Data from FDA - Curated by Toby Galbraith - Last updated 18 April 2017

Licensing authority

FDA (Food and Drug Administration, USA)

Indication(s)

1 INDICATIONS AND USAGE COAGADEX, Coagulation Factor X (Human), is a plasma-derived human blood coagulation Factor indicated in adults and children (aged 12 years and above) with hereditary Factor X deficiency for: On-demand treatment and control of bleeding episodes Perioperative management of bleeding in patients with mild hereditary Factor X deficiency.

COAGADEX, Coagulation Factor X (Human), is a plasma-derived human blood coagulation factor indicated in adults and children (aged 12 years and above) with hereditary Factor X deficiency for: On-demand treatment and control of bleeding episodes (1) Perioperative management of bleeding in patients with mild hereditary Factor X deficiency (1).

Limitation of Use Perioperative management of bleeding in major surgery in patients with moderate and severe hereditary Factor X deficiency has not been studied.

Limitation of Use Perioperative management of bleeding in major surgery in patients with moderate and severe hereditary

Factor X deficiency has not been studied.

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Advisory information

contraindications
4 CONTRAINDICATIONS COAGADEX is contraindicated in patients who have had life-threatening hypersensitivity reactions to COAGADEX or any of the components [see Description (11) ]. Do not use in patients who have had life-threatening hypersensitivity reactions to COAGADEX or any of the components (4).
Adverse reactions

6 ADVERSE REACTIONS The most common adverse drug reactions (frequency?

5 % of subjects) observed in clinical trials were infusion site erythema, infusion site pain, fatigue, and back pain.

The most common adverse drug reactions (frequency?

5 % of subjects) observed in clinical trials were infusion site erythema, infusion site pain, fatigue and back pain (6).

To report SUSPECTED ADVERSE REACTIONS, contact BPL Inc, at 1-866-398-0825 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience As clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug can not 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 two multicenter, open-label, non-randomized clinical studies, 18 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 and 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 [5.6 %]), fatigue (2 reports in 1 subject [5.6 %]), back pain (1 report [5.6 %]) and infusion site pain (1 report [5.6 %]).

6.2 Immunogenicity All subjects 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.

Usage information

Dosing and administration

2 DOSAGE AND ADMINISTRATION For intravenous use after reconstitution only.

For intravenous use only after reconstitution.

Each vial of COAGADEX contains the labeled amount of Factor X in international units (IU) (2).

The dosage and duration of treatment depend on the severity of the Factor X deficiency, on the location and extent of the bleeding and on the patient 's clinical condition (2.1).

For treatment of bleeding episodes: use 25 IU per kg body weight, repeated at intervals of 24 hours until the bleed stops (2.1).

For perioperative management: Pre-surgery, raise plasma Factor X levels to 70-90 IU/dL. Post-surgery, maintain plasma Factor X levels at a minimum of 50 IU/dL until the patient is no longer at risk of bleeding due to surgery.

Required dose (IU) = Body weight (kg)?

Desired Factor X rise (IU/dL or % of normal)?

0.5 2.1 Dose Dose and duration of the treatment depend on the severity of the Factor X deficiency, location and extent of the bleeding, and on the patient 's clinical condition.

Base the dose and frequency on the individual clinical response.

Do not administer more than 60 IU/kg daily.

Each vial of COAGADEX is labeled with the actual Factor X potency/content in International Units (IU).

Estimate the expected in_vivo peak increase in Factor X level expressed as IU/dL (or % of normal) using the following formula: Estimated Increment of Factor X (IU/dL or % of normal) = [Total Dose (IU)/Body Weight (kg)]?

2 The dose to achieve a desired in_vivo peak increase in Factor X level may be calculated using the following formula: Dose (IU) = Body Weight (kg)?

Desired Factor X Rise (IU/dL)?

0.5 Note:

The desired Factor X rise is the difference between the patient 's plasma Factor X level and the desired level.

The dosing formula is based on the observed recovery of 2 IU/dL per IU/kg.

On-demand Treatment and Control of Bleeding Episodes Infuse 25 IU/kg of COAGADEX when the first sign of bleeding occurs.

Repeat at intervals of 24 hours until the bleed stops.

Perioperative Management of Bleeding Measure post-infusion plasma Factor X levels for each patient before and after surgery, to ensure that hemostatic levels are obtained and maintained.

Pre-surgery: Calculate the dose of COAGADEX to raise plasma Factor X levels to 70-90 IU/dL using the following formula: Required dose (IU) = Body Weight (kg)?

Desired Factor X Rise (IU/dL)?

