Profilnine SD

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Profilnine SD

Classes

Blood Coagulation Factors

Administration

Factor IX activity is expressed in International Units. Factor IX potency is assigned using an in vitro, activated partial thromboplastin time (aPTT)-based, one-stage clotting assay calibrated against the World Health Organization (WHO) international standard for factor IX concentrates. One International Unit approximates the activity of factor IX present in 1 mL of normal pooled plasma.
The actual potency per vial of factor IX is stated on each vial.
To ensure the desired factor IX activity level has been achieved, monitoring of factor IX activity by a validated one-stage clotting or chromogenic assay is recommended. Factor IX activity measurements in the clinical laboratory may be affected by the type of aPTT reagent or reference standard used.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Do not administer factor IX products in the same tubing or container with other medicinal products.

Intravenous Administration

Reconstitution
AlphaNine SD
Bring concentrate and diluent to room temperature. Use aseptic technique to reconstitute.
Open the Mix2Vial package by peeling away the lid; do not remove the device from the clear outer packaging.
Place the diluent vial on a flat surface and hold tightly. Pick up the Mix2Vial in its clear outer packaging. With the Mix2Vial still in its clear outer packaging, hold it securely and push the blue end down vertically through the diluent vial stopper.
Carefully remove the clear outer packaging from the Mix2Vial set.
Invert the diluent vial with the Mix2Vial set attached and push the clear end of the Mix2Vial down vertically through the concentrate vial stopper. The diluent will automatically transfer into the vial. If the Mix2Vial is connected at an angle, the vacuum may be released and the diluent will not transfer.
With both vials still attached to the Mix2Vial set, gently swirl (do not shake) the concentrate vial until fully dissolved then unscrew the transfer set into 2 pieces. Reconstitution requires less than 5 minutes.
Draw air into an empty, sterile syringe. Keeping the concentrate vial upright with the clear end of the Mix2Vial attached, screw the syringe onto the Luer lock portion of the Mix2Vial device and inject air into the concentrate vial.
Keep the plunger depressed, invert the system upside down, and draw the reconstituted product into the syringe by pulling the plunger back slowly.
Unscrew the syringe from the Mix2Vial transfer set.
If the patient is to receive more than 1 vial of concentrate, the contents of 2 vials may be drawn into the same syringe through separate unused Mix2Vial sets before attaching to the venipuncture set.
Storage: Use as soon as possible within 3 hours of reconstitution.

Alprolix
Bring concentrate and diluent to room temperature. Use aseptic technique to reconstitute.
Peel back the lid of the vial adapter package; do not remove the vial adapter from the package or touch the inside of the adapter package.
Place the vial on a flat surface and hold tightly. Pick up the vial adapter and push down vertically through the vial stopper. Discard package cover.
Hold the plunger rod at the circular disk and place the tip of the plunger rod into the end of the syringe. Turn clockwise until it is securely attached. Only use the provided diluent syringe.
Hold the diluent syringe with one hand by the ridged part directly under the cap with the cap pointing up. Do not use if the cap has been removed or is not securely attached. Grasp the cap with the other hand and bend it at a 90 degree angle until it snaps off. Do not touch the glass tip of the syringe or the inside of the cap.
Insert the tip of the syringe into the adapter opening and turn the syringe clockwise until it is securely attached to the adapter. Slowly depress the plunger rod to inject all of the diluent into the vial. The plunger rod may rise slightly after this process; this is normal.
With the syringe still connected to the adapter, gently swirl (do not shake) the vial until the product is completely dissolved. The final solution should be clear to slightly opalescent and colorless.
Completely depress the plunger rod. Turn the vial upside down and slowly pull on the plunger rod to draw the solution into the syringe. Be careful not to pull the plunger rod completely out of the syringe.
Gently unscrew the syringe from the vial adapter.
If combining 2 or more vials, leave the vial adapter attached to the vial. Do not detach the diluent syringe or the large Luer lock syringe until ready to attach the large Luer lock syringe to the next vial (with vial adapter attached). Remove the diluent syringe from the vial adapter by turning it counterclockwise until it is completely detached. Attach a separate, large Luer lock syringe by turning clockwise until it is securely in place. Slowly pull on the plunger rod to draw the solution into the syringe. Repeat this pooling procedure with each vial necessary to obtain the required dose.
Attach the syringe to the connector end of the infusion set tubing. Depress plunger until all air is removed from the syringe and concentrate has reached the end of the infusion set tubing.
Storage: Store reconstituted product at room temperature (not to exceed 30 degrees C [86 degrees F]). Administer within 3 hours of reconstitution. Protect from direct sunlight.

Bebulin
Bring concentrate and diluent to room temperature. Use aseptic technique to reconstitute.
Remove the protective covering from one end of the double-ended needle and insert the exposed end through the diluent vial stopper.
Remove the protective covering from the other end of the double-ended needle being careful not to touch the exposed end.
Invert the diluent vial over the concentrate vial and insert the free end of the needle into the concentrate vial stopper. The diluent will be drawn into the concentrate vial by vacuum.
Disconnect the vials by removing the needle from the concentrate vial stopper.
Gently agitate or rotate the concentrate vial until all material is dissolved. The reconstituted product should be a colorless to slightly yellowish and clear to slightly turbid solution.
Attach the enclosed filter needle to a sterile disposable syringe. Insert filter needle through the concentrate vial stopper.
Inject air and withdraw the solution into the syringe.
Remove and discard filter needle. Attach a suitable intravenous needle or infusion set with winged adapter.
Storage: Administer within 3 hours of reconstitution. Do not refrigerate.

BeneFIX
Bring concentrate and diluent to room temperature (if refrigerated). Use aseptic technique to reconstitute.
Peel back the cover from the clear plastic vial adapter package; do not remove the adapter from the package.
Place the vial on a flat surface. Pick up the adapter and press down firmly on the package until the adapter snaps into place on top of the vial and the adapter spike has penetrated the vial stopper.
Attach the threaded end of the plunger rod to the diluent syringe plunger by pushing and turning firmly. Break off the plastic-tip cap from the diluent syringe by snapping the perforation of the cap. Place the cap on its tip on a clean surface where it will stay clean in case the diluent syringe needs to be recapped. Lift the package away from the adapter.
Place the vial on a flat surface and connect the diluent syringe to the vial adapter by inserting the tip of the syringe into the adapter opening while firmly pushing and turning the syringe clockwise until the connection is secured.
Slowly depress the plunger rod to inject all the diluent into the concentrate vial.
With the syringe connected to the adapter, gently swirl the contents of the vial until the powder is dissolved. The solution should be clear to colorless.
With the syringe plunger rod fully pressed down, turn the vial over and slowly pull the solution into the syringe.
If the dosage requires more than 1 vial, remove the diluent syringe from the vial adapter and leave the vial adapter attached to the vial. Quickly attach a separate large Luer lock syringe to withdraw the solution; repeat this procedure with each vial so that the entire dose is contained within the large Luer lock syringe.
Once the entire dose has been drawn into the syringe, detach the syringe from the vial adapter by gently pulling and turning the syringe counterclockwise.
If not using the solution immediately, carefully replace the syringe cap.
Storage: The solution may be stored at room temperature for up to 3 hours after reconstitution.

Idelvion
Bring concentrate and diluent vials to room temperature. Use aseptic technique to reconstitute.
Open the Mix2Vial package by peeling away the lid; do not remove the device from the clear outer packaging.
Place the diluent vial on a flat surface and hold tightly. Pick up the Mix2Vial in its clear outer packaging. With the Mix2Vial still in its clear outer packaging, hold it securely and push the blue end down vertically through the diluent vial stopper.
Carefully remove the clear package from the Mix2Vial set. Do not remove the Mix2Vial transfer set or touch the exposed end of the device.
Invert the diluent vial with the Mix2Vial set attached and push the clear end of the Mix2Vial down vertically through the concentrate vial stopper. The diluent will automatically transfer into the vial.
With both vials still attached to the Mix2Vial set, gently swirl (do not shake) the concentrate vial to ensure the powder is fully dissolved then unscrew the transfer set into 2 pieces. The reconstituted solution should be a clear or yellow to colorless solution.
Draw air into an empty, sterile syringe. Keeping the product vial upright with the clear end of the Mix2Vial attached, screw the syringe onto the Luer lock portion of the Mix2Vial device and inject air into the product vial.
Keep the plunger depressed, invert the system upside down, and draw the reconstituted product into the syringe by pulling the plunger back slowly.
Unscrew the syringe from the Mix2Vial transfer set.
If the patient is to receive more than 1 vial of concentrate, the contents of multiple vials may be drawn into the same syringe through separate unused Mix2Vial sets before attaching to the venipuncture set.
Storage: Use immediately or within 4 hours of reconstitution. Store reconstituted solution at room temperature. Do not refrigerate.

Ixinity
Bring concentrate and diluent to room temperature. Use aseptic technique to reconstitute.
Peel back the cover of the vial adapter package; do not remove adapter from the package. Place the adapter open end up on the clean surface with the Luer lock pointing up.
Twist off the cap of the prefilled diluent syringe.
Firmly hold the package containing the adapter with one hand and the barrel of the syringe with the other, and connect the prefilled syringe to the vial adapter by pushing the syringe tip down onto the Luer lock in the center of the vial adapter; turn clockwise until the syringe is secured.
Carefully lift the combined syringe and vial adapter and remove it from the plastic package.
Hold the combined syringe and vial adapter in one hand and the concentrate vial with the other hand. Firmly push the filter spike of the vial adapter through the center of the concentrate vial's rubber circle until the clear plastic cap snaps onto the vial.
Slowly push the plunger rod down to transfer all of the liquid from the syringe into the vial.
With the syringe and vial still attached, gently swirl, in a circular motion, the vial until the product is fully dissolved. The reconstituted solution should be clear and colorless.
Remove the diluent syringe from the vial adapter by turning it counterclockwise until it is completely detached.
Remove the administration syringe (provided) from its packaging. Attach to the reconstituted vial and vial adapter by turning the syringe clockwise until it is securely attached.
Keeping the administration syringe plunger pressed, turn the concentrate vial upside down and draw the solution from the vial into the administration syringe slowly.
Detach the administration syringe from the vial. The administration syringe provided may be used to pool up to 3 vials of concentrate. If more than 3 vials are required, use a larger (more than 20 mL) sterile Luer lock syringe (not provided).
Storage: Infuse immediately or within 3 hours of reconstitution. Store reconstituted solution at room temperature. Do not refrigerate.

Mononine
Bring concentrate and diluent to room temperature. Use aseptic technique to reconstitute.
Insert one end of the double-ended needle into the diluent vial. Invert the diluent vial and insert the other end of the double-ended needle into the concentrate vial.
Direct the diluent, which will be drawn in by vacuum, over the surface of the powder cake. Rotate the vial to ensure complete wetting of the cake during the transfer process.
Remove the diluent vial to release the vacuum, and then remove the double-ended needle from the concentrate vial.
Gently swirl the vial until the powder is dissolved. Powder should completely dissolve within a minute.
Attach the vented filter spike (provided) to a sterile disposable syringe. Use of other, non-vented filter needles or spikes without the proper procedure may result in an air lock. Do not inject air into the vial.
Insert the vented spike into the vial, invert the vial, and position the filter spike so that the orifice is at the inside edge of the stopper.
Withdraw the appropriate amount. Perform venipuncture using the winged needle with microbore tubing (provided).
Storage: Administer within 3 hours of reconstitution. Do not refrigerate.

Profilnine SD
Bring concentrate and diluent to room temperature. Use aseptic technique to reconstitute.
Open the Mix2Vial package by peeling away the lid; do not remove the device from the clear outer packaging.
Place the diluent vial on a flat surface and hold tightly. Pick up the Mix2Vial in its clear outer packaging. With the Mix2Vial still in its clear outer packaging, hold it securely and push the blue end down vertically through the diluent vial stopper.
Carefully remove the clear outer packaging from the Mix2Vial set.
Invert the diluent vial with Mix2Vial set attached and push the clear end of the Mix2Vial down vertically through the concentrate vial stopper. The diluent will automatically transfer into the vial. If the Mix2Vial is connected at an angle, the vacuum may be released and the diluent will not transfer.
With both vials attached to the Mix2Vial set, gently swirl (do not shake) the concentrate vial until fully dissolved then unscrew the transfer set into 2 pieces. Reconstitution requires less than 10 minutes.
Draw air into an empty, sterile syringe. Keeping the concentrate vial upright with the clear end of the Mix2Vial attached, screw the syringe onto the Luer lock portion of the Mix2Vial device and inject air into the product vial.
Keep the plunger depressed, invert the system upside down, and draw the reconstituted product into the syringe by pulling the plunger back slowly.
Unscrew the syringe from the Mix2Vial transfer set.
To administer, attach the syringe to a suitable intravenous administration set.
If the patient is to receive more than 1 vial of concentrate, the contents of multiple vials may be drawn into the same syringe through separate unused Mix2Vial sets before attaching to the venipuncture set.
Storage: Administer as soon as possible within 3 hours of reconstitution. Do not refrigerate.

Rixubis
Bring concentrate and diluent to room temperature. Use aseptic technique to reconstitute.
Peel back the cover from the BAXJECT II device; do not remove the device from the package.
Turn the package over. Press straight down to fully insert the clear plastic spike through the diluent vial stopper. Grip the BAXJECT II package at its edge and pull the package off the device. Do not remove the blue cap from the BAXJECT II device. Do not touch the exposed white plastic spike.
Turn the system over so that the diluent vial is on top. Quickly insert the white plastic spike fully into the concentrate vial stopper by pushing straight down. The vacuum will draw the diluent into the concentrate vial.
Swirl gently until the powder is completely dissolved. The solution should be clear and colorless.
Connect a plastic syringe to the BAXJECT II device. Do not inject air. Turn the system upside down so the concentrate vial is on top.
Pull the plunger back slowly to draw the factor concentrate into the syringe. Disconnect the syringe.
The BAXJECT II device is intended for use with a single vial of concentrate and diluent only; therefore, reconstituting and withdrawing a second vial into the syringe requires a second BAXJECT II device. If a patient is to receive more than 1 vial, the contents of multiple vials may be drawn into the same syringe.
Storage: Administer within 3 hours of reconstitution. Do not refrigerate.

Rebinyn
Bring concentrate and diluent to room temperature. Use aseptic technique to reconstitute.
Remove the protective paper from the vial adapter, but do not remove the vial adapter from the protective cap.
Place the vial on a solid surface. While holding the protective cap, place the vial adapter over the concentrate vial and press down firmly until the vial adapter spike penetrates the rubber stopper.
Remove the protective cap from the vial adapter.
Grasp the plunger rod. 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 prefilled diluent syringe until resistance is felt.
Break off the syringe cap from the prefilled diluent syringe by snapping the perforation of the cap.
Connect the prefilled diluent syringe to the vial adapter by turning it clockwise until it is secured.
Push the plunger rod to slowly inject all the diluent into the vial.
Without removing the syringe, gently swirl the concentrate vial until all of the powder is dissolved. The solution should be clear and have no particles.
Invert the concentrate vial and slowly draw the solution into the syringe. Detach the syringe from the vial adapter and attach to the Luer end of an infusion needle set.
If more than 1 vial of concentrate per infusion is required, reconstitute each vial as detailed above.
Storage: Administer immediately. May store the reconstituted solution in the vial with the vial adapter and syringe attached at room temperature (not to exceed 30 degrees C [86 degrees F]) for up to 4 hours.

Intermittent IV Infusion
AlphaNine SD
Administer at a rate not to exceed 10 mL/minute.

Alprolix
Determine rate of administration by the patient's comfort level; do not to exceed 10 mL/minute.

Bebulin
Determine rate of administration by the patient's comfort level; do not to exceed 2 mL/minute.

BeneFIX
Determine rate of administration by the patient's comfort level; infuse over several minutes.

Idelvion
Determine rate of administration by the patient's comfort level; do not to exceed 10 mL/minute.

Ixinity
Determine rate of administration by the patient's comfort level; usually administered over 5 minutes, do not to exceed 10 mL/minute.

Mononine
Determine rate of administration by the patient's comfort level; administer Mononine at a rate of approximately 2 mL/minute when reconstituted to approximately 100 International Units/mL (as directed by FDA-approved labeling). Administration rates up to 225 International Units/minute have been regularly tolerated.

Profilnine SD
Administer at a rate not to exceed 10 mL/minute.

Rixubis
Administer at a rate not to exceed 10 mL/minute.

Rebinyn
Infuse slowly over 1 to 4 minutes.

Continuous IV Infusion
NOTE: Factor IX is not approved by the FDA for continuous infusion.
BeneFIX
In 1 study, BeneFIX was reconstituted to a final concentration of 100 International Units/mL using Sterile Water for Injection; the solution was drawn into 50 mL Luer lock syringes. In some patients, 4 units/mL of unfractionated heparin was added to minimize thrombophlebitis.
The solution was administered using a syringe driver. In addition, 0.9% Sodium Chloride Injection (via an IVAC pump and Y-site connector) was administered at a rate of 10 to 100 mL/hour.
Storage: Syringes were stored for up to 3 days prior to use and were kept at room temperature for 24 hours or less. Stability data indicate the solution (with or without heparin) retained 90% of its clinical activity for up to 14 days when stored at 4 degrees C. When stored at room temperature, 90% of activity was retained for 4 days, and 80% of activity was retained for 6 days.

Mononine
In 1 study, Mononine was reconstituted to a concentration of 100 units/mL following the manufacturer’s directions. Subsequent dilution to either 10 units/mL or 5 units/mL with 0.9% Sodium Chloride Injection was permitted at the discretion of the investigator.
The continuous infusion was administered using an approved IV infusion pump; a filtered line for infusion was not required.
Storage: The reconstituted solution was discarded and replaced every 12 hours.

Adverse Reactions

Severe

anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known
nephrotic syndrome / Delayed / Incidence not known
stroke / Early / Incidence not known
disseminated intravascular coagulation (DIC) / Delayed / Incidence not known
thrombosis / Delayed / Incidence not known
pulmonary embolism / Delayed / Incidence not known
myocardial infarction / Delayed / Incidence not known
bronchospasm / Rapid / Incidence not known
cyanosis / Early / Incidence not known

Moderate

antibody formation / Delayed / 0-21.0
dyspnea / Early / 3.2-3.2
phlebitis / Rapid / 1.5-1.5
hypoxia / Early / 1.5-1.5
blurred vision / Early / 1.5-1.5
depression / Delayed / 1.3-1.3
hypotension / Rapid / 0.7-0.7
palpitations / Early / 0.7-0.7
hematuria / Delayed / 0.7-0.7
sinus tachycardia / Rapid / Incidence not known
wheezing / Rapid / Incidence not known
erythema / Early / Incidence not known
hepatitis / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known

Mild

headache / Early / 1.3-10.8
dizziness / Early / 0.7-7.7
injection site reaction / Rapid / 0.7-7.7
nausea / Early / 6.2-6.2
rash / Early / 0.9-6.2
dysgeusia / Early / 0.7-4.6
fever / Early / 3.1-3.1
flushing / Rapid / 3.1-3.1
pruritus / Rapid / 3.0-3.0
chills / Rapid / 1.6-1.6
vomiting / Early / 1.5-1.5
drowsiness / Early / 1.5-1.5
tremor / Early / 1.5-1.5
cough / Delayed / 1.5-1.5
paresthesias / Delayed / 1.3-1.3
influenza / Delayed / 1.3-1.3
asthenia / Delayed / 1.3-1.3
lethargy / Early / 1.3-1.3
halitosis / Early / 0.7-0.7
anorexia / Delayed / 0.7-0.7
fatigue / Early / 0.7-0.7
abdominal pain / Early / Incidence not known
diaphoresis / Early / Incidence not known
restlessness / Early / Incidence not known
urticaria / Rapid / Incidence not known
infection / Delayed / Incidence not known

Common Brand Names

Bebulin, Profilnine, Profilnine SD

Dea Class

Description

Coagulation factor available as both plasma-derived and recombinant products
Used for control and prevention of bleeding in patients with hemophilia B
Recombinant products are often first choice of treatment due to better safety profile; several products link factor IX to another molecule to extend half-life

Dosage And Indications

For the prevention and control of hemorrhage in patients with hemophilia B (congenital factor IX deficiency or Christmas disease).
NOTE: Factor IX concentration may be expressed as % or International Units/dL.
Intravenous dosage (general dosing for recombinant products) Adults

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.8 International Units/dL. For joint bleeding, the circulating factor IX activity required is 40% to 60% for 1 to 2 days or longer if response is inadequate. For superficial muscle without neurovascular compromise, the circulating factor IX activity required is 40% to 60% for 2 to 3 days or longer if response is inadequate. For iliopsoas and deep muscle with neurovascular compromise or substantial blood loss, the circulating factor IX activity required is 60% to 80% for 1 to 2 days, then 30% to 60% for 3 to 5 days (sometimes longer as secondary prophylaxis during physiotherapy). For CNS/head bleeding, the circulating factor IX activity required is 60% to 80% for 1 to 7 days, then 30% for 8 to 21 days. For throat and neck bleeding, the circulating factor IX activity required is 60% to 80% for 1 to 7 days, then 30% for 8 to 14 days. For gastrointestinal bleeding, the circulating factor IX activity required is 60% to 80% for 7 to 14 days, then 30% (duration unspecified). For renal bleeding, the circulating factor IX activity required is 40% for 3 to 5 days. For deep lacerations, the circulating factor IX activity required is 40% for 5 to 7 days. The following formula may be used to estimate the initial dose: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x 1.25 (International Units/kg per International Units/dL). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Adolescents 15 to 17 years

Infants, Children, and Adolescents younger than 15 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.7 International Units/dL. For joint bleeding, the circulating factor IX activity required is 40% to 60% for 1 to 2 days or longer if response is inadequate. For superficial muscle without neurovascular compromise, the circulating factor IX activity required is 40% to 60% for 2 to 3 days or longer if response is inadequate. For iliopsoas and deep muscle with neurovascular compromise or substantial blood loss, the circulating factor IX activity required is 60% to 80% for 1 to 2 days, then 30% to 60% for 3 to 5 days (sometimes longer as secondary prophylaxis during physiotherapy). For CNS/head bleeding, the circulating factor IX activity required is 60% to 80% for 1 to 7 days, then 30% for 8 to 21 days. For throat and neck bleeding, the circulating factor IX activity required is 60% to 80% for 1 to 7 days, then 30% for 8 to 14 days. For gastrointestinal bleeding, the circulating factor IX activity required is 60% to 80% for 7 to 14 days, then 30% (duration unspecified). For renal bleeding, the circulating factor IX activity required is 40% for 3 to 5 days. For deep lacerations, the circulating factor IX activity required is 40% for 5 to 7 days. The following formula may be used to estimate the initial dose: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x 1.43 (International Units/kg per International Units/dL). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Intravenous dosage (general dosing for plasma-derived products) Adults

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 1 International Unit/dL. For joint bleeding, the circulating factor IX activity required is 40% to 60% for 1 to 2 days or longer if response is inadequate. For superficial muscle without neurovascular compromise, the circulating factor IX activity required is 40% to 60% for 2 to 3 days or longer if response is inadequate. For iliopsoas and deep muscle with neurovascular compromise or substantial blood loss, the circulating factor IX activity required is 60% to 80% for 1 to 2 days, then 30% to 60% for 3 to 5 days (sometimes longer as secondary prophylaxis during physiotherapy). For CNS/head bleeding, the circulating factor IX activity required is 60% to 80% for 1 to 7 days, then 30% for 8 to 21 days. For throat and neck bleeding, the circulating factor IX activity required is 60% to 80% for 1 to 7 days, then 30% for 8 to 14 days. For gastrointestinal bleeding, the circulating factor IX activity required is 60% to 80% for 7 to 14 days, then 30% (duration unspecified). For renal bleeding, the circulating factor IX activity required is 40% for 3 to 5 days. For deep lacerations, the circulating factor IX activity required is 40% for 5 to 7 days. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Infants, Children, and Adolescents

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 1 International Unit/dL. For joint bleeding, the circulating factor IX activity required is 40% to 60% for 1 to 2 days or longer if response is inadequate. For superficial muscle without neurovascular compromise, the circulating factor IX activity required is 40% to 60% for 2 to 3 days or longer if response is inadequate. For iliopsoas and deep muscle with neurovascular compromise or substantial blood loss, the circulating factor IX activity required is 60% to 80% for 1 to 2 days, then 30% to 60% for 3 to 5 days (sometimes longer as secondary prophylaxis during physiotherapy). For CNS/head bleeding, the circulating factor IX activity required is 60% to 80% for 1 to 7 days, then 30% for 8 to 21 days. For throat and neck bleeding, the circulating factor IX activity required is 60% to 80% for 1 to 7 days, then 30% for 8 to 14 days. For gastrointestinal bleeding, the circulating factor IX activity required is 60% to 80% for 7 to 14 days, then 30% (duration unspecified). For renal bleeding, the circulating factor IX activity required is 40% for 3 to 5 days. For deep lacerations, the circulating factor IX activity required is 40% for 5 to 7 days. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Intravenous dosage (AlphaNine SD) Adults

Adolescents 17 years

Infants†, Children†, and Adolescents younger than 17 years†

Safety and efficacy have not been established; however, per FDA-approved product labeling, anecdotal evaluation of use in pediatric patients younger than 17 years indicates no safety and efficacy differences between pediatric and adult populations. Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 1 International Unit/dL. For minor bleeding (e.g., bruises, cuts or scrapes, uncomplicated joint hemorrhage), the circulating factor IX activity required is at least 20% to 30%; repeat dose every 12 hours until bleeding stops and healing is achieved (1 to 2 days). For moderate bleeding (e.g., nose bleeds, mouth and gum bleeds, hematuria), the circulating factor IX activity required is 25% to 50%; repeat dose every 12 hours until healing is achieved (2 to 7 days, on average). For major bleeding (e.g., joint/muscle hemorrhage, major trauma, hematuria, intracranial and intraperitoneal bleeding), the circulating factor IX activity should be at least 50% for at least 3 to 5 days (dose given twice daily), then maintained at 20% (dose given twice daily) until healing is achieved (up to 10 days). The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x 1 (International Unit/kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Neonates†

Safety and efficacy have not been established; however, per FDA-approved product labeling, anecdotal evaluation of use in pediatric patients younger than 17 years (exact age unspecified) indicates no safety and efficacy differences between pediatric and adult populations. Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 1 International Unit/dL. For minor bleeding (e.g., bruises, cuts or scrapes, uncomplicated joint hemorrhage), the circulating factor IX activity required is at least 20% to 30%; repeat dose every 12 hours until bleeding stops and healing is achieved (1 to 2 days). For moderate bleeding (e.g., nose bleeds, mouth and gum bleeds, hematuria), the circulating factor IX activity required is 25% to 50%; repeat dose every 12 hours until healing is achieved (2 to 7 days, on average). For major bleeding (e.g., joint/muscle hemorrhage, major trauma, hematuria, intracranial and intraperitoneal bleeding), the circulating factor IX activity should be at least 50% for at least 3 to 5 days (dose given twice daily), then maintained at 20% (dose given twice daily) until healing is achieved (up to 10 days). The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x 1 (International Unit/kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Intravenous dosage (Alprolix) Adults

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating level of factor IX by 1 International Unit/dL. For minor or moderate bleeding (e.g., uncomplicated hemarthrosis, superficial muscle (except iliopsoas) without neurovascular compromise, superficial soft tissue, mucous membrane), the circulating factor IX activity required is 30% to 60%; repeat every 48 hours if there is further evidence of bleeding. For major bleeding (e.g., iliopsoas and deep muscle with neurovascular injury, or substantial blood loss; pharyngeal, retropharyngeal, retroperitoneal, CNS), the circulating factor IX activity required is 80% to 100%; consider a repeat dose after 6 to 10 hours and then every 24 hours for the first 3 days. Due to the long half-life, the dose may be reduced and frequency of dosing may be extended after day 3 to every 48 hours or longer until bleeding stops and healing is achieved. Verify the target concentration has been achieved for major bleeds. The following formulas may be used to estimate the required dose or the in vivo peak increase in factor IX concentration: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL) or Estimated Increment of Factor IX (International Units/dL or % of normal) = [Total Dose (International Units)/Body Weight (kg)] x Recovery (International Units/dL per International Unit/kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Children and Adolescents 6 to 17 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 1 International Unit/dL. Pediatric patients younger than 12 years may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. For minor or moderate bleeding (e.g., uncomplicated hemarthrosis, superficial muscle (except iliopsoas) without neurovascular compromise, superficial soft tissue, mucus membrane), the circulating factor IX activity required is 30% to 60%; repeat every 48 hours if there is further evidence of bleeding. For major bleeding (e.g., iliopsoas and deep muscle with neurovascular injury, or substantial blood loss; pharyngeal, retropharyngeal, retroperitoneal, CNS), the circulating factor IX activity required is 80% to 100%; consider a repeat dose after 6 to 10 hours and then every 24 hours for the first 3 days. Due to the long half-life, the dose may be reduced and frequency of dosing may be extended after day 3 to every 48 hours or longer until bleeding stops and healing is achieved. Verify the target concentration has been achieved for major bleeds. The following formulas may be used to estimate the required dose or the in vivo peak increase in factor IX concentration: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL) or Estimated Increment of Factor IX (International Units/dL or % of normal) = [Total Dose (International Units)/Body Weight (kg)] x Recovery (International Units/dL per International Unit/kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Infants and Children younger than 6 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.6 International Units/dL. Pediatric patients younger than 12 years, especially those younger than 6 years, may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. For minor or moderate bleeding (e.g., uncomplicated hemarthrosis, superficial muscle (except iliopsoas) without neurovascular compromise, superficial soft tissue, mucus membrane), the circulating factor IX activity required is 30% to 60%; repeat every 48 hours if there is further evidence of bleeding. For major bleeding (e.g., iliopsoas and deep muscle with neurovascular injury, or substantial blood loss; pharyngeal, retropharyngeal, retroperitoneal, CNS), the circulating factor IX activity required is 80% to 100%; consider a repeat dose after 6 to 10 hours and then every 24 hours for the first 3 days. Due to the long half-life, the dose may be reduced and frequency of dosing may be extended after day 3 to every 48 hours or longer until bleeding stops and healing is achieved. Verify the target concentration has been achieved for major bleeds. The following formulas may be used to estimate the required dose or the in vivo peak increase in factor IX concentration: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL) or Estimated Increment of Factor IX (International Units/dL or % of normal) = [Total Dose (International Units)/Body Weight (kg)] x Recovery (International Units/dL per International Unit/kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Neonates

