This policy addresses the use of the intravenous Factor VIII in the outpatient setting only. This policy does not apply to the use of factor VIII in inpatient or emergency room settings.
INITIAL AND CONTINUATION APPROVAL will be for duration of treatment course or 12 months (whichever comes first). Approval timeframes may differ for members/participants of Self-Insured plans.
Effective November 15, 2025
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Factor VIII (e.g., Advate, Adynovate, Afstyla, Alphanate, Altuviiio, Eloctate, Esperoct, Jivi, Hemofil-M, Humate-P, Koate, Kovaltry, Novoeight, Nuwiq, Obizur, Recombinate, Wilate, Xyntha) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when
ALL the following criteria are met:
HEMOPHILIA A
INITIAL APPROVAL:
1. Individual has a diagnosis of severe hemophilia A (see policy guidelines);
AND individual is using for one of the following:
a. Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes;
OR
b. On-demand treatment and control of bleeding episodes;
OR
c. Peri-procedural management for surgical, invasive, or interventional radiology procedures;
OR
2. Individual has a diagnosis of mild to moderate hemophilia A (see policy guidelines);
AND individual is using for one of the following:
a. On-demand treatment and control of bleeding episodes;
OR
b. Peri-procedural management for surgical, invasive, or interventional radiology procedures;
OR
3. Individual has diagnosis of mild to moderate hemophilia A (see policy guidelines) with intention to use factor VIII as routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes
AND one of the following criteria is met (NHF, Srivastava 2020):
a. One or more episodes of spontaneous bleeding into joint;
OR
b. One or more episodes of spontaneous bleeding into the central nervous system;
OR
c. Four or more episodes of soft tissue bleeding in an 8-week period;
OR
d. Individual’s risk factors increase the risk of a clinically significant bleed, including but not limited to, participation in activities likely to cause injury/trauma, procoagulant and anticoagulant protein levels, comorbid conditions affecting functional ability and physical coordination, or history of a clinically significant bleed;
AND
4. Factor VIII replacement is prescribed by or in consultation with a hemophilia specialist.
CONTINUATION OF THERAPY:
1. Individual continues to meet initial approval criteria;
AND
2. Individual experienced clinical improvement while on factor VIII therapy (e.g., decreased frequency or severity of bleeds).
VON WILLEBRAND DISEASE PERI-PROCEDURAL ADMINISTRATION
INITIAL APPROVAL:
1. Individual has an established diagnosis of von Willebrand disease type 1, 2A, 2M or 2N
AND meets ALL the following:
a. Individual has had an insufficient response to at least 3-month trial of desmopressin or has had intolerance/contraindication to desmopressin (see policy guidelines);OR
2. Individual has type 2B or type 3 disease and request is for Wilate;
AND
3. Factor VIII replacement is prescribed by or in consultation with a hemophilia specialist;
AND
4. Request is for either Alphanate, Humate-P or Wilate (other products not indicated for treatment of Von Willebrand Disease).
NOTE: Pure Factor VIII replacement is not indicated for individuals with severe Von Willebrand Disease (Type 3) undergoing major surgery.
VON WILLEBRAND DISEASE ROUTINE PROPHYLAXIS
INITIAL APPROVAL:
1. Individual is 6 years of age or older;
AND
2. Individual has a diagnosis of von Willebrand disease requiring routine prophylaxis;
AND
3. Request is for Wilate (other products not indicated for routine prophylaxis in Von Willebrand Disease);
AND
4. Wilate is prescribed by or in consultation with a hemophilia specialist.
CONTINUATION OF THERAPY:
1. Individual continues to meet initial approval criteria;
AND
2. Individual experienced clinical improvement while on von Willebrand therapy (e.g., decreased frequency or severity of bleeds).
Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria
Factor VIII (e.g., Advate, Adynovate, Afstyla, Alphanate, Altuviiio, Eloctate, Esperoct, Jivi, Hemofil-M, Humate-P, Koate, Kovaltry, Novoeight, Nuwiq, Obizur, Recombinate, Xyntha), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, factor VIII (e.g., Advate, Adynovate, Afstyla, Alphanate, Altuviiio, Eloctate, Esperoct, Jivi, Hemofil-M, Humate-P, Koate, Kovaltry, Novoeight, Nuwiq, Obizur, Recombinate, Xyntha), for any indication or circumstance not described above, is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
POLICY GUIDELINES
Severe Hemophilia A is defined as less than 1% of normal endogenous factor VIII or less than 1 international unit per deciliter of blood of endogenous factor VIII (NHF, Srivastava, 2020).
Mild to moderate Hemophilia A is defined as greater than 1% but less than 40% of normal endogenous factor VIII or greater than 1 but less than 40 international unit per deciliter of blood of endogenous factor VIII (NHF, Srivastava, 2020).
Management of von Willebrand Disease:
Desmopressin (DDAVP) is recommended for the majority of type 1 individuals and for clinically responsive type 2A individuals. VWF-containing Factor VIII concentrates are recommended for type 1 and 2A individuals who become transiently unresponsive to DDAVP and in surgical situations and for type 2B and 3 VWD that do not respond to DDAVP. While not FDA-approved for VWD, Koate- is listed as possibly effective for some individuals (NHF, 2015).
The expected in vivo peak AHF level, expressed as IU/dL of plasma or % (percent) of normal, can be calculated by multiplying the dose administered per kg body weight (IU/kg) by two. This calculation is based on the clinical finding by Abildgaard, et al which is supported by data from the collaborative study of in vivo recovery and survival with 15 different lots of Hemofil M on 56 hemophiliacs that demonstrated a mean peak recovery point above the mean pre-infusion baseline of about 2.0 IU/dL per infused IU/kg body weight (Addiego et al, 1992).
Contraindications to desmopressin in Type 1, 2A, 2N and 2M disease:
1. Individual is pregnant;
2. Individual has a fluid or electrolyte imbalance;
3. Individual is at a high risk for cardiovascular or cerebrovascular disease;
4. Individual has a documented predisposition to thrombus formation (e.g., past thrombotic episodes);
5. Individual has a documented severe Type 1 disease;
6. Individual has a hypersensitivity to recombinant von Willebrand factor, tri-sodium citrate-dihydrate, glycine, mannitol, trehalose-dihydrate polysorbate 80, or hamster or mouse proteins.
There are two forms of von Willebrand disease, inherited and acquired. The inherited form is the most common and is divided into three major types:
- Type 1 VWD is characterized by a partial quantitative deficiency of VWF due to decreased production or secretion and increased clearance of VWF. This is the most common type and constitutes 75% of VWD cases.
- Type 2 VWD is due to the qualitative abnormalities of VWF and is subdivided into the following:
- Type 2A is characterized by a loss of VWF-mediated binding to the platelets and a decrease in the functional high-molecular-weight multimers of VWF. It constitutes 10-20% of VWD cases.
