Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Coagadex: 250 units (1 ea); 500 units (1 ea) [latex free]
Pharmacology
Mechanism of Action
Replaces deficient clotting factor X needed for effective hemostasis. Factor X, an inactive zymogen, can be activated by factor IXa via the intrinsic pathway or by factor IIa via the extrinsic pathway. Factor X is then converted from its inactive form to the active form (factor Xa) by the cleavage of a 52-residue peptide from the heavy chain. Factor Xa associates with factor Va on the phospholipid surface to form the prothrombinase complex, which actives prothrombin to thrombin in the presence of calcium ions. Thrombin then acts upon soluble fibrinogen and factor XIII to generate a cross-linked fibrin clot.
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: Children ≥12 years, Adolescents, and Adults: 56.3 mL/kg
Half-Life Elimination
Single dose: Children ≥12 years, Adolescents, and Adults: 30.3 hours
Use: Labeled Indications
Bleeding episodes and perioperative management of bleeding: Prophylaxis and treatment of bleeding episodes in children and adults with hereditary factor X deficiency and perioperative management of bleeding episodes in children and adults with mild and moderate hereditary factor X deficiency.
Limitations of use: Perioperative management of bleeding in major surgery in patients with severe hereditary Factor X deficiency has not been studied.
Contraindications
Life-threatening hypersensitivity reactions to factor X (human) or any component of the formulation
Dosage and Administration
Dosing: Adult
Factor X deficiency: Dose, dosing frequency, and duration are based on location and severity of bleeding, and the patient’s clinical condition. In general, administration of factor X 1 unit/kg will increase circulating factor X levels by ~2 units/dL
Bleeding episodes: IV:
Prophylaxis: Initial: 25 units/kg twice weekly. Adjust dose to clinical response and factor X trough levels targeting ≥ 5 units/dL; do not exceed a peak of 120 units/dL
Treatment: 25 units/kg/dose. Repeat every 24 hours until bleeding stops.
Perioperative management of bleeding: IV:
Pre-surgery, the calculated dose should raise plasma factor X levels to 70 to 90 units/dL (or % of normal) using the following equation:
Number of factor X units required = Body weight (kg) x desired factor X increase (units/dL or % of normal) x 0.5
For example: 50 kg x 30 (% increase) x 0.5 = 750 units factor X
Maximum daily dose: 60 units/kg/day
The expected % factor X increase may also be determined by the following equation:
Expected % factor X increase = [# units administered x 2] divided by body weight (kg)
For example: [1,400 units x 2] divided by 70 kg = 40%
Post-surgery, the calculated dose should maintain plasma factor X levels at ≥50 units/dL (or % of normal) until patient is no longer at risk of bleeding; Maximum daily dose: 60 units/kg/day
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Factor X deficiency: Dose, dosing frequency, and duration are based on location and severity of bleeding, patient age, and the patient's clinical condition. In general, administration of 1 unit/kg of factor X will increase circulating factor X concentrations by ~1.7 units/dL in children <12 years or by ~2 units/dL in children ≥12 years and adolescents.
Bleeding episodes:
Prophylaxis: Adjust dose to clinical response and factor X trough concentration targeting ≥5 units/dL; do not exceed a peak of 120 units/dL
Children <12 years: IV: Initial: 40 units/kg/dose twice weekly
Children ≥12 years and Adolescents: IV: Initial: 25 units/kg/dose twice weekly
Treatment:
Children <12 years: IV: 30 units/kg/dose. Repeat every 24 hours until bleeding stops.
Children ≥12 years and Adolescents: IV: 25 units/kg/dose. Repeat every 24 hours until bleeding stops.
