Factor VIII, human plasma-derived: Pediatric drug information

For additional information see "Factor VIII, human plasma-derived: Drug information" and "Factor VIII, human plasma-derived: Patient drug information"

For abbreviations, symbols, and age group definitions show table

Brand Names: US

Hemofil M;
Koate;
Koate-DVI

Therapeutic Category

Antihemophilic Agent;
Blood Product Derivative

Dosing: Pediatric

Hemophilia A

Hemophilia A: Individualize dosage based on clinical response and factor VIII activity evaluated at baseline and at regular intervals during treatment. Patients with inhibitory antibodies to factor VIII may require higher doses, more frequent administration, and/or selection of alternative therapy.

Treatment and control of bleeding episodes or perioperative management: Note: Dosage is expressed in units of factor VIII activity and must be individualized based on formulation, severity of factor VIII deficiency, extent and location of bleed, individualized incremental recovery using factor VIII activity assays, and clinical situation of patient. Ages vary by product; see product-specific labeling for approved ages.

Infants, Children, and Adolescents: IV:

Intermittent IV bolus dosing: IV: Utilize steps 1 through 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. These recommendations reflect WFH guidelines for higher-dose practice patterns; this dosing is typically used in areas where no significant resource constraints exist; recommendations may vary from those found within prescribing information or practitioner preference. Frequency is based on type of bleed or surgery and varies by product; see specific product labeling for details. Dosing frequency most commonly corresponds to the half-life of factor VIII but should be determined based on an assessment of factor VIII levels (if available) before the next dose (Ref).

**WFH Treatment Recommendations^a**
Site of hemorrhage/clinical situation	Desired factor VIII peak level	Duration^b
^a WFH = World Federation of Hemophilia; (WFH [Srivastava 2020]).
^b Depending on procedure; the number of doses would depend on the half-life of the clotting factor concentrate (CFC) used.
^c May be longer if response is inadequate.
^d A single dose may be sufficient for some joint bleeds; determine need for additional doses based on clinical response.
^e Sometimes longer as secondary prophylaxis during physical therapy.
Joint	40 to 60 units/dL	1 to 2 days^c,d
Superficial muscle/no neurovascular compromise	40 to 60 units/dL	2 to 3 days^c
Iliopsoas or deep muscle with neurovascular injury, or substantial blood loss	Initial: 80 to 100 units/dL	1 to 2 days
	Maintenance: 30 to 60 units/dL	3 to 5 days^e
CNS/Head	Initial: 80 to 100 units/dL	1 to 7 days
CNS/Head	Maintenance: 50 units/dL	8 to 21 days
Throat and neck	Initial: 80 to 100 units/dL	1 to 7 days
Throat and neck	Maintenance: 50 units/dL	8 to 14 days
Gastrointestinal	Initial: 80 to 100 units/dL	7 to 14 days
Gastrointestinal	Maintenance: 50 units/dL	Not specified
Renal	50 units/dL	3 to 5 days
Deep laceration	50 units/dL	5 to 7 days
Surgery (major)	Preop: 80 to 100 units/dL	Single dose
	Postop: 60 to 80 units/dL	1 to 3 days
	Postop: 40 to 60 units/dL	4 to 6 days
	Postop: 30 to 50 units/dL	7 to 14 days
Surgery (minor)	Preop: 50 to 80 units/dL	Single dose
Surgery (minor)	Postop: 30 to 80 units/dL	1 to 5 days

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

Formula for units required to raise blood level:

Factor VIII units required =

[(desired peak factor VIII level − baseline factor VIII level) × body weight (kg)]/2

Note: Factor VIII level units are units/dL.

Example for 25 kg patient with a 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) × 25 (kg)]/2 = 375 units of factor VIII

Step 3: Determine the frequency of repeat dosing based on half-life of product used (see product-specific labeling for details), type of bleed or surgery, and patient response. If subsequent factor VIII levels are available for individual patients, these should be taken into consideration when determining the frequency of repeat dose.

