1.2% of drug in diet. Tranexamic acid had no effect on fertility or reproductive function of male or female rats at dose multiples of 4 or 5 times the maximum recommended human dose based on body surface area, respectively.

NDC 0013-1114-01

Contains 1 Ampule 10 mL

Cyklokapron^®

tranexamic acid injection

1000 mg/10 mL

(100 mg/mL)

Solution for intravenous injection

Single-Dose ONLY

Discard any remaining portion

after single use

Rx only

Pfizer Injectables

NDC 0013-1114-15

Contains 1 Ampule 10 mL

Cyklokapron^®

(tranexamic acid injection)

1,000 mg/10 mL

(100 mg/mL)

Intravenous Use Only

Single-Dose Ampule

Discard Unused Portion

Rx only

Pfizer

Hospital

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.

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 [see Warnings and Precautions (5.1)].

For patients with moderate to severe impaired renal function, the following dosages are recommended: