ESPEROCT: Package Insert and Label Information

ESPEROCT- antihemophilic factor (recombinant), glycopegylated-exei
Novo Nordisk

1 INDICATIONS AND USAGE

ESPEROCT [antihemophilic factor (recombinant), glycopegylated-exei] is a recombinant DNA-derived coagulation Factor VIII concentrate indicated for use in adults and children with hemophilia A for:

On-demand treatment and control of bleeding episodes
Perioperative management of bleeding
Routine prophylaxis to reduce the frequency of bleeding episodes

Limitation of Use:

ESPEROCT is not indicated for the treatment of von Willebrand disease. (1)

2 DOSAGE AND ADMINISTRATION

For intravenous infusion after reconstitution only.

2.1 Dose

Dosage and duration of treatment depend on the severity of the Factor VIII deficiency, on the location and extent of bleeding, and on the patient’s clinical condition. Careful monitoring of replacement therapy is necessary in cases of major surgery or life-threatening bleeding episodes.
Each vial of ESPEROCT contains the labeled amount of recombinant Factor VIII in international units (IU).One IU of Factor VIII activity corresponds to the quantity of Factor VIII in one milliliter of normal human plasma. The calculation of the required dosage of Factor VIII is based on the empirical finding that one IU of Factor VIII per kg body weight raises the plasma Factor VIII activity by two IU/dL.

On–demand Treatment and Control of Bleeding Episodes

Table 1 can be used to guide dosing of ESPEROCT for treatment of bleeding episodes.

Table 1: Dosing of ESPEROCT to Control Bleeding Episodes
Type of bleeding Adolescents/Adults ≥12 years Dose (IU/kg) Children <12 years Dose (IU/kg) Additional doses

Minor

Early hemarthrosis, mild muscle bleeding, or oral bleeding

40

65

One dose should be sufficient

Moderate

More extensive hemarthrosis, muscle bleeding, or hematoma

40

65

An additional dose may be administered after 24 hours

Major

Life- or limb-threatening hemorrhages, gastro- intestinal bleeding, intracranial, intra-abdominal or intrathoracic bleeding, fractures

50

65

Additional dose(s) may be administered approximately every 24 hours

Perioperative Management

The dose level and dosing intervals for surgery depend on the procedure and local practice. A guide for dosing with ESPEROCT during surgery (perioperative management) is provided in Table 2 below.

Table 2: Dosing for Perioperative Management with ESPEROCT

Type of surgery

Adolescents/Adults

≥12 years

Pre-operative Dose (IU/kg)

Children

<12 years

Pre-operative Dose (IU/kg)

Additional Doses

Minor

Including tooth extraction

50

65

Additional dose(s) can be administered after 24 hours if necessary

Major

Intracranial,

intra-abdominal, intrathoracic, or joint replacement surgery

50

65

Additional doses can be administered approximately every 24 hours for the first week and then approximately every 48 hours until wound healing has occurred

Routine Prophylaxis

Adults and adolescents (≥ 12 years): The recommended starting dose is 50 IU of ESPEROCT per kg body weight every 4 days. This regimen may be individually adjusted to less or more frequent dosing based on bleeding episodes.

Children (< 12 years): A dose of 65 IU of ESPEROCT per kg body weight twice weekly. This regimen may be individually adjusted to less or more frequent dosing based on bleeding episodes.

ESPEROCT also may be dosed to achieve a specific target Factor VIII activity level, depending on the severity of hemophilia, for on-demand treatment/control of bleeding episodes or perioperative management. To achieve a specific target Factor VIII activity level, use the following formula:
Dosage (IU) = Body Weight (kg) × Desired Factor VIII Increase (IU/dL or % normal) × 0.5
Base the dose and frequency of ESPEROCT on the individual clinical response. Patients may vary in their pharmacokinetic and clinical responses.
If monitoring of Factor VIII activity is performed, use a chromogenic or one-stage clotting assay appropriate for use with ESPEROCT [see Warnings and Precautions (5.3) ].

2.2 Preparation and Reconstitution

Always wash hands and ensure that the area is clean before performing the reconstitution procedures.
Use aseptic technique during the reconstitution procedures.
If the dose requires more than one vial of ESPEROCT per infusion, reconstitute each vial according to the following instructions.