0.5 Post-surgery: Repeat dose as necessary to maintain plasma Factor X levels at a minimum of 50 IU/dL until the patient is no longer at risk of bleeding due to surgery.

2.2 Preparation and Reconstitution The procedures below are provided as general guidelines for the preparation and reconstitution of COAGADEX.

Always work on a clean surface and wash your hands before performing the following procedures.

To reconstitute, use the diluent (Sterile Water for Injection) and transfer device (Mix2Vial) provided in the COAGADEX carton.

To administer, you will also need a syringe and suitable needle (not provided in the COAGADEX carton).

Bring the vials of COAGADEX and the Sterile Water for Injection to room temperature before mixing.

The reconstitution is performed as follows:

Table 1 COAGADEX Reconstitution Instructions Step 1 Remove the cap from the vial of COAGADEX and clean the top of the rubber stopper with an alcohol swab (not supplied) and allow to dry prior to opening the Mix2Vial package.

Repeat this step with the vial of sterile water.

Step 2 Peel back the top of the Mix2Vial package.

Do not remove the device from the package.

Step 3 Place the blue end of the Mix2Vial over the water vial and push straight down until the spike penetrates the rubber stopper and snaps into place.

Remove the plastic outer packaging from the Mix2Vial and discard it.

Do not touch the exposed end of the device.

Step 4 With the COAGADEX vial placed on a flat surface, invert the water vial with the Mix2Vial device still attached.

Place the clear end of the Mix2Vial on the product vial and push straight down until the spike penetrates the rubber stopper and snaps into place.

The water will automatically transfer into the COAGADEX vial by the vacuum contained within it.

Do not use if the water is not pulled into the vial of COAGADEX.

Step 5 Gently swirl the COAGADEX vial to make sure that the powder is fully dissolved.

Do not shake the vial.

The reconstituted solution should be clear or a slightly pearl-like solution.

Do not use if particulate matter or discoloration is observed and contact BPL. Step 6 Separate the empty water vial and blue part of the Mix2Vial from the clear part that is attached to the COAGADEX vial by unscrewing counter-clockwise.

Step 7 Draw air into an empty, sterile syringe (not supplied) by pulling the plunger to the volume of water added.

Connect the syringe to the clear part of the Mix2Vial and push the air in the syringe into the vial.

Step 8 Immediately invert the COAGADEX vial.

The solution will automatically be drawn into the syringe.

Draw the remaining solution into the syringe by pulling the plunger back slowly.

Disconnect the filled syringe from the device.

Use the product immediately after reconstitution.

Do not store the reconstituted product.

Step 1 and 2 Step 3 Step 4 Step 5 Step 6 and 7 Step 8 2.3 Administration For intravenous administration only If the dose requires more than one vial of COAGADEX: Reconstitute each vial (steps 1 to 5) using a new Mix2Vial for each vial.

Draw up all the solution into a single syringe (steps 6 to 8).

Visually inspect the final solution for particulate matter and discoloration prior to administration, and whenever solution and container permit.

Do not use if particulate matter or discoloration is observed.

Attach a suitable needle to the syringe.

Administer by intravenous infusion at a rate of 10 mL/min, but no more than 20 mL/min.

Use in special populations

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no data with COAGADEX use 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.

COAGADEX should be given to a pregnant woman only if clearly needed.

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.

8.2 Lactation Risk Summary There is no information regarding the presence of COAGADEX in human milk, the effects on the breastfed infant, or the effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother 's clinical need for COAGADEX and any potential adverse effects on the breast-fed infant from COAGADEX or from the underlying maternal condition.

8.4 Pediatric Use Safety and efficacy in patients under the age of 12 years have not been studied.

8.5 Geriatric Use Clinical studies of COAGADEX did not include any subjects aged 65 and over to determine whether they respond differently from younger subjects.

Individualize dose selection for geriatric patients.

Interactions

7 DRUG INTERACTIONS 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 [see Clinical Pharmacology (12.1) ].

More information

Category Value
Authorisation number BLA125506
Orphan designation No
Product NDC 64208-7752,64208-7753
Date Last Revised 28-10-2015
Type HUMAN PRESCRIPTION DRUG
RXCUI 1719235
Storage and handling

Storage and Handling Store COAGADEX in its original package to protect it from light.

Store the COAGADEX package in a refrigerator or at room temperature (36°F to 86°F).

Do not freeze.

Do not use COAGADEX or the Sterile Water for Injection after the expiration date printed on the vial and carton labels.

Use reconstituted COAGADEX within one hour of reconstitution.

Do not use COAGADEX if the reconstituted solution is cloudy or contains any particles.

Marketing authorisation holder Bio Products Laboratory Limited

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