- Type 2B involves increased binding of VWF HMW multimers to glycoprotein Ib (GPIb) on the platelets, which results in increased clearance of platelet bound VWF HMW multimers. This type constitutes 5% of VWD cases.
- Type 2M is characterized by a reduction in the binding of VWF to collagen or GPIb on the platelets with the preserved multimers of VWF. This subtype is less common than Types 2A and 2B.
- Type 2N is characterized by a reduction in the binding of VWF to factor VIII.
- Type 3 VWD is a rare type (estimated prevalence of 1 in 1 million) of VWD characterized by severe reduction or absence of VWF; hence, it is a severe type of VWD.
VWD screening tests assess the quantity and function of VWF. The quantity of VWF is measured by VWF antigen (VWF:Ag), and the function (platelet dependent VWF activity) of VWF is measured by VWF:RCo (ristocetin cofactor) or VWF:GPIbM assays. VWF:Ag or VWF activity less than 30% confirms the diagnosis of VWD in individuals without bleeding history. VWF:Ag or VWF activity should be 30-50% in individuals with a positive bleeding history to confirm the diagnosis.
DOSAGE AND ADMINISTRATION
For FDA labeled indications, factor VIII (e.g., Advate, Adynovate, Afstyla, Alphanate, Altuviiio, Eloctate, Esperoct, Jivi, Hemofil-M, Humate-P, Koate, Kovaltry, Novoeight, Nuwiq, Obizur, Recombinate, Xyntha) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified below.
Authorizations for routine prophylaxis will be given to allow for both prophylactic and doses required to be on hand in the event of acute bleed.
The dosing of clotting factor concentrates is highly individualized. MASAC provides recommendations regarding doses of clotting factor concentrate in the home (MASAC, 2016). The number of required doses varies greatly and is dependent on the severity of the disorder and the prescribed regimen. Per MASAC guidance, individuals on prophylaxis should also have at least one major dose and two minor doses on hand for breakthrough episodes and the prophylactic doses used monthly. The guidance also notes that an adequate supply of clotting factor concentrate is needed to accommodate weekends and holidays. Therefore, maximum doses in this policy allows for prophylactic dosing plus three days of acute episodes or perioperative management per 28 days. Doses exceeding this quantity will be reviewed on a case-by-case basis by a clinician.
1. The recommended dose of factor VIII antihemophilic factor, recombinant (e.g., Advate) is as follows:
a. For intravenous injection after reconstitution only.
b. Each vial of Advate contains the labeled amount of recombinant Factor VIII in International Units (IU).
c. Control and prevention of bleeding episodes and peri-operative management:
i. Dose (IU) = body weight (kg) × desired factor VIII rise (IU/dL or % of normal) × 0.5 (IU/kg per IU/dL).
ii. Determine treatment frequency based on type of bleeding episode.
d. Routine Prophylaxis o 20 to 40 IU per kg every other day (3 to 4 times weekly).
i. Alternatively, use every third day dosing regimen targeted to maintain FVIII trough levels
≥ 1%
Factor VIII antihemophilic factor, recombinant (e.g., Advate) is available as 250, 500, 1000, 1500, 2000, 3000 or 4000 international unit vials.
2. The recommended dose of Factor VIII antihemophilic factor, recombinant PEGylated (e.g., Adynovate) is as follows:
a. For intravenous use after reconstitution only.
b. One unit per kilogram body weight will raise the factor VIII level by 2% international units per deciliter (IU per dL).
c. Each vial of ADYNOVATE is labeled with the actual amount of recombinant factor VIII present in IU.
d. On-demand treatment and control of bleeding episodes and peri-operative management:
i. Estimated Increment of factor VIII (IU/dL or % of normal) = [Total Dose (IU)/body weight (kg)] x 2 (IU/dL per IU/kg) Dose (IU) = Body Weight (kg) x Desired factor VIII Rise (IU/dL or % of Normal) x 0.5 (IU/kg per IU/dL).
e. Routine prophylaxis: Administer 40-50 IU per kg body weight 2 times a week (Starting dose of 55 IU per kg body weight 2 times a week.
Factor VIII antihemophilic factor, recombinant PEGylated (e.g., Adynovate) is available as 250, 500, 750, 1000, 1500, 2000 or 3000 international unit vials.
3. The recommended dose of Factor VIII coagulation recombinant single chain (e.g., Afstyla) is as follows:
a. For intravenous use after reconstitution only.
b. Each vial of Afstyla is labeled with the amount of recombinant Factor VIII in international units (IU or unit). One unit per kilogram body weight will raise the Factor VIII level by 2 IU/dL.
c. Plasma Factor VIII levels can be monitored using either a chromogenic assay or a one-stage clotting assay – routinely used in US clinical laboratories. If the one-stage clotting assay is used, multiply the result by a conversion factor of 2 to determine the individual’s Factor VIII activity level.
i. Calculating Required Dose: Dose (IU) = Body Weight (kg) x Desired Factor VIII Rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL).
d. Routine Prophylaxis:
i. Adults and adolescents (greater than or equal to
12 years): The recommended starting regimen is 20 to 50 IU per kg of Afstyla administered 2 to 3 times weekly.
ii. Children (less than 12 years): The recommended starting regimen is 30 to 50 IU per kg of Afstyla administered 2 to 3 times weekly. More frequent or higher doses may be required in children greater than 12 years of age to account for the higher clearance in this age group. The regimen may be adjusted based on individual response.
e. Peri-operative Management: Ensure the appropriate Factor VIII activity level is achieved and maintained.
Factor VIII coagulation recombinant single chain (e.g., Afstyla) is available as 250, 500, 1000, 1500, 2000, 2500, or 3000 international unit vials.
4. The recommended dose of Factor VIII coagulation factor with von Willebrand factor (e.g., Alphanate) is as follows:
a. For Intravenous injection after reconstitution only.
b. Alphanate contains the labeled amount of Factor VIII expressed in International Units (IU) FVIII/vial and von Willebrand Factor: Ristocetin Cofactor activity in IU VWF:RCo/vial.
c. Dose: Treatment and Prevention of Bleeding Episodes and Excess Bleeding During and After Surgery in Individuals with Hemophilia A.
i. Dose (units) = body weight (kg) x desired FVIII rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL).
ii. Dosing frequency determined by the type of bleeding episode and the recommendation of the treating physician. Treatment and Prevention of Excess Bleeding During and After Surgery or Other Invasive Procedures in Individuals with von Willebrand Disease.
iii. Adults: Pre-operative dose of 60 IU VWF:RCo/kg body weight; subsequent doses of 40-60 IU VWF:RCo/kg body weight.
iv. Pediatric: Pre-operative dose of 75 IU VWF:RCo/kg body weight; subsequent doses of 50-75 IU VWF:RCo/kg body weight.
Factor VIII coagulation factor with von Willebrand factor (e.g., Alphanate) is available as 250, 500, 1000, 1500 or 2000 international unit vials.