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.6 International Units/dL. Compared to older patients, pediatric patients younger than 12 years, especially those younger than 6 years, may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. Specific neonatal dosing is not provided in the FDA-approved product labeling. For minor or moderate bleeding (e.g., uncomplicated hemarthrosis, superficial muscle (except iliopsoas) without neurovascular compromise, superficial soft tissue, mucus membranes), the circulating factor IX activity required is 30% to 60%; repeat every 48 hours if there is further evidence of bleeding. For major bleeding (e.g., iliopsoas and deep muscle with neurovascular injury, or substantial blood loss; pharyngeal, retropharyngeal, retroperitoneal, CNS), the circulating factor IX activity required is 80% to 100%; consider a repeat dose after 6 to 10 hours and then every 24 hours for the first 3 days. Due to the long half-life, the dose may be reduced and frequency of dosing may be extended after day 3 to every 48 hours or longer until bleeding stops and healing is achieved. Verify the target concentration has been achieved for major bleeds. The following formulas may be used to estimate the required dose or the in vivo peak increase in factor IX concentration: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL) or Estimated Increment of Factor IX (International Units/dL or % of normal) = [Total Dose (International Units)/Body Weight (kg)] x Recovery (International Units/dL per International Unit/kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Intravenous dosage (Bebulin) Adults

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating level of factor IX by 0.8 International Units/dL. For minor bleeding (e.g., early hemarthrosis, minor epistaxis, gingival bleeding, mild hematuria), the circulating factor IX activity required is 20% (typical initial dose is 25 to 35 International Units/kg); a single dose is usually sufficient but can be repeated in 24 hours if necessary. For moderate bleeding (e.g., severe joint bleeding, early hematoma, major open bleeding, minor trauma, minor hemoptysis, hematemesis, and melena, major hematuria), the circulating factor IX activity required is 40% (typical initial dose is 50 to 65 International Units/kg); administer at approximately 24 hour intervals for 2 days or until healing is achieved. For major bleeding (e.g., severe hematoma, major trauma, severe hemoptysis, hematemesis, and melena), the circulating factor IX activity required is 60% or more (typical initial dose is 75 to 90 International Units/kg); administer at approximately 24 hour intervals for 2 to 3 days or until healing is achieved. For maintenance therapy, usually two-thirds of the initial dose is administered. The following formula may be used to estimate the required dose: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x 1.2 (International Units/kg per International Unit/dL). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Intravenous dosage (BeneFIX) Adults

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating activity of factor IX by 0.8 +/- 0.2 International Units/dL (range: 0.4 to 1.2 International Units/dL). For minor bleeding (e.g., uncomplicated hemarthrosis, superficial muscle, soft tissue), the circulating factor IX activity required is 20% to 30%; repeat dose every 12 to 24 hours for 1 to 2 days. For moderate bleeding (e.g., intramuscle or soft tissue with dissection, mucous membranes, hematuria), the circulating factor IX activity required is 25% to 50%; repeat dose every 12 to 24 hours until bleeding stops and healing begins (approximately 2 to 7 days). For major bleeding (e.g., pharyngeal, retropharyngeal, retroperitoneal, CNS), the circulating factor IX activity required is 50% to 100%; repeat dose every 12 to 24 hours for 7 to 10 days. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). To estimate the dose with an average incremental recovery of 0.8 International Units/dL, the following formula may be used: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x 1.3 (International Units/kg per International Units/dL). In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Adolescents 15 to 17 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating activity of factor IX by 0.8 +/- 0.2 International Units/dL (range: 0.4 to 1.2 International Units/dL). For minor bleeding (e.g., uncomplicated hemarthrosis, superficial muscle, soft tissue), the circulating factor IX activity required is 20% to 30%; repeat dose every 12 to 24 hours for 1 to 2 days. For moderate bleeding (e.g., intramuscle or soft tissue with dissection, mucous membranes, hematuria), the circulating factor IX activity required is 25% to 50%; repeat dose every 12 to 24 hours until bleeding stops and healing begins (approximately 2 to 7 days). For major bleeding (e.g., pharyngeal, retropharyngeal, retroperitoneal, CNS), the circulating factor IX activity required is 50% to 100%; repeat dose every 12 to 24 hours for 7 to 10 days. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). To estimate the dose with an average incremental recovery of 0.8 International Units/dL, the following formula may be used: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x 1.3 (International Units/kg per International Units/dL). In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Infants, Children, and Adolescents younger than 15 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating activity of factor IX by 0.7 +/- 0.3 International Units/dL (range: 0.2 to 2.1 International Units/dL). Compared to older patients, patients younger than 15 years may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. For minor bleeding (e.g., uncomplicated hemarthrosis, superficial muscle, soft tissue), the circulating factor IX activity required is 20% to 30%; repeat dose every 12 to 24 hours for 1 to 2 days. For moderate bleeding (e.g., intramuscle or soft tissue with dissection, mucous membranes, hematuria), the circulating factor IX activity required is 25% to 50%; repeat dose every 12 to 24 hours until bleeding stops and healing begins (approximately 2 to 7 days). For major bleeding (e.g., pharyngeal, retropharyngeal, retroperitoneal, CNS), the circulating factor IX activity required is 50% to 100%; repeat dose every 12 to 24 hours for 7 to 10 days. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). To estimate the dose with an average incremental recovery of 0.7 International Units/dL, the following formula may be used: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x 1.4 (International Units/kg per International Units/dL). In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Neonates

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating activity of factor IX by 0.7 +/- 0.3 International Units/dL (range: 0.2 to 2.1 International Units/dL). Compared to older patients, patients younger than 15 years may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. Specific neonatal dosing is not provided in the FDA-approved product labeling. For minor bleeding (e.g., uncomplicated hemarthrosis, superficial muscle, soft tissue), the circulating factor IX activity required is 20% to 30%; repeat dose every 12 to 24 hours for 1 to 2 days. For moderate bleeding (e.g., intramuscle or soft tissue with dissection, mucous membranes, hematuria), the circulating factor IX activity required is 25% to 50%; repeat dose every 12 to 24 hours until bleeding stops and healing begins (approximately 2 to 7 days). For major bleeding (e.g., pharyngeal, retropharyngeal, retroperitoneal, CNS), the circulating factor IX activity required is 50% to 100%; repeat dose every 12 to 24 hours for 7 to 10 days. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). To estimate the dose with an average incremental recovery of 0.7 International Units/dL, the following formula may be used: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x 1.4 (International Units/kg per International Units/dL). In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Intravenous dosage (Idelvion) Adults

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 1.3 International Units/dL. For minor to moderate bleeding (e.g., uncomplicated hemarthrosis, muscle bleeding except iliopsoas, oral bleeding), the circulating factor IX activity required is 30% to 60%. A single dose should be sufficient; repeat as needed every 48 to 72 hours until bleeding stops and healing is achieved. For major bleeding (e.g., life- or limb-threatening hemorrhage, deep muscle bleeding including iliopsoas, intracranial, retropharyngeal), the circulating factor IX activity required is 60% to 100%. Repeat dose every 48 to 72 hours for 7 to 14 days, until bleeding stops and healing is achieved; administer maintenance dose weekly. The following formulas may be used to estimate the required dose or the in vivo peak increase in factor IX concentration: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x (Reciprocal of Recovery [International Units/kg per International Units/dL]) or Estimated Increment of Factor IX (International Units/dL or % of normal) = Dose (International Units) x Recovery (International Units/dL per International Unit/kg)/Body Weight (kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Children and Adolescents 12 to 17 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 1.3 International Units/dL. Compared to adults, pediatric patients may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. For minor to moderate bleeding (e.g., uncomplicated hemarthrosis, muscle bleeding except iliopsoas, oral bleeding), the circulating factor IX activity required is 30% to 60%. A single dose should be sufficient; repeat as needed every 48 to 72 hours until bleeding stops and healing is achieved. For major bleeding (e.g., life- or limb-threatening hemorrhage, deep muscle bleeding including iliopsoas, intracranial, retropharyngeal), the circulating factor IX activity required is 60% to 100%. Repeat dose every 48 to 72 hours for 7 to 14 days, until bleeding stops and healing is achieved; administer maintenance dose weekly. The following formulas may be used to estimate the required dose or the in vivo peak increase in factor IX concentration: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x (Reciprocal of Recovery [International Units/kg per International Units/dL]) or Estimated Increment of Factor IX (International Units/dL or % of normal) = Dose (International Units) x Recovery (International Units/dL per International Unit/kg)/Body Weight (kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Infants and Children younger than 12 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 1 International Unit/dL. Compared to adults, pediatric patients may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. For minor to moderate bleeding (e.g., uncomplicated hemarthrosis, muscle bleeding except iliopsoas, oral bleeding), the circulating factor IX activity required is 30% to 60%. A single dose should be sufficient; repeat as needed every 48 to 72 hours until bleeding stops and healing is achieved. For major bleeding (e.g., life- or limb-threatening hemorrhage, deep muscle bleeding including iliopsoas, intracranial, retropharyngeal), the circulating factor IX activity required is 60% to 100%. Repeat dose every 48 to 72 hours for 7 to 14 days, until bleeding stops and healing is achieved; administer maintenance dose weekly. The following formulas may be used to estimate the required dose or the in vivo peak increase in factor IX concentration: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x (Reciprocal of Recovery [International Units/kg per International Units/dL]) or Estimated Increment of Factor IX (International Units/dL or % of normal) = Dose (International Units) x Recovery (International Units/dL per International Unit/kg)/Body Weight (kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Neonates

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 1 International Unit/dL. Compared to adults, pediatric patients may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. Specific neonatal dosing is not provided in the FDA-approved product labeling. For minor to moderate bleeding (e.g., uncomplicated hemarthrosis, muscle bleeding except iliopsoas, oral bleeding), the circulating factor IX activity required is 30% to 60%. A single dose should be sufficient; repeat as needed every 48 to 72 hours until bleeding stops and healing is achieved. For major bleeding (e.g., life- or limb-threatening hemorrhage, deep muscle bleeding including iliopsoas, intracranial, retropharyngeal), the circulating factor IX activity required is 60% to 100%. Repeat dose every 48 to 72 hours for 7 to 14 days, until bleeding stops and healing is achieved; administer maintenance dose weekly. The following formulas may be used to estimate the required dose or the in vivo peak increase in factor IX concentration: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x (Reciprocal of Recovery [International Units/kg per International Units/dL]) or Estimated Increment of Factor IX (International Units/dL or % of normal) = Dose (International Units) x Recovery (International Units/dL per International Unit/kg)/Body Weight (kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Intravenous dosage (Ixinity) Adults

