Factor VIII, recombinant human with Fc fusion: Drug information

(For additional information see "Factor VIII, recombinant human with Fc fusion: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Brand Names: US

Eloctate

Brand Names: Canada

Eloctate

Pharmacologic Category

Antihemophilic Agent

Dosing: Adult

Hemophilia A, without inhibitors

Hemophilia A, without inhibitors:

Treatment and control of bleeding episodes or perioperative management:

Intermittent IV bolus dosing: IV: Utilize steps 1 to 3 to determine intermittent bolus dosing strategy. Individualize dosage based on coagulation studies performed prior to treatment and at regular intervals during treatment. In general, administration of factor VIII 1 unit/kg will increase circulating factor VIII levels by ~2 units/dL (Ref).

Step 1: Determine desired factor VIII peak level and anticipated duration of therapy based on the World Federation of Hemophilia (WFH) treatment recommendations; see table. Selection of the lower-dose practice pattern requires closer observation with the potential for requiring escalation to higher doses based on clinical response.

Note: For patients without inhibitors and receiving emicizumab who experience breakthrough bleeding, antihemophilic factor (recombinant [Fc fusion protein]) should be dosed to target the desired peak factor VIII levels outlined in the table as emicizumab is not indicated for treatment of bleeding episodes.

**Antihemophilic Factor (Recombinant [Fc Fusion Protein]) World Federation of Hemophilia Treatment Recommendations^d**
Type of hemorrhage or surgery	Lower-dose practice pattern		Higher-dose practice pattern
Type of hemorrhage or surgery	Desired peak factor VIII level (units/dL)	Treatment duration (days)	Desired peak factor VIII level (units/dL)	Treatment duration (days)
^aMay be longer if response is inadequate.
^bSometimes longer as secondary prophylaxis during physical therapy.
^cA single dose may be sufficient for some joint bleeds; determine need for additional doses based on clinical response.
^dWFH [Srivastava 2020].
Joint	10 to 20	1 to 2^a,c	40 to 60	1 to 2^a,c
Superficial muscle/no neurovascular compromise (except iliopsoas)	10 to 20	2 to 3^a	40 to 60	2 to 3^a
Iliopsoas or deep muscle with neurovascular injury or substantial blood loss:
Initial	20 to 40	1 to 2	80 to 100	1 to 2
Maintenance	10 to 20	3 to 5^b	30 to 60	3 to 5^b
Intracranial:
Initial	50 to 80	1 to 3	80 to 100	1 to 7
Maintenance	30 to 50	4 to 7	50	8 to 21
Maintenance	20 to 40	8 to 14	-	-
Throat and Neck:
Initial	30 to 50	1 to 3	80 to 100	1 to 7
Maintenance	10 to 20	4 to 7	50	8 to 14
Gastrointestinal:
Initial	30 to 50	1 to 3	80 to 100	7 to 14
Maintenance	10 to 20	4 to 7	50	-
Renal	20 to 40	3 to 5	50	3 to 5
Deep laceration	20 to 40	5 to 7	50	5 to 7
Surgery (major):
Preop	60 to 80	-	80 to 100	-
Postop	30 to 40	1 to 3	60 to 80	1 to 3
	20 to 30	4 to 6	40 to 60	4 to 6
	10 to 20	7 to 14	30 to 50	7 to 14
Surgery (minor):
Preop	40 to 80	-	50 to 80	-
Postop	20 to 50	1 to 5	30 to 80	1 to 5

Step 2: Calculate dose using desired peak factor VIII level from step 1 and the following equation:

Factor VIII units required = [(desired peak factor VIII level − patient's baseline factor VIII level) × body weight (kg)]/2

Note: Factor VIII level units are units/dL.

Example for 50 kg patient with desired peak factor VIII level of 35 units/dL and baseline factor VIII level of 5 units/dL:

Factor VIII units required = [(35 units/dL − 5 units/dL) × 50 kg]/2 = 750 units of factor VIII

Step 3: Determine need for repeat dosing based on manufacturer's recommended frequency of repeat dosing. Note: Frequency of administration must also take into consideration subsequent factor VIII activity measurements and clinical response.

