ELOCTATE

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ELOCTATE

Classes

Blood Coagulation Factors

Administration

 
Factor VIII activity is expressed in International Units; the actual potency per vial of factor VIII is stated on each vial.
Plasma factor VIII concentrations can be monitored using either a chromogenic substrate assay (Eloctate only) or a 1-stage clotting assay.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intravenous Administration

Reconstitution (Altuviiio and Eloctate)
Use aseptic technique and a flat work surface throughout the entire reconstitution process.
Allow vial and pre-filled diluent syringe (provided) to reach room temperature.
Peel back the lid from the vial adapter package. Do not remove the vial adapter from the package or touch the inside of the adapter package.
Place the vial adapter over the vial. Place the adapter spike directly above the center of the rubber stopper and push the adapter straight down until the spike punctures the center of the vial stopper and is fully inserted. Discard package cover.
Hold the plunger rod at the circular disk on the end and place the tip of the plunger rod into the end of the syringe. Turn the plunger rod to the right until it is securely attached. Only use the provided diluent syringe.
Hold diluent syringe with 1 hand by the ridged part directly under cap with 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 to the right until it is securely attached to the adapter. Slowly depress the plunger rod to inject all the diluent into the vial. The plunger rod may rise slightly after this process.
With the syringe still connected to the adapter, gently swirl the vial until the product is completely dissolved. The final solution should be clear to slightly opalescent and colorless. Do not shake. Do not use the reconstituted solution if it contains visible particles or is cloudy.
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 and dispose of the vial with the adapter still attached. Do not touch the syringe tip or the inside of the cap.
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 until it is completely detached. Use a larger luer lock plastic syringe to combine the contents of the reconstituted vials into the syringe. Repeat this pooling procedure with each vial necessary to obtain the required dose.
Storage: Use the reconstituted solution as soon as possible, but no later than 3 hours after reconstitution. Do not touch the glass tip of the syringe if not used immediately after reconstitution. Protect from direct sunlight. Do not refrigerate after reconstitution.
 
Intermittent IV Infusion
Do not administer reconstituted solution in the same tubing or container with other medications.
Attach the syringe to the connector end of the infusion set tubing by turning it to the right until it is securely attached. Push the plunger rod until all air is removed from the syringe and solution has filled the infusion set needle. Do not push solution through the needle. Remove the protective needle cover from the infusion set needle.
Altuviiio: Administer via intravenous bolus infusion at a rate of administration determined by the patient's comfort level, and no faster than the below recommendations for age/weight:
Adults and Adolescents: Administer each vial over 1 to 2 minutes.
Pediatric patients weighing 20 kg or more: Administer each vial over 2 to 3 minutes.
Pediatric patients weighing less than 20 kg: Administer each vial over 6 minutes.
Eloctate: Administer via intravenous bolus infusion at a rate of administration determined by the patient's comfort level, and no faster than 10 mL/minute.

Adverse Reactions
Severe

thrombosis / Delayed / 1.0-1.9
bradycardia / Rapid / 0.4-0.4
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known

Moderate

antibody formation / Delayed / 2.2-27.0
hypotension / Rapid / 0.4-0.4
hypertension / Early / 0.4-0.4
chest pain (unspecified) / Early / 0.4-0.4
wheezing / Rapid / Incidence not known
dyspnea / Early / Incidence not known

Mild

headache / Early / 0.7-21.0
arthralgia / Delayed / 0.7-16.0
back pain / Delayed / 0.4-6.0
rash / Early / 0.7-1.0
myalgia / Early / 0.7-0.7
malaise / Early / 0.7-0.7
dysgeusia / Early / 0.4-0.4
dizziness / Early / 0.4-0.4
abdominal pain / Early / 0.4-0.4
cough / Delayed / 0.4-0.4
injection site reaction / Rapid / 0.4-0.4
urticaria / Rapid / Incidence not known
pruritus / Rapid / Incidence not known

Common Brand Names

ALTUVIIIO, ELOCTATE

Dea Class

Rx

Description

Recombinant, fusion protein with antihemophilic factor linked to Fc protein fragment of antibodies
Used for control and prevention of bleeding in patients with hemophilia A
Linking to Fc protein prolongs factor circulation and allows for extended time between prophylactic infusions; Altuviiio product has a prolonged half-life compared to Eloctate product, allowing for even less frequent dosing

Dosage And Indications
For the on-demand treatment and control of hemorrhage in patients with hemophilia A (classical hemophilia). For control of minor and moderate bleeding (e.g., uncomplicated joint bleeds, minor muscle bleeds, oral bleeds) in patients with hemophilia A.
NOTE: For minor or moderate bleeding, the circulating factor VIII activity required is 40% to 60% of normal.
Intravenous dosage (Altuviiio) Adults

50 International Units/kg/dose IV as a single dose. For minor and moderate bleeding episodes occurring within 2 to 3 days after a prophylactic dose, a lower dose of 30 International Units/kg/dose IV may be used. May give additional doses of 30 or 50 International Units/kg/dose IV every 2 to 3 days if needed.