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.98 International Units/dL. For minor bleeding (e.g., early bleeds, uncomplicated hemarthroses and superficial muscle bleeds except iliopsoas, other soft tissue), the circulating factor IX activity required is 30% to 60%; repeat dose every 24 hours for 1 to 3 days until healing is achieved. For moderate bleeding (hemarthrosis of longer duration, recurrent hemarthrosis, mucous membranes, deep lacerations, hematuria), the circulating factor IX activity required is 40% to 60%; repeat dose every 24 hours for 2 to 7 days until healing is achieved. For major bleeding (e.g., iliopsoas, deep muscle with neurovascular injury, substantial blood loss, CNS, pharyngeal, retropharyngeal, retroperitoneal), the circulating factor IX activity required is 60% to 100%; repeat dose every 12 to 24 hours for 2 to 14 days until healing is achieved. The following formula may be used to estimate the initial dose: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). To estimate the dose with an average incremental recovery of 0.98 International Units/dL, the following formula may be used: Dose (International Units) = Body Weight (kg) x Desired Factor IX Increase (International Units/dL or % of normal) x 1.02 dL/kg. In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays, due to the wide range of interindividual differences in incremental recovery. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Children and Adolescents 12 to 17 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.98 International Units/dL. For minor bleeding (e.g., early bleeds, uncomplicated hemarthroses and superficial muscle bleeds except iliopsoas, other soft tissue), the circulating factor IX activity required is 30% to 60%; repeat dose every 24 hours for 1 to 3 days until healing is achieved. For moderate bleeding (hemarthrosis of longer duration, recurrent hemarthrosis, mucous membranes, deep lacerations, hematuria), the circulating factor IX activity required is 40% to 60%; repeat dose every 24 hours for 2 to 7 days until healing is achieved. For major bleeding (e.g., iliopsoas, deep muscle with neurovascular injury, substantial blood loss, CNS, pharyngeal, retropharyngeal, retroperitoneal), the circulating factor IX activity required is 60% to 100%; repeat dose every 12 to 24 hours for 2 to 14 days until healing is achieved. The following formula may be used to estimate the initial dose: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). To estimate the dose with an average incremental recovery of 0.98 International Units/dL, the following formula may be used: Dose (International Units) = Body Weight (kg) x Desired Factor IX Increase (International Units/dL or % of normal) x 1.02 dL/kg. In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays, due to the wide range of interindividual differences in incremental recovery. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Intravenous dosage (Mononine) Adults

Infants, Children, and Adolescents

Neonates

Intravenous dosage (Profilnine) Adults

Intravenous dosage (Rixubis) Adults

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.9 International Units/dL. For minor bleeding (e.g., uncomplicated hemarthrosis, superficial muscular or soft tissue), the circulating factor IX activity required is 20% to 30%; repeat dose every 12 to 24 hours for at least 1 day until healing is achieved. For moderate bleeding (e.g., intramuscular or soft tissue with dissection, mucous membranes, hematuria), the circulating factor IX activity required is 25% to 50%; repeat dose every 12 to 24 hours for 2 to 7 days until bleeding stops and healing is achieved. For major bleeding (e.g., pharyngeal, retropharyngeal, retroperitoneal, CNS), the circulating factor IX activity required is 50% to 100%; repeat dose every 12 to 24 hours for 7 to 10 days until bleeding stops and healing is achieved. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). For an incremental recovery of 0.9 International Units/dL of plasma (0.9% of normal), the dose is calculated as follows: Dose (International Units) = Body Weight (kg) x Desired Factor IX Increase (International Units/dL or % of normal) x 1.1 dL/kg. In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays, due to the wide range of interindividual differences in incremental recovery. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Children and Adolescents 12 to 17 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.9 International Units/dL. For minor bleeding (e.g., uncomplicated hemarthrosis, superficial muscular or soft tissue), the circulating factor IX activity required is 20% to 30%; repeat dose every 12 to 24 hours for at least 1 day until healing is achieved. For moderate bleeding (e.g., intramuscular or soft tissue with dissection, mucous membranes, hematuria), the circulating factor IX activity required is 25% to 50%; repeat dose every 12 to 24 hours for 2 to 7 days until bleeding stops and healing is achieved. For major bleeding (e.g., pharyngeal, retropharyngeal, retroperitoneal, CNS), the circulating factor IX activity required is 50% to 100%; repeat dose every 12 to 24 hours for 7 to 10 days until bleeding stops and healing is achieved. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). For an incremental recovery of 0.9 International Units/dL of plasma (0.9% of normal), the dose is calculated as follows: Dose (International Units) = Body Weight (kg) x Desired Factor IX Increase (International Units/dL or % of normal) x 1.1 dL/kg. In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays, due to the wide range of interindividual differences in incremental recovery. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Infants and Children younger than 12 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.7 International Units/dL. Compared to older patients, pediatric patients younger than 12 years may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. For minor bleeding (e.g., uncomplicated hemarthrosis, superficial muscular or soft tissue), the circulating factor IX activity required is 20% to 30%; repeat dose every 12 to 24 hours for at least 1 day until healing is achieved. For moderate bleeding (e.g., intramuscular or soft tissue with dissection, mucous membranes, hematuria), the circulating factor IX activity required is 25% to 50%; repeat dose every 12 to 24 hours for 2 to 7 days until bleeding stops and healing is achieved. For major bleeding (e.g., pharyngeal, retropharyngeal, retroperitoneal, CNS), the circulating factor IX activity required is 50% to 100%; repeat dose every 12 to 24 hours for 7 to 10 days until bleeding stops and healing is achieved. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). For an incremental recovery of 0.7 International Units/dL of plasma (0.7% of normal), the dose is calculated as follows: Dose (International Units) = Body Weight (kg) x Desired Factor IX Increase (International Units/dL or % of normal) x 1.4 dL/kg. In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays, due to the wide range of interindividual differences in incremental recovery. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Neonates

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.7 International Units/dL. Compared to older patients, pediatric patients younger than 12 years may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. Specific neonatal dosing is not provided in the FDA-approved product labeling. For minor bleeding (e.g., uncomplicated hemarthrosis, superficial muscular or soft tissue), the circulating factor IX activity required is 20% to 30%; repeat dose every 12 to 24 hours for at least 1 day until healing is achieved. For moderate bleeding (e.g., intramuscular or soft tissue with dissection, mucous membranes, hematuria), the circulating factor IX activity required is 25% to 50%; repeat dose every 12 to 24 hours for 2 to 7 days until bleeding stops and healing is achieved. For major bleeding (e.g., pharyngeal, retropharyngeal, retroperitoneal, CNS), the circulating factor IX activity required is 50% to 100%; repeat dose every 12 to 24 hours for 7 to 10 days until bleeding stops and healing is achieved. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). For an incremental recovery of 0.7 International Units/dL of plasma (0.7% of normal), the dose is calculated as follows: Dose (International Units) = Body Weight (kg) x Desired Factor IX Increase (International Units/dL or % of normal) x 1.4 dL/kg. In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays, due to the wide range of interindividual differences in incremental recovery. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Intravenous dosage (Rebinyn) Adults

Dose and duration of treatment depend on the location and extent of bleeding and the patient's clinical condition. For minor and moderate bleeding (e.g., uncomplicated joint bleeds, minor muscular bleeds, mucosal or subcutaneous bleeds), a single 40 International Unit/kg IV dose should be sufficient; additional doses can be given if needed. For major bleeding (e.g., intracranial, retroperitoneal, iliopsoas, and neck bleeds with compartment syndrome and bleeds associated with a significant decrease in hemoglobin), administer 80 International Units/kg IV as a single dose; additional doses of 40 International Units/kg IV can be given if needed.

Infants, Children, and Adolescents

Continuous Intravenous Infusion dosage† Adults

Dosage is variable. Limited data suggest an initial IV bolus followed by continuous IV infusion (adjusted to maintain factor IX activity concentrations 40% to 100% depending on clinical situation) has been shown to be safe and cost-effective. Protocols vary based on pharmacokinetics of the various factor IX products in each patient; many patients have had baseline pharmacokinetic studies performed prior to surgery. The continuous infusion dosage used in several studies was calculated by multiplying the clearance (mL/kg/hour) by desired factor IX increase at steady state (units/mL). In clinical trials, a total of 42 patients receiving 49 continuous infusions (38 for surgeries) over a range of 1 to 54 days experienced excellent or good hemostatic effect; the bolus dose ranged from 12.5 to 155 International Units/kg IV, and the continuous IV rate of infusion was 1.7 to 8.6 International Units/kg/hour. The goal factor IX concentrations ranged from 40% to 100%; monitoring of factor IX activity concentrations occurred 1 to 2 times/day.

Children and Adolescents

tive. Protocols vary based on pharmacokinetics of the various factor IX products in each patient; many patients have had baseline pharmacokinetic studies performed prior to surgery. The continuous infusion dosage used in several studies was calculated by multiplying the clearance (mL/kg/hour) by desired factor IX increase at steady state (units/mL). In clinical trials, a total of 42 patients receiving 49 continuous infusions (38 for surgeries) over a range of 1 to 54 days experienced excellent or good hemostatic effect; the bolus dose ranged from 12.5 to 155 International Units/kg IV, and the continuous IV rate of infusion was 1.7 to 8.6 International Units/kg/hour. The goal factor IX concentrations ranged from 40% to 100%; monitoring of factor IX activity concentrations occurred 1 to 2 times/day.