**Antihemophilic Factor (Human) Administration Frequency According to Clinical Scenario**
Product	Type of bleeding event			Type of surgery
Product	Minor severity^a	Moderate severity^b	Major severity^c	Minor bleeding risk^d	Major bleeding risk^e
^a Minor bleeds include early hemarthrosis, mild muscle bleeding, or mild oral bleeding episode.
^b Moderate bleeds include muscle bleeding, moderate bleeding into the oral cavity (including from dental extractions), definite hemarthroses, and known trauma.
^c Major bleeds include significant GI bleeding, intracranial, intra-abdominal or intrathoracic bleeding, CNS bleeding, bleeding in the retropharyngeal or retroperitoneal spaces or iliopsoas sheath, fractures, head trauma.
^d Including tooth extraction.
^e For example: intracranial, intra-abdominal, or intrathoracic surgery; joint replacement surgery.
Hemofil-M	Every 12 to 24 hours	Every 12 to 24 hours	Every 8 to 24 hours	Single dose typically adequate	Every 8 to 24 hours
Koate	Every 12 hours	Every 12 hours	Every 12 hours	Every 12 hours	Every 12 hours

Continuous IV infusion dosing: Limited data available (Ref):

Note: Continuous infusion administration is preferred over intermittent bolus administration for patients requiring prolonged treatment courses (eg, postoperative management after surgery with major bleeding risk) to avoid peaks and troughs associated with intermittent infusions. To ensure safe and effective use, only products with extended stability information should be used. Extended stability information may not be available for all products; contact product manufacturer to obtain current recommendations. Use of a smart infusion pump with small volume infusion capability is also necessary. In general, administration of factor VIII 4 units/kg/hour will increase circulating factor VIII levels by 1 unit/mL.

Infants, Children, and Adolescents: Continuous IV infusion: Note: Use with caution and consider risk versus benefit in patients with <20 exposure days or mild hemophilia due to increased risk of inhibitor development (Ref).

Following initial bolus to achieve the desired factor VIII level (see steps 1 and 2 under "Intermittent IV Bolus Dosing"): Initial dosing: 2 to 4 units/kg/hour; adjust dose based on frequent factor VIII assays and calculation of factor VIII clearance at steady state using the following equations:

Factor VIII clearance (mL/kg/hour) = (current infusion rate in units/kg/hour) / (measured factor VIII level in units/mL)

New infusion rate (units/kg/hour) = (factor VIII clearance in mL/kg/hour) × (desired factor VIII level in units/mL)

Note: With infusion dose increases, re-bolus should be considered to achieve target factor VIII level more quickly. See steps 1 and 2 under "Intermittent IV Bolus Dosing" to determine re-bolus dose.

Routine prophylaxis to prevent or reduce the frequency of bleeding episodes:

Note: Dose should be individualized; dose intensity should take into account disease severity, patient's activity and lifestyle, and pharmacokinetic properties of product, and should be adjusted if breakthrough bleeding occurs. See WFH guidelines for in-depth discussion of risks and benefits of each approach (Ref).

Infants, Children, and Adolescents:

High dose: IV: 25 to 40 units/kg/dose every 2 days.

Intermediate dose: IV: 15 to 25 units/kg/dose 3 times weekly.

Low dose: IV: 10 to 15 units/kg/dose 2 to 3 times weekly. Note: Low-dose prophylaxis may be used in young patients as initial therapy to allow patients and families to gradually adjust to prophylaxis and improve adherence; close monitoring is required since patients are at a higher risk for bleeding until escalation occurs.

Dosing: Kidney Impairment: Pediatric

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

Dosing: Liver Impairment: Pediatric

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

Dosing: Adult

(For additional information see "Factor VIII, human plasma-derived: Drug information")

Hemophilia A, treatment and control of bleeding episodes in patients receiving fitusiran

Hemophilia A, treatment and control of bleeding episodes in patients receiving fitusiran:

During first 7 days of fitusiran initiation: IV: Manage bleeding with patient's previously established regimen of clotting factor concentrate or bypassing agent (Ref).

After 7 days from first fitusiran dose: IV: Initial: 10 to 20 units/kg; reassess clinical status and need for repeat doses; in general, dose should not be repeated within 24 hours. Higher doses or more frequent administration may be considered based on clinical judgment (Ref).