Infants, Children, and Adolescents

50 International Units/kg/dose IV as a single dose. For minor and moderate bleeding episodes occurring within 2 to 3 days after a prophylactic dose, a lower dose of 30 International Units/kg/dose IV may be used. May give additional doses of 30 or 50 International Units/kg/dose IV every 2 to 3 days if needed.

Intravenous dosage (Eloctate) Adults

20 to 30 International Units/kg/dose IV every 24 to 48 hours until bleeding is resolved.[57379]

Children and Adolescents 6 to 17 years

20 to 30 International Units/kg/dose IV every 24 to 48 hours until bleeding is resolved.[57379]

Infants and Children 1 to 5 years

20 to 30 International Units/kg/dose IV every 12 to 24 hours until bleeding is resolved.[57379]

For control of major bleeding (e.g., life- or limb-threatening, intracranial, gastrointestinal, retroperitoneal, deep muscle with neurovascular injury) in patients with hemophilia A.
NOTE: For major bleeding, the circulating factor VIII activity required is 80% to 100% of normal.
Intravenous dosage (Altuviiio) Adults

50 International Units/kg/dose IV as a single dose. May give additional doses of 30 or 50 International Units/kg/dose IV every 2 to 3 days if needed.

Infants, Children, and Adolescents

50 International Units/kg/dose IV as a single dose. May give additional doses of 30 or 50 International Units/kg/dose IV every 2 to 3 days if needed.

Intravenous dosage (Eloctate) Adults

40 to 50 International Units/kg/dose IV every 12 to 24 hours until bleeding is resolved (approximately 7 to 10 days).[57379]

Children and Adolescents 6 to 17 years

40 to 50 International Units/kg/dose IV every 12 to 24 hours until bleeding is resolved (approximately 7 to 10 days).[57379]

Infants and Children 1 to 5 years

40 to 50 International Units/kg/dose IV every 8 to 24 hours until bleeding is resolved (approximately 7 to 10 days).[57379]

For the perioperative management of surgical bleeding in patients with hemophilia A. For the perioperative management of surgical bleeding with minor surgery (e.g., uncomplicated dental extraction).
NOTE: For minor surgery, the circulating factor VIII activity required is 50% to 80% of normal.
Intravenous dosage (Altuviiio) Adults

50 International Units/kg/dose IV as a single dose preoperatively. May give an additional dose of 30 or 50 International Units/kg/dose IV after 2 to 3 days if needed.

Infants, Children, and Adolescents

50 International Units/kg/dose IV as a single dose preoperatively. May give an additional dose of 30 or 50 International Units/kg/dose IV after 2 to 3 days if needed.

Intravenous dosage (Eloctate) Adults

25 to 40 International Units/kg/dose IV every 24 hours; continue for at least 1 day until wound healing is achieved.

Children and Adolescents 6 to 17 years

25 to 40 International Units/kg/dose IV every 24 hours; continue for at least 1 day until wound healing is achieved.

Infants and Children 1 to 5 years

25 to 40 International Units/kg/dose IV every 12 to 24 hours; continue for at least 1 day until wound healing is achieved.

For the perioperative management of surgical bleeding with major surgery (e.g., intracranial, intra-abdominal, joint replacement surgery, complicated dental procedures).
NOTE: for major surgery, the circulating factor VIII activity required is 80% to 120% of normal.
Intravenous dosage (Altuviiio) Adults

50 International Units/kg/dose IV as a single dose preoperatively. May give additional doses of 30 or 50 International Units/kg/dose IV every 2 to 3 days as clinically needed.

Infants, Children, and Adolescents

50 International Units/kg/dose IV as a single dose preoperatively. May give additional doses of 30 or 50 International Units/kg/dose IV every 2 to 3 days as clinically needed.

Intravenous dosage (Eloctate) Adults

40 to 60 International Units/kg/dose IV as a single dose preoperatively, followed by 40 to 50 International Units/kg/dose IV after 8 to 24 hours. Repeat every 24 hours until adequate wound healing and then continue for at least 7 days to maintain a factor VIII activity within the target range.

Children and Adolescents 6 to 17 years

40 to 60 International Units/kg/dose IV as a single dose preoperatively, followed by 40 to 50 International Units/kg/dose IV after 8 to 24 hours. Repeat every 24 hours until adequate wound healing and then continue for at least 7 days to maintain a factor VIII activity within the target range.

Infants and Children 1 to 5 years

40 to 60 International Units/kg/dose IV as a single dose preoperatively, followed by 40 to 50 International Units/kg/dose IV after 6 to 24 hours. Repeat every 24 hours until adequate wound healing and then continue for at least 7 days to maintain a factor VIII activity within the target range.

For routine bleeding prophylaxis to prevent or reduce the frequency of bleeding episodes. Intravenous dosage (Altuviiio) Adults

50 International Units/kg/dose IV once weekly.

Infants, Children, and Adolescents

50 International Units/kg/dose IV once weekly.

Intravenous dosage (Eloctate) Adults

50 International Units/kg/dose IV every 4 days initially. Adjust dose based on response. The typical dosing range is 25 to 65 International Units/kg/dose IV every 3 to 5 days.

