Coagadex Drug Information
Generic name: COAGULATION FACTOR X HUMAN
Uses of Coagadex
COAGADEX, Coagulation Factor X (Human), is a plasma-derived human blood coagulation Factor indicated in adults and children with hereditary Factor X deficiency for: Routine prophylaxis to reduce the frequency of bleeding episodes On-demand treatment and control of bleeding episodes Perioperative management of bleeding in patients with mild, moderate, and severe hereditary Factor X deficiency COAGADEX, Coagulation Factor X (Human), is a plasma-derived human blood coagulation factor indicated in adults and children with hereditary Factor X deficiency for: Routine prophylaxis to reduce the frequency of bleeding episodes On-demand treatment and control of bleeding episodes Perioperative management of bleeding in patients with mild, moderate and severe hereditary Factor X deficiency
Dosage & Administration of Coagadex
| 40 IU/kg twice weekly | |
| 25 IU/kg twice weekly |
Side Effects of Coagadex
Clinical Trials Experience As clinical trials are conducted under widely varying conditions
adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in clinical practice. During the clinical development of COAGADEX involving three multicenter, open-label, non-randomized clinical studies, 27 individual subjects with hereditary Factor X deficiency received at least one dose of COAGADEX. Sixteen subjects aged 12 to 58 years with moderate to severe hereditary Factor X deficiency (basal FX:C < 5 IU/dL) received doses of COAGADEX for pharmacokinetic evaluation, on-demand treatment for control of bleeding episodes, and/or perioperative management of minor surgical or dental procedures. A total of 468 infusions were administered, including 242 for on-demand treatment and control of bleeding episodes, 6 for perioperative management and 31 for PK assessments.
Spontaneous, traumatic and menorrhagic bleeding episodes were treated with an on-demand dose of 25 IU/kg for up to 2 years. Two subjects aged 55 and 59 years with mild hereditary Factor X deficiency (basal FX:C 6 IU/dL and 8 IU/dL) received COAGADEX for perioperative management of four major surgical procedures. There were 40 exposure days to COAGADEX. Six adverse reactions were reported in 2 of the 18 subjects.
These were infusion site erythema (2 reports in 1 subject ), fatigue (2 reports in 1 subject ), back pain (1 report ) and infusion site pain (1 report ). In a separate study, nine children (aged 2 to 11 years), of whom four were less than 6 years of age, received 537 (mean 59.7) doses of COAGADEX as routine prophylaxis of bleeding episodes during a period of at least 6 months. In addition, 22 infusions were given to treat a bleed, equivalent to 2.1 bleeds per subject per year. There were no adverse drug reactions in this study.
Immunogenicity Immunogenicity was evaluated in three studies and all subjects (adults and
children) underwent Factor X inhibitor testing (inhibitor screen and Nijmegen-Bethesda assay) at baseline, end of study and at 3-monthly intervals in between. For subjects who underwent surgery, inhibitor testing was done pre-surgery and on discharge. All inhibitor tests were negative.
Additionally, comparison of pharmacokinetic (PK) parameters at the repeat PK assessment with those at first dose did not suggest development of any inhibitors to Factor X. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, it may be misleading to compare the incidence of antibodies to COAGADEX in the studies described above with the incidence of antibodies in other studies or to other products.
Warnings & Cautions for Coagadex
Hypersensitivity Reactions Allergic type hypersensitivity reactions, including anaphylaxis, are possible. Early signs
of hypersensitivity reactions including angioedema, infusion site inflammation (e.g. burning, stinging, erythema), 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. If hypersensitivity symptoms occur, discontinue use of the product immediately and administer appropriate emergency treatment. COAGADEX contains traces of human proteins other than Factor X.
Neutralizing Antibodies
The formation of neutralizing antibodies (inhibitors) to Factor X may occur. Monitor all patients treated with COAGADEX for the development of inhibitors by appropriate clinical observations and laboratory tests. 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.
Transmissible Infectious Agents As
COAGADEX is made from human blood, it may carry a risk of transmitting infectious agents, e.g. viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. There is also the possibility that unknown infectious agents may be present in the product. The risk that the product will transmit viruses has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and removing certain viruses during manufacture.