Hemophilia A, without inhibitors

Hemophilia A, without inhibitors:

Treatment and control of bleeding episodes or perioperative management (when baseline factor VIII level is known):

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 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 (Human) WFH 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 units/dL	1 to 2 days^a,c	40 to 60 units/dL	1 to 2 days^a,c
Superficial muscle/no neurovascular compromise (except iliopsoas)	10 to 20 units/dL	2 to 3 days^a	40 to 60 units/dL	2 to 3 days^a
Iliopsoas or deep muscle with neurovascular injury or substantial blood loss:
Initial	20 to 40 units/dL	1 to 2 days	80 to 100 units/dL	1 to 2 days
Maintenance	10 to 20 units/dL	3 to 5 days^b	30 to 60 units/dL	3 to 5 days^b
Intracranial:
Initial	50 to 80 units/dL	1 to 3 days	80 to 100 units/dL	1 to 7 days
Maintenance	30 to 50 units/dL	4 to 7 days	50 units/dL	8 to 21 days
Maintenance	20 to 40 units/dL	8 to 14 days	-	-
Throat and neck:
Initial	30 to 50 units/dL	1 to 3 days	80 to 100 units/dL	1 to 7 days
Maintenance	10 to 20 units/dL	4 to 7 days	50 units/dL	8 to 14 days
Gastrointestinal:
Initial	30 to 50 units/dL	1 to 3 days	80 to 100 units/dL	7 to 14 days
Maintenance	10 to 20 units/dL	4 to 7 days	50 units/dL	-
Renal	20 to 40 units/dL	3 to 5 days	50 units/dL	3 to 5 days
Deep laceration	20 to 40 units/dL	5 to 7 days	50 units/dL	5 to 7 days
Surgery (major):
Preop	60 to 80 units/dL	-	80 to 100 units/dL	-
Postop	30 to 40 units/dL	1 to 3 days	60 to 80 units/dL	1 to 3 days
	20 to 30 units/dL	4 to 6 days	40 to 60 units/dL	4 to 6 days
	10 to 20 units/dL	7 to 14 days	30 to 50 units/dL	7 to 14 days
Surgery (minor):
Preop	40 to 80 units/dL	-	50 to 80 units/dL	-
Postop	20 to 50 units/dL	1 to 5 days	30 to 80 units/dL	1 to 5 days

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 the clinical response.

**Antihemophilic Factor (Human) Administration Frequency According to Clinical Scenario**
Product	Bleeding event			Surgery
Product	Minor severity	Moderate severity	Major severity	Minor bleeding risk	Major bleeding risk
Hemofil-M	Every 12 to 24 hours	Every 12 to 24 hours	Every 8 to 24 hours	Single dose typically adequate	Every 8 to 24 hours
Koate	Every 12 hours	Every 12 hours	Every 12 hours	Every 12 hours	Every 12 hours

Continuous infusion dosing (Ref):

Note: Continuous infusion administration is preferred over intermittent bolus administration for patients requiring prolonged treatment courses (eg, postoperative management after surgery with major bleeding risk). To ensure safe and effective use, only products with extended stability information should be used. Extended stability information may not be available for all products; contact product manufacturer to obtain current recommendations. Use of a smart infusion pump with small volume infusion capability is also necessary.

IV: Administer an initial bolus to achieve the desired factor VIII level (see steps 1 and 2 under intermittent bolus dosing), then initiate continuous infusion at 2 to 4 units/kg/hour. Adjust dose based on frequent factor assays (at least daily) and calculation of factor VIII clearance at steady-state using the below equations.

Factor VIII clearance (mL/kg/hour) = (current infusion rate in units/kg/hour) divided by (measured factor VIII level in units/mL)

New infusion rate (units/kg/hour) = (factor VIII clearance in mL/kg/hour) x (desired factor VIII level in units/mL)

Note: With infusion dose increases, re-bolus should be considered to achieve target factor VIII level more quickly. See steps 1 and 2 under intermittent bolus dosing to determine re-bolus dose.

Treatment and control of bleeding episodes (when baseline factor VIII level is not known):

Note: After the loading dose, if possible, it is preferred to obtain a factor VIII level to determine subsequent doses based on patient needs rather than continuing an empiric dosing regimen. In general, administration of factor VIII 1 unit/kg will increase circulating factor VIII levels by ~2 units/dL (Ref). Consider transfer of care to comprehensive hemophilia treatment center with capacity to perform clotting factor assays and inhibitor testing. For patients without inhibitors and receiving emicizumab who experience breakthrough bleeding, antihemophilic factor should be dosed to target the desired peak factor VIII level as emicizumab is not indicated for treatment of bleeding episodes (Ref).

