"The U.S. Food and Drug Administration today approved Tretten, Coagulation Factor XIII A-Subunit (Recombinant), the first recombinant product for use in the routine prevention of bleeding in adults and children who have a rare clotting disorder, k"...
- Control and prevention of bleeding episodes
- Perioperative management
- Routine prophylaxis to prevent or reduce the frequency of bleeding episodes
Novoeight® is not indicated for the treatment of von Willebrand disease.
DOSAGE AND ADMINISTRATION
For intravenous injection after reconstitution only.
- Dosage and duration of treatment depend on the severity of the factor VIII deficiency, on the location and extent of bleeding, and 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 Novoeight® 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. This relationship causes a factor of 0.5 to be present in the dose calculation formula shown below.
- The required dosage can be determined using the following formula:
Dosage (IU) = Body Weight (kg)
× Desired Factor VIII
Increase (IU/dL or % normal) × 0.5
The final dose calculated is expressed as IU
- Base the dose and frequency of Novoeight® on the individual clinical response. Patients may vary in their pharmacokinetic and clinical responses.
Control And Prevention Of Bleeding Episodes
A guide for dosing Novoeight® for the control and prevention of bleeding episodes is provided in Table 1. Dosing should aim at maintaining a plasma factor VIII activity level at or above the plasma levels (in % of normal or in IU/dL) outlined in Table 1.
Table 1: Dosing for Control
and Prevention of Bleeding Episodes
|Type of Bleeding Episodes||Factor VIII Level Required (IU/dL or % of normal)||Frequency of Doses (hours)||Duration of Therapy (days)|
|Early hemarthrosis, minor muscle or oral bleeding||20-40||12-24||At least 1 day until bleeding resolution is achieved|
|Muscle bleeding, bleeding into the oral cavity or mild head trauma||30-60||12-24||Until pain and acute disability are resolved (approximately 3-4 days)|
|Life or limb threatening hemorrhage, Gastrointestinal bleeding, intracranial, intra-abdominal or intrathoracic bleeding, fractures||60-100||8-24||Until resolution of bleed (approximately 7-10 days)|
A guide for dosing Novoeight® during surgery (perioperative management) is provided in Table 2. Consideration should be given to maintaining a plasma factor VIII activity level at or above the plasma levels (in % of normal or in IU/dL) outlined in Table 2.
Table 2: Dosing for
|Type of Surgery||Factor VIII Level Required (IU/dL or % of normal)||Frequency of Doses (hours)||Duration of Therapy (days)|
|Including tooth extraction||30-60||24||At least 1 day until healing is achieved|
|Intracranial, intraabdominal, intrathoracic, or joint replacement surgery||80-100 (pre-and post-operative)||8-24||Until adequate wound healing, then continue therapy for at least 7 days to maintain a factor VIII activity of 30% to 60% (IU/dL)|
A guide for dosing Novoeight® for routine prophylaxis is included below in Table 3.
Table 3: Dosing for Routine
|Patient Population||Factor VIII Dose Required (IU/kg)||Frequency of Doses|
|Adults and adolescents ( ≥ 12 years)||20-50||3 times weekly|
|20-40||Every other day|
|Children ( < 12 years)||25-60||3 times weekly|
|25-50||Every other day|
Preparation And Reconstitution
- Always wash hands and ensure that the area is clean before performing the procedures.
- Use aseptic technique during the reconstitution procedures.
- If the patient uses more than one vial of Novoeight® per injection, reconstitute each vial according to the following instructions.
Overview Of Novoeight® Package
The instructions below serve as a general guideline for preparation and reconstitution of Novoeight®. For full instructions, refer to the FDA-approved patient information and Instructions for Use.
1. Bring the Novoeight® vial and the pre-filled diluent syringe to room temperature.
2. Remove the plastic cap from the Novoeight® vial.
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.
5. Place the vial on a flat and solid surface. While holding the protective cap, place the vial adapter over the Novoeight® vial and press down firmly on the protective cap until the vial adapter spike penetrates the rubber stopper.
6. Remove the protective cap from the vial adapter.
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.
