Skip to Content

Antihemophilic Factor (Human)

Medically reviewed by Drugs.com. Last updated on Aug 26, 2020.

Pronunciation

(an tee hee moe FIL ik FAK tor HYU man)

Index Terms

  • AHF (Human)
  • Factor VIII (Human)
  • Koate DVI

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Kit, Intravenous:

Monoclate-P: ~1000 units [DSC], ~1500 units [DSC] [contains albumin human]

Solution Reconstituted, Intravenous:

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

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

Brand Names: U.S.

  • Hemofil M
  • Koate
  • Koate-DVI
  • Monoclate-P [DSC]

Pharmacologic Category

  • Antihemophilic Agent
  • Blood Product Derivative

Pharmacology

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

Distribution

Does not readily cross the placenta

Half-Life Elimination

Mean: 14.8 to 17.5 hours

Use: Labeled Indications

Hemophilia A: Control and prevention of bleeding episodes in patients with hemophilia A (classic hemophilia); perioperative management of hemophilia A.

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

Contraindications

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

Dosing: Adult

Hemophilia A: 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. Refer to product information for specific manufacturer recommended dosing. Alternatively, the World Federation of Hemophilia (WFH) has recommended general dosing for factor VIII products.

Dosage based on desired factor VIII increase (%):

To calculate dosage needed based on desired factor VIII increase (%):

Body weight (kg) x 0.5 units/kg x desired factor VIII increase (%) = units factor VIII required

For example:

50 kg x 0.5 units/kg x 30 (% increase) = 750 units factor VIII

Dosage based on expected factor VIII increase (%):

It is also possible to calculate the expected % factor VIII increase:

(# units administered x 2%/units/kg) divided by body weight (kg) = expected % factor VIII increase

For example:

(1400 units x 2%/units/kg) divided by 70 kg = 40%

World Federation of Hemophilia (WFH) treatment recommendations when no significant resource constraint exists (WFH [Srivastava 2013]):

2013 World Federation of Hemophilia Treatment Recommendations (When No Significant Resource Constraint Exists)

Site of Hemorrhage/Clinical Situation

Desired Factor VIII Level to Maintain

Duration

Note: Factor VIII level may either be expressed as units/dL or as %. Dosing frequency most commonly corresponds to the half-life of factor VIII but should be determined based on an assessment of factor VIII levels before the next dose.

Joint

40 to 60 units/dL

1 to 2 days, may be longer if response is inadequate

Superficial muscle/no neurovascular compromise

40 to 60 units/dL

2 to 3 days, sometimes longer if response is inadequate

Iliopsoas and deep muscle with neurovascular injury, or substantial blood loss

Initial: 80 to 100 units/dL

Initial: 1 to 2 days

Maintenance: 30 to 60 units/dL

Maintenance: 3 to 5 days, sometimes longer as secondary prophylaxis during physiotherapy

CNS/Head

Initial: 80 to 100 units/dL

Initial: 1 to 7 days

Maintenance: 50 units/dL

Maintenance: 8 to 21 days

Throat and neck

Initial: 80 to 100 units/dL

Initial: 1 to 7 days

Maintenance: 50 units/dL

Maintenance: 8 to 14 days

Gastrointestinal

Initial: 80 to 100 units/dL

Initial: 7 to 14 days

Maintenance: 50 units/dL

Maintenance: 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

Postop: 60 to 80 units/dL

Postop: 1 to 3 days

Postop: 40 to 60 units/dL

Postop: 4 to 6 days

Postop: 30 to 50 units/dL

Postop: 7 to 14 days

Surgery (minor)

Preop: 50 to 80 units/dL

Postop: 30 to 80 units/dL

Postop: 1 to 5 days depending on procedure type

Continuous infusion (for patients who require prolonged periods of treatment [eg, intracranial hemorrhage or surgery] to avoid peaks and troughs associated with intermittent infusions) (Batorova 2002; Batorova 2012; Poon 2012; Rickard 1995; WFH [Srivastava 2013]): Following initial bolus to achieve the desired factor VIII level, initiate 2 to 4 units/kg/hour; adjust dose based on frequent factor 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) divided by (plasma level in units/mL)

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

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Hemophilia A: Individualize dosage based on clinical response and factor VIII activity evaluated at baseline and at regular intervals during treatment. In general, administration of factor VIII 1 unit/kg will increase circulating factor VIII levels by ~2% of normal. Patients with inhibitory antibodies to factor VIII may require higher doses, more frequent administration, and/or selection of alternative therapy.

General dosing for control and prevention 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.

Infants, Children, and Adolescents (ages vary by product; see product-specific labeling for approved ages): IV:

Formula for units required to raise blood level:

Number of Factor VIII Units required = body weight (in kg) x 0.5 units/kg per units/dL x desired factor VIII level increase (units/dL or %)

For example, for a desired 100% level in a 25 kg patient who has an actual level of 20%: Number of Factor VIII Units needed = 25 kg x 0.5 units/kg per units/dL x 80% = 1,000 units

Treatment recommendations (WFH [Srivastava 2013]): Note: Factor VIII level may either be expressed as % or as units/dL.

Intermittent IV: Infants, Children and Adolescents: The following recommendations reflect guideline recommendations for general dosing requirements; 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.

Site of Hemorrhage/Clinical Situation

Desired Factor VIII Peak Level

FrequencyA

Duration

AFrequency is based on type of bleed or surgery and varies by product; see specific product labeling for details.

