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Coagadex

Generic Name: Factor X (Human)
Class: Hemostatics
VA Class: BL500

Medically reviewed by Drugs.com. Last updated on Feb 18, 2019.

Introduction

Preparation of blood coagulation factor X derived from pooled human plasma.1 3 21

Uses for Coagadex

Hereditary Factor X Deficiency

On-demand treatment and control of bleeding episodes in patients with hereditary factor X deficiency.1 2 3 4 10 11 21

Perioperative management of bleeding in patients with mild hereditary factor X deficiency.1 2 3 4 10 11 21 23

Designated an orphan drug by FDA for treatment of hereditary factor X deficiency.23

Safety and efficacy for perioperative management of bleeding in patients with moderate or severe hereditary factor X deficiency undergoing major surgery not established.1 10 11

Hereditary factor X deficiency is a rare but serious bleeding disorder manifested by a lifelong bleeding tendency that typically includes umbilical bleeding during the neonatal period, easy bruising, mucosal bleeding, hemarthrosis, hematomas, intracranial hemorrhage, and GI bleeding.5 6 7 Women of reproductive age with factor X deficiency also may experience menorrhagia and postpartum hemorrhage.5

Factor X (human) is a specific factor X concentrate and does not contain substantial amounts of other clotting proteins.1 11 Alternative treatment options such as other plasma-derived products (e.g., fresh frozen plasma, prothrombin complex concentrates [PCCs]) have disadvantages for factor X-deficient patients because in addition to factor X, they contain other plasma proteins that may contribute to adverse events.10 18 19

Coagadex Dosage and Administration

Administration

IV Administration

Administer by IV infusion.1

May be self-administered if clinician determines that the patient and/or their caregiver is competent to safely administer the drug.1

Do not mix with any other drugs or solutions.1

Reconstitution

Prior to reconstitution, allow drug and manufacturer-supplied sterile water for injection diluent to warm to room temperature.1

Reconstitute single-use vials of lyophilized drug by adding 2.5 or 5 mL of sterile water for injection to vial containing approximately 250 or 500 units, respectively, of factor X (human) using transfer device provided by manufacturer; resulting solution contains approximately 100 units of factor X (human) activity per mL.1 20 Swirl vial gently until powder is completely dissolved.1

If more than 1 vial is required to obtain a dose, may pool reconstituted contents of multiple vials; use a separate transfer set to reconstitute each vial.1

Administer reconstituted solutions promptly or within 1 hour.1

Rate of Administration

10 mL/minute; do not exceed 20 mL/minute.1

Dosage

Dosage expressed in international units (IU, units) of factor X activity.1 Each vial contains approximately 250 or 500 units of factor X (human); actual number of units indicated on each vial and carton.1 Generally, 1 unit/kg of factor X (human) increases plasma factor X levels by 2 units/dL.1 4

Dose and duration of therapy dependent upon severity of the factor X deficiency, the location and extent of bleeding, and the patient's clinical condition and individual response.1

Pediatric Patients

Hereditary Factor X Deficiency
On-demand Treatment and Control of Bleeding Episodes
IV

Pediatric patients ≥12 years of age: 25 units/kg, repeat dose every 24 hours until bleeding stops.1

Perioperative Management
IV

Pediatric patients ≥12 years of age: Dose based upon the degree of deficiency of blood coagulation factor X, desired factor X plasma level, and the patient's body weight.1 The desired factor X increase is the difference between the patient's plasma factor X level and the desired level.1 Use the following calculations for administering the drug:1

Approximate increase in factor X level expected from a given dosage:

Estimated increment of factor X (units/dL or % of normal) = [total dose (units) ÷ body weight (kg)] × 2

Dose required to achieve desired factor X levels:

Dose required (units) = body weight (kg) × desired factor X increase (units/dL) × 0.5

Presurgery dose in pediatric patients ≥12 years of age: Administer loading dose to increase plasma factor X levels to 70–90 units/dL.1

Postsurgery dose in pediatric patients ≥12 years of age: Repeat dose as necessary to maintain plasma factor X levels ≥50 units/dL until patient no longer at risk of bleeding due to surgery.1