For the perioperative management of surgical bleeding in patients with hemophilia B.
NOTE: Factor IX concentration may be expressed as % or International Units/dL.
Intravenous dosage (general dosing for recombinant products) Adults

Adolescents 15 to 17 years

Infants, Children, and Adolescents younger than 15 years

Intravenous dosage (general dosing for plasma-derived products) Adults

Infants, Children, and Adolescents

Intravenous dosage (AlphaNine SD) Adults

Adolescents 17 years

Infants†, Children†, and Adolescents younger than 17 years†

Safety and efficacy have not been established; however, per FDA-approved product labeling, anecdotal evaluation of use in pediatric patients younger than 17 years indicates no safety and efficacy differences between pediatric and adult populations. Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 1 International Unit/dL. For minor surgery (e.g., dental extraction), the circulating factor IX activity required is 25% to 50%; repeat dose every 12 hours until healing is achieved (2 to 7 days on average). For major surgery, the circulating factor IX activity required is 50% to 100%; repeat every 12 hours for 7 to 10 days or until healing is achieved. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x 1 (International Unit/kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Neonates†

Safety and efficacy have not been established; however, per FDA-approved product labeling, anecdotal evaluation of use in pediatric patients younger than 17 years (exact age unspecified) indicates no safety and efficacy differences between pediatric and adult populations. Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 1 International Unit/dL. For minor surgery, the circulating factor IX activity required is 25% to 50%; repeat dose every 12 hours until healing is achieved (2 to 7 days on average). For major surgery, the circulating factor IX activity required is 50% to 100%; repeat every 12 hours for 7 to 10 days or until healing is achieved. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x 1 (International Unit/kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Intravenous dosage (Alprolix) Adults

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 1 International Unit/dL. For minor surgery (including uncomplicated tooth extraction), the circulating factor IX activity required is 50% to 80%; a single infusion may be sufficient. Repeat as needed after 24 to 48 hours until bleeding stops and healing is achieved. For major surgery, the circulating factor IX activity required is 60% to 100% (initial concentration); consider a repeat dose after 6 to 10 hours and then every 24 hours for the first 3 days. Due to the long half-life, the dose may be reduced and frequency of dosing in the postsurgical setting may be extended after day 3 to every 48 hours or longer until bleeding stops and healing is achieved. Consider determining the patient's in vivo recovery prior to elective major surgery and verify the target concentration has been achieved prior to surgery. The following formulas may be used to estimate the required dose or the expected in vivo peak increase in factor IX concentration: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL) or Estimated Increment of Factor IX (International Units/dL or % of normal) = [Total Dose (International Units)/Body Weight (kg)] x Recovery (International Units/dL per International Unit/kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Children and Adolescents 6 to 17 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 1 International Unit/dL. Pediatric patients younger than 12 years may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. For minor surgery (including uncomplicated dental extraction), the circulating factor IX activity required is 50% to 80%; a single infusion may be sufficient. Repeat as needed after 24 to 48 hours until bleeding stops and healing is achieved. For major surgery, the circulating factor IX activity required is 60% to 100% (initial concentration); consider a repeat dose after 6 to 10 hours and then every 24 hours for the first 3 days. Due to the long half-life, the dose may be reduced and frequency of dosing in the postsurgical setting may be extended after day 3 to every 48 hours or longer until bleeding stops and healing is achieved. Consider determining the patient's in vivo recovery prior to elective major surgery and verify the target concentration has been achieved prior to surgery. The following formulas may be used to estimate the required dose or the in vivo peak increase in factor IX concentration: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL) or Estimated Increment of Factor IX (International Units/dL or % of normal) = [Total Dose (International Units)/Body Weight (kg)] x Recovery (International Units/dL per International Unit/kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Infants and Children younger than 6 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.6 International Units/dL. Pediatric patients younger than 12 years, especially those younger than 6 years, may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. For minor surgery (including uncomplicated dental extraction), the circulating factor IX activity required is 50% to 80%; a single infusion may be sufficient. Repeat as needed after 24 to 48 hours until bleeding stops and healing is achieved. For major surgery, the circulating factor IX activity required is 60% to 100% (initial concentration); consider a repeat dose after 6 to 10 hours and then every 24 hours for the first 3 days. Due to the long half-life, the dose may be reduced and frequency of dosing in the postsurgical setting may be extended after day 3 to every 48 hours or longer until bleeding stops and healing is achieved. Consider determining the patient's in vivo recovery prior to elective major surgery and verify the target concentration has been achieved prior to surgery. The following formulas may be used to estimate the required dose or the in vivo peak increase in factor IX concentration: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL) or Estimated Increment of Factor IX (International Units/dL or % of normal) = [Total Dose (International Units)/Body Weight (kg)] x Recovery (International Units/dL per International Unit/kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Neonates

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.6 International Units/dL. Compared to older patients, pediatric patients younger than 12 years, especially those younger than 6 years, may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. Specific neonatal dosing is not provided in the FDA-approved product labeling. For minor surgery, the circulating factor IX activity required is 50% to 80%; a single infusion may be sufficient. Repeat as needed after 24 to 48 hours until bleeding stops and healing is achieved. For major surgery, the circulating factor IX activity required is 60% to 100% (initial concentration); consider a repeat dose after 6 to 10 hours and then every 24 hours for the first 3 days. Due to the long half-life, the dose may be reduced and frequency of dosing in the postsurgical setting may be extended after day 3 to every 48 hours or longer until bleeding stops and healing is achieved. Consider determining the patient's in vivo recovery prior to elective major surgery and verify the target concentration has been achieved prior to surgery. The following formulas may be used to estimate the required dose or the in vivo peak increase in factor IX concentration: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL) or Estimated Increment of Factor IX (International Units/dL or % of normal) = [Total Dose (International Units)/Body Weight (kg)] x Recovery (International Units/dL per International Unit/kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Intravenous dosage (Bebulin) Adults

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.8 International Units/dL. For minor surgery, the circulating factor IX activity required preoperatively is 40% to 60% the day of surgery and postoperatively is 20% to 40% for 7 to 14 days; administer 50 to 75 International Units/kg as a loading dose 1 hour prior to surgery and continue replacement therapy (25 to 65 International Units/kg/dose every 12 to 24 hours) for 1 to several weeks until healing is achieved. For tooth extraction, 1 infusion should be sufficient. For extraction of several teeth, replacement therapy may be necessary for up to 1 week. For major surgery, the circulating factor IX activity required preoperatively is 60% or more and postoperatively is 20% to 60% for 7 to 14 days, then 20% thereafter; administer 75 to 90 International Units/kg as a loading dose 1 hour prior to surgery and continue replacement therapy (25 to 75 International Units/kg/dose every 12 to 24 hours for the first 2 weeks, then 25 to 35 International Units/kg/dose every 24 hours thereafter) until adequate wound healing is achieved. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x 1.2 (International Units/kg per International Units/dL). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Intravenous dosage (BeneFIX) Adults

Adolescents 15 to 17 years

Infants, Children, and Adolescents younger than 15 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating activity of factor IX by 0.7 +/- 0.3 International Units/dL (range: 0.2 to 2.1 International Units/dL). Compared to older patients, patients younger than 15 years may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. For minor surgery (including dental extractions), the circulating factor IX activity required is 25% to 50%; repeat dose every 12 to 24 hours until bleeding stops and healing begins, about 2 to 7 days. For major surgery, the circulating factor IX activity required is 50% to 100%; repeat dose every 12 to 24 hours for 7 to 10 days. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). To estimate the dose with an average incremental recovery of 0.7 International Units/dL, the following formula may be used: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x 1.4 (International Units/kg per International Units/dL). In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Neonates

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating activity of factor IX by 0.7 +/- 0.3 International Units/dL (range: 0.2 to 2.1 International Units/dL). Compared to older patients, patients younger than 15 years may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. Specific neonatal dosing is not provided in the FDA-approved product labeling. For minor surgery, the circulating factor IX activity required is 25% to 50%; repeat dose every 12 to 24 hours until bleeding stops and healing begins, about 2 to 7 days. For major surgery, the circulating factor IX activity required is 50% to 100%; repeat dose every 12 to 24 hours for 7 to 10 days. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). To estimate the dose with an average incremental recovery of 0.7 International Units/dL, the following formula may be used: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x 1.4 (International Units/kg per International Units/dL). In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Intravenous dosage (Idelvion) Adults

Children and Adolescents 12 to 17 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 1.3 International Units/dL. Compared to adults, pediatric patients may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. For minor surgery (e.g., uncomplicated dental extraction), the circulating factor IX activity required is 50% to 80%. A single dose should be sufficient; repeat as needed every 48 to 72 hours until healing is achieved. For major surgery (e.g., intracranial, pharyngeal, retropharyngeal, retroperitoneal), the circulating factor IX activity required is 60% to 100% (initial concentration). Repeat dose every 48 to 72 hours for 7 to 14 days or until bleeding stops and healing is achieved; administer maintenance dose 1 to 2 times per week. The following formulas may be used to estimate the required dose or the in vivo peak increase in factor IX concentration: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x (Reciprocal of Recovery [International Units/kg per International Units/dL]) or Estimated Increment of Factor IX (International Units/dL or % of normal) = Dose (International Units) x Recovery (International Units/dL per International Unit/kg)/Body Weight (kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Infants and Children younger than 12 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 1 International Unit/dL. Compared to adults, pediatric patients may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. For minor surgery (e.g., uncomplicated dental extraction), the circulating factor IX activity required is 50% to 80%. A single dose should be sufficient; repeat as needed every 48 to 72 hours until healing is achieved. For major surgery (e.g., intracranial, pharyngeal, retropharyngeal, retroperitoneal), the circulating factor IX activity required is 60% to 100% (initial concentration). Repeat dose every 48 to 72 hours for 7 to 14 days or until bleeding stops and healing is achieved; administer maintenance dose 1 to 2 times per week. The following formulas may be used to estimate the required dose or the in vivo peak increase in factor IX concentration: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x (Reciprocal of Recovery [International Units/kg per International Units/dL]) or Estimated Increment of Factor IX (International Units/dL or % of normal) = Dose (International Units) x Recovery (International Units/dL per International Unit/kg)/Body Weight (kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Neonates

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 1 International Unit/dL. Compared to adults, pediatric patients may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. Specific neonatal dosing is not provided in the FDA-approved product labeling. For minor surgery, the circulating factor IX activity required is 50% to 80%. A single dose should be sufficient; repeat as needed every 48 to 72 hours until healing is achieved. For major surgery (e.g., intracranial, pharyngeal, retropharyngeal, retroperitoneal), the circulating factor IX activity required is 60% to 100% (initial concentration). Repeat dose every 48 to 72 hours for 7 to 14 days or until bleeding stops and healing is achieved; administer maintenance dose 1 to 2 times per week. The following formulas may be used to estimate the required dose or the in vivo peak increase in factor IX concentration: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x (Reciprocal of Recovery [International Units/kg per International Units/dL]) or Estimated Increment of Factor IX (International Units/dL or % of normal) = Dose (International Units) x Recovery (International Units/dL per International Unit/kg)/Body Weight (kg). Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Intravenous dosage (Ixinity) Adults