8. Break off the syringe cap from the pre-filled diluent syringe by snapping the perforation of the cap.
9. Connect the pre-filled diluent syringe to the vial adapter by turning it clockwise until it is secured.
10. Push the plunger rod to slowly inject all the diluent into the vial.
11. Without removing the syringe, gently swirl the Novoeight® vial until all of the powder is dissolved. The reconstituted solution should be inspected visually for particulate matter before administration. Do not use if particulate matter or discoloration is observed.
12. Use the Novoeight® solution immediately. If not, store the solution in the vial with the vial adapter and the syringe attached, at room temperature ≤ 86°F (30°C) for no longer than 4 hours.
For intravenous injection only.
- Accidental needle stick with a needle contaminated with blood can transmit infectious viruses including HIV (AIDS) and hepatitis. Obtain immediate medical attention if injury occurs. Place needles in a sharps container after single-use.
- Inspect the reconstituted Novoeight® solution visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if particulate matter or discoloration is observed.
- Do not administer Novoeight® in the same tubing or container with other medicinal products.
1. Invert the Novoeight® vial and slowly draw the solution into the syringe.
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. Inject the reconstituted Novoeight® intravenously slowly over 2 to 5 minutes.
5. After injection, safely dispose of the syringe with the infusion set, the vial with the vial adapter, any unused Novoeight® and other waste materials.
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 Novoeight® through incompatible needleless connectors, withdraw the reconstituted product into a standard 10 mL sterile Luer-lock plastic syringe.
If you encounter any problems with attaching the pre-filled sodium chloride diluent syringe to any Luer-lock compatible device, please contact Novo Nordisk at (844) 303-4448.
Dosage Forms And Strengths
Novoeight® is available as a white lyophilized powder in single-use vials containing 250, 500, 1000, 1500, 2000 and 3000 international units per vial.
After reconstitution with 4 mL of 0.9% sodium chloride solution, each mL of reconstituted solution contains approximately 62.5, 125, 250, 375, 500 or 750 international units of Novoeight®, respectively.
- Novoeight® is supplied in packages comprised of a single-use vial containing nominally 250, 500, 1000, 1500, 2000, or 3000 international units (IU) of FVIII potency, a MixPro® pre-filled diluent syringe containing 0.9% sodium chloride solution, and sterile vial adapter with 25 micrometer filter, which serves as a needleless reconstitution device.
- The actual amount of FVIII potency in IU is stated on each carton and vial.
|Presentation (Nominal Product Strength)||Carton Number||Components|
|250 International Units||NDC 0169 7825 01||
|500 International Units||NDC 0169 7850 01||
|1000 International Units||NDC 0169 7810 01||
|1500 International Units||NDC 0169 7815 01||
|2000 International Units||NDC 0169 7820 01||
|3000 International Units||NDC 0169 7830 01||
- The Novoeight® vials are made of glass, closed with a chlorobutyl rubber stopper not made with natural rubber latex, and sealed with an aluminum cap.
- The pre-filled diluent syringes are made of glass, with a siliconised bromobutyl rubber plunger not made with natural rubber latex.
- The closed vials and pre-filled diluent syringes are equipped with a tamper-evident snap-off cap which is made of polypropylene.
Storage And Handling
- Store Novoeight® in the original package in order to protect from light.
- Store Novoeight® under refrigeration at a temperature of 36°F–46°F (2°C – 8°C) for up to 30 months from the date of manufacture until the expiration date stated on the label. Within the 30-month period, Novoeight® may also be stored at room temperature not to exceed 86°F (30°C) for up to twelve (12) months.
- If you choose to store Novoeight® at room temperature, clearly record the date when the product was removed from the refrigerator in the space provided on the outer carton. The total time of storage at room temperature should not exceed 12 months. Do not return the product to the refrigerator.
- Do not use Novoeight® after the end of the 12-month period at room temperature storage, or after the expiration date stated on the vial, whichever occurs earlier.
- Do not freeze Novoeight®.
- Use Novoeight® within 4 hours after reconstitution when stored at room temperature. Store the reconstituted product in the vial.
- Discard any unused reconstituted product stored at room temperature for more than 4 hours.
Manufactured by: Novo Nordisk A/S DK-2880 Bagsvaerd, Denmark. Revised: Sep 2015This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 4/5/2016
Additional Novoeight Information
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