Despite these measures, this product may still potentially transmit diseases. All infections suspected by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare providers to Kedrion Biopharma, Inc. at 1-855-3KDRION (1-855-353-7466) or [email protected]
Monitoring and Laboratory Tests
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. Monitor for the development of Factor X inhibitors. Perform a Nijmegen-Bethesda inhibitor assay if expected Factor X plasma levels are not attained, or if bleeding is not controlled with the expected dose of COAGADEX. Use Nijmegen-Bethesda Units (BU) to report inhibitor levels.
Drug Interactions with Coagadex
Drug interaction studies have not been performed. Use with caution in patients who are receiving other plasma products that may contain Factor X (e.g. fresh frozen plasma, prothrombin complex concentrates). Based on the mechanism of action, COAGADEX is likely to be counteracted by direct and indirect Factor Xa inhibitors.
Pregnancy Safety for Coagadex
Pregnancy Risk Summary There is limited data with COAGADEX in pregnant women to inform on drug-associated risk. Animal reproduction studies have not been conducted using COAGADEX. It is not known whether COAGADEX can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Pediatric Use of Coagadex
Pediatric Use A prospective, open-label, multicenter study was conducted in nine pediatric patients (0-5 years, n=4; 6-11 years, n=5) with severe (n=8) or moderate (n=1) hereditary factor X deficiency, to assess safety, efficacy, and pharmacokinetics of COAGADEX used prophylactically and on-demand. Patients had baseline FX levels < 5 IU/dL, and were dosed to achieve post-treatment levels of at least 5 IU/dL. After ≥26 weeks and ≥50 exposure days, investigators rated pdFX efficacy for preventing/decreasing bleeds. At end of study, investigators rated pdFX efficacy excellent for all subjects.
Ten bleeds occurred (n = 3 subjects; 6 major, 3 minor, 1 unassessed for severity). Trough FX:C levels remained >5 IU/dL for all subjects after achievement of steady state. All AEs were unrelated to treatment; no inhibitor development or clinically significant changes in laboratory parameters were observed. Six additional pediatric subjects aged 12 to 17 years were included in a prospective, open-label, multicenter study of COAGADEX to treat spontaneous, traumatic and menorrhagic bleeding episodes.
Overall efficacy and safety outcomes were comparable to those in the younger age groups..
Contraindications for Coagadex
is contraindicated in patients who have had life-threatening hypersensitivity reactions to COAGADEX. Do not use in patients who have had life-threatening hypersensitivity reactions to COAGADEX.
Overdosage Information for Coagadex
One case of accidental overdosage was reported in the clinical trials, in which a subject received approximately 80 IU/kg Factor X to treat a bleed. No adverse events were reported relating to this overdose.
Clinical Studies of Coagadex
IU/kg. Median and mean doses per infusion in the four children less
than 6 years of age were both
IU/kg (95% CI 30.70, 49.57) and in the five children 6 to
11 years of age inclusive, median dose was
IU/kg and mean dose was 37.7 IU/kg (95% CI: 23.42, 51.91).
The median dosing interval for all of the nine children was 3 days (range 2 to 8 days). Investigators' assessment following 6 months of routine prophylaxis was rated excellent in all 9 subjects; excellent was defined as 'no minor or major bleeds occurred during the study period' or 'lower frequency of bleeds than expected, given subject's medical/treatment history'. In addition, 22 infusions were given to treat a bleed, equivalent to 2.1 bleeds per subject per year. One subject had three episodes of epistaxis and the other bleeds were due to trauma or menorrhagia. All bleeds were treated with a single infusion; the median and mean doses per subject were both
IU/kg (range 24.6 to 38.8 IU/kg) and all recorded efficacy ratings were
categorized as 'excellent' i.e. Overt bleed: bleeding stopped within 12 hours with a single dose; Menorrhagic bleed: no additional doses required; Covert bleeds: there were none in this study. On-demand Treatment and Control of Bleeding Episodes In a multicenter, open-label, non-randomized clinical trial to evaluate the pharmacokinetics, safety and efficacy of COAGADEX, 16 subjects with moderate to severe hereditary Factor X deficiency (FX:C < 5 IU/dL) received a dose of 25 IU/kg COAGADEX to treat spontaneous, traumatic and menorrhagic bleeding episodes.
