Coagulation Factor X Human
FDA Drug Information • Also known as: Coagadex
- Brand Names
- Coagadex
- Dosage Form
- KIT
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION COAGADEX is a plasma-derived, sterile, purified concentrate of human coagulation Factor X that contains sucrose as a stabilizer. It is formulated as a lyophilized powder for solution for intravenous administration. When reconstituted with Sterile Water for Injection it forms a colorless, clear or slightly pearl-like solution. COAGADEX contains nominally (approximately) 100 IU/mL of coagulation Factor X and the following inactive ingredients: chloride, phosphate, citrate, sucrose and sodium. Each vial of COAGADEX is labeled with the actual Factor X activity/content expressed in IU per vial. Factor X activity in IU is determined using an in vitro chromogenic assay and a Factor X concentrate reference standard calibrated against the current WHO International Standard for Blood Coagulation Factors II and X Concentrate. COAGADEX contains no added biological components such as heparin, albumin or anti-thrombin. The content of Factor II and Factor IX are ≤ 1 IU/mL of the reconstituted product. Factor Xa and Factor IIa were not detectable by Non-activated Partial Thromboplastin Time (NaPTT) or Fibrinogen Clotting Time (FCT) tests for potential thrombogenicity, and comprised < 10 parts per million by weight when tested by more sensitive analytical methods. The specific activity of COAGADEX is typically 80-137 IU per mg protein. The product contains no preservatives. COAGADEX is manufactured from plasma, obtained from healthy US donors, who have passed viral screening tests. All donors are subjected to medical examinations, laboratory tests, and a review of their medical history before being allowed to donate blood or plasma. All plasma donations are screened for antibody to human immunodeficiency virus (HIV)-1/2, hepatitis C virus (HCV), and hepatitis B surface antigen (HBsAg). Additional testing of donations is carried out in plasma mini-pools (512 donations per pool) with nucleic acid amplification testing (NAT) for HIV, hepatitis B virus (HBV), hepatitis C...
What Is Coagulation Factor X Human Used For?
1 INDICATIONS AND USAGE COAGADEX, Coagulation Factor X (Human), is a plasma-derived human blood coagulation Factor indicated in adults and children with hereditary Factor X deficiency for: Routine prophylaxis to reduce the frequency of bleeding episodes On-demand treatment and control of bleeding episodes Perioperative management of bleeding in patients with mild, moderate, and severe hereditary Factor X deficiency COAGADEX, Coagulation Factor X (Human), is a plasma-derived human blood coagulation factor indicated in adults and children with hereditary Factor X deficiency for: Routine prophylaxis to reduce the frequency of bleeding episodes ( 1 ) On-demand treatment and control of bleeding episodes ( 1 ) Perioperative management of bleeding in patients with mild, moderate and severe hereditary Factor X deficiency ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION For intravenous use after reconstitution only For intravenous use only after reconstitution. Each vial of COAGADEX contains the labeled amount of Factor X in international units (IU) ( 2 ) The dosage and duration of treatment depend on the severity of the Factor X deficiency, the location and extent of the bleeding and the patient's clinical condition ( 2.1 ) For prophylaxis of bleeding episodes ( 2.1 ): Age Initial dose Further management Children: Less than 12 years of age 40 IU/kg twice weekly Monitor trough blood levels of Factor X targeting ≥5 IU/dL and adjust dosage to clinical response and trough levels. Do not exceed a peak level of 120 IU/dL. Adults and adolescents: 12 years of age or older 25 IU/kg twice weekly For treatment of bleeding episodes ( 2.1 ): Age Initial dose Further management Children: Less than 12 years of age 30 IU/kg Infuse at first sign of bleeding. Repeat at intervals of 24 hours until the bleed stops. Adults and adolescents: 12 years of age or older 25 IU/kg For perioperative management ( 2.1 ): Age Initial dose Further management Children: Less than 12 years of age Use a factor of 0.6 to calculate the required dose Pre-surgery: raise plasma Factor X levels to 70-90 IU/dL. Post-surgery: maintain plasma Factor X levels at ≥50 IU/dL until the patient is no longer at risk of bleeding due to surgery. Dose (IU) = body weight (kg) × desired factor X rise † (IU/dL or % of normal) × 0.6 Adults and adolescents: 12 years of age or older Use a factor of 0.5 to calculate the required dose Dose (IU) = body weight (kg) × desired factor X rise ‡ (IU/dL or % of normal) × 0.5 2.1 Dose Dose and duration of the treatment depend on the severity of the Factor X deficiency, location and extent of the bleeding, the patient's age (<12 years or >12 years) and the patient's clinical condition. Base the dose and frequency on the individual clinical response. Do not administer more than 60 IU/kg daily. Each vial of COAGADEX is labeled with the actual Factor X potency/content in International Units (IU). Prophylaxis of bleeding episodes Age Initial dose Further management Children: Less than 12 years of age 40 IU/kg twice weekly Due to inter-and intra-patient variability, it is recommended that trough blood levels of Factor X should be monitored at intervals, especially in the first weeks of therapy or after dosages changes. Adjust dosage regimen to clinical response and trough levels of Factor X of at least 5 IU/dL. Do not exceed a peak level of 120 IU/dL. [For more detailed calculations of dose, see Detailed Dose Calculation (2.1) ] . Adults and adolescents: 12 years of age or older 25 IU/kg twice weekly On–demand treatment and control of bleeding episodes Age Initial dose Further management Children: Less than 12 years of age 30 IU/kg Infuse COAGADEX when the first sign of bleeding occurs [see Clinical Trial Experience (6.1) ] . Repeat at intervals of 24 hours until the bleed stops. [For more detailed calculations...