Cyklokapron Drug Information

® 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.

• 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 of CYKLOKAPRON with medical products that are prothrombotic because concomitant use can further increase the risk of thromboembolic adverse reactions associated with tranexamic acid .

Pregnancy 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. Data Human Data Tranexamic acid passes through the placenta.

The concentration in cord blood after an intravenous injection of 10 mg/kg to pregnant women is about 30 mg/L, as high as in the maternal blood. There were 13 clinical studies that described fetal and/or neonatal functional issues such as low Apgar score, neonatal sepsis, cephalohematoma and 9 clinical studies that discussed alterations to growth including low birth weight and preterm birth at 22–36 weeks of gestation in fetuses and infants exposed to tranexamic acid in-utero. Animal Data In embryo-fetal development studies, tranexamic acid was administered to pregnant mice from Gestation Day (GD) 6 through GD 12 and rats from GD 9 through GD 14 at daily doses of 0.3 or 1.5 g/kg.

There was no evidence of adverse developmental outcomes in mice and rats at multiple of 3 and 6 times the maximum recommended human dose based on body surface area in the mouse and rat, respectively. In rabbits, tranexamic acid was administered intravenously at doses of 50, 100, or 200 mg/kg/day or orally at doses of 100, 200, or 400 mg/kg/day from GD 6 through GD 18. There was no evidence of adverse developmental outcomes at dose multiples of 2 or 3 times, respectively, the maximum recommended human dose based on body surface area. Intravenous doses of 200 mg/kg/day showed slightly retarded weight gain in pregnant rabbits.

Pediatric Use 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.

• 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 )

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.