A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Benefix Indications, Dosage, Storage, Stability - Coagulation Factor IX (Recombinant)
Benefix Indications, Dosage, Storage, Stability - Coagulation Factor IX (Recombinant)
INDICATIONS
AND USES
BeneFIX®, Coagulation Factor IX (Recombinant), is indicated for the control
and prevention of hemorrhagic episodes in patients with hemophilia B (congenital
factor IX deficiency or Christmas disease), including control and prevention
of bleeding in surgical settings.
BeneFIX®, Coagulation Factor IX (Recombinant), is not indicated for the treatment
of other factor deficiencies (e.g., factors II, VII, and X), nor for the treatment
of hemophilia A patients with inhibitors to factor VIII, nor for the reversal
of coumarin-induced anticoagulation, nor for the treatment of bleeding due to
low levels of liver-dependent coagulation factors.
DOSAGE AND ADMINISTRATION
Treatment with BeneFIX®, Coagulation Factor IX (Recombinant), should be initiated
under the supervision of a physician experienced in the treatment of hemophilia
B.
Dosage and duration of treatment for all factor IX products depend on the severity
of the factor IX deficiency, the location and extent of bleeding, and the patient's
clinical condition, age and recovery of factor IX.
To ensure that the desired factor IX activity level has been achieved, precise
monitoring using the factor IX activity assay is advised. Doses should be
titrated using the factor IX activity, pharmacokinetic parameters, such as half-life
and recovery, as well as taking the clinical situation into consideration in
order to adjust the dose as appropriate.
In an eleven patient, crossover, randomized PK evaluation of BeneFIX® and a
single lot of high-purity plasma-derived factor IX, the recovery was lower for
BeneFIX® (see CLINICAL PHARMACOLOGY). In the clinical efficacy studies,
patients were initially administered the same dose previously used for plasma-derived
factor IX. Even in the absence of factor IX inhibitor, approximately half of
the patients increased their dose in these studies. Titrate the initial dose
upward if necessary to achieve the desired clinical response. As with some plasma-derived
factor IX products, patients at the low end of the observed factor IX recovery
may require upward dosage adjustment to as much as two times (2 × ) the initial
empirically calculated dose in order to achieve the intended rise in circulating
factor IX activity.
BeneFIX® is administered by IV infusion over several minutes after reconstitution
of the lyophilized powder with Sterile Water for Injection (USP).
Method of Calculating Dose
The method of calculating the factor IX dose is shown in the following equation:
|
number of
factor IX I.U.
required (I.U.)
|
=
|
body
weight
(kg)
|
×
|
desired
factor IX
increase
(% or
I.U./dL)
|
×
|
reciprocal
of observed
recovery (I.U./kg per
I.U./dL)
|
In the presence of an inhibitor, higher doses may be required.
Adult Patients
In adult PTPs, on average, one international unit of BeneFIX® per kilogram
of body weight increased the circulating activity of factor IX by 0.8 ± 0.2
(ranged from 0.3 to 1.4) I.U./dL. The method of dose estimation is illustrated
in the following example. If you use 0.8 I.U./dL average increase of factor
IX per I.U./kg body weight administered, then:
|
number of
factor IX I.U.
required (I.U.)
|
=
|
body
weight
(kg)
|
×
|
desired
factor IX
increase
(% or
I.U./dL)
|
×
|
1.2 (I.U./kg
per I.U./dL)
|
Pediatric Patients (< 15 years)
In pediatric patients, on average, one international unit of BeneFIX® per kilogram
of body weight increased the circulating activity of factor IX by 0.7 ± 0.2
(ranged from 0.3 to 1.1) I.U./dL. The method of dose estimation is illustrated
in the following example. If you use 0.7 I.U./dL average increase of factor
IX per I.U./kg body weight administered, then:
|
number of
factor IX I.U.
required (I.U.)
|
=
|
body
weight
(kg)
|
×
|
desired
factor IX
increase
(% or
I.U./dL)
|
×
|
1.4 (I.U./kg
per I.U./dL)
|
The following chart 3 may be used to guide dosing in bleeding episodes
and surgery:
|
Type of
Hemorrhage
|
Circulating
Factor IX
Activity
Required
[% or
(I.U./dL)] |
Dosing
Interval
[hours] |
Duration
of Therapy
[days] |
|
Minor
|
|
Uncomplicated
hemarthroses,
superficial muscle,
or soft tissue
|
20-30 |
12-24 |
1-2 |
|
Moderate
|
|
Intramuscle or
soft tissue with
dissection,
mucous
membranes,
dental extractions,
or hematuria
|
25-50 |
12-24 |
Treat until
bleeding
stops and
healing
begins; about
2 to 7 days
|
|
Major
|
|
Pharynx,
retropharynx,
retroperitoneum,
CNS, surgery
|
50-100 |
12-24 |
7-10 |
|
Adapted from: Roberts and Eberst 3
|
INSTRUCTIONS FOR USE
The procedures below are provided as general guidelines for the reconstitution
and administration of BeneFIX®. Patients should follow the specific reconstitution
and administration procedures provided by their physicians.