5. The recommended dose of Factor VIII antihemophilic factor recombinant, Fc-VWF-XTEN fusion protein-ehtl (e.g., Altuviiio) is as follows:
a. The recommended dosing for routine prophylaxis for adults and children is 50 IU/kg of Altuviiio administered once weekly.
b. Each Altuviiio vial label states the Factor VIII potency in international units (IU). One IU corresponds to the Factor VIII activity contained in one milliliter of normal human plasma, as defined by the current World Health Organization (WHO) international standard for Factor VIII concentrate.
c. Potency assignment for Altuviiio is determined using an activated partial thromboplastin time (aPTT)-based one-stage clotting assay. It is recommended to use a validated one-stage clotting assay to measure Altuviiio Factor VIII activity in plasma. The Altuviiio Factor VIII activity level is overestimated by the chromogenic assay and a specific ellagic acid based aPTT reagent in one-stage clotting assay by approximately 2.5-fold. For the dose of 50 IU/kg, the expected in vivo peak increase in Factor VIII level expressed as IU/dL (or % of normal) is estimated using the following formula:
i. Estimated Increment of Factor VIII (IU/dL or % of normal) = 50 IU/kg × 2 (IU/dL per IU/kg) To achieve a specific target Factor VIII activity level, use the following formula: Dosage (IU) = Body Weight (kg) × Desired Factor VIII Increase (IU/dL or % normal) × 0.5 (IU/kg per IU/dL).
Factor VIII antihemophilic factor recombinant, Fc-VWF-XTEN fusion protein-ehtl (e.g., Altuviiio) is available as 250, 500, 750, 1000, 2000, 3000, or 4000 IU, lyophilized powder in single-dose vials for reconstitution.
6. The recommended dose of Factor VIII antihemophilic factor, Fc fusion protein (e.g., Eloctate) is as follows:
a. For intravenous use after reconstitution only.
b. Each vial of Eloctate is labeled with the amount of recombinant Factor VIII in international units (IU or unit). One unit per kilogram body weight will raise the Factor VIII level by 2% (IU/dL).
c. For on-demand treatment and control of bleeding episodes and peri-operative management, calculate dose using the following formulas:
i. Estimated Increment of Factor VIII (IU/dL or % of normal) = [Total Dose (IU)/body weight (kg)] x 2 (IU/dL per IU/kg);
OR
ii. Required Dose (IU) = Body Weight (kg) x Desired Factor VIII Rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL).
d. For routine prophylaxis: 50 IU/kg every 4 days. Adjust dose based on individual response with dosing in the range of 25-65 IU/kg at 3–5-day intervals.
e. For routine prophylaxis in children less than 6 years of age: 50 IU/kg twice weekly. Adjust dose based on individual response with dosing in the range of 25-65 IU/kg at 3–5-day intervals. More frequent or higher doses up to 80 IU/kg may be required.
Factor VIII antihemophilic factor, Fc fusion protein (e.g., Eloctate) is available as 250, 500, 750, 1000, 1500, 2000, 3000 4000, 5000 or 6000 international unit vials.
7. The recommended dose of Factor VIII antihemophilic factor, glycopegylated-exei (e.g., Esperoct) is as follows:
a. For intravenous infusion after reconstitution only.
b. Each vial label for Esperoct states the actual Factor VIII activity in international units (IU).
c. On-demand treatment/control of bleeding episodes:
i. In adolescents/adults, 40 IU/kg body weight for minor/moderate bleeds and 50 IU/kg body weight for major bleeds; children (less than 12 years), 65 IU/kg body weight for minor/moderate/major bleeds.
d. Peri-operative management:
i. For minor/major surgery: In adolescents / adults: pre-operative dose of 50 IU/kg body weight; in children (less than 12 years), pre-operative dose of 65 IU/kg body weight. Frequency of administration is determined by the treating physician.
e. Routine prophylaxis:
i. In adolescents/adults, 50 IU/kg every 4 days; in children (less than 12 years), 65 IU/kg twice weekly. A regiment may be individually adjusted to less or more frequent dosing based on bleeding episodes.
f. Esperoct also may be dosed to achieve a specific target Factor VIII activity level, depending on the severity of hemophilia, for on-demand treatment/control of bleeding episodes or peri-operative management. To achieve a specific target Factor VIII activity level, use the following formula:
i. Dosage (IU) = Body Weight (kg) x Desired Factor VIII Increase (IU/dL or % normal) x 0.5 (IU/kg per IU/dL).
Factor VIII antihemophilic factor, glycopegylated-exei (e.g., Esperoct) is available as 500, 1000, 1500, 2000 and 3000 international unit vials.
8. The recommended dose of Factor VIII coagulation factor (human) (e.g., Hemofil-M) is as follows:
a. For intravenous use only.
b. The expected in vivo peak AHF level, expressed as IU/dL of plasma or % (percent) of normal, can be calculated by multiplying the dose administered per kg body weight (IU/kg) by two. This calculation is based on the clinical finding by Abildgaard, et al which is supported by data from the collaborative study of in vivo recovery and survival with 15 different lots of Hemofil M on 56 hemophiliacs that demonstrated a mean peak recovery point above the mean pre-infusion baseline of about 2.0 IU/dL per infused IU/kg body weight. [Addiego, et al].
i. Examples: (1) A dose of 1750 IU AHF administered to a 70 kg individual, i.e., 25 IU/kg (1750/70), should be expected to cause a peak post-infusion AHF increase of 25 x 2 = 50 IU/dL (50% of normal). (2. A peak level of 70% is required in a 40 kg child. In this situation the dose would be 70/2 x 40 = 1400 IU. If bleeding is not controlled with the prescribed dose, determine the plasma level of Factor VIII and administer a sufficient dose of Hemofil M to achieve a satisfactory clinical response.
c. Under certain circumstances (e.g., presence of a low titer inhibitor) doses larger than those recommended may be necessary as per standard care. In individuals with high titer Factor VIII inhibitors, Hemofil M therapy may not be effective and other therapeutic options should be considered.
d. The dosage and duration of treatment depend on the severity of Factor VIII deficiency, the location and extent of the bleeding, and the individual’s clinical condition. Careful control of replacement therapy is especially important in cases of major surgery or life-threatening hemorrhages.
Factor VIII coagulation factor (human) (e.g., Hemofil-M) is available as 250 IU, 500 IU, 1000 IU, or 1700 international unit vials.
9. The recommended dose of Factor VIII coagulation factor; von Willebrand factor (e.g., Humate-P) is as follows:
a. For intravenous use only.
b. Hemophilia A
i. One International Unit (IU) of factor VIII (FVIII) activity per kg body weight increases the circulating FVIII level by approximately 2.0 IU/dL. Individualize dosage based on the individual’s weight, type and severity of hemorrhage, FVIII level, and presence of inhibitors.
c. Von Willebrand Disease Treatment of bleeding episodes – 40-80 IU VWF:Ristocetin Cofactor (RCo) per kg body weight (BW) every 8-12 hours. o Prevention of excessive bleeding during and after surgery for all types of VWD.
