Cyklokapron: Package Insert and Label Information (Page 2 of 2)

12.3 Pharmacokinetics

Distribution

The initial volume of distribution is about 9 to 12 liters. The plasma protein binding of tranexamic acid is about 3% at therapeutic plasma levels and seems to be fully accounted for by its binding to plasminogen. Tranexamic acid does not bind to serum albumin.

Elimination

After an intravenous dose of 1 g, the plasma concentration time curve shows a triexponential decay with a half-life of about 2 hours for the terminal elimination phase.

Excretion

Urinary excretion is the main route of elimination via glomerular filtration. Overall renal clearance is equal to overall plasma clearance (110 to 116 mL/min), and more than 95% of the dose is excreted in the urine as unchanged drug. Excretion of tranexamic acid is about 90% at 24 hours after intravenous administration of 10 mg/kg body weight.

Specific Populations

Patients with Renal Impairment

The blood levels of tranexamic acid are increased in patients with renal insufficiency. Urinary excretion following a single intravenous injection of tranexamic acid declines as renal function decreases. Following a single 10 mg/kg intravenous injection of tranexamic acid, the 24-hour urinary fractions of tranexamic acid with serum creatinine concentrations 1.4 – 2.8, 2.8 – 5.7, and greater than 5.7 mg/dL were 51, 39, and 19%, respectively. The 24-hour tranexamic acid plasma concentrations for these patients demonstrated a direct relationship to the degree of renal impairment. Therefore, dose adjustment is needed in patients with renal impairment [see Dosage and Administration (2.2), Use in Specific Populations (8.6)].

Drug Interaction Studies

No studies of interactions between CYKLOKAPRON and other drugs have been conducted.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

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.

13.2 Animal Toxicology and/or Pharmacology

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.

16 HOW SUPPLIED/STORAGE AND HANDLING

CYKLOKAPRON Injection 100 mg/mL
NDC 0013-1114-10 10 × 10 mL single-dose ampules
NDC 0013-1114-15 1 × 10 mL single-dose ampule
CYKLOKAPRON Injection 100 mg/mL
NDC 0013-1114-21 10 × 10 mL single-dose vials

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].

17 PATIENT COUNSELING INFORMATION

Thromboembolic Risk

Inform patients that CYKLOKAPRON may increase the risk of venous and arterial thrombosis or thromboembolism and to contact their healthcare provider for any signs or symptoms suggestive of thromboembolism.

Advise patients using hormonal contraception that combined use with CYKLOKAPRON may increase the risk for thromboembolic adverse reactions and to use effective alternative (nonhormonal) contraception during therapy with CYKLOKAPRON [see Warnings and Precautions (5.1), Drug Interactions (7.1), Use in Specific Populations (8.3)].

Seizures

Inform patients that CYKLOKAPRON may cause seizures and to contact their healthcare provider for any signs or symptoms suggestive of seizures [see Warnings and Precautions (5.3)].

Hypersensitivity Reactions

Inform patients that CYKLOKAPRON may cause hypersensitivity reactions and to contact their healthcare provider for any signs or symptoms of hypersensitivity reactions [see Warnings and Precautions (5.4)].

Visual Disturbances

Inform patients that CYKLOKAPRON can cause visual disturbance and that they should report any eye symptoms or change in their vision to their healthcare provider and to follow-up with an ophthalmologist for a complete ophthalmologic evaluation, including dilated retinal examination of the retina [see Warnings and Precautions (5.5)].

Risk of Driving and Operating Machinery

Inform patients that CYKLOKAPRON may cause dizziness, and that the patient should be cautioned about driving, operating machinery, or performing hazardous tasks while taking CYKLOKAPRON [see Warnings and Precautions (5.6)].

This product’s labeling may have been updated. For the most recent prescribing information, please visit www.pfizer.com.

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LAB-0258-15.0

PRINCIPAL DISPLAY PANEL — 10 mL Ampule Label

Pfizer Injectables

Rx only

NDC 0013-1114-01

10 mL ampule
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

PAA058409

PRINCIPAL DISPLAY PANEL -- 10 mL Ampule Label
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 10 mL Ampule Carton — NDC 0013-1114-01

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 portionafter single use

Rx only

Pfizer Injectables

PRINCIPAL DISPLAY PANEL -- 10 mL Ampule Carton -- NDC 0013-1114-01
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 10 mL Ampule Carton — NDC 0013-1114-15

NDC 0013-1114-15

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 portionafter single use

Rx only

Pfizer Injectables

PRINCIPAL DISPLAY PANEL -- 10 mL Ampule Carton -- NDC 0013-1114-15
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 10 x 10 mL Ampule Box Label

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

PRINCIPAL DISPLAY PANEL -- 10 x 10 mL Ampule Box Label
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 10 mL Vial Label

NDC 0013-1114-20

10 mL Vial

Cyklokapron®

(tranexamic acid injection)

1000 mg/10 mL

(100 mg/mL)Rx only

PRINCIPAL DISPLAY PANEL -- 10 mL Vial Label
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 10 mL Vial Box

NDC 0013-1114-21
Contains 10 of NDC 0013-1114-20
Rx only

10 x 10 mL Vials

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

Pfizer Injectables

TEAR HERE

PRINCIPAL DISPLAY PANEL -- 10 mL Vial Box
(click image for full-size original)
CYKLOKAPRON tranexamic acid injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0013-1114
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
TRANEXAMIC ACID (TRANEXAMIC ACID) TRANEXAMIC ACID 100 mg in 1 mL
Inactive Ingredients
Ingredient Name Strength
WATER
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0013-1114-10 10 CARTON in 1 BOX contains a CARTON
1 1 AMPULE in 1 CARTON This package is contained within the BOX (0013-1114-10) and contains a AMPULE (0013-1114-01)
1 NDC:0013-1114-01 10 mL in 1 AMPULE This package is contained within a CARTON and a BOX (0013-1114-10)
2 NDC:0013-1114-21 10 VIAL in 1 BOX contains a VIAL (0013-1114-20)
2 NDC:0013-1114-20 10 mL in 1 VIAL This package is contained within the BOX (0013-1114-21)
3 NDC:0013-1114-15 1 AMPULE in 1 CARTON contains a AMPULE (0013-1114-01)
3 NDC:0013-1114-01 10 mL in 1 AMPULE This package is contained within the CARTON (0013-1114-15)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA019281 12/30/1986
Labeler — Pfizer Laboratories Div Pfizer Inc (134489525)
Establishment
Name Address ID/FEI Operations
Pfizer Manufacturing Belgium NV 370156507 ANALYSIS (0013-1114), MANUFACTURE (0013-1114), PACK (0013-1114), LABEL (0013-1114)
Establishment
Name Address ID/FEI Operations
Kyowa Pharma Chemical Co., Ltd. 690852371 API MANUFACTURE (0013-1114), ANALYSIS (0013-1114)

Revised: 04/2021 Pfizer Laboratories Div Pfizer Inc

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