Children and Adolescents 6 to 17 years

50 International Units/kg/dose IV every 4 days initially. Adjust dose based on response. The typical dosing range is 25 to 65 International Units/kg/dose IV every 3 to 5 days.

Infants and Children 1 to 5 years

50 International Units/kg/dose IV twice weekly initially. Adjust dose based on response. The typical dosing range is 25 to 65 International Units/kg/dose IV every 3 to 5 days. More frequent or higher doses up to 80 International Units/kg/dose IV may be needed in some patients.

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

There are no drug interactions associated with Antihemophilic Factor, Fc Fusion Protein, Recombinant products.

How Supplied

ALTUVIIIO/Antihemophilic Factor VIII (Recombinant), Fc Fusion Protein/ELOCTATE Intravenous Inj Pwd F/Sol

Maximum Dosage

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

Mechanism Of Action

In patients with hemophilia A, there is a deficiency of functional coagulation factor VIII (FVIII) leading to a prolonged clotting time in the activated partial thromboplastin time (aPTT) assay. Administration of recombinant antihemophilic factor Fc fusion protein normalizes the aPTT over the effective dosing period. Antihemophilic factor Fc fusion protein is a fully recombinant, fusion protein that temporarily replaces the missing coagulation factor VIII needed for effective hemostasis. Antihemophilic factor Fc fusion protein 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.
 
Mechanism of half-life extension with Altuviiio
Altuviiio is a recombinant FVIII analogue fusion protein that is independent of endogenous von Willebrand factor (VWF) in order to overcome the half-life limit imposed by FVIII-VWF interactions. The D'D3 domain of VWF is the region that interacts with FVIII. Appending the D'D3 domain of VWF to a recombinant FVIII-Fc fusion protein provides protection and stability to FVIII, and prevents FVIII interaction with endogenous VWF, thus overcoming the limitation on FVIII half-life imposed by VWF clearance. Altuviiio contains 2 XTEN polypeptides, which alter the hydrodynamic radius of the fusion protein, thus reducing rates of clearance and degradation, and improving pharmacokinetic properties. In Altuviiio, the natural FVIII B domain (except 5 amino acids) is replaced with the first XTEN, inserted in between FVIII N745 and E1649 amino acid residues, and the second XTEN is inserted in between the D'D3 domain and Fc.

Pharmacokinetics

Recombinant antihemophilic factor Fc fusion protein is administered intravenously. Pharmacokinetic parameters obtained in clinical studies with both products were based on plasma factor VIII activity measured by the 1-stage clotting assay. Altuviiio has demonstrated 3- to 4-fold prolonged half-life relative to other standard and extended half-life factor VIII products.
 
Altuviiio
The pharmacokinetics of Altuviiio were evaluated in clinical studies in adult patients (n = 134) receiving weekly IV doses of 50 International Units/kg. After a single dose of 50 International Units/kg, Altuviiio exhibited high sustained factor VIII activity with prolonged half-life across age cohorts. The pharmacokinetic profile at steady state (Week 26) was comparable with the pharmacokinetic profile obtained after the first dose. The factor VIII activity over 10 International units/dL was maintained in 83.5% of adults throughout the study.
Vd (mL/kg)
Adults: 31
AUC (International Units x hours/dL)
Adults: 9,850
t1/2 (hours)
Adults: 48.2
CL (mL/hour/kg)
Adults: 0.493
IR (International Units/dL per International Units/kg)
Adults: 2.64
 
Eloctate
The pharmacokinetics of Eloctate were evaluated in clinical studies in adult patients (n = 26) receiving a single 50 International Unit/kg/dose. The pharmacokinetic profile at steady state (Week 14) was comparable with the pharmacokinetic profile obtained after the first dose.[57379]
Vd (mL/kg)
Adults: 49.5
AUC/dose (International Units x hour/dL per International Units/kg)
Adults: 54.1
t1/2 (hours)
Adults: 19.7
CL (mL/hour/kg)
Adults: 2.06
IR (International Units/dL per International Units/kg)
Adults: 2.26
 
Affected cytochrome P450 isoenzymes: none

Pregnancy And Lactation
Pregnancy

There are no data regarding recombinant antihemophilic factor Fc fusion protein use in pregnant women to inform a drug-associated risk. Animal reproductive and developmental toxicity studies have not been conducted. In a placental transfer study, antihemophilic factor Fc fusion protein was detected in murine fetal blood at approximately 1% of the maternal blood concentrations, 3 to 4 hours after a dose 260 to 650 times the clinical human dose. Administer antihemophilic factor Fc fusion protein during pregnancy only if clearly needed. If administered, advise the patient that the risks to the mother and fetus are unknown.

There are no data on the presence of antihemophilic factor Fc fusion protein in human milk, the effects on the breast-fed infant, or the effects on milk production. Consider the benefits of breast-feeding along with the mother's clinical need for antihemophilic factor Fc fusion protein, and any potential adverse effects on the breast-fed infant from antihemophilic factor Fc fusion protein or the underlying maternal condition.