Factor VIII coagulation factor; von Willebrand factor (e.g., Humate-P) is available as single-use vials that contain the labeled amount of VWF:RCo and FVIII activity expressed in IU. Refer to the product label for additional details.
10. The recommended dose of Factor VIII antihemophilic factor, PEGylated-aucl (e.g., Jivi) is as follows:
a. For intravenous use after reconstitution only.
b. Control of bleeding episodes and peri-operative management o Expected recovery: one unit per kilogram body weight of Jivi will increase the Factor VIII level by 2 international units per deciliter (IU/dL).
c. Each vial of Jivi contains the labeled amount of recombinant Factor VIII in IU.
i. Required dose (IU) = body weight (kg) x desired Factor VIII rise (% of normal or IU/dL) x reciprocal of expected recovery (or observed recovery, if available). o Estimated Increment of Factor VIII (IU/dL or % of normal) = [Total Dose (IU)/body weight (kg)] x 2 (IU/dL per IU/kg).
d. Routine prophylaxis: The recommended initial regimen is 30–40 IU/kg twice weekly.
e. Based on the bleeding episodes: The regimen may be adjusted to 45–60 IU/kg every 5 days. A regimen may be further individually adjusted to less or more frequent dosing.
Factor VIII antihemophilic factor, PEGylated-aucl (e.g., Jivi) is available as 500, 1000, 2000, or 3000 international unit vials.
11. The recommended dose of Factor VIII antihemophilic factor (human) (e.g., Koate) is as follows:
a. For intravenous use after reconstitution only.
b. Each vial of KOĀTE contains the labeled amount of Factor VIII in international units (IU).
c. Required Dose (IU) = Body Weight (kg) x Desired Factor VIII Rise (IU/dL or % of normal) x 0.5.
d. Frequency of KOĀTE administration is determined by the type of bleeding episode and the recommendation of the treating physician
Factor VIII antihemophilic factor (human) (e.g., Koate) is available as single-use vials of 250, 500 or 1,000 international units of Factor VIII activity.
12. The recommended dose of Factor VIII antihemophilic factor, recombinant (e.g., Kovaltry) is as follows:
a. For intravenous use after reconstitution only.
b. Control of bleeding episodes and peri-operative management.
i. Required dose (IU) = body weight (kg) x desired Factor VIII rise (% of normal or IU/dL) x reciprocal of expected/observed recovery (e.g., 0.5 for a recovery of 2 IU/dL per IU/kg).
ii. Estimated Increment of Factor VIII (IU/dL or % of normal) = [Total Dose (IU)/body weight (kg)] x 2 (IU/dL per IU/kg).
c. Routine prophylaxis
i. Adults and adolescents: 20-40 IU/kg 2 or 3 times per week.
ii. Children less than or equal to
12 years old: 25-50 IU/kg 2 times per week, 3 times per week or every other day.
Factor VIII antihemophilic factor, recombinant (e.g., Kovaltry) is available as single-use vials containing nominally: 250, 500, 1000, 2000, or 3000 international units.
13. The recommended dose of Factor VIII coagulation factor, recombinant (e.g., NovoEight) is as follows:
a. For intravenous injection after reconstitution only.
b. Each vial of Novoeight contains the labeled amount of recombinant Factor VIII in international units (IU).
c. The required dosage is determined using the following formula: Dosage Required (IU) = Body Weight (kg) × Desired Factor VIII Increase (IU/dL or % normal) × 0.5 (IU/kg per IU/dL).
d. Frequency of Novoeight administration is determined by the type of bleeding episode and the recommendation of the treating physician.
Factor VIII coagulation factor, recombinant (e.g., NovoEight) is available as single-use vials of 250, 500, 1000, 1500, 2000 or 3000 international units.
14. The recommended dose of Factor VIII coagulation factor, recombinant human (e.g., Nuwiq) is as follows:
a. For intravenous use after reconstitution.
b. Each vial of NUWIQ is labeled with the actual amount of Factor VIII potency in international units (IU). 3. Determine dose using the following formula for adolescents and adults: Required IU = body weight (kg) x desired Factor VIII rise (%) (IU/dL) x 0.5 (IU/kg per IU/dL). Frequency and duration of therapy depends on severity of the FVIII deficiency, location and extent of bleeding and individual’s clinical condition.
Factor VIII coagulation factor, recombinant human (e.g., Nuwiq) is available as single-use vials containing nominally: 250, 500, 1000 2000, 2500, 3000 or 4000 IU of Factor VIII potency.
15. The recommended dose of Factor VIII coagulation factor, recombinant porcine sequence (e.g., Obizur) is as follows:
a. For intravenous use after reconstitution only.
b. Initial dose of Obizur is 200 units per kg.
c. Titrate dose and frequency of administration based on factor VIII recovery levels and individual clinical response.
Factor VIII coagulation factor, recombinant porcine sequence (e.g., Obizur) is available as single-use vials containing nominally 500 units per vial.
16. The recommended dose of Factor VIII coagulation factor, recombinant (e.g., Recombinate) is as follows:
a. Each vial of Recombinate is labeled with the Factor VIII activity expressed in IU per vial. This potency assignment is referenced to the World Health Organization International Standard for Factor VIII:C Concentrate and is evaluated by appropriate methodology to ensure accuracy of the results.
b. The expected in vivo peak increase in Factor VIII level expressed as IU/dL of plasma or % (percent) of normal can be estimated by multiplying the dose administered per kg body weight (IU/kg) by two. This calculation is based on the clinical findings of Abildgaard et al (N Eng J Med 1966; 275: 471-475) and is supported by the data generated by 419 clinical pharmacokinetic studies with Recombinate in 67 individuals over time. This pharmacokinetic data demonstrated a peak recovery point above the pre-infusion baseline of approximately 2.0 IU/dL per IU/kg body weight.
Factor VIII coagulation factor, recombinant (e.g., Recombinate) is available as single-dose vials in five different strengths. Refer to the product label for additional details.
17. The recommended dose of Factor VIII coagulation factor, recombinant (e.g., Xyntha) is as follows:
a. For intravenous use after reconstitution only.
b. The required dosage is determined using the following formula: Required units = body weight (kg) × desired factor VIII rise (IU/dL or % of normal) × 0.5 (IU/kg per IU/dL) where IU = International Unit.
c. Frequency of XYNTHA administration is determined by the type of bleeding episode and the recommendation of the treating physician.
Factor VIII coagulation factor, recombinant (e.g., Xyntha) is available as single-use vials containing nominally: 250, 500, 1000, or 2000 international units.
Factor VIII (e.g., Advate, Adynovate, Afstyla, Alphanate, Altuviiio, Eloctate, Esperoct, Jivi, Hemofil-M, Humate-P, Koate, Kovaltry, Novoeight, Nuwiq, Obizur, Recombinate, Xyntha) should be administered as an IV infusion by a healthcare professional or a trained individual.