**Antihemophilic Factor (Recombinant [Fc Fusion Protein]) Administration Frequency According to Clinical Scenario**
Clinical scenario	Eloctate Administration Frequency
Bleeding event
Minor severity	Every 24 to 48 hours
Moderate severity	Every 24 to 48 hours
Major severity	Every 12 to 24 hours
Surgery
Minor bleeding risk	Every 24 hours
Major bleeding risk	Every 8 to 24 hours

Routine prophylaxis to prevent or reduce the frequency of bleeding episodes: IV: 50 units/kg every 4 days; at 3- to 5-day intervals, may adjust dose within the range of 25 to 65 units/kg based on patient response. Preferably, dosing should be tailored to ensure trough factor VIII levels of at least 1% and ideally ≥3% to 5% are achieved, but prophylaxis targets should be tailored to individual level of activity, lifestyle, and pharmacokinetics. Dose escalation should be considered for patients adherent to prescribed prophylaxis but still experiencing breakthrough bleeding events (Ref).

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; however, renal impairment has no bearing.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Obesity: Adult

There are insufficient data to recommend the best dosing weight to use in patients with obesity. Dose adjustments should ultimately be made based on individual patient response to therapy. Due to the paucity of data, refer to institutional protocols. Refer to adult dosing for indication-specific dosing.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

Hemophilia A

Hemophilia A: Children and Adolescents: IV: Individualize dosage based on coagulation studies performed prior to treatment and at regular intervals during treatment. In general, administration of factor VIII 1 unit/kg will increase circulating factor VIII levels by ~2 units/dL. Children <6 years may require higher doses and/or more frequent administration.

Control and prevention of bleeding episodes or perioperative management: Refer to adult dosing.

Routine prophylaxis to prevent bleeding episodes:

Children <6 years: 50 units/kg twice weekly; at 3- to 5-day intervals, may adjust dose within the range of 25 to 65 units/kg based on patient response. More frequent or higher doses (up to 80 units/kg) may be required.

Children ≥6 years and Adolescents: Refer to adult dosing.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; however, renal impairment has no bearing.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Hematologic & oncologic: Increased factor VIII inhibitors (previously untreated patients; neutralizing: 27%)

1% to 10%:

Cardiovascular: Catheter site thrombosis (indwelling central venous catheter: 2%)

Dermatologic: Papular rash (1%)

<1%:

Cardiovascular: Bradycardia, chest pain, deep vein thrombosis, flushing, hypertension, procedural hypotension

Dermatologic: Skin rash

Gastrointestinal: Dysgeusia, lower abdominal pain

Local: Injection site reaction (vascular pain post injection)

Nervous system: Dizziness, feeling hot, headache, malaise, sensation of cold

Neuromuscular & skeletal: Arthralgia, back pain, joint swelling, myalgia

Respiratory: Cough

Postmarketing: Hypersensitivity: Hypersensitivity reaction

Contraindications

Life-threatening hypersensitivity to antihemophilic factor or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Antibody formation: The development of factor VIII antibodies has been reported with antihemophilic factors; monitor for signs of formation of antibodies to factor VIII; may occur at any time but more common in young children with severe hemophilia. Suspect factor VIII antibodies if the plasma factor VIII level does not increase as expected or if bleeding is not controlled after administration.

• Hypersensitivity reactions: Allergic hypersensitivity reactions (including anaphylaxis) may occur; discontinue if hypersensitivity symptoms occur and administer appropriate treatment.

Dosage form specific issues:

• Sucrose: May contain sucrose.

Other warnings/precautions:

• Dose requirements: The dosage requirement will vary in patients with factor VIII inhibitors; optimal treatment should be determined by clinical response.