**Antihemophilic Factor (Human) D** **ose and** **Frequency According to Clinical Scenario^a**
Product and bleeding severity	Loading dose (units/kg), IV	Desired peak factor VIII level (units/dL)^b	Maintenance dose (units/kg)^b, IV	Frequency of maintenance dose^b	Treatment duration (days)^c
^aManufacturer’s labeling.
^bDesired peak factor VIII level, dose, and frequency of maintenance dose administration may change as bleeding becomes more controlled. Individualize dosing to patient-specific needs by evaluating circulating factor VIII levels.
^c Dosing continues until bleeding resolves and may extend beyond what is indicated in this table. It is preferable to individualize dosing based on patient-specific needs by evaluating circulating factor VIII levels.
^dNational Bleeding Disorders Foundation, Medical and Scientific Advisory Council of the National Hemophilia Foundation, document #257.
^eApproximate dose based on estimated incremental recovery of 2 units/dL (manufacturer’s labeling).
Hemofil-M
Minor bleeding	10 to 20 units/kg^e	20 to 40 units/dL	10 to 20 units/kg^e	Every 12 to 24 hours	1 to 3 days
Moderate bleeding	15 to 30 units/kg^e	30 to 60 units/dL	15 to 30 units/kg^e	Every 12 to 24 hours	≥3 days
Major bleeding	50 units/kg^d	80 to 100 units/dL^d	30 to 50 units/kg^e	Every 8 to 24 hours	Not specified
Koate
Minor bleeding	15 units/kg	30 units/dL	15 units/kg	Every 12 hours	1 to 2 days
Moderate bleeding	25 units/kg	50 units/dL	25 units/kg	Every 12 hours	2 to 7 days
Major bleeding	50 units/kg^d	80 to 100 units/dL^d	25 units/kg	Every 12 hours	3 to 10 days

Routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with moderate/severe hemophilia A, without inhibitors: IV: 25 to 40 units/kg of factor VIII concentrate every 2 to 3 days. 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.

Dosing: Liver Impairment: Adult

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.

1% to 10%:

Gastrointestinal: Abdominal pain (5%), nausea (5%)

Hematologic & oncologic: Increased factor VIII inhibitors (6%)

Local: Inflammation at injection site (2%)

Nervous system: Headache (≤5%), nervousness (10%), paresthesia (5%)

Ophthalmic: Blurred vision (5%)

<1%:

Cardiovascular: Chest tightness

Gastrointestinal: Dysgeusia

Nervous system: Dizziness

Miscellaneous: Fever

Postmarketing:

Cardiovascular: Bradycardia, chest pain, edema, flushing, hypotension, tachycardia

Dermatologic: Hyperhidrosis, pruritus, skin rash, urticaria

Gastrointestinal: Diarrhea, vomiting

Hematologic & oncologic: Hemolytic anemia

Hypersensitivity: Facial edema, hypersensitivity reaction (including anaphylaxis)

Nervous system: Chills, fatigue, irritability, tonic-clonic seizure

Neuromuscular & skeletal: Musculoskeletal pain

Ophthalmic: Ocular hyperemia, visual impairment

Respiratory: Bronchospasm, cough, cyanosis, dyspnea, hyperventilation

Contraindications

Hypersensitivity (eg, anaphylaxis) to antihemophilic factor (human) or any component of the formulation; hypersensitivity to mouse proteins (Hemofil M only).

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

Special populations:

• Blood types A, B, and AB: Contains trace amounts of blood groups A and B isohemagglutinins; use caution when large or frequently repeated doses are given to individuals with blood groups A, B, and AB. Monitor patients for signs of intravascular hemolysis and falling hematocrit; discontinue therapy and consider administration of serologically compatible type O red blood cells if progressive hemolytic anemia occurs.

Dosage form specific issues:

• Albumin: Products vary by preparation method; final formulations contain human albumin.

• Human plasma: Product of human plasma; may potentially contain infectious agents which could transmit disease. Screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces the risk. Infections thought to be transmitted by this product should be reported to the manufacturer. Hepatitis A and B vaccination is recommended for all patients receiving plasma derivatives.