Measure post-infusion plasma factor X levels before and after surgery to ensure that hemostatic levels are achieved and maintained.1

Adults

Hereditary Factor X Deficiency
On-demand Treatment and Control of Bleeding Episodes
IV

25 units/kg, repeat dose every 24 hours until bleeding stops.1

Perioperative Management
IV

Dose based upon the degree of deficiency of blood coagulation factor X, desired factor X plasma level, and the patient's body weight.1 The desired factor X increase is the difference between the patient's plasma factor X level and the desired level.1 Use the following calculations for administering the drug:1

Approximate increase in factor X levels expected from a given dosage:

Estimated increment of factor X (units/dL or % of normal) = [total dose (units) ÷ body weight (kg)] × 2

Dose required to achieve desired factor X levels:

Dose required (units) = body weight (kg) × desired factor X increase (units/dL) × 0.5

Presurgery: Administer loading dose to increase plasma factor X levels to 70–90 units/dL.1

Postsurgery: Repeat dose as necessary to maintain plasma factor X levels ≥50 units/dL until patient no longer at risk of bleeding due to surgery.1

Measure post-infusion plasma factor X levels before and after surgery to ensure that hemostatic levels are achieved and maintained.1

Prescribing Limits

Pediatric Patients

IV

On-demand Treatment and Control of Bleeding or Perioperative Management: Maximum 60 units/kg daily recommended by manufacturer.1

Adults

IV

On-demand Treatment and Control of Bleeding or Perioperative Management: Maximum 60 units/kg daily recommended by manufacturer.1

Cautions for Coagadex

Contraindications

  • Known life-threatening hypersensitivity reactions to factor X (human) or any component in the formulation.1

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (including anaphylaxis) may occur.1 20

Discontinue administration immediately and institute appropriate treatment if early manifestations of hypersensitivity reactions occur; such reactions include angioedema, infusion site inflammation (e.g., burning, stinging, erythema), chills, cough, dizziness, fever, flushing, generalized urticaria, headache, hives, hypotension, lethargy, musculoskeletal pain, nausea, pruritus, rash, restlessness, tachycardia, chest tightness, tingling, vomiting, and wheezing.1

Immunogenicity

Neutralizing antibodies (inhibitors) against factor X may occur in patients receiving factor X (human).1 10 Presence of inhibitors may manifest as inadequate response to treatment.1

Monitor patients for possible development of inhibitors.1 If expected plasma factor X activity levels not attained or bleeding not controlled with an appropriate dose, measure factor X inhibitory antibody concentrations using an appropriate assay (e.g., Nijmegen-Bethesda inhibitor assay).1

Risk of Transmissible Agents in Plasma-derived Preparations

Factor X (human) is prepared from human blood and may carry risk of transmitting infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.1 10 Possibility that unknown infectious agents exist in such products.1

Report any suspected infections associated with factor X (human) to Bio Products Laboratory at 866-398-0825 or to FDA at 800-FDA-1088 or [Web].1

Laboratory Monitoring

Monitor plasma factor X activity by performing a validated test (e.g., one-stage clotting assay) to confirm that adequate factor X levels have been achieved and maintained with factor X (human) therapy.1

If expected plasma factor X activity levels not attained or bleeding not controlled with an appropriate dose, measure factor X inhibitory antibody concentrations.1 (See Immunogenicity under Cautions.)

Specific Populations

Pregnancy

No adequate and well-controlled studies of factor X (human) in pregnant women.1 Animal reproductive and development studies with factor X (human) lacking.1 Use during pregnancy only when clearly needed.1

Lactation

Not known whether factor X (human) is distributed into human milk.1 10 20 Use with caution.1 10 20

Pediatric Use

Safety and efficacy in patients <12 years of age not established.1

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.1 Important to individualize dosage.1

Common Adverse Effects

Infusion site erythema, infusion site pain, fatigue, back pain.1 3

Interactions for Coagadex

No formal drug interaction studies to date.1

Specific Drugs

Drug

Interaction

Comments

Plasma products (fresh frozen plasma, prothrombin complex concentrates [PCCs])