Perioperative management of bleeding: IV:
Pre-surgery: Formula to calculate dosage required is based on desired increase in factor X concentrations (may be expressed as units/dL or as %). The calculated dose should raise plasma factor X concentrations to a desired target of 70 to 90 units/dL (or % of normal) using the following equation:
Children <12 years:
Dose (units) = Body weight (kg) x desired factor X increase (units/dL or % of normal) x 0.6
For example: 25 kg x 30 (% increase) x 0.6 = 450 units factor X
Maximum daily dose: 60 units/kg/day
The estimated factor X increase may be determined by the following equation:
Estimated increase of factor X (units/dL or % of normal) = [Total dose administered (units) x 1.7] divided by body weight (kg)
For example: [1,400 units x 1.7] divided by 35 kg = 68%
Children ≥12 years and Adolescents:
Dose (units) = Body weight (kg) x desired factor X increase (units/dL or % of normal) x 0.5
For example: 50 kg x 30 (% increase) x 0.5 = 750 units factor X
Maximum daily dose: 60 units/kg/day
The estimated factor X increase may be determined by the following equation:
Estimated increase of factor X (units/dL or % of normal) = [Total dose administered (units) x 2] divided by body weight (kg)
For example: [1,400 units x 2] divided by 70 kg = 40%
Post-surgery: Children and Adolescents: Repeat pre-surgery dose as needed to maintain plasma factor X concentrations at ≥50 units/dL (or % of normal) until patient is no longer at risk of bleeding; maximum daily dose: 60 units/kg/day
Reconstitution
Refer to instructions provided by the manufacturer. Bring diluent and vial to room temperature before combining. To reconstitute, use the diluent (SWFI) and transfer device provided. Swirl vial gently to dissolve powder; do not shake. The reconstituted solution should be clear or slightly pearl-like in color.
Administration
IV: For IV administration only. Administer at a rate of 10 to 20 mL/minute within 1 hour of reconstitution.
Storage
Store intact vials at 2°C to 30°C (36°F to 86°F); do not freeze. Protect from light. After reconstitution, use within 1 hour.
Drug Interactions
Anticoagulants (Inhibitors of Factor Xa): May diminish the therapeutic effect of Factor X (Human). Monitor therapy
Adverse Reactions
Frequency not always defined.
Central nervous system: Fatigue (6%), infusion-site pain (6%)
Hypersensitivity: Anaphylaxis, hypersensitivity reaction
Local: Infusion site reaction (6%; erythema)
Neuromuscular & skeletal: Back pain (6%)
Warnings/Precautions
Concerns related to adverse effects:
- Antibody formation: The development of inhibitory antibodies may occur. Factor X inhibitory antibodies should be measured when bleeding is not controlled and/or factor X levels are suboptimal after apparent adequate dosing.
- Hypersensitivity reactions: Hypersensitivity and anaphylactic reactions may occur with use; discontinue immediately if hypersensitivity reaction develops and initiate appropriate management.
Dosage form specific issues:
- Human plasma: Product of human plasma; may potentially contain infectious agents which could transmit disease. Screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces the risk. Infections thought to be transmitted by this product should be reported to the manufacturer.
- Human proteins: Contains traces of human proteins other than factor X.
Monitoring Parameters
Factor X levels in conjunction with clinical response to assess efficacy. Factor X inhibitory antibodies if inadequate clinical response and/or factor X trough levels are suboptimal. Signs/symptoms of hypersensitivity reactions, bleeding and thrombotic events, and infection.
Pregnancy
Pregnancy Considerations
Pregnant patients with factor X deficiency may have an increased risk of bleeding following abortion, antenatal procedures, delivery, and miscarriage; close surveillance is recommended. Clotting factors should be monitored at the first antenatal visit, once or twice during the third trimester, at delivery, and prior to surgical or invasive procedures. Although factor X concentrations may increase during pregnancy, patients with severe deficiency remain at risk for bleeding. In addition, treatment may be needed if concentrations are <0.3 IU/mL at term or prior to procedure. Hemostatic concentrations should be maintained for at least 3 days following procedures or postpartum. When available, factor X concentrate may be used (RCOG [Pavord 2017]).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience injection site pain or back pain. Have patient report immediately to prescriber injection site burning, stinging, or redness; chills; dizziness; passing out; flushing; headache; severe loss of strength and energy; muscle pain; nausea; vomiting; agitation; tingling; wheezing; or fast heartbeat (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