• Mouse protein: Hemofil M contains trace amounts of mouse protein; use is contraindicated in patients with hypersensitivity to mouse protein.

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

• von Willebrand factor: Some products may contain naturally occurring von Willebrand factor for stabilization; however, efficacy has not been established for the treatment of von Willebrand disease.

Other warnings/precautions:

• Appropriate use: Dosage requirements will vary in patients with factor VIII inhibitors; optimal treatment should be determined by clinical response. Frequency of use is determined by the severity of the disorder or bleeding pattern.

Warnings: Additional Pediatric Considerations

Formation of factor VIII inhibitors (neutralizing antibodies to AHF human) may occur; reported incidence is 3% to 52%; an increase of inhibitor antibody concentration is seen at 2 to 7 days, with peak concentrations at 1 to 3 weeks after therapy; children <5 years of age are at greatest risk; higher doses of AHF may be needed if antibody is present; if antibody concentration is >10 Bethesda units/mL, patients may not respond to larger doses and alternative treatment modalities may be needed; monitor patients appropriately. Allergic-type hypersensitivity reactions, including anaphylaxis, may occur; discontinue therapy immediately if urticaria, hives, hypotension, tightness of the chest, wheezing, dyspnea, faintness, or anaphylaxis develop; emergency treatment and resuscitative measures (eg, epinephrine, oxygen) may be needed.

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. [DSC] = Discontinued product

Solution Reconstituted, Intravenous:

Koate: ~250 units (1 ea); ~500 units (1 ea); ~1000 units (1 ea) [contains albumin human, polyethylene glycol (macrogol), polysorbate 80]

Solution Reconstituted, Intravenous [preservative free]:

Hemofil M: ~250 units (1 ea); ~500 units (1 ea); ~1000 units (1 ea); ~1700 units (1 ea) [contains albumin human, polyethylene glycol (macrogol)]

Koate-DVI: ~500 units (1 ea [DSC]); ~1000 units (1 ea) [contains albumin human, polyethylene glycol (macrogol), polysorbate 80]

Generic Equivalent Available: US

Pricing: US

Solution (reconstituted) (Hemofil M Intravenous)

250 unit (Price provided is per AHF Unit): $1.98

500 unit (Price provided is per AHF Unit): $1.98

1000 unit (Price provided is per AHF Unit): $1.98

1700 unit (Price provided is per AHF Unit): $1.98

Solution (reconstituted) (Koate Intravenous)

250 unit (Price provided is per AHF Unit): $1.73

500 unit (Price provided is per AHF Unit): $1.73

1000 unit (Price provided is per AHF Unit): $1.73

Solution (reconstituted) (Koate-DVI Intravenous)

1000 unit (per each): $1.73

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.

Additional Information

One unit of AHF is equal to the factor VIII activity present in 1 mL of normal human plasma. If bleeding is not controlled with adequate dose, test for the presence of factor VIII inhibitor; larger doses of AHF may be therapeutic with inhibitor titers <10 Bethesda units/mL; it may not be possible or practical to control bleeding if inhibitor titers >10 Bethesda units/mL (due to the very large AHF doses required); other treatments [eg, antihemophilic factor (porcine), factor IX complex concentrates, recombinant factor VIIa, or anti-inhibitor coagulant complex] may be needed in patients with inhibitor titers >10 Bethesda units/mL.

Administration: Pediatric

Parenteral: IV administration only; use administration sets/tubing provided by manufacturer (if provided). Administer through a separate line, do not mix with drugs or other IV fluids.

Intermittent IV: Rate of administration should be determined by patient tolerability; maximum rate 10 mL/minute.

Continuous IV infusion: Further dilution after initial reconstitution is unnecessary (Ref). Use a smart infusion pump with small volume infusion capability (Ref).

Administration: Adult

IV: Administer at a rate comfortable to the patient (≤10 mL/minute).

Continuous infusion (off-label rate): Has also been administered as a continuous infusion to avoid peaks and troughs associated with intermittent infusions in patients who require prolonged treatment periods. Use a smart infusion pump with small volume infusion capability. Refer to protocols for product selection and preparation details (Ref).