May contain factor X1

Use with caution1

Direct and indirect factor Xa inhibitors

May counteract effects of factor X (human)1

Coagadex Pharmacokinetics

Absorption

Plasma Concentrations

Peak plasma concentrations attained in approximately 0.5 hours following a single 25-unit/kg dose in patients with moderate or severe hereditary factor X deficiency.1 4

Distribution

Extent

Not known whether distributed into human milk.1 10 20

Elimination

Elimination Route

Slow rate of elimination from plasma via hepatic route.4

Half-life

Approximately 30 hours.1 4 10

Special Populations

Effect of renal or hepatic impairment on pharmacokinetics not established.1

Stability

Storage

Parenteral

Powder for Injection

2–30°C; do not freeze.1 20 Store in original carton and protect from light.1

Reconstituted solutions: Use within 1 hour after reconstitution.1

Actions

  • Lyophilized concentrate of blood coagulation factor X derived from pooled human plasma.1 3 20 21

  • Factor X is synthesized in the liver and circulates in plasma as a 2-chain glycoprotein.5 12 13 18

  • Factor X is first enzyme in the common pathway of thrombus formation;1 5 8 13 activated by factor IXa (via the intrinsic pathway) or by factor VIIa (via the extrinsic pathway).1 5 13 18 22 Factor X is a proenzyme that is activated by cleavage of a 52-residue peptide from the heavy chain to become activated factor X (factor Xa).1 5 18

  • Factor Xa associates with factor Va on a phospholipid surface to form the prothrombinase complex, which activates prothrombin to thrombin in the presence of calcium ions.1 5 13 22 Thrombin then acts upon soluble fibrinogen and factor XIII to generate a cross-linked fibrin clot.1 22

Advice to Patients

  • Importance of instructing patients to read the manufacturer's patient information.1 Importance of patient not attempting to infuse factor X (human) unless instructed how to do so by clinician or hemophilia center.1

  • Importance of patients immediately informing a clinician of any early signs or symptoms of hypersensitivity, including angioedema, infusion site inflammation (burning, stinging, erythema), chills, cough, dizziness, fever, flushing, generalized urticaria, headache, hives, hypotension, lethargy, musculoskeletal pain, nausea, pruritus, rash, restlessness, tachycardia, chest tightness, tingling, vomiting, or wheezing.1

  • Importance of informing patients that the development of neutralizing antibodies (inhibitors) to factor X is a possible complication of treatment with factor X (human) and of advising patients to contact their healthcare provider for further treatment and/or assessment if they experience a lack of clinical response to factor X (human).1

  • Importance of informing patients that factor X (human) is made from human plasma.1 While various screening and viral inactivation procedures have been used during the manufacturing process, factor X (human) may still carry a risk of transmitting infectious agents.1 Advise patients to report any concerning symptoms.1 (See Risk of Transmissible Agents in Plasma-derived Preparations under Cautions.)

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Factor X (Human)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use

number of units indicated on label (nominally 250 or 500 units)

Coagadex (available as kit with sterile water for injection diluent and transfer set)

Bio Products Laboratory

AHFS DI Essentials™. © Copyright 2019, Selected Revisions February 18, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Bio Products Laboratory. Coagadex (coagulation factor X [human]) prescribing information. Durham, NC; 2015 Oct.

2. Escobar M, Auerwald G, Austin S et al. Experience of factor X, a new high-purity factor X concentrate in subjects with factor X deficiency undergoing surgery. Haemophilia. 2015; 21:e262 Abstract.

3. Austin SK, Kavakli K, Norton M et al. Efficacy, safety, and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency. Haemophilia. 2016;

4. Austin SK, Brindley C, Kavakli K et al. Pharmacokinetics of a high-purity plasma-derived factor X concentrate in subjects with moderate or severe hereditary factor X deficiency. Haemophilia. 2016; http://www.ncbi.nlm.nih.gov/pubmed/26879266?dopt=AbstractPlus

5. Brown DL, Kouides PA. Diagnosis and treatment of inherited factor X deficiency. Haemophilia. 2008; 14:1176-82. http://www.ncbi.nlm.nih.gov/pubmed/19141158?dopt=AbstractPlus

