Drug information of Factor X

Factor X

Drug group:

Brand drugs:Coagadex

Coagulation Factor X (Human), is a plasma-derived human blood coagulation factor is used by adults and children (aged 12 years and above) with hereditary Factor X deficiency. However its use is limited in the perioperative setting for the management of bleeding in major surgery in patients with moderate and severe hereditary Factor X deficiency.

Coagulation Factor X is a vitamin K-dependent, liver-produced serine protease that serves as the first enzyme in the coagulation cascade to form fibrin. It is a two-chain glycoprotein with the molecular weight of approximately 59 kDa . While Factor X normally circulates in the plasma as inactive molecules, the activation of Factor X is involved in both the intrinsic and extrinsic coagulation pathways. Inherited factor X deficiency is a rare autosomal recessive bleeding disorder that is estimated to occur in 1:1 000 000 individuals up to 1:500 carriers . Administration of coagulation Factor X from healthy donor serves to restore and achieve effective hemostasis.

Coagulation Factor X (Human) solution is approved by the FDA for intravenous injection under the market name Coagadex which contains normally 100 IU/mL of coagulation Factor X derived from healthy donors who have passed viral screening tests

Drug forms
  • 250 IU/vial of factor X activity
  • 500 IU/vial of factor X activity

Mechanism of effect

Factor X is an inactive zymogen that is synthesized in the liver, which can be activated by Factor IXa (via the intrinsic pathway) or by Factor VIIa (via the extrinsic pathway). It is composed of a light chain which contains the Gla (glutamic acid) domain and two epidermal growth factor domains, and a heavy chain that contains the catalytic serine protease domain . The conversion of inactive Factor X into the active form Factor Xa requires the cleavage of a 52-residue peptide from the heavy chain  and the release of 52-residue activation peptide that contains the His236, Asp228 and Ser379 catalytic site. This activation step can occur through the extrinsic or intrinsic pathway and is considered to be the first step in the common pathway to fibrin formation .

Factor Xa plays a critical initiation step of the coagulation pathway by cleaving and activating prothrombin to thrombin in complex with FVa, Ca2+ and phospholipids. This complex is also known as the prothrombinase complex. Thrombin then acts upon soluble fibrinogen and Factor XIII to generate a cross-linked fibrin clot 

Pharmacodynamic

Clinical human coagulation Factor X solution increases plasma levels of Factor X and can temporarily correct the coagulation defect in these patients, as reflected by decrease in the activated Partial Thromboplastin Time (aPTT) and prothrombin time (PT)

Pharmacokinetics

Absorption

Peak plasma concentration: 0.504 IU/mL

AUC: 18 IU·hr/mL

Distribution

Vd: 56.3 mL/kg

Elimination

Half-life: 30.3 hr

Clearance: 1.35 mL/kg/hr

Mean residence time: 41.8 hr

Dosage

Usual Adult Dose for Factor X Deficiency

On-demand Treatment and Control:
25 international units/kg IV infusion at the first sign of bleeding; repeat every 24 hours until bleeding stops.

Maximum dose: 60 international units/kg/day


Perioperative Management:
Pre-surgery:
-Calculate and administer dose needed to increase Factor X levels to 70 to 90 international units/dL (required dose [international units] = body weight [kg] x desired Factor X increase [international units/dL] x 0.5).
Post-surgery:
-Repeat pre-surgery dose as needed to maintain Factor X levels at a minimum of 50 international units/dL until patient is no longer at risk of bleeding due to surgery.

Maximum dose: 60 international units/kg/day

Comments: Measure post-infusion Factor X levels before and after surgery.

Use: Perioperative bleeding management in patients with mild hereditary Factor X deficiency.

Drug contraindications

Hypersensitivity to this drug

Alerts

Allergic-type hypersensitivity reactions may occur (eg, anaphylaxis, angioedema, infusion site inflammation, chills, cough, dizziness, fever, flushing, generalized urticaria, headache, hives, hypotension, lethargy, musculoskeletal pains, nausea, pruritus, rash, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing); discontinue product immediately and administer appropriate emergency treatment

Formation of neutralizing antibodies (inhibitors) to factor X may occur; if expected factor X activity levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures factor X inhibitor concentration

Transmission of infectious agents may occur; the product is derived from human blood, and despite measures to screen and inactivate/remove certain viruses, it may carry risk of transmitting infectious agents (eg, viruses, the variant Creutzfeldt-Jakob disease [vCJD] agent and, theoretically, the Creutzfeldt-Jakob disease [CJD] agent)

Monitor plasma factor X activity and monitor for factor X inhibitors

Caution when coadministered with other plasma products that may contain factor X (eg, fresh frozen plasma, prothrombin complex concentrates)

Based on the mechanism of action, factor X, human is likely to be counteracted by direct and indirect factor Xa inhibitors (eg, apixaban, edoxaban, dabigatran)

Points of recommendation

IV Preparation

Lyophilized powder for reconstitution using Mix2Vial transfer device provided in the kit

Vials contain ~250 IU or 500 IU of factor X

When vials are reconstituted using the sterile water for injection supplied with the kit, the final concentration is ~100 IU/mL

See prescribing information for full instructions

Note: Do not shake; gently swirl during mixing process

IV Administration

For intravenous administration only following reconstitution

Use solution within 1 hr following reconstitution

Reconstituted solution should be clear or a slightly pearl-like solution; do not use if the solution is cloudy, discolored, or contains any particles

Following reconstitution, draw up solution for dose into a single syringe

Attach a suitable needle to the syringe

Administer by IV infusion at a rate of 10 mL/min; may increase rate if tolerated, but do not exceed 20 mL/min

Storage

Store in original package to protect it from light

Store in refrigerator or at room temperature (36-86°F)

Do not freeze

Do not use after the expiration date printed on the vial and carton labels (expiration date refers to the last day of that month)

Do not store reconstituted solution (use within 1 hr)

Pregnancy level

HAVE NOT BEEN ESTABLISHED

There are no data with factor X concentrate use in pregnant women to inform on drug-associated risk

Animal reproduction studies have not been conducted

It is not known whether factor X concentrate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity

Should be given to a pregnant woman only if clearly needed

Breast feeding warning

Unknown if distributed in human breast milk

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition


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