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Effective January 1, 2025 to November 14, 2025
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Factor VIII (e.g., Advate, Adynovate, Afstyla, Alphanate, Altuviiio, Eloctate, Esperoct, Jivi, Hemofil-M, Humate-P, Koate, Kogenate, Kovaltry, Novoeight, Nuwiq, Obizur, Recombinate, Wilate, Xyntha) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when
ALL the following criteria are met:
HEMOPHILIA A
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
1. Individual has a diagnosis of severe hemophilia A (see policy guidelines);
AND individual is using for one of the following:
a. Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes;
OR
b. On-demand treatment and control of bleeding episodes; OR
c. Peri-procedural management for surgical, invasive, or interventional radiology procedures;
OR
2. Individual has a diagnosis of mild to moderate hemophilia A (see policy guidelines);
AND individual is using for one of the following:
a. On-demand treatment and control of bleeding episodes; OR
b. Peri-procedural management for surgical, invasive, or interventional radiology procedures;
OR
3. Individual has diagnosis of mild to moderate hemophilia A (see policy guidelines) with intention to use factor VIII as routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes
AND one of the following criteria is met (NHF, Srivastava 2020):
a. One or more episodes of spontaneous bleeding into joint;
OR
b. One or more episodes of spontaneous bleeding into the central nervous system;
OR
c. Four or more episodes of soft tissue bleeding in an 8-week period;
OR
d. Individual’s risk factors increase the risk of a clinically significant bleed, including but not limited to, participation in activities likely to cause injury/trauma, procoagulant and anticoagulant protein levels, comorbid conditions affecting functional ability and physical coordination, or history of a clinically significant bleed;
AND
4. Factor VIII replacement is prescribed by or in consultation with a hemophilia specialist.
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet initial approval criteria;
AND
2. Individual experienced clinical improvement while on factor VIII therapy (e.g., decreased frequency or severity of bleeds).
VON WILLEBRAND DISEASE PERI-PROCEDURAL ADMINISTRATION
INITIAL APPROVAL STANDARD REVIEW for up to 6 months:
1. Individual has an established diagnosis of von Willebrand disease type 1, 2A, 2M or 2N
AND meets ALL the following
a. Individual has had an insufficient response to at least 3-month trial of desmopressin or has had intolerance/contraindication to desmopressin (see policy guidelines);OR
2. Individual has type 2B or type 3 disease and request is for Wilate;AND
3. Factor VIII replacement is prescribed by or in consultation with a hemophilia specialist;
AND
4. Request is for either Alphanate, Humate-P or Wilate (other products not indicated for treatment of Von Willebrand Disease).
NOTE: Pure Factor VIII replacement is not indicated for individuals with severe Von Willebrand Disease (Type 3) undergoing major surgery.
VON WILLEBRAND DISEASE ROUTINE PROPHYLAXIS
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
1. Individual is 6 years of age or older;
AND
2. Individual has a diagnosis of von Willebrand disease requiring routine prophylaxis;
AND
3. Request is for Wilate (other products not indicated for routine prophylaxis in Von Willebrand Disease);
AND
4. Wilate is prescribed by or in consultation with a hemophilia specialist.
CONTINUED APPROVAL for up to 12 months:
1. Individual continues to meet initial approval criteria;
AND
2. Individual experienced clinical improvement while on von Willebrand therapy (e.g., decreased frequency or severity of bleeds).
Policy Guidelines
Severe Hemophilia A is defined as less than 1% of normal endogenous factor VIII or less than 1 international unit per deciliter of blood of endogenous factor VIII (NHF, Srivastava, 2020).
Mild to moderate Hemophilia A is defined as greater than 1% but less than 40% of normal endogenous factor VIII or greater than 1 but less than 40 international unit per deciliter of blood of endogenous factor VIII (NHF, Srivastava, 2020).
Management of von Willebrand Disease:
Desmopressin (DDAVP) is recommended for the majority of type 1 individuals and for clinically responsive type 2A individuals. VWF-containing Factor VIII concentrates are recommended for type 1 and 2A individuals who become transiently unresponsive to DDAVP and in surgical situations and for type 2B and 3 VWD that do not respond to DDAVP. While not FDA-approved for VWD, Koate- is listed as possibly effective for some individuals (NHF, 2015).
The expected in vivo peak AHF level, expressed as IU/dL of plasma or % (percent) of normal, can be calculated by multiplying the dose administered per kg body weight (IU/kg) by two. This calculation is based on the clinical finding by Abildgaard, et al which is supported by data from the collaborative study of in vivo recovery and survival with 15 different lots of Hemofil M on 56 hemophiliacs that demonstrated a mean peak recovery point above the mean pre-infusion baseline of about 2.0 IU/dL per infused IU/kg body weight (Addiego et al, 1992).
Contraindications to desmopressin in Type 1, 2A, 2N and 2M disease:
1. Individual is pregnant;
2. Individual has a fluid or electrolyte imbalance;
3. Individual is at a high risk for cardiovascular or cerebrovascular disease;
4. Individual has a documented predisposition to thrombus formation (e.g., past thrombotic episodes);
5. Individual has a documented severe Type 1 disease;
6. Individual has a hypersensitivity to recombinant von Willebrand factor, tri-sodium citrate-dihydrate, glycine, mannitol, trehalose-dihydrate polysorbate 80, or hamster or mouse proteins.
There are two forms of von Willebrand disease, inherited and acquired. The inherited form is the most common and is divided into three major types:
- Type 1 VWD is characterized by a partial quantitative deficiency of VWF due to decreased production or secretion and increased clearance of VWF. This is the most common type and constitutes 75% of VWD cases.
- Type 2 VWD is due to the qualitative abnormalities of VWF and is subdivided into the following:
- Type 2A is characterized by a loss of VWF-mediated binding to the platelets and a decrease in the functional high-molecular-weight multimers of VWF. It constitutes 10-20% of VWD cases.
- Type 2B involves increased binding of VWF HMW multimers to glycoprotein Ib (GPIb) on the platelets, which results in increased clearance of platelet bound VWF HMW multimers. This type constitutes 5% of VWD cases.
- Type 2M is characterized by a reduction in the binding of VWF to collagen or GPIb on the platelets with the preserved multimers of VWF. This subtype is less common than Types 2A and 2B.
- Type 2N is characterized by a reduction in the binding of VWF to factor VIII.
- Type 3 VWD is a rare type (estimated prevalence of 1 in 1 million) of VWD characterized by severe reduction or absence of VWF; hence, it is a severe type of VWD.
VWD screening tests assess the quantity and function of VWF. The quantity of VWF is measured by VWF antigen (VWF:Ag), and the function (platelet dependent VWF activity) of VWF is measured by VWF:RCo (ristocetin cofactor) or VWF:GPIbM assays. VWF:Ag or VWF activity less than 30% confirms the diagnosis of VWD in individuals without bleeding history. VWF:Ag or VWF activity should be 30-50% in individuals with a positive bleeding history to confirm the diagnosis.
