Profilnine (factor IX complex, prothrombin complex conc no.4, 3-factor)

Dose (potency) of factor IX (human) and factor IX complex (human) is expressed in terms of international units (IU, units) of factor IX activity. One unit is approximately equivalent to the amount of factor IX activity in 1 mL of pooled normal human plasma. The dosage of factor IX (human) or factor IX complex (human) required to establish hemostasis in patients with hemophilia B will vary with each patient and circumstance since there is considerable variability among patients and their clinical conditions. Therefore, dosage should be carefully individualized and factor IX levels monitored frequently during therapy with the drugs. Close monitoring of factor IX levels is particularly important in cases of severe hemorrhage or major surgery. The dosing frequency for maintaining sufficiently increased levels of a deficient factor also is variable; although minor bleeding episodes may be controlled with a single dose, more severe bleeding may require administration of additional doses.

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No dosing information is available for this tab.

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There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Factor Ix; Anti-Inhibitor Coagulant Conc/Antifibrinolytics

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Concurrent use may result in additive or synergistic effects on the coagulation pathways.(1-3)

CLINICAL EFFECTS: Concurrent use may result in thrombosis.(1-3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of aminocaproic acid states that aminocaproic acid should not be administered concomitantly with Factor IX Complex concentrates or Anti-inhibitor Coagulant concentrates.(1) The US manufacturer of tranexamic acid states that concomitant use with Factor IX Complex concentrates or with Anti-inhibitor Coagulant concentrates should be avoided.(2,3) The Japanese manufacturer of tranexamic acid recommends caution when coadministered with drugs such as coagulation factor agents as coagulation may be further activated at sites with enhanced local fibrinolysis.(4) Concurrent use may be warranted in select patients with hemophilia A or hemophilia B or in select major trauma scenarios. Monitor patients closely for signs of thrombosis, disseminated intravascular coagulation, and hypercoagulability if concurrent use is deemed necessary.(5-13)

DISCUSSION: There is very limited data on the risk of thrombosis with combination therapy. In a study, eight hemophilia B patients undergoing dental extraction procedures received combination therapy with aminocaproic acid or tranexamic acid and monoclonal antibody purified factor IX for bleeding prophylaxis. All patients achieved hemostasis without clinical evidence of thrombosis as well as no changes were seen in hemoglobin, hematocrit, or in markers of hemostatic system activation.(5) In a study, seven hemophilia A patients with inhibitors and one with acquired hemophilia patient received activated prothrombin complex concentrate (APCC) and tranexamic acid for management of bleeding episodes and prevention of hemorrhage during surgery. Hemostatic outcomes were rated excellent or good in 10 out of 11 (91%) treatment episodes. No episodes of thrombosis or disseminated intravascular coagulation occurred during treatment.(6) A study in six hemophilia A patients and five healthy volunteers evaluated the use of tranexamic acid as an adjunct to APCC to control bleeding. Patients who received tranexamic acid had a significant increase in maximum clot firmness compared to healthy controls. No clinical or laboratory signs of thromboembolic events, disseminated intravascular coagulation, or hypercoagulability were observed.(7) In a retrospective cohort of 76 patients who received PCC for bleeding not caused by anticoagulation, some patients received additional hemostatic agents (protamine (59%), desmopressin (43%), and tranexamic acid (42%). Eight patients (11%) suffered thromboembolic complications but this was not stratified by the hemostatic agent.(8) In a prospective case crossover study, five healthy volunteers and six hemophilia patients with inhibitors received tranexamic acid with single-dose activated PCC or with recombinant activated factor VII. There were no thromboembolic events during the study.(9) In a double-blind, randomized, placebo-controlled superiority trial to investigate the efficacy and safety of 4-factor prothrombin complex concentrate (4F-PCC) administration in trauma patients at risk of massive transfusion, a significantly higher risk of thromboembolic events occurred in the 4F-PCC group compared to the placebo group (35% vs 24%; relative risk 1.48 [95% CI, 1.04-2.10]). This was observed despite more frequent use of tranexamic acid in the placebo group (86% vs 76%).(10) Case reports reviewed the use of recombinant factor VIIa and FEIBA in 4 patients with severe hemophilia with inhibitors who underwent major surgery. The patients were also treated with tranexamic acid. Non-surgical bleeding was encountered in 4 of 8 surgical procedures. The overall outcome was good for all procedures.(11) In a retrospective cohort of 112 ambulatory tooth extractions in 23 hemophilia patients using a coagulation factor replacement therapy in combination with tranexamic acid, only one episode of mild postoperative bleeding occurred after seven days in a patient who did not have good treatment compliance.(12) In a prospective study evaluating the use of initial hemoglobin levels as a guideline for the initial treatment of clotting disorders in multiple trauma patients, 25 patients received a combination of hemostatic agents (fibrinogen (100%), PCC (96%), desmopressin (56%), tranexamic acid (52%), and factor VIIa (44%). Of the 25 patients treated, 16 (64%) survived. Two patients (8%) suffered thromboembolic complications but this was not stratified by the hemostatic agent. One patient survived after developing a grade II pulmonary embolism caused by deep leg vein trombosis and one patient died from multi-organ failure after developing multiple small vessel thrombosis.(13)

There are no moderate interactions for this drug.

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• Disseminated intravascular coagulation
• Heparin-induced thrombocytopenia

• Thromboembolic disorder

There are no moderate contraindications for this drug.

There is no enhanced messaging for this drug.

More Frequent

• Acute myocardial infarction
• Disseminated intravascular coagulation
• Pulmonary thromboembolism
• Thromboembolic disorder
• Thrombotic disorder

Less Frequent

• Anaphylaxis
• Urinary tract obstructive uropathy

Rare or Very Rare

• Hypersensitivity drug reaction
• Hypotension
• Renal colic

Less Frequent

• Chills
• Injection site sequelae
• Nausea
• Oral paresthesia

Rare or Very Rare

• Anorexia
• Dizziness
• Dysgeusia
• Fatigue
• Fever
• Halitosis
• Headache disorder
• Hematuria
• Lethargy
• Palpitations
• Paresthesia
• Urticaria

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Animal reproduction studies have not been performed with factor IX (human) or factor IX complex (human). It is not known whether the preparations can cause fetal harm when administered to pregnant women or affect reproduction capacity. Factor IX (human) and factor IX complex (human) should be used during pregnancy only when clearly needed.

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