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The most common adverse drug reactions (frequency ≥ 5% of subjects) observed in clinical trials were infusion site erythema, infusion site pain, fatigue, and back pain. The most common adverse drug reactions (frequency ≥ 5% of subjects) observed in clinical trials were infusion site erythema, infusion site pain, fatigue and back pain ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact BPL USA Inc., at 1-844-427-5872 or [email protected] or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience As clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in clinical practice. During the clinical development of COAGADEX involving three multicenter, open-label, non-randomized clinical studies, 27 individual subjects with hereditary Factor X deficiency received at least one dose of COAGADEX. Sixteen subjects aged 12 to 58 years with moderate to severe hereditary Factor X deficiency (basal FX:C < 5 IU/dL) received doses of COAGADEX for pharmacokinetic evaluation, on-demand treatment for control of bleeding episodes, and/or perioperative management of minor surgical or dental procedures. A total of 468 infusions were administered, including 242 for on-demand treatment and control of bleeding episodes, 6 for perioperative management and 31 for PK assessments. Spontaneous, traumatic and menorrhagic bleeding episodes were treated with an on-demand dose of 25 IU/kg for up to 2 years. Two subjects aged 55 and 59 years with mild hereditary Factor X deficiency (basal FX:C 6 IU/dL and 8 IU/dL) received COAGADEX for perioperative management of four major surgical procedures. There were 40 exposure days to COAGADEX. Six adverse reactions were reported in 2 of the 18 subjects. These were infusion site erythema (2 reports in 1 subject [5.6%]), fatigue (2 reports in 1 subject [5.6%]), back pain (1 report [5.6%]) and infusion site pain (1 report [5.6%]). In a separate study, nine children (aged 2 to 11 years), of whom four were less than 6 years of age, received 537 (mean 59.7) doses of COAGADEX as routine prophylaxis of bleeding episodes during a period of at least 6 months. In addition, 22 infusions were given to treat a bleed, equivalent to 2.1 bleeds per subject per year. There were no adverse drug reactions in this study. 6.2 Immunogenicity Immunogenicity was evaluated in three studies and all subjects (adults and children) underwent Factor X inhibitor testing (inhibitor screen and Nijmegen-Bethesda assay) at baseline, end of study and at 3-monthly intervals in between. For subjects who underwent surgery, inhibitor testing was done pre-surgery and on discharge. All inhibitor tests were negative. Additionally, comparison of pharmacokinetic (PK) parameters at the repeat PK assessment with those at first dose did not suggest development of any inhibitors to Factor X. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, it may be misleading to compare the incidence of antibodies to COAGADEX in the studies described above with the incidence of antibodies in other studies or to other products.
Drug Interactions
7 DRUG INTERACTIONS Drug interaction studies have not been performed. Use with caution in patients who are receiving other plasma products that may contain Factor X (e.g. fresh frozen plasma, prothrombin complex concentrates). Based on the mechanism of action, COAGADEX is likely to be counteracted by direct and indirect Factor Xa inhibitors [ see Clinical Pharmacology (12.1) ].
Contraindications
4 CONTRAINDICATIONS COAGADEX is contraindicated in patients who have had life-threatening hypersensitivity reactions to COAGADEX [ see Description (11) ]. Do not use in patients who have had life-threatening hypersensitivity reactions to COAGADEX ( 4 ).
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There is limited data with COAGADEX in pregnant women to inform on drug-associated risk. Animal reproduction studies have not been conducted using COAGADEX. It is not known whether COAGADEX can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Overdosage
10 OVERDOSAGE One case of accidental overdosage was reported in the clinical trials, in which a subject received approximately 80 IU/kg Factor X to treat a bleed. No adverse events were reported relating to this overdose.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied COAGADEX is supplied in single-dose glass vials containing a nominal (approximate) 250 IU or 500 IU (approximately 100 IU/mL after reconstitution) of Factor X activity, packaged with 2.5 mL or 5 mL of Sterile Water for Injection, respectively, and a Mix2Vial transfer device. The vials are closed with a synthetic rubber stopper. The stopper is not made with natural rubber latex. The stopper is secured with an aluminum overseal with a flip-off polypropylene cap. Strength Kit NDC Number 250 IU Range 64208-7752-1 500 IU Range 64208-7753-1 Storage and Handling Store COAGADEX in its original package to protect it from light. Store the COAGADEX package in a refrigerator or at room temperature at 36°F to 86°F (2°C to 30°C). Do not freeze. Do not use COAGADEX or the Sterile Water for Injection after the expiration date printed on the vial and carton labels. Use reconstituted COAGADEX within one hour of reconstitution. Do not use COAGADEX if the reconstituted solution is cloudy or contains any particles.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.