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.98 International Units/dL. For minor surgery (including uncomplicated dental extraction), the circulating factor IX activity required preoperatively is 50% to 80% and postoperatively is 30% to 80%; repeat every 24 hours for 1 to 5 days depending on the type of procedure. For major surgery, the circulating factor IX activity required preoperatively is 60% to 80% and postoperatively is 40% to 60% for 1 to 3 days, 30% to 50% for 4 to 6 days, and 20% to 40% for 7 to 14 days; repeat dose every 8 to 24 hours. The following formula may be used to estimate the initial dose: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). To estimate the dose with an average incremental recovery of 0.98 International Units/dL, the following formula may be used: Dose (International Units) = Body Weight (kg) x Desired Factor IX Increase (International Units/dL or % of normal) x 1.02 dL/kg. In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays, due to the wide range of interindividual differences in incremental recovery. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Children and Adolescents 12 to 17 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.98 International Units/dL. For minor surgery (including uncomplicated dental extraction), the circulating factor IX activity required preoperatively is 50% to 80% and postoperatively is 30% to 80%; repeat every 24 hours for 1 to 5 days depending on the type of procedure. For major surgery, the circulating factor IX activity required preoperatively is 60% to 80% and postoperatively is 40% to 60% for 1 to 3 days, 30% to 50% for 4 to 6 days, and 20% to 40% for 7 to 14 days; repeat dose every 8 to 24 hours. The following formula may be used to estimate the initial dose: Dose (International Units) = Body weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). To estimate the dose with an average incremental recovery of 0.98 International Units/dL, the following formula may be used: Dose (International Units) = Body Weight (kg) x Desired Factor IX Increase (International Units/dL or % of normal) x 1.02 dL/kg. In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays, due to the wide range of interindividual differences in incremental recovery. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Intravenous dosage (Mononine) Adults

Infants, Children, and Adolescents

Neonates

Intravenous dosage (Profilnine) Adults

Intravenous dosage (Rixubis) Adults

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.9 International Units/dL. For minor surgery (e.g., dental extraction), the circulating factor IX activity required is 30% to 60%; repeat dose every 24 hours for at least 1 day until healing is achieved. For major surgery (e.g., intracranial, intraabdominal, intrathoracic, joint replacement), the circulating factor IX activity required is 80% to 100%; repeat dose every 8 to 24 hours for 7 to 10 days, until bleeding stops and healing is achieved. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). For an incremental recovery of 0.9 International Units/dL of plasma (0.9% of normal), the dose is calculated as follows: Dose (International Units) = Body Weight (kg) x Desired Factor IX Increase (International Units/dL or % of normal) x 1.1 dL/kg. In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays, due to the wide range of interindividual differences in incremental recovery. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Children and Adolescents 12 to 17 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.9 International Units/dL. For minor surgery (e.g., dental extraction), the circulating factor IX activity required is 30% to 60%; repeat dose every 24 hours for at least 1 day until healing is achieved. For major surgery (e.g., intracranial, intraabdominal, intrathoracic, joint replacement), the circulating factor IX activity required is 80% to 100%; repeat dose every 8 to 24 hours for 7 to 10 days, until bleeding stops and healing is achieved. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). For an incremental recovery of 0.9 International Units/dL of plasma (0.9% of normal), the dose is calculated as follows: Dose (International Units) = Body Weight (kg) x Desired Factor IX Increase (International Units/dL or % of normal) x 1.1 dL/kg. In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays, due to the wide range of interindividual differences in incremental recovery. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Infants and Children younger than 12 years

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.7 International Units/dL. Compared to older patients, pediatric patients younger than 12 years may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. For minor surgery (e.g., dental extraction), the circulating factor IX activity required is 30% to 60%; repeat dose every 24 hours for at least 1 day until healing is achieved. For major surgery (e.g., intracranial, intraabdominal, intrathoracic, joint replacement), the circulating factor IX activity required is 80% to 100%; repeat dose every 8 to 24 hours for 7 to 10 days, until bleeding stops and healing is achieved. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). For an incremental recovery of 0.7 International Units/dL of plasma (0.7% of normal), the dose is calculated as follows: Dose (International Units) = Body Weight (kg) x Desired Factor IX Increase (International Units/dL or % of normal) x 1.4 dL/kg. In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays, due to the wide range of interindividual differences in incremental recovery. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Neonates

Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating concentration of factor IX by 0.7 International Units/dL. Compared to older patients, pediatric patients younger than 12 years may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. Specific neonatal dosing is not provided in the FDA-approved product labeling. For minor surgery, the circulating factor IX activity required is 30% to 60%; repeat dose every 24 hours for at least 1 day until healing is achieved. For major surgery (e.g., intracranial, intraabdominal, intrathoracic), the circulating factor IX activity required is 80% to 100%; repeat dose every 8 to 24 hours for 7 to 10 days, until bleeding stops and healing is achieved. The following formula may be used to estimate the initial dose: Dose (International Units) = Body Weight (kg) x Desired Factor IX Rise (International Units/dL or % of normal) x Reciprocal of Recovery (International Units/kg per International Units/dL). For an incremental recovery of 0.7 International Units/dL of plasma (0.7% of normal), the dose is calculated as follows: Dose (International Units) = Body Weight (kg) x Desired Factor IX Increase (International Units/dL or % of normal) x 1.4 dL/kg. In previously treated patients, calculate the dose based on the patient's individual incremental recovery using serial factor IX activity assays, due to the wide range of interindividual differences in incremental recovery. Titrate the dose based on the patient's clinical response and individual pharmacokinetics (e.g., incremental recovery, half-life).

Intravenous dosage (Rebinyn) Adults

Dose and duration of treatment depend on the location and extent of bleeding and the patient's clinical condition. For minor surgery (e.g., dental procedures, skin biopsies), a single 40 International Units/kg IV dose given preoperatively should be sufficient; additional doses can be given if needed. For major surgery, administer 80 International Units/kg IV as a single dose preoperatively and 40 International Units/kg/dose IV as needed perioperatively for the management of bleeding. Repeat doses of 40 International Units/kg/dose IV every 1 to 3 days for the first week after surgery as needed; may extend dosing to once weekly after the first week until bleeding stops and healing is achieved.

Infants, Children, and Adolescents

Continuous Intravenous Infusion dosage† Adults

Children and Adolescents

For routine bleeding prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia B.
NOTE: Factor IX concentration may be expressed as % or International Units/dL.
Intravenous dosage (general dosing) Adults

25 to 40 International Units/kg/dose IV twice weekly (known as the Malmo/Swedish method) or 15 to 30 International Units/kg/dose IV twice weekly (known as the Utrecht protocol) are 2 prophylaxis protocols in use with long-term data. Goal is to maintain factor IX activity trough concentrations more than 1%. In the Netherlands, a dose of 30 to 50 International Units/kg/dose IV once or twice weekly is also used. Optimum regimen remains to be defined. Prophylactic regimens should be modified to meet a patient's specific requirements.

Infants, Children, and Adolescents

Intravenous dosage (Alprolix) Adults

50 International Units/kg/dose IV once weekly or 100 International Units/kg/dose IV once every 10 days. Adjust dose based on individual response.

Children and Adolescents 12 to 17 years

50 International Units/kg/dose IV once weekly or 100 International Units/kg/dose IV once every 10 days. Adjust dose based on individual response.

Infants and Children younger than 12 years

60 International Units/kg/dose IV once weekly. Adjust dose based on individual response. Pediatric patients younger than 12 years, especially those younger than 6 years, may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery.

Neonates

60 International Units/kg/dose IV once weekly. Adjust dose based on individual response. Compared to older patients, pediatric patients younger than 12 years, especially those younger than 6 years, may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery. Specific neonatal dosing is not provided in the FDA-approved product labeling.

Intravenous dosage (Idelvion) Adults

Children and Adolescents 12 to 17 years

25 to 40 International Units/kg/dose IV every 7 days. Patients who are well-controlled on this regimen may be switched to 50 to 75 International Units/kg/dose IV every 14 days. Adjust dose based on individual response. Compared to adults, pediatric patients may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery.

Infants and Children younger than 12 years

40 to 55 International Units/kg/dose IV every 7 days. Adjust dose based on individual response. Compared to adults, pediatric patients may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery.

Neonates

Intravenous dosage (Rixubis) Adults

40 to 60 International Units/kg/dose IV twice weekly. Adjust dose based on individual patient's age, bleeding pattern, and physical activity.

Children and Adolescents 12 to 17 years

40 to 60 International Units/kg/dose IV twice weekly. Adjust dose based on individual patient's age, bleeding pattern, and physical activity.

Infants and Children younger than 12 years

60 to 80 International Units/kg/dose IV twice weekly. Adjust dose based on individual patient's age, bleeding pattern, and physical activity. Compared to older patients, pediatric patients younger than 12 years may require a higher dose per kg bodyweight or more frequent dosing because they may have higher factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery.

Neonates

Dosing Considerations

Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Drug Interactions

Aminocaproic Acid: (Major) In general, aminocaproic acid should not be administered simultaneously with factor IX complex, factor IX concentrates, factor IX Fc fusion protein, recombinant, and factor IX albumin fusion protein, recombinant due to the increased risk of thrombosis. Some hematologists recommend separating administration of aminocaproic acid from these clotting factor complexes by 8 hours. Aminocaproic acid has been used concurrently with human factor IX complexes or anti-inhibitor coagulant complex perioperatively in hemophiliac patients. The risk of developing thrombosis, however, is increased. In rare instances, thrombosis leading to acute myocardial infarction or gangrene has been reported in patients with hemophilia receiving combination therapy with factor IX concentrate and aminocaproic acid. Concomitant administration of aminocaproic acid with purer formulations of factor IX may also result in an increased risk of thrombosis.
Factor VIIa, Recombinant: (Major) The risk of a potential interaction between factor VIIa, recombinant, and factor IX replacement products has not been adequately evaluated. Simultaneous use of these products should be avoided due to the potential for increased risk of thrombosis.
Tranexamic Acid: (Major) Tranexamic acid should not be administered concomitantly with factor IX complex, Factor IX Fc fusion protein, recombinant, or Factor IX concentrates, due to the increased risk of thrombosis.