Dosage and Administration
Dosing per FDA Guidelines
Authorizations for routine prophylaxis will be given to allow for both prophylactic and doses required to be on hand in the event of acute bleed.
The dosing of clotting factor concentrates is highly individualized. MASAC provides recommendations regarding doses of clotting factor concentrate in the home (MASAC, 2016). The number of required doses varies greatly and is dependent on the severity of the disorder and the prescribed regimen. Per MASAC guidance, individuals on prophylaxis should also have at least one major dose and two minor doses on hand for breakthrough episodes and the prophylactic doses used monthly. The guidance also notes that an adequate supply of clotting factor concentrate is needed to accommodate weekends and holidays. Therefore, maximum doses in this policy allows for prophylactic dosing plus three days of acute episodes or perioperative management per 28 days. Doses exceeding this quantity will be reviewed on a case-by-case basis by a clinician.
A. The recommended dose of factor VIII antihemophilic factor, recombinant (e.g., Advate) is as follows:
1. For intravenous injection after reconstitution only.
2. Each vial of Advate contains the labeled amount of recombinant Factor VIII in International Units (IU).
3. Control and prevention of bleeding episodes and peri-operative management:
- Dose (IU) = body weight (kg) × desired factor VIII rise (IU/dL or % of normal) × 0.5 (IU/kg per IU/dL).
- Determine treatment frequency based on type of bleeding episode.
4. Routine Prophylaxis o 20 to 40 IU per kg every other day (3 to 4 times weekly).
- Alternatively, use every third day dosing regimen targeted to maintain FVIII trough levels
≥ 1%
Factor VIII antihemophilic factor, recombinant (e.g., Advate) is available as 250, 500, 1000, 1500, 2000, 3000 or 4000 international unit vials.
B. The recommended dose of Factor VIII antihemophilic factor, recombinant PEGylated (e.g., Adynovate) is as follows:
1. For intravenous use after reconstitution only.
2. One unit per kilogram body weight will raise the factor VIII level by 2% international units per deciliter (IU per dL).
3. Each vial of ADYNOVATE is labeled with the actual amount of recombinant factor VIII present in IU.
4. On-demand treatment and control of bleeding episodes and peri-operative management:
- Estimated Increment of factor VIII (IU/dL or % of normal) = [Total Dose (IU)/body weight (kg)] x 2 (IU/dL per IU/kg) Dose (IU) = Body Weight (kg) x Desired factor VIII Rise (IU/dL or % of Normal) x 0.5 (IU/kg per IU/dL)
5. Routine prophylaxis: Administer 40-50 IU per kg body weight 2 times a week (Starting dose of 55 IU per kg body weight 2 times a week.
Factor VIII antihemophilic factor, recombinant PEGylated (e.g., Adynovate) is available as 250, 500, 750, 1000, 1500, 2000 or 3000 international unit vials.
C. The recommended dose of Factor VIII coagulation recombinant single chain (e.g., Afstyla) is as follows:
1. For intravenous use after reconstitution only.
2. Each vial of Afstyla is labeled with the amount of recombinant Factor VIII in international units (IU or unit). One unit per kilogram body weight will raise the Factor VIII level by 2 IU/dL.
3. Plasma Factor VIII levels can be monitored using either a chromogenic assay or a one-stage clotting assay – routinely used in US clinical laboratories. If the one-stage clotting assay is used, multiply the result by a conversion factor of 2 to determine the individual’s Factor VIII activity level.
- Calculating Required Dose: Dose (IU) = Body Weight (kg) x Desired Factor VIII Rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL)
4. Routine Prophylaxis: o
- Adults and adolescents (≥12 years): The recommended starting regimen is 20 to 50 IU per kg of Afstyla administered 2 to 3 times weekly.
- Children (< 12 years): The recommended starting regimen is 30 to 50 IU per kg of Afstyla administered 2 to 3 times weekly. More frequent or higher doses may be required in children < 12 years of age to account for the higher clearance in this age group. The regimen may be adjusted based on individual response.
5. Peri-operative Management: Ensure the appropriate Factor VIII activity level is achieved and maintained.
Factor VIII coagulation recombinant single chain (e.g., Afstyla) is available as 250, 500, 1000, 1500, 2000, 2500, or 3000 international unit vials.
D. The recommended dose of Factor VIII coagulation factor with von Willebrand factor (e.g., Alphanate) is as follows:
1. For Intravenous injection after reconstitution only.
2. Alphanate contains the labeled amount of Factor VIII expressed in International Units (IU) FVIII/vial and von Willebrand Factor: Ristocetin Cofactor activity in IU VWF:RCo/vial.
3. Dose: Treatment and Prevention of Bleeding Episodes and Excess Bleeding During and After Surgery in Individuals with Hemophilia A
- Dose (units) = body weight (kg) x desired FVIII rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL).
- Dosing frequency determined by the type of bleeding episode and the recommendation of the treating physician. Treatment and Prevention of Excess Bleeding During and After Surgery or Other Invasive Procedures in Individuals with von Willebrand Disease
- Adults: Pre-operative dose of 60 IU VWF:RCo/kg body weight; subsequent doses of 40-60 IU VWF:RCo/kg body weight.
- Pediatric: Pre-operative dose of 75 IU VWF:RCo/kg body weight; subsequent doses of 50-75 IU VWF:RCo/kg body weight.
Factor VIII coagulation factor with von Willebrand factor (e.g., Alphanate) is available as 250, 500, 1000, 1500 or 2000 international unit vials.
E. The recommended dose of Factor VIII antihemophilic factor recombinant, Fc-VWF-XTEN fusion protein-ehtl (e.g., Altuviiio) is as follows:
1. The recommended dosing for routine prophylaxis for adults and children is 50 IU/kg of Altuviiio administered once weekly.
2. Each Altuviiio vial label states the Factor VIII potency in international units (IU). One IU corresponds to the Factor VIII activity contained in one milliliter of normal human plasma, as defined by the current World Health Organization (WHO) international standard for Factor VIII concentrate.
3. Potency assignment for Altuviiio is determined using an activated partial thromboplastin time (aPTT)-based one-stage clotting assay. It is recommended to use a validated one-stage clotting assay to measure Altuviiio Factor VIII activity in plasma. The Altuviiio Factor VIII activity level is overestimated by the chromogenic assay and a specific ellagic acid based aPTT reagent in one-stage clotting assay by approximately 2.5-fold. For the dose of 50 IU/kg, the expected in vivo peak increase in Factor VIII level expressed as IU/dL (or % of normal) is estimated using the following formula:
- Estimated Increment of Factor VIII (IU/dL or % of normal) = 50 IU/kg × 2 (IU/dL per IU/kg) To achieve a specific target Factor VIII activity level, use the following formula: Dosage (IU) = Body Weight (kg) × Desired Factor VIII Increase (IU/dL or % normal) × 0.5 (IU/kg per IU/dL).