Reconstitution
Always wash your hands before performing the following procedures. Aseptic
technique should be used during the reconstitution procedure.
BeneFIX®, Coagulation Factor IX (Recombinant), will be administered by intravenous
(IV) infusion after reconstitution with Sterile Water for Injection (diluent).
- Allow the vials of lyophilized BeneFIX® and diluent to reach room temperature.
- Remove the plastic flip-top caps from the BeneFIX® vial and the diluent
vial to expose the central portions of the rubber stoppers.
- Wipe the tops of both vials with the alcohol swab provided, or use another
antiseptic solution, and allow to dry.
- Remove the protective cover from the short end of the sterile double-ended
needle and insert the short end into the diluent vial at the center of the
stopper.
- Remove the protective cover from the long end of the needle. Invert the
solvent vial and, to minimize leakage, quickly insert the long end of the
needle through the center of the stopper of the upright BeneFIX® vial.
Note: Point the double-ended needle toward the wall of the BeneFIX® vial
to prevent excessive foaming.
- The vacuum will draw the diluent into the BeneFIX® vial.
- Once the transfer is complete, remove the long end of the needle from the
BeneFIX® vial, and properly discard the needle with the diluent vial.
Note: If the diluent does not transfer completely into the BeneFIX® vial,
DO NOT USE the contents of the vial. Note that it is acceptable for a small
amount of fluid to remain in the diluent vial after transfer.
- Gently rotate the vial to dissolve the powder.
- Parenteral drug products should be inspected visually for particulate matter
and discoloration prior to administration, whenever solution and container
permit. Reconstituted BeneFIX® should appear clear and colorless.
BeneFIX® should be administered within 3 hours after reconstitution. The reconstituted
solution may be stored at room temperature prior to administration.
Administration (Intravenous Injection)
BeneFIX®, Coagulation Factor IX (Recombinant), should be administered using
a single sterile disposable plastic syringe. In addition, the solution should
be withdrawn from the vial using the sterile filter spike.
- Using aseptic technique, attach the sterile filter spike to the sterile
disposable syringe.
Note: Do NOT inject air into the BeneFIX® vial. This may cause partial
loss of product.
- Insert the filter spike end into the stopper of the BeneFIX® vial.
- Invert the vial and withdraw the reconstituted solution into the syringe.
- Remove and discard the filter spike.
Note: If you use more than one vial of BeneFIX®, the contents of multiple
vials may be drawn into the same syringe through a separate, unused filter
spike.
- Attach the syringe to the Luer end of the infusion set tubing and perform
venipuncture as instructed by your physician.
Note: Agglutination of red blood cells in the tubing/syringe has been reported
with the administration of BeneFIX®. No adverse events have been reported
in association with this observation. To minimize the possibility of agglutination,
it is important to limit the amount of blood entering the tubing. Blood should
not enter the syringe. If red blood cell agglutination is observed in the
tubing or syringe, discard all material (tubing, syringe and BeneFIX® solution)
and resume administration with a new package.
After reconstitution, BeneFIX® should be injected intravenously over several
minutes. The rate of administration should be determined by the patient's comfort
level (see ADVERSE REACTIONS).
Dispose of all unused solution, empty vials, and used needles and syringes
in an appropriate container for throwing away waste that might hurt others if
not handled properly.
Storage
Product as packaged for sale: BeneFIX®, Coagulation Factor IX (Recombinant),
should be stored under refrigeration at a temperature of 2 to 8°C (36 to 46°F).
Prior to the expiration date, BeneFIX® may also be stored at room temperature
not to exceed 25°C (77°F) for up to 6 months. The patient should make note of
the date the product was placed at room temperature in the space provided on
the outer carton. Freezing should be avoided to prevent damage to the diluent
vial. Do not use BeneFIX® after the expiry date on the label.
Product after reconstitution: The product does not contain a preservative and
should be used within 3 hours.
HOW SUPPLIED
BeneFIX®, Coagulation Factor IX (Recombinant), is supplied in single use vials
which contain nominally 250, 500, or 1000 I.U. per vial (NDC # 58394-003-01,
58394-002-01, and 58394-001-01, respectively) with sterile diluent, sterile
double-ended needle for reconstitution, sterile filter spike for withdrawal,
sterile infusion set, and two (2) alcohol swabs. Actual factor IX activity in
I.U. is stated on the label of each vial.
REFERENCES
- Lusher JM. Thrombogenicity associated with factor IX complex concentrates.
Semin Hematol . 1991;28(3 Suppl. 6):3-5.
- Shapiro AD, Ragni MV, Lusher JM, et al. Safety and efficacy of monoclonal
antibody purified factor IX concentrate in previously untreated patients with
hemophilia B. Thromb Haemost . 1996;75(1):30-35.
- Roberts HR, Eberst ME. Current management of hemophilia B. Hematol Oncol
Clin North Am . 1993;7(6):1269-1280.
Manufactured by
Genetics Institute, Inc.
Cambridge MA 02140-2387, USA
Imported and Distributed in
Canada by:
WYETH-AYERST CANADA INC.
Montreal, Canada
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