How Supplied

Bebulin/Profilnine/Profilnine SD Intravenous Inj Pwd F/Sol

Maximum Dosage

Specific maximum dosage information is not available. Individualize dosage based on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s age and clinical condition.

Mechanism Of Action

Factor IX is a vitamin K-dependent clotting factor that is synthesized in the liver. In patients with hemophilia B there is a deficiency in functional coagulation factor IX leading to a prolonged clotting time in the activated partial thromboplastin time (aPTT) assay. The administration of factor IX replacement to deficient patients results in increased levels of factor IX thereby decreasing the risk of hemorrhage or restoring hemostasis.

Human plasma-derived products (AlphaNine SD, Mononine, Bebulin, Profilnine) contain factors II, VII, IX, and X. Administration of factor IX complex (Bebulin and Profilnine) will increase plasma concentrations of functional vitamin-K dependent coagulation factors II, IX, and X; however, no clinical studies have been conducted to show benefit from these products other than factor IX deficiency. Concentrations of factor VII are nontherapeutic.

Some recombinant products join factor IX to another molecule to extend the plasma half-life of factor IX. Factor IX Fc fusion protein (Alprolix) contains the Fc region of human IgG1, which binds to the neonatal Fc receptor (FcRn). FcRn is part of a naturally occurring pathway that delays lysosomal degradation of immunoglobulins by cycling them back into circulation and prolonging their plasma half-life. The genetic fusion of recombinant albumin to recombinant factor IX, as seen with Idelvion, also extends the half-life of factor IX. The factor IX in Rebinyn is conjugated to a 40-kDa polyethylene glycol molecule, which slows down its removal from the blood circulation.

Pharmacokinetics

Factor IX replacement products are administered intravenously. The mean half-life of factor IX products ranges from roughly 16 to 25 hours; however, some recombinant products (e.g., Alprolix, Idelvion, Rebinyn) join factor IX to another molecule to significantly extend factor IX half-life. The pharmacokinetic properties of plasma-derived and recombinant factor IX differ from each other. Although the plasma half-lives are equivalent, in vivo recovery for recombinant factor IX is approximately 30% lower than that of plasma-derived factor IX. Young pediatric patients have a lower recovery due to their larger plasma Vd, higher plasma clearance, and shorter half-life.

Factor IX concentrate
AlphaNine SD
Mean half-life and recovery were approximately 21 hours and 48%, respectively, during clinical evaluation of 18 patients receiving a single infusion of 40 to 50 International Units/kg.

BeneFIX
Mean pharmacokinetic parameters during clinical evaluation of 23 patients older than 15 years receiving 75 International Units/kg/dose IV for 6 months were as follows: Cmax = 57.3 International Units/dL; AUC = 923 International Units x hour/dL; half-life = 23.8 hours; CL = 8.54 mL/kg/hour; incremental recovery (IR) = 0.76 International Unit/dL per International Unit/kg; in vivo recovery = 36.8%. Pharmacokinetic parameters at 6 months were unchanged compared to those obtained at initial evaluation.

Ixinity
Initial recovery ranged from 51% to 113% (median 70%) after administration of 75 International Units/kg/dose IV to 32 previously treated patients 12 years of age and older. Mean pharmacokinetic parameters during clinical evaluation of 14 patients receiving routine treatment for a median of 5.8 months were as follows: Vd = 185 mL/kg; Cmax = 73 International Units/dL; AUC = 1,530 International Units x hour/dL; half-life = 24 hours; CL = 5.3 mL/kg/hour; IR = 0.95 International Unit/dL per International Unit/kg. Repeat dosing did not impact pharmacokinetic parameters.

Mononine
Mean half-life and recovery were 25.3 hours and 0.68 International Unit/dL per International Unit/kg, respectively, in 9 patients receiving repeated infusions for 6 months. These parameters were comparable to those observed with the initial infusion (22.6 hours and 0.67 International Units/dL per International Units/kg, respectively).

In 2 studies where extensive replacement was required, overall mean recovery was 1.23 (range = 0.59 to 2.92; n = 55) International Units/dL per International Units/kg and 1.12 (range 0.61 to 2.08; n = 10) International Units/dL per International Units/kg. Mean recovery (International Units/dL per International Units/kg), which was analyzed in 67 of 100 high dose infusions (range 71 to 161 International Units/kg), tended to decrease as the dose of Mononine increased: 1.09 at doses of 76 to 95 International Units/kg (n = 38), 0.98 at doses of 96 to 115 International Units/kg (n = 21), 0.7 at doses of 116 to 135 International Units/kg (n = 2), 0.67 at doses of 136 to 155 International Units/kg (n = 1), and 0.73 at doses of more than 155 International Units/kg (n = 5).

Rixubis
Mean pharmacokinetic parameters during clinical evaluation of 23 patients 12 years of age and older receiving a mean dose of 75 International Units/kg/dose IV for 26 weeks of routine prophylaxis were as follows: Vd = 178.6 mL/kg; Cmax = 72.7 International Units/dL; AUC = 1,305 International Units x hour/dL; half-life = 25.4 hours; CL = 6 mL/kg/hour; IR = 0.95 International Unit/dL per International Unit/kg; mean residence time (MRT) = 29.9 hours. Incremental recovery was consistent over time from day 1 to trial completion (at least 26 weeks).

Factor IX complex
Bebulin
Half-life and in vivo recovery are as follows, respectively: factor IX = 19.4 hours and 53.3%; factor II = 24.6 hours and 57.5%; factor X = 19.97 hours and 53.24%.

Profilnine
Half-life and recovery were 24.68 hours and 1.15 International Units/dL per International Unit/kg, respectively, during clinical evaluation of 12 patients.

Factor IX Fc fusion protein
Alprolix
Mean pharmacokinetic parameters during clinical evaluation of 22 adult patients receiving a single dose of 50 International Units/kg IV over 10 minutes were as follows: Vd = 327 mL/kg; Cmax = 46 International Units/dL; AUC = 1,619 International Units x hour/dL; half-life = 86 hours; CL = 3.3 mL/kg/hour; IR = 1.02 International Unit/dL per International Unit/kg; MRT = 102 hours; time to 1% factor IX activity = 12 days.

Mean pharmacokinetic parameters during clinical evaluation of 24 adult patients receiving a 100 International Unit/kg dose were as follows: Vd = 236 mL/kg; Cmax = 101 International Units/dL; AUC = 3,964 International Units x hour/dL; half-life = 97 hours; CL = 2.6 mL/kg/hour; IR = 1.12 International Unit/dL per International Unit/kg; MRT = 91 hours; time to 1% factor IX activity = 16 days.

Pharmacokinetic parameters were stable over repeated dosing.

Factor IX albumin fusion protein
Idelvion
Mean pharmacokinetic parameters during clinical evaluation of 7 adult patients administered a single 25 International Units/kg IV dose are as follows: Vd = 0.86 dL/kg; Cmax = 41.1 International Units/dL; AUC = 4,658 International Units x hour/dL; half-life = 118 hours; CL = 0.57 mL/kg/hour; IR = 1.65 International Units/dL per International Units/kg; MRT = 153 hours; time to 5% factor IX activity = 10 days; time to 3% factor IX activity = 14 days; time to 1% factor IX activity = 22 days.

Mean pharmacokinetic parameters during clinical evaluation of 47 adult patients administered a single 50 International Units/kg IV dose are as follows: Vd = 1.02 dL/kg; Cmax = 66.6 International Units/dL; AUC = 7,482 International Units x hour/dL; half-life = 104 hours; CL = 0.73 mL/kg/hour; IR = 1.3 International Units/dL per International Units/kg; MRT = 143 hours; time to 5% factor IX activity = 13 days; time to 3% factor IX activity = 17 days; time to 1% factor IX activity = 23 days.

Mean pharmacokinetic parameters during clinical evaluation of 8 adult patients administered a single 75 International Units/kg IV dose are as follows: Vd = 1.2 dL/kg; Cmax = 82 International Units/dL; AUC = 9,345 International Units x hour/dL; half-life = 104 hours; CL = 0.84 mL/kg/hour; IR = 1.08 International Units/dL per International Units/kg; MRT = 145 hours; time to 5% factor IX activity = 15 days; time to 3% factor IX activity = 18 days; time to 1% factor IX activity = 25 days.

Pharmacokinetic parameters after single or repeat dosing for up to 30 weeks were similar.

Factor IX glycoPEGylated
Rebinyn
Mean pharmacokinetic parameters during clinical evaluation of 6 adult patients administered 40 International Units/kg IV as a single dose are as follows: Vd = 47 mL/kg; AUC = 9,063 International Units x hour/dL; half-life = 83 hours; CL = 0.4 mL/kg/hour; IR = 2.34 International Units/dL per International Units/kg; MRT = 115.5 hours; factor IX activity 168 hours after dosing = 16.8%.

Mean pharmacokinetic parameters during clinical evaluation of 6 adult patients administered 40 International Units/kg IV once weekly are as follows: Vd = 65.8 mL/kg; AUC = 9,280 International Units x hour/dL; half-life = 114.9 hours; CL = 0.4 mL/kg/hour; IR = 1.92 International Units/dL per International Units/kg; MRT = 158.1 hours; factor IX activity 168 hours after dosing = 32.4%.

After an 80 International Unit/kg infusion during major surgery, median factor IX activity was 143% at 30 minutes (n = 13), 138% at 8 hours (n = 12), 112% at 24 hours (n = 12), and 73% at 48 hours (n = 7).

Mean Cmax and Cmin at steady state with a 40 International Unit/kg dose in adult patients (n = 20) were 97.9% and 29.3%, respectively.

Affected cytochrome P450 isoenzymes: none

Pregnancy And Lactation

Pregnancy

There are no data with factor IX product use during pregnancy to determine whether there is a drug-associated risk. It is not known whether these products can cause fetal harm when administered to a pregnant woman. Factor IX should be administered to a pregnant woman only if clearly indicated.

There is no information of the presence of factor IX products in human milk, the effect on the breast-fed infant, or the effects on milk production. Exercise caution when used in breast-feeding mothers. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.