6. Herrmann FH, Auerswald G, Ruiz-Saez A et al. Factor X deficiency: clinical manifestation of 102 subjects from Europe and Latin America with mutations in the factor 10 gene. Haemophilia. 2006; 12:479-89. http://www.ncbi.nlm.nih.gov/pubmed/16919077?dopt=AbstractPlus

7. Peyvandi F, Duga S, Akhavan S et al. Rare coagulation deficiencies. Haemophilia. 2002; 8:308-21. http://www.ncbi.nlm.nih.gov/pubmed/12010428?dopt=AbstractPlus

8. Uprichard J, Perry DJ. Factor X deficiency. Blood Rev. 2002; 16:97-110. http://www.ncbi.nlm.nih.gov/pubmed/12127953?dopt=AbstractPlus

9. Food and Drug Administration. Clinical pharmacology review: STN BLA#12556. From FDA website. http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM472562.pdf

10. Food and Drug Administration. Clinical review: STN BLA#12556/0. From FDA website. http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM472311.pdf

11. Bio Products Laboratory. AMCP formulary submission dossier for Coagadex (coagulation factor X [human]). Durham, NC; 2015. http://www.ncbi.nlm.nih.gov/pubmed/16556896?dopt=AbstractPlus

12. Venkateswarlu D, Perera L, Darden T et al. Structure and dynamics of zymogen human blood coagulation factor X. Biophys J. 2002; 82:1190-206. http://www.ncbi.nlm.nih.gov/pubmed/11867437?dopt=AbstractPlus

13. Karimi M, Menegatti M, Afrasiabi A et al. Phenotype and genotype report on homozygous and heterozygous patients with congenital factor X deficiency. Haematologica. 2008; 93:934-8. http://www.ncbi.nlm.nih.gov/pubmed/18403394?dopt=AbstractPlus

14. Peyvandi F, Palla R, Menegatti M et al. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. J Thromb Haemost. 2012; 10:615-21. http://www.ncbi.nlm.nih.gov/pubmed/22321862?dopt=AbstractPlus

15. Bolton-Maggs PH, Perry DJ, Chalmers EA et al. The rare coagulation disorders--review with guidelines for management from the United Kingdom Haemophilia Centre Doctors' Organisation. Haemophilia. 2004; 10:593-628. http://www.ncbi.nlm.nih.gov/pubmed/15357789?dopt=AbstractPlus

16. Medical and Scientific Advisory Council (MASAC), National Hemophilia Foundation. MASAC recommendation concerning products licensed for the treatment of hemophilia and other bleeding disorders (Aug 15, 2015). MASAC recommendation #237. From National Hemophilia Foundation website. https://www.hemophilia.org/sites/default/files/document/files/237Text.pdf

17. Auerswald G. Prophylaxis in rare coagulation disorders -- factor X deficiency. Thromb Res. 2006; 118 Suppl 1:S29-31. http://www.ncbi.nlm.nih.gov/pubmed/16574201?dopt=AbstractPlus

18. Menegatti M, Peyvandi F. Factor X deficiency. Semin Thromb Hemost. 2009; 35:407-15. http://www.ncbi.nlm.nih.gov/pubmed/19598069?dopt=AbstractPlus

19. Food and Drug Administration. Statistical review: STN BLA#12556. From FDA website. http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM472539.pdf

20. Food and Drug Administration. Summary basis for regulatory action: STN BLA#12556/0. From FDA website. http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM472266.pdf

21. Food and Drug Administration. FDA news release: FDA approves first factor X concentrate to treat patients with rare hereditary bleeding disorder. Silver Spring, MD; 2015 Oct 20. From FDA web site http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm468038.htm

22. Riddel JP, Aouizerat BE, Miaskowski C et al. Theories of blood coagulation. J Pediatr Oncol Nurs. 2007 May-Jun; 24:123-31. http://www.ncbi.nlm.nih.gov/pubmed/17475978?dopt=AbstractPlus

23. Food and Drug Administration. FDA Application: Search Orphan Drug Designations and Approvals. Silver Spring, MD. From FDA web site. http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm

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