Factor VIII antihemophilic factor recombinant, Fc-VWF-XTEN fusion protein-ehtl (e.g., Altuviiio) is available as 250, 500, 750, 1000, 2000, 3000, or 4000 IU, lyophilized powder in single-dose vials for reconstitution.
F. The recommended dose of Factor VIII antihemophilic factor, Fc fusion protein (e.g., Eloctate) is as follows:
1. For intravenous use after reconstitution only.
2. Each vial of Eloctate is labeled with the amount of recombinant Factor VIII in international units (IU or unit). One unit per kilogram body weight will raise the Factor VIII level by 2% (IU/dL).
3. For on-demand treatment and control of bleeding episodes and peri-operative management, calculate dose using the following formulas:
- Estimated Increment of Factor VIII (IU/dL or % of normal) = [Total Dose (IU)/body weight (kg)] x 2 (IU/dL per IU/kg)
OR
- Required Dose (IU) = Body Weight (kg) x Desired Factor VIII Rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL)
4. For routine prophylaxis: 50 IU/kg every 4 days. Adjust dose based on individual response with dosing in the range of 25-65 IU/kg at 3–5-day intervals.
5. For routine prophylaxis in children less than 6 years of age: 50 IU/kg twice weekly. Adjust dose based on individual response with dosing in the range of 25-65 IU/kg at 3–5-day intervals. More frequent or higher doses up to 80 IU/kg may be required.
Factor VIII antihemophilic factor, Fc fusion protein (e.g., Eloctate) is available as 250, 500, 750, 1000, 1500, 2000, 3000 4000, 5000 or 6000 international unit vials.
G. The recommended dose of Factor VIII antihemophilic factor, glycopegylated-exei (e.g., Esperoct) is as follows:
1. For intravenous infusion after reconstitution only.
2. Each vial label for Esperoct states the actual Factor VIII activity in international units (IU).
3. On-demand treatment/control of bleeding episodes:
- In adolescents/adults, 40 IU/kg body weight for minor/moderate bleeds and 50 IU/kg body weight for major bleeds; children (<12 years), 65 IU/kg body weight for minor/moderate/major bleeds.
4. Peri-operative management:
- For minor/major surgery: In adolescents / adults: pre-operative dose of 50 IU/kg body weight; in children (<12 years), pre-operative dose of 65 IU/kg body weight. Frequency of administration is determined by the treating physician.
5. Routine prophylaxis:
- In adolescents/adults, 50 IU/kg every 4 days; in children (<12 years), 65 IU/kg twice weekly. A regiment may be individually adjusted to less or more frequent dosing based on bleeding episodes.
6. Esperoct also may be dosed to achieve a specific target Factor VIII activity level, depending on the severity of hemophilia, for on-demand treatment/control of bleeding episodes or peri-operative management. To achieve a specific target Factor VIII activity level, use the following formula:
- Dosage (IU) = Body Weight (kg) x Desired Factor VIII Increase (IU/dL or % normal) x 0.5 (IU/kg per IU/dL).
Factor VIII antihemophilic factor, glycopegylated-exei (e.g., Esperoct) is available as 500, 1000, 1500, 2000 and 3000 international unit vials.
H. The recommended dose of Factor VIII coagulation factor (human) (e.g., Hemofil-M) is as follows:
1. For intravenous use only.
2. The expected in vivo peak AHF level, expressed as IU/dL of plasma or % (percent) of normal, can be calculated by multiplying the dose administered per kg body weight (IU/kg) by two. This calculation is based on the clinical finding by Abildgaard, et al which is supported by data from the collaborative study of in vivo recovery and survival with 15 different lots of Hemofil M on 56 hemophiliacs that demonstrated a mean peak recovery point above the mean pre-infusion baseline of about 2.0 IU/dL per infused IU/kg body weight. [Addiego, et al]
- Examples: (1) A dose of 1750 IU AHF administered to a 70 kg individual, i.e., 25 IU/kg (1750/70), should be expected to cause a peak post-infusion AHF increase of 25 x 2 = 50 IU/dL (50% of normal). (2. A peak level of 70% is required in a 40 kg child. In this situation the dose would be 70/2 x 40 = 1400 IU. If bleeding is not controlled with the prescribed dose, determine the plasma level of Factor VIII and administer a sufficient dose of Hemofil M to achieve a satisfactory clinical response.
4. Under certain circumstances (e.g., presence of a low titer inhibitor) doses larger than those recommended may be necessary as per standard care. In individuals with high titer Factor VIII inhibitors, Hemofil M therapy may not be effective and other therapeutic options should be considered.
5. The dosage and duration of treatment depend on the severity of Factor VIII deficiency, the location and extent of the bleeding, and the individual’s clinical condition. Careful control of replacement therapy is especially important in cases of major surgery or life-threatening hemorrhages.
Factor VIII coagulation factor (human) (e.g., Hemofil-M) is available as 250 IU, 500 IU, 1000 IU, or 1700 international unit vials.
I. The recommended dose of Factor VIII coagulation factor; von Willebrand factor (e.g., Humate-P) is as follows:
1. For intravenous use only.
2. Hemophilia A
- One International Unit (IU) of factor VIII (FVIII) activity per kg body weight increases the circulating FVIII level by approximately 2.0 IU/dL. Individualize dosage based on the individual’s weight, type and severity of hemorrhage, FVIII level, and presence of inhibitors.
3. Von Willebrand Disease Treatment of bleeding episodes – 40-80 IU VWF:Ristocetin Cofactor (RCo) per kg body weight (BW) every 8-12 hours. o Prevention of excessive bleeding during and after surgery for all types of VWD.
Factor VIII coagulation factor; von Willebrand factor (e.g., Humate-P) is available as single-use vials that contain the labeled amount of VWF:RCo and FVIII activity expressed in IU. Refer to the product label for additional details.
J. The recommended dose of Factor VIII antihemophilic factor, PEGylated-aucl (e.g., Jivi) is as follows:
1. For intravenous use after reconstitution only.
2. Control of bleeding episodes and peri-operative management o Expected recovery: one unit per kilogram body weight of Jivi will increase the Factor VIII level by 2 international units per deciliter (IU/dL).
3. Each vial of Jivi contains the labeled amount of recombinant Factor VIII in IU.
- Required dose (IU) = body weight (kg) x desired Factor VIII rise (% of normal or IU/dL) x reciprocal of expected recovery (or observed recovery, if available). o Estimated Increment of Factor VIII (IU/dL or % of normal) = [Total Dose (IU)/body weight (kg)] x 2 (IU/dL per IU/kg).
4. Routine prophylaxis: The recommended initial regimen is 30–40 IU/kg twice weekly.
Based on the bleeding episodes: The regimen may be adjusted to 45–60 IU/kg every 5 days. A regimen may be further individually adjusted to less or more frequent dosing.
Factor VIII antihemophilic factor, PEGylated-aucl (e.g., Jivi) is available as 500, 1000, 2000, or 3000 international unit vials.