Joint

40% to 60%

Every 8 to 24 hours

1 to 2 days, may be longer if response is inadequate

Superficial muscle/no neurovascular compromise

40% to 60%

Every 8 to 24 hours

2 to 3 days, sometimes longer if response is inadequate

Iliopsoas and deep muscle with neurovascular injury, or substantial blood loss

Initial: 80% to 100%

Every 8 to 24 hours

Initial: 1 to 2 days

Maintenance: 30% to 60%

Maintenance: 3 to 5 days, sometimes longer as secondary prophylaxis during physiotherapy

CNS/Head

Initial: 80% to 100%

Every 8 to 24 hours

Initial: 1 to 7 days

Maintenance: 50%

Maintenance: 8 to 21 days

Throat and neck

Initial: 80% to 100%

Every 8 to 24 hours

Initial: 1 to 7 days

Maintenance: 50%

Maintenance: 8 to 14 days

Gastrointestinal

Initial: 80% to 100%

Every 8 to 24 hours

Initial: 7 to 14 days

Maintenance: 50%

Maintenance: Not specified

Renal

50%

Every 8 to 24 hours

3 to 5 days

Deep laceration

50%

Every 8 to 24 hours

5 to 7 days

Surgery (major)

Preop: 80% to 100%

Single dose

Postop: 60% to 80%

Every 8 to 24 hours

Postop: 1 to 3 days

Postop: 40% to 60%

Postop: 4 to 6 days

Postop: 30% to 50%

Postop: 7 to 14 days

Surgery (minor)

Preop: 50% to 80%

Single dose

Postop: 30% to 80%

Every 8 to 24 hours

Postop: 1 to 5 days depending on procedure type

Continuous IV infusion: Infants, Children, and Adolescents: Note: In general, administration of factor VIII 4 units/kg/hour will increase circulating factor VIII levels by 1 unit/mL (Prelog 2016).

Control and prevention of bleeding episodes: Limited data available: Note: For patients who require prolonged periods of treatment (eg, intracranial hemorrhage or surgery) to avoid peaks and troughs associated with intermittent infusions (Batorova 2002; Poon 2012; Prelog 2016; WFH [Srivastava 2013]):

Following initial bolus to achieve the desired factor VIII level: 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) / (plasma factor VIII level in units/mL)

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

Perioperative management: Limited data available: Initial: 25 to 50 units/kg prior to surgery, followed by continuous infusion at a rate of 3 to 5 units/kg/hour; regimen based on 2 studies evaluating use in pediatric surgery patients (age range: 0.9 to 17 years); rate was adjusted and additional boluses given as needed to maintain desired factor VIII level (Batorova 2012; Dingli 2002).

Reconstitution

If refrigerated, the dried concentrate and diluent should be warmed to room temperature before reconstitution. Gently swirl or rotate vial after adding diluent; do not shake vigorously.

Continuous infusion (off-label method of administration): Further dilution after initial reconstitution is unnecessary (Batorova 2012).

Administration

IV:

Hemofil M, Koate: Administer at a rate comfortable to the patient (≤10 mL/minute).

Monoclate-P: Administer at a rate comfortable to the patient (~2 mL/minute).

According to the World Federation of Hemophilia (WFH), infuse by slow IV injection at a rate not to exceed 3 mL/minute; may also administer as a continuous infusion in select patients (WFH [Srivastava 2013]). When administering as a continuous infusion, may use a portable mini-pump or syringe pump (Batorova 2012).

Storage

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

Drug Interactions

There are no known significant interactions.

Adverse Reactions

1% to 10%:

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

Local: Inflammation at injection site (2%)

<1%: Chest tightness, dizziness, dysgeusia, fever, headache

Frequency not defined: Hypersensitivity: Hypersensitivity reaction

Postmarketing: Abdominal pain, anaphylaxis, bradycardia, bronchospasm, chest pain, chills, cough, cyanosis, diarrhea, dyspnea, edema, facial edema, fatigue, flushing, hyperhidrosis, hyperventilation, hypotension, irritability, musculoskeletal pain, nausea, ocular hyperemia, pruritus, skin rash, tachycardia, urticaria, visual impairment, vomiting

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 and Monoclate-P contain 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.

Monitoring Parameters

Heart rate and blood pressure (before and during IV administration); AHF levels prior to and during treatment; in patients with circulating inhibitors, the inhibitor level should be monitored; hematocrit; monitor for signs and symptoms of intravascular hemolysis; bleeding

When administering as a continuous infusion, monitor frequently for pump failure (WFH [Srivastava 2013]).

Pregnancy Considerations

Pregnant hemophilia A carriers may have an increased bleeding risk following abortion, invasive procedures, miscarriage, 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 <0.5 IU/mL 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 2013]).

Patient Education

What is this drug used for?

• It is used to treat hemophilia.

• It is used to treat or prevent bleeding.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Anxiety

• Headache

• Abdominal pain

• Nausea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Parvovirus B19 or hepatitis A infection like chills, severe fatigue, runny nose, rash, joint pain, lack of appetite, nausea, vomiting, abdominal pain, or yellow skin or eyes

• Shortness of breath

• Severe dizziness

• Passing out

• Burning or numbness feeling

• Restlessness

• Blurred vision

• Flushing

• Severe loss of strength and energy

• Fast heartbeat

• Chest pain

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Related questions