Storage/Stability

Store under refrigeration, 2°C to 8°C (36°F to 46°F); do not freeze. Use within 3 hours of reconstitution. Do not refrigerate after reconstitution, precipitation may occur.

Hemofil M: May also be stored at room temperature not to exceed 30°C (86°F).

Koate: May also be stored at 25°C (77°F) for ≤6 months. Store in original package to protect from light.

Use

Control and prevention of bleeding episodes in patients with hemophilia A (classical hemophilia) and perioperative management of patients with hemophilia A (Hemofil M: FDA-approved in pediatric patients [age not specified] and adults; Koate: FDA approved in ages ≥2.5 years and adults). Has also been used for routine prophylaxis to reduce the frequency of bleeding episodes in patients with hemophilia A and to provide therapeutic effects in patients with acquired factor VIII inhibitors <10 Bethesda units/mL.

Note: Antihemophilic factor (human) is 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

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program

Fitusiran: May increase thrombogenic effects of Clotting Factor Concentrates (CFCs) and Bypassing Agents (BPAs). Management: Stop CFC/BPA prophylaxis no later than 7 days after starting fitusiran. If bleeding occurs during the first 7 days of fitusiran, manage with the prior dosing regimen of CFC/BPA. If bleeding occurs after 7 days, use reduced CFC/BPA doses and frequencies. Risk D: Consider Therapy Modification

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 (NBDF 2017; RCOG [Pavord 2017]; WFH [Srivastava 2020]).

Monitoring Parameters

Note: 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 World Health Organization (WHO) international standard for monitoring (WFH [Srivastava 2020]).

Monitor factor VIII levels prior to and during treatment; typically during treatment of an acute bleeding event or in the perioperative setting, factor VIII levels should be measured at baseline, as peak levels 15 to 30 minutes after infusion to assess target level achievement and as trough levels to aid in calculation of subsequent doses. The frequency of monitoring depends on the indication, clinical response, and treatment day (WFH [Srivastava 2020]). When administered as a continuous infusion, monitor factor VIII activity at baseline, peak factor VIII activity 15 to 30 minutes after initial bolus administration, and at least daily while on continuous infusion therapy. Frequently assess proper functioning of vascular access devices and infusion pumps for pump failure (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 (WFH [Srivastava 2020]).

Heart rate and blood pressure (before and during IV administration); monitor for signs and symptoms of bleeding, Hb and Hct, and for hypersensitivity reactions; monitor for development of inhibitor antibodies by clinical observation (eg, inadequate control of bleeding with adequate doses) and laboratory tests (eg, inhibitor level, Bethesda assay). In patients with blood groups A, B, or AB who receive large or frequent doses, monitor Hct, direct Coombs' test, and signs of intravascular hemolysis.

Reference Range

Classification of hemophilia; normal is defined as 1 unit/mL of 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

Protein (factor VIII) in normal plasma which is necessary for clot formation and maintenance of hemostasis; 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: Does not readily cross the placenta