K. The recommended dose of Factor VIII antihemophilic factor (human) (e.g., Koate) is as follows:
1. For intravenous use after reconstitution only.
2. Each vial of KOĀTE contains the labeled amount of Factor VIII in international units (IU).
3. Required Dose (IU) = Body Weight (kg) x Desired Factor VIII Rise (IU/dL or % of normal) x 0.5
4. Frequency of KOĀTE administration is determined by the type of bleeding episode and the recommendation of the treating physician
Factor VIII antihemophilic factor (human) (e.g., Koate) is available as single-use vials of 250, 500 or 1,000 international units of Factor VIII activity.
L The recommended dose of Factor VIII octocog alfa (e.g., Kogenate FS) is as follows:
1. For intravenous use only.
2. Each vial of Kogenate FS contains the labeled amount of recombinant factor VIII in international units (IU, unit)
3. Control and prevention of bleeding episodes and peri-operative management: o Dose (units) = body weight (kg) x desired factor VIII rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL). o Titrate doses to individual’s clinical response.
- Determine treatment frequency based on type of bleeding episode.
4. For routine prophylaxis in adults: 25 units per kg three times a week.
5. For routine prophylaxis in children: 25 units per kg every other day.
Factor VIII octocog alfa (e.g., Kogenate FS) is available as single-use vials containing nominally: 250, 500, 1000, 2000, or 3000 international units.
M. The recommended dose of Factor VIII antihemophilic factor, recombinant (e.g., Kovaltry) is as follows:
1. For intravenous use after reconstitution only.
2. Control of bleeding episodes and peri-operative management
- Required dose (IU) = body weight (kg) x desired Factor VIII rise (% of normal or IU/dL) x reciprocal of expected/observed recovery (e.g., 0.5 for a recovery of 2 IU/dL per IU/kg).
- Estimated Increment of Factor VIII (IU/dL or % of normal) = [Total Dose (IU)/body weight (kg)] x 2 (IU/dL per IU/kg).
3. Routine prophylaxis
- Adults and adolescents: 20-40 IU/kg 2 or 3 times per week.
- Children ≤12 years old: 25-50 IU/kg 2 times per week, 3 times per week or every other day.
Factor VIII antihemophilic factor, recombinant (e.g., Kovaltry) is available as single-use vials containing nominally: 250, 500, 1000, 2000, or 3000 international units.
N. The recommended dose of Factor VIII coagulation factor, recombinant (e.g., NovoEight) is as follows:
1. For intravenous injection after reconstitution only.
2. Each vial of Novoeight contains the labeled amount of recombinant Factor VIII in international units (IU).
3. The required dosage is determined using the following formula: Dosage Required (IU) = Body Weight (kg) × Desired Factor VIII Increase (IU/dL or % normal) × 0.5 (IU/kg per IU/dL)
4) Frequency of Novoeight administration is determined by the type of bleeding episode and the recommendation of the treating physician.
Factor VIII coagulation factor, recombinant (e.g., NovoEight) is available as single-use vials of 250, 500, 1000, 1500, 2000 or 3000 international units.
O. The recommended dose of Factor VIII coagulation factor, recombinant human (e.g., Nuwiq) is as follows:
1. For intravenous use after reconstitution.
2. Each vial of NUWIQ is labeled with the actual amount of Factor VIII potency in international units (IU). 3. Determine dose using the following formula for adolescents and adults: Required IU = body weight (kg) x desired Factor VIII rise (%) (IU/dL) x 0.5 (IU/kg per IU/dL). Frequency and duration of therapy depends on severity of the FVIII deficiency, location and extent of bleeding and individual’s clinical condition.
Factor VIII coagulation factor, recombinant human (e.g., Nuwiq) is available as single-use vials containing nominally: 250, 500, 1000 2000, 2500, 3000 or 4000 IU of Factor VIII potency.
P. The recommended dose of Factor VIII coagulation factor, recombinant porcine sequence (e.g., Obizur) is as follows:
1. For intravenous use after reconstitution only.
2. Initial dose of Obizur is 200 units per kg.
3. Titrate dose and frequency of administration based on factor VIII recovery levels and individual clinical response.
Factor VIII coagulation factor, recombinant porcine sequence (e.g., Obizur) is available as single-use vials containing nominally 500 units per vial.
Q. The recommended dose of Factor VIII coagulation factor, recombinant (e.g., Recombinate) is as follows:
1. Each vial of Recombinate is labeled with the Factor VIII activity expressed in IU per vial. This potency assignment is referenced to the World Health Organization International Standard for Factor VIII:C Concentrate and is evaluated by appropriate methodology to ensure accuracy of the results.
2. The expected in vivo peak increase in Factor VIII level expressed as IU/dL of plasma or % (percent) of normal can be estimated by multiplying the dose administered per kg body weight (IU/kg) by two. This calculation is based on the clinical findings of Abildgaard et al (N Eng J Med 1966; 275: 471-475) and is supported by the data generated by 419 clinical pharmacokinetic studies with Recombinate in 67 individuals over time. This pharmacokinetic data demonstrated a peak recovery point above the pre-infusion baseline of approximately 2.0 IU/dL per IU/kg body weight.
Factor VIII coagulation factor, recombinant (e.g., Recombinate) is available as single-dose vials in five different strengths. Refer to the product label for additional details.
R. The recommended dose of Factor VIII coagulation factor, recombinant (e.g., Xyntha) is as follows:
1. For intravenous use after reconstitution only.
2. The required dosage is determined using the following formula: Required units = body weight (kg) × desired factor VIII rise (IU/dL or % of normal) × 0.5 (IU/kg per IU/dL) where IU = International Unit
3. Frequency of XYNTHA administration is determined by the type of bleeding episode and the recommendation of the treating physician.
Factor VIII coagulation factor, recombinant (e.g., Xyntha) is available as single-use vials containing nominally: 250, 500, 1000, or 2000 international units.
Factor VIII (e.g., Advate, Adynovate, Afstyla, Alphanate, Altuviiio, Eloctate, Esperoct, Jivi, Hemofil-M, Humate-P, Koate, Kogenate, Kovaltry, Novoeight, Nuwiq, Obizur, Recombinate, Xyntha) should be administered as an IV infusion by a healthcare professional or a trained individual.
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Factor VIII (e.g., Advate, Adynovate, Afstyla, Alphanate, Altuviiio, Eloctate, Esperoct, Jivi, Hemofil-M, Humate-P, Koate, Kogenate, Kovaltry, Novoeight, Nuwiq, Obizur, Recombinate, Xyntha), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, factor VIII (e.g., Advate, Adynovate, Afstyla, Alphanate, Altuviiio, Eloctate, Esperoct, Jivi, Hemofil-M, Humate-P, Koate, Kogenate, Kovaltry, Novoeight, Nuwiq, Obizur, Recombinate, Xyntha), for any indication or circumstance not described above, is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