Dosage Forms Considerations

Strengths expressed with approximate values. Consult individual vial labels for exact potency within each vial.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Eloctate: 250 units (1 ea); 500 units (1 ea); 750 units (1 ea); 1000 units (1 ea); 1500 units (1 ea); 2000 units (1 ea); 3000 units (1 ea); 4000 units (1 ea); 5000 units (1 ea); 6000 units (1 ea)

Generic Equivalent Available: US

Pricing: US

Solution (reconstituted) (Eloctate Intravenous)

250 unit (Price provided is per AHF Unit): $3.10

500 unit (Price provided is per AHF Unit): $3.10

750 unit (Price provided is per AHF Unit): $3.10

1000 unit (Price provided is per AHF Unit): $3.10

1500 unit (Price provided is per AHF Unit): $3.10

2000 unit (Price provided is per AHF Unit): $3.10

3000 unit (Price provided is per AHF Unit): $3.10

4000 unit (Price provided is per AHF Unit): $3.10

5000 unit (Price provided is per AHF Unit): $3.10

6000 unit (Price provided is per AHF Unit): $3.10

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Kit, Intravenous:

Eloctate: 250 units, 500 units, 750 units, 1000 units, 1500 units, 2000 units, 3000 units

Administration: Adult

IV: Infuse at a rate of ≤10 mL/minute (maximum: 10 mL/minute).

Administration: Pediatric

IV: IV administration only. Administer through a separate line, do not mix with drugs or other IV fluids. Infuse at a rate of ≤10 mL/minute and adjust administration rate based on patient response; maximum: 10 mL/minute.

World Federation of Hemophilia (WFH) recommendations: Infuse slowly with maximum rate determined by age: Young children: 100 units/minute; Adults: 3 mL/minute; may also administer as a continuous infusion in select patients (Ref).

Use: Labeled Indications

Hemophilia A:

Control and prevention of bleeding episodes: For the prevention and control of bleeding episodes in adults and children with hemophilia A.

Perioperative management: For surgical prophylaxis in adults and children with hemophilia A.

Routine prophylaxis to prevent or reduce the frequency of bleeding: For routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes in adults and children with hemophilia A.

Limitation of use: Not indicated for the treatment of von Willebrand disease.

Medication Safety Issues

Sound-alike/look-alike issues:

Factor VIII may be confused with Factor XIII

Other safety concerns:

Confusion may occur due to the omitting of "Factor VIII" from some product labeling. Review product contents carefully prior to dispensing any antihemophilic factor.

Metabolism/Transport Effects

None known.

Drug Interactions

There are no known significant interactions.

Pregnancy Considerations

Pregnant carriers of hemophilia A may have an increased bleeding risk following invasive procedures, spontaneous miscarriage, termination of pregnancy, and delivery; close surveillance is recommended. Factor VIII levels should be monitored at the first antenatal visit, once or twice during the third trimester, prior to surgical or invasive procedures, and at delivery. Although factor VIII concentrations increase in pregnant patients, factor VIII replacement is recommended if concentrations are <50 units/dL and any of the following occur: need for invasive procedures (including delivery), spontaneous miscarriage, insertion and removal of epidural catheters, or active bleeding. Hemostatic factor VIII concentrations should be maintained for at least 3 to 5 days following invasive procedures or postpartum. If a replacement product is indicated, a recombinant product is preferred (NHF 2017; RCOG [Pavord 2017]; WFH [Srivastava 2020]).

Breastfeeding Considerations

It is not known if antihemophilic factor (recombinant [Fc Fusion Protein]) is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring Parameters

Monitoring assay selection: For recombinant Fc fusion protein products, the World Federation of Hemophilia (WFH) recommends use of a one-stage or chromogenic factor VIII activity assay calibrated with a plasma standard traceable to a WHO international standard. Note: For patients receiving concomitant emicizumab therapy, emicizumab interferes with chromogenic factor VIII assays which use human factor IXa and factor X; use of chromogenic assays with bovine factor IXa and X is required to obtain reliable factor VIII activity when emicizumab is present (WFH [Srivastava 2020]).

Monitoring frequency: During treatment of an acute bleeding event or in the perioperative setting using intermittent bolus administration, factor VIII levels should be measured at baseline, and as peaks 15 to 30 minutes after infusion to assess target level achievement. Measurement of FVIII trough levels may aid in calculation of subsequent doses. Subsequent doses should ideally be based on the FVIII half-life and on the factor recovery of the individual patients. The frequency of peak factor VIII activity monitoring during active treatment depends on the indication, clinical response, and treatment day (WFH [Srivastava 2020]).