Overview of ESPEROCT Package

ESPEROCT -- Overview
(click image for full-size original)

Reconstitution

1.
Bring the ESPEROCT vial and the pre-filled diluent syringe to room temperature.
Fig. A
2.
Remove the plastic cap from the ESPEROCT vial.
Fig. B
(click image for full-size original)
3.
Wipe the rubber stopper on the vial with a sterile alcohol swab and allow it to dry prior to use.
4.
Remove the protective paper from the vial adapter. Do not remove the vial adapter from the protective cap.
Fig. C
(click image for full-size original)
5.
Place the ESPEROCT vial on a flat and solid surface. While holding the protective cap, place the vial adapter over the ESPEROCT vial and press down firmly on the protective cap until the vial adapter spike penetrates the rubber stopper.
Fig. D
(click image for full-size original)
6.
Carefully remove the protective cap from the vial adapter.
Fig. E
7.
Grasp the plunger rod as shown in the diagram. Attach the plunger rod to the syringe by holding the plunger rod by the wide top end. Turn the plunger rod clockwise into the rubber plunger inside the pre-filled diluent syringe until resistance is felt.
Fig. F
8.
Break off the syringe cap from the pre-filled diluent syringe by snapping the perforation of the cap.
Fig. G
(click image for full-size original)
9.
Connect the pre-filled diluent syringe to the vial adapter by turning it clockwise until it is secured.
Fig. H
10.
Push the plunger rod to slowly inject all the diluent into the vial.
Fig. I
(click image for full-size original)
11.
Without removing the syringe, gently swirl the ESPEROCT vial until all of the powder is dissolved. Avoid shaking the vial and foaming the solution.
Fig. J
(click image for full-size original)

2.3 Administration

For intravenous infusion only.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be clear and have no particles. Do not use if particulate matter or discoloration is observed.
Do not administer ESPEROCT in the same tubing or container with other medicinal products.
Administer the ESPEROCT solution immediately. If not, store the solution in the vial with the vial adapter and the syringe attached. Use ESPEROCT within 4 hours when stored at ≤86°F (30°C) or within 24 hours when stored in a refrigerator at 36°F to 46°F (2°C to 8°C).
1.
Invert the ESPEROCT vial and slowly draw the solution into the syringe.
Fig. K
(click image for full-size original)
2.
Detach the syringe from the vial adapter by turning the syringe counterclockwise.
3.
Attach the syringe to the luer end of an infusion needle set.
4.
Infuse the reconstituted ESPEROCT intravenously slowly over approximately 2 minutes.
5.
After infusion, safely dispose of the syringe with the infusion set, the vial with the vial adapter, any unused ESPEROCT, and other waste materials.

Caution: The pre-filled diluent syringe is made of glass with an internal tip diameter of 0.037 inches and is compatible with a standard Luer-lock connector.

Some needleless connectors for intravenous catheters are incompatible with the glass diluent syringes (for example, certain connectors with an internal spike, such as Clave® /MicroClave® , InVision-Plus® , InVision-Plus CS® , Invision-Plus Junior® , Bionector®), and their use can damage the connector and affect administration. To administer ESPEROCT through incompatible needleless connectors, withdraw the reconstituted product into a standard 10 mL sterile Luer-lock plastic syringe.

3 DOSAGE FORMS AND STRENGTHS

ESPEROCT is available as a sterile white to off-white lyophilized powder supplied in single-dose vials containing nominally 500, 1000, 1500, 2000 or 3000 IU. The actual FVIII activity is printed on each ESPEROCT vial and carton.

After reconstitution with 4 mL of saline diluent, the reconstituted solution contains approximately 125, 250, 375, 500 or 750 IU per mL of ESPEROCT, respectively.

4 CONTRAINDICATIONS

ESPEROCT is contraindicated in patients who have known hypersensitivity to ESPEROCT or its components (including hamster proteins) [see Warnings and Precautions (5.1) and Description (11)].

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

Allergic-type hypersensitivity reactions, including anaphylaxis, are possible with ESPEROCT. The product contains traces of hamster proteins, which in some patients may cause allergic reactions [see Description (11)]. Early signs of allergic reactions, which can progress to anaphylaxis, may include angioedema, chest tightness, difficulty breathing, wheezing, rash, hives, and itching. Observe patients for signs and symptoms of acute hypersensitivity reactions, particularly during the early phases of exposure to the product. Discontinue use of ESPEROCT if allergic- or anaphylactic-type reactions occur, and initiate appropriate treatment.

5.2 Neutralizing Antibodies

The formation of neutralizing antibodies (inhibitors) to Factor VIII has occurred following administration of ESPEROCT. Monitor patients for the development of Factor VIII inhibitors by appropriate clinical observations and laboratory tests. If expected Factor VIII activity plasma levels are not attained, or if bleeding is not controlled after ESPEROCT administration, suspect the presence of an inhibitor (neutralizing antibody) [see Warnings and Precautions (5.3) ].

5.3 Monitoring Laboratory Tests

If monitoring of Factor VIII is performed, use a chromogenic or one-stage clotting assay appropriate for use with ESPEROCT [see Dosage and Administration (2)].

Factor VIII activity levels can be affected by the type of activated partial thromboplastin time (aPTT) reagent used in the assay. Some silica-based aPTT reagents can underestimate the activity of ESPEROCT by up to 60%; other reagents may overestimate the activity by 20%. If an appropriate one-stage clotting or chromogenic assay is not available locally, then use a reference laboratory.

If bleeding is not controlled with the recommended dose of ESPEROCT or if the expected Factor VIII activity levels in plasma are not attained, then perform a Bethesda assay to determine if Factor VIII inhibitors are present.

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