Half-life elimination: Mean: 14.8 to 17.5 hours

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Factor viii | Koate dvi;
(AR) Argentina: Beriate | Beriate p | Emoclot | Fanhdi | Hemofil m | Koate dvi | Octanate | Optivate;
(AT) Austria: Beriate p | Haemoctin sdh | Octanate;
(BE) Belgium: Factane | Monoclate P;
(BG) Bulgaria: Beriate | Emoclot DI | Hemofil m | Koate | Octanate;
(BR) Brazil: Beriate p | Fanhdi | Hemofil | Koate dvi;
(CH) Switzerland: Beriate | Haemoctin | Octanate;
(CL) Chile: Koate dvi | Octanate;
(CN) China: Hemoraas | Kang si ping;
(CO) Colombia: Beriate | Emoclot | Factane | Fanhdi | Haemoctin sdh | Hemofil m | Koate | Koate dvi | Koate mr dvi | Octanate | Optivate;
(CZ) Czech Republic: Beriate | Beriate p | Criostat | Fanhdi | Haemoctin sdh | Octanate;
(DE) Germany: Beriate | Beriate p | Fanhdi | Haemoctin sdh | Hemofil m | Monoclate P | Octanate | Optivate | Profilate;
(EC) Ecuador: Beriate | Emoclot | Fanhdi | Octanate | Plasmaclot;
(EE) Estonia: Beriate | Hemofil m | Octanate | Octonativ-M;
(EG) Egypt: Koate dvi | Octanate;
(ES) Spain: Beriate p | Fanhdi | Haemoctin | Hemofil m | Octanate;
(FI) Finland: Amofil | Octafil | Octafil low;
(FR) France: Factane | Hemofil m | Monoclate | Octanate LV;
(GB) United Kingdom: Beriate p | Fanhdi | Haemoctin | Hemofil m | Monoclate P | Octanate | Optivate | Profilate;
(GR) Greece: Fanhdi | Haemoctin | Octanate;
(HK) Hong Kong: Haemoctin sdh | Koate | Koate dvi;
(HU) Hungary: Beriate | Beriate hs | Beriate p | Fanhdi | Haemoctin sdh | Hemofil m | Koate dvi | Octanate | Octonativ-M;
(ID) Indonesia: Aafact | Beriate | Haemoctin | Koate dvi | Koate HP | Koate HT | Octanate;
(IN) India: Beriate | Hemorel a;
(IT) Italy: Beriate p | Emoclot d.i. | Fanhdi | Haemoctin | Hemofil m | Koate | Octanate;
(JP) Japan: Koate | Profilate;
(KR) Korea, Republic of: Monoclate P;
(KW) Kuwait: Beriate;
(LB) Lebanon: Beriate;
(LT) Lithuania: Haemoctin sdh | Hemofil m | Koate HP | Octanate;
(LU) Luxembourg: Octanate;
(LV) Latvia: Cilveka koagulacijas faktora VIII | Haemoctin sdh | Hemofil m | Kaote dvi | Koate dvi | Octanate;
(MX) Mexico: Beriate | Fanhdi | Haemoctin sdh | Hemofil m | Koate dvi | Monoclate P | Octanate | Optivate | Plasmaclot;
(MY) Malaysia: Beriate | Factor viii | Hemofil m | Octanate | Optivate;
(NL) Netherlands: Aafact | Octanate;
(NO) Norway: Octanate;
(PE) Peru: Factor viii | Octanate | Optivate;
(PH) Philippines: Hemofil m | Koate | Octanate;
(PL) Poland: Beriate | Emoclot | Fanhdi | Octanate;
(PR) Puerto Rico: Hemofil m | Koate dvi | Koate HP;
(PT) Portugal: Beriate p | Emoclot | Factor viii | Fanhdi | Hemofil m | Monoclate P | Octanate;
(PY) Paraguay: Factor viii green cross | Koate dvi;
(RO) Romania: Fanhdi | Haemoctin sdh | Octanate | Optivate;
(RU) Russian Federation: Agemfil a | Beriate | Emoclot | Emoclot d.i. | Fanhdi | Haemoctin | Hemofil m | Koate dvi | Octanate;
(SA) Saudi Arabia: Factor viii | Koate dvi | Octanate | Optivate;
(SE) Sweden: Ahf-Koncentrat | Beriate | Beriate p | Hemofil m | Koate | Monoclate P | Octanate | Octonativ-M | Profilate;
(SG) Singapore: Octanate;
(SI) Slovenia: Octanate;
(SK) Slovakia: Fanhdi;
(TH) Thailand: Fanhdi | Haemoctin sdh | Hemofil m | Profilate;
(TN) Tunisia: Beriate | Emoclot DI | Haemoctin sdh | Octanate;
(TR) Turkey: AHF M | Beriate p | Emoclot | Factane | Factor viii | Fanhdi | Haemoctin sdh | Hemofil m | Koate dvi | Koate HP | Nordiate | Octanate;
(TW) Taiwan: Beriate p | Factor viii | Haemoctin sdh | Koate dvi | Koate HP | Monoclate P;
(UA) Ukraine: Beriate | Emoclot | Koate dvi | Octanate;
(UG) Uganda: Octanate;
(UY) Uruguay: Emoclot | Haemoctin sdh | Hemofil m | Koate dvi | Koate HP;
(VE) Venezuela, Bolivarian Republic of: Factor viii

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Topic 12748 Version 231.0

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Factor VIII, human plasma-derived: Pediatric drug information