If hemostasis was not achieved with a single dose of COAGADEX, additional doses could be given until the bleed stopped. Subjects could also continue with treatment after the bleed had stopped to reduce the risk of recurrence of a given bleed. Subjects were aged 12 to 58 years, including 6 pediatric subjects aged 12 to 17 years.
Six subjects were male, 10 were female, and 12 were Caucasian. The efficacy of COAGADEX in treating bleeding episodes was assessed by the subject and/or investigator for each new bleeding episode, using a bleed-specific ordinal rating scale of excellent, good, poor and unassessable for each type of bleed (overt, covert or menorrhagic). Overt bleed: 'excellent' if bleeding stopped within 12 hours with a single dose; 'good' if within 24 hours with ≤2 doses. Covert bleed: 'excellent' if bleeding stopped within 48 hours with 1 or 2 doses; 'good' if within 48 hours with ≤3 doses.
Menorrhagic bleed: 'excellent' if ≤2 doses within 48 hours; 'good' if 2 doses over >48 hours. Each bleed was reviewed by a Data Review Committee for its suitability for the efficacy evaluation. Of the 208 bleeding episodes treated with COAGADEX, 187 bleeding episodes in 15 subjects were evaluated for efficacy.
Of these 187 bleeding episodes, 79 (42%) occurred spontaneously, 47 (25%) were traumatic and 61 (33%) were menorrhagic. Seventy three (39%) were mucosal in origin, 63 (34%) were joint bleeds, 26 (14%) were muscle bleeds, and 25 (13%) were located elsewhere. Ninety eight (53%) were major bleeding episodes, and 88 (47%) were minor bleeds (one bleed not assessed). COAGADEX was considered to be good (7%) or excellent (91%) in treating 98% of bleeding episodes.
Of the 187 bleeding episodes in the efficacy analysis, a total of 155 bleeds (83%) were treated with one infusion, 28 bleeds (15%) with two infusions, 3 bleeds (2%) with three infusions and 1 bleed (0.5%) with four infusions. The mean dose per infusion and total dose of COAGADEX were
IU/kg and 30.4 IU/kg, respectively. Four bleeding episodes in two subjects were
considered treatment failures. The recommended dose of 25 IU/kg COAGADEX to treat a bleed was maintained during the study for 14 of the 16 subjects. The other two subjects used doses up to 30 IU/kg and 33 IU/kg.
Perioperative Management of Bleeding In two multicenter, open-label, non-randomized clinical trials, subjects requiring surgery received a pre-surgical COAGADEX dose to raise plasma Factor X levels to 70-90 IU/dL, followed by post-surgical doses as necessary to maintain plasma Factor X levels at a minimum of 50 IU/dL until the subject was no longer at risk of bleeding due to surgery. The safety and efficacy of COAGADEX for perioperative management was evaluated in five subjects aged 14 to 59 years with mild, moderate or severe hereditary Factor X deficiency, who underwent a total of seven surgical procedures. For all surgical procedures, COAGADEX was assessed as excellent by the investigator for overall hemostatic control of peri-operative blood loss.
Assessment of hemostatic efficacy was based on parameters including: blood loss during surgery, blood transfusion requirements, bleeding episodes and hemoglobin levels. An excellent score required the achievement of outcomes in these parameters similar to patients without a bleeding disorder. For major surgeries, a median of 13 infusions (range 2 to 15 infusions) and a median cumulative dose of 181 IU/kg (range 45 to 210 IU/kg) were required to maintain hemostasis.
For minor surgeries, a median of 2.5 infusions (range 1 to 4 infusions) and a median cumulative dose of 89 IU/kg (range 51 to 127 IU/kg) were required to maintain hemostasis. One subject had insertion of a central venous access device (Portacath) and was given 6 infusions of COAGADEX during 5 days, a total of 2,750 IU (27 IU/kg); there were no bleeding complications or safety concerns. In a post-marketing registry study, 3 subjects (aged 21 to 30 years) with severe hereditary Factor X deficiency received a total of 10 (mean 3.3) doses of COAGADEX for perioperative hemostatic cover.
The median initial (pre-surgery) dose was
IU/kg (mean 40.6; range 28.6 to 48.9).
A median of 4 (range 1 to 5) infusions was administered, with median cumulative dose
IU/kg (range 28.6 to 171.8). All three subjects achieved excellent hemostatic efficacy
outcomes.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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