For long-term bleeding prophylaxis, trough factor VIII measurements should be obtained to tailor prophylaxis regimens, with the goal of achieving factor VIII troughs >3 to 5 units/dL; prophylaxis targets should be tailored to individual level of activity, lifestyle, and pharmacokinetics.

Patients with low-titer inhibitors receiving factor VIII concentrate products should undergo frequent assessment of factor VIII levels and inhibitor titers to ensure response is maintained.

Additional monitoring considerations: Heart rate and BP before and during IV administration; signs of hypersensitivity reactions, hemoglobin/hematocrit; and signs and symptoms of intravascular hemolysis.

Lower than expected factor VIII recovery or reduced half-life are early signs of inhibitor formation.

Reference Range

Classification of hemophilia; normal is defined as 100% factor VIII (WFH [Srivastava 2020]):

Severe: Factor level <1% of normal.

Moderate: Factor level 1% to 5% of normal.

Mild: Factor level >5% to <40% of normal.

Mechanism of Action

Factor VIII replacement, necessary for clot formation and maintenance of hemostasis. It activates factor X in conjunction with activated factor IX; activated factor X converts prothrombin to thrombin, which converts fibrinogen to fibrin, and with factor XIII forms a stable clot.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_ss: Children <12 years: ~0.52 to 0.59 dL/kg; Children ≥12 years, Adolescents, and Adults: ~0.50 to 0.6 dL/kg

Half-life elimination: Children <12 years: 12.7 to 14.9 hours; Children ≥12 years, Adolescents, and Adults: 16.4 to 19.7 hours

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Pediatric: Compared to adults, children have a shorter half-life and lower recovery of factor VIII; clearance (based on per kg body weight) is higher in pediatric patients.

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Elocta;
(AT) Austria: Elocta;
(AU) Australia: Eloctate;
(BE) Belgium: Elocta;
(BG) Bulgaria: Elocta;
(BR) Brazil: Eloctate;
(CH) Switzerland: Elocta;
(CO) Colombia: Eloctate;
(CZ) Czech Republic: Elocta;
(DE) Germany: Elocta;
(EE) Estonia: Elocta;
(ES) Spain: Elocta;
(FI) Finland: Elocta;
(FR) France: Elocta;
(GB) United Kingdom: Elocta;
(GR) Greece: Elocta;
(HK) Hong Kong: Eloctate;
(HU) Hungary: Elocta;
(IE) Ireland: Elocta;
(IT) Italy: Elocta;
(JP) Japan: Eloctate;
(LU) Luxembourg: Elocta;
(NO) Norway: Elocta;
(PL) Poland: Elocta;
(PT) Portugal: Elocta;
(RO) Romania: Elocta;
(SE) Sweden: Elocta;
(SI) Slovenia: Elocta;
(SK) Slovakia: Elocta;
(TW) Taiwan: Eloctate;
(ZA) South Africa: Eloctate

Eloctate (antihemophilic factor [recombinant]) [prescribing information]. Waltham, MA: Bioverativ Therapeutics Inc; May 2023.
National Hemophilia Foundation (NHF). Medical and Scientific Advisory Council (MASAC) guidelines for perinatal management of women with bleeding disorders and carriers of hemophilia A and B (MASAC document 251). https://www.hemophilia.org/node/3660. Published September 17, 2017. Accessed June 7, 2018.
Pavord S, Rayment R, Madan B, et al; for the Royal College of Obstetricians and Gynaecologists. Management of inherited bleeding disorders in pregnancy: Green-top Guideline No. 71 (joint with UKHCDO). BJOG. 2017;124(8):e193-e263. doi: 10.1111/1471-0528.14592. [PubMed 28447403]
Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al; Treatment Guidelines Working Group on Behalf of The World Federation Of Hemophilia. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1-e47. doi:10.1111/j.1365-2516.2012.02909.x [PubMed 22776238]
Srivastava A, Santagostino E, Dougall A, et al; WFH Guidelines for the Management of Hemophilia panelists and co-authors. WFH guidelines for the management of hemophilia, 3rd edition. Haemophilia. 2020;26(suppl 6):1-158. doi:10.1111/hae.14046 [PubMed 32744769]

Topic 109079 Version 96.0

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Factor VIII, recombinant human with Fc fusion: Drug information