Coagulation Factor VIIa (Recombinant)

Pronunciation: koe-AG-yoo-lay-shun
Class: Antihemophilic agent

Trade Names

NovoSeven RT
- Injection, lyophilized powder for solution 1 mg
- Injection, lyophilized powder for solution 2 mg
- Injection, lyophilized powder for solution 5 mg
- Injection, lyophilized powder for solution 8 mg

Pharmacology

Coagulation factor VIIa, when complexed with tissue factor, can activate coagulation factor X to Xa. Factor Xa, in complex with other factors, converts prothrombin to thrombin, leading to formation of a hemostatic plug by converting fibrinogen to fibrin, thereby inducing local hemostasis.

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Pharmacokinetics

Distribution

Vd at steady state ranged from 130 to 165 (healthy patients); 103 mL/kg (hemophelia A or B).

Elimination

Mean Cl is 33 to 37 mL/kg/h (healthy patients); 33 mL/kg/h (hemophilia A or B). Mean terminal half-life is 3.9 to 6 h (healthy patients). Half-life is 2.3 h (hemophilia A or B).

Indications and Usage

Treatment of bleeding episodes in hemophilia A or B patients with inhibitors to factors VIII or IX, and in patients with acquired hemophilia; prevention of bleeding in surgical interventions or invasive procedures in hemophilia A or B patients with inhibitors to factors VIII or IX, and in patients with acquired hemophilia; treatment of bleeding episodes in patients with congenital factor VII deficiency; prevention of bleeding in surgical interventions or invasive procedures in patents with congenital factor VII deficiency.

Contraindications

None well documented.

Dosage and Administration

Use evaluation of hemostasis to determine the effectiveness of recombinant coagulation factor VIIa and to provide a basis for modification of the treatment schedule. Coagulation parameters do not necessarily correlate with or predict efficacy of coagulation factor VIIa.

Acquired Hemophilia
Adults and Children

IV 70 to 90 mcg/kg repeated every 2 to 3 h until hemostasis is achieved.

Congenital Factor VII Deficiency
Adults and Children

IV 15 to 30 mcg/kg every 4 to 6 h until hemostasis is achieved. Effective treatment has been achieved with doses as low as 10 mcg/kg.

Hemophilia A or B With Inhibitors
Adults and Children

IV

Bleeding episodes

90 mcg/kg every 2 h by bolus infusion until hemostasis is achieved or until treatment is judged to be inadequate. Doses between 35 and 120 mcg/kg have been used successfully in clinical trials.

Posthematic dosing

For severe bleeds, continue dosing at 3- to 6-h intervals after hemostasis is achieved to maintain the hemostatic plug.

Surgical interventions

90 mcg/kg immediately prior to the intervention and repeat at 2-h intervals for the duration of surgery. For minor surgery, postsurgical dosing by bolus infusion should occur at 2-h intervals for the first 48 h, and then at 2- to 6-h intervals until healing has occurred. For major surgery, postsurgical dosing by bolus infusion should occur at 2-h intervals for 5 days, followed by 4-h intervals until healing occurs. Administer additional bolus doses if needed.

General Advice

  • For IV bolus administration only.
  • Before reconstitution, bring coagulation factor VIIa to room temperature, but not above 37°C (98.6°F).
  • Refer to the prescribing information for reconstitution instructions.
  • Reconstitute only with the histidine diluent provided. Do not reconstitute with sterile water or other diluent.
  • When reconstituting, gently swirl the vial until all material is dissolved. The reconstituted solution is a clear, colorless solution.
  • Visually inspect reconstituted solution for particulate matter and discoloration prior to administration. Do not administer if particulate matter or discoloration is observed.
  • Do not mix with infusion solutions.
  • Administer within 3 h after reconstitution.

Storage/Stability

Store under between 36° and 46°F. Do not freeze. Protect from light. After reconstitution, may be stored at room temperature or refrigerated for up to 3 h. Do not freeze reconstituted product or store in syringes. Discard any unused solution. Do not store reconstituted solution in a syringe.

Drug Interactions

Activated prothrombin complex concentrates, prothrombin complex concentrates

Avoid simultaneous use with coagulation factor VIIa.

Adverse Reactions

Cardiovascular

Hypertension (9%); bradycardia, hypotension (1%); angina pectoris; deep vein thrombosis; internal jugular thrombosis; MI; myocardial ischemia; postoperative hemarthrosis; thromboembolic events, including arterial thrombosis, pulmonary embolism, and phlebitis; thrombophlebitis; thrombosis (postmarketing).

CNS

Headache (1%); cerebral infarction, cerebral ischemia, intracranial hemorrhage, peripheral ischemia, subdural hematoma (postmarketing).

Dermatologic

Pruritus, purpura, rash (1%).

GI

Vomiting (1%) bowel infarction, GI bleeding, hepatic artery thrombosis, portal vein thrombosis, splenic hematoma (postmarketing).

Genitourinary

Abnormal renal function (1%); renal artery thrombosis, renal failure complicating a retroperitonial bleed, worsening of CRF (postmarketing).

Hematologic-Lymphatic

Hemorrhage (15%); decreased fibrinogen plasma (10%); coagulation disorder, decreased prothrombin, DIC, increased fibrinolysis (1%); consumptive coagulopathy and high D-dimer levels (postmarketing).

Hypersensitivity

Hypersensitivity reactions, including anaphylactic shock, angioedema, flushing, rash, and urticaria (postmarketing).

Miscellaneous

Fever (16%); hemarthrosis (14%); allergic reaction, arthrosis, decreased therapeutic response, edema, injection-site reaction, pain, pneumonia (1%); anesthesia complications during proctoscopy, ruptured abscess leading to sepsis and DIC (postmarketing).

Precautions

Warnings

Arterial and venous thrombotic and thromboembolic events following administration have been reported during postmarketing surveillance. Fatal and non-fatal thrombotic events have been reported.


Monitor

Monitor PT and factor VII coagulant activity before and after administration. Monitor for signs and symptoms of activation of the coagulation system and/or thrombosis.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy were not determined to be different in various age groups (infants to adolescents). Clinical trials were conducted by dosing according to body weight and not age.

Hypersensitivity

Use with caution in patients with known hypersensitivity to any component of the product, or in patients with known hypersensitivity to bovine, hamster, or mouse proteins.

Antibody formation

If factor VIIa activity fails to reach the expected level, PT is not corrected, or bleeding is not controlled after treatment, suspect antibody formation and perform analysis for antibodies.

Prolonged dosing

Because of limited data, use with caution for prolonged administration.

Thrombotic events

The risk of developing thrombotic events may be increased in patients with DIC, advanced atherosclerotic disease, crush injury, septicemia, or concomitant treatment with activated or nonactivated prothrombin complex concentrates. Use with caution in patients with an increased risk of thrombotic complications (eg, coronary heart disease, liver disease, DIC, postoperative immobilization, elderly, neonates).

Overdosage

Symptoms

Antibodies against recombinant factor VIIa, occipital stroke.

Patient Information

  • Inform patients about the early signs of hypersensitivity reactions, including hives, urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis.
  • Warn patients about the signs of thrombosis, including new onset swelling and pain in the limbs or abdomen, new onset chest pain, shortness of breath, loss of sensation or motor power, or altered consciousness or speech.

Copyright © 2009 Wolters Kluwer Health.

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