ph-0345
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Hemophilia Products - Factor VIII/VWF Complex: Alphanate, Humate-P, Wilate

Policy Number: PH-0345

(Intravenous)

Last Review Date: 02/04/2020

Date of Origin: 12/16/2014

Dates Reviewed: 12/2014, 04/2015, 05/2015, 09/2015, 12/2015, 03/2016, 06/2016, 12/2016, 06/2017, 09/2017, 11/2017, 11/2018, 03/2019, 11/2019, 02/2020

  1. Length of Authorization

Unless otherwise specified*, the initial authorization will be provided for 3 months and may be renewed.

Note: The cumulative amount of medication the patient has on-hand will be taken into account for authorizations. Up to 5 ‘on-hand’ doses for the treatment of acute bleeding episodes will be permitted at the time of the authorization request.

* Initial and renewal authorization periods may vary by specific covered indication

  1. Dosing Limits
  1. Quantity Limit (max daily dose) [NDC unit]:

N/A

  1. Max Units (per dose and over time) [HCPCS Unit]:
  • Alphanate: 55,200 billable units per 28 day supply
  • Humate-P: 55,200 billable units per 28 day supply
  • Wilate: 55,200 billable units per 28 day supply
  1. Initial Approval Criteria 1-3,4,5,10

Hemophilia Management Program

Requirements for half-life study and inhibitor tests are a part of the hemophilia management program. This information is not meant to replace clinical decision making when initiating or modifying medication therapy and should only be used as a guide.

Coverage is provided in the following conditions:

Universal Criteria

  1. Alphanate, Humate-P ONLY

Hemophilia A (congenital factor VIII deficiency) †

  • Diagnosis of congenital factor VIII deficiency has been confirmed by blood coagulation testing; AND
  • Used as treatment for control and prevention of bleeding episodes (episodic treatment of acute hemorrhage); OR
  • Routine prophylaxis to prevent or reduce the frequency of bleeding episodes; AND
          • Patient must have severe hemophilia A (factor VIII level of <1%); OR
          • Patient has at least two documented episodes of spontaneous bleeding into joints; OR
    • Perioperative management (*Authorization is valid for 1 month)

Hemophilia Management Program

  • If the request is for routine prophylaxis and the requested dose exceeds dosing limits under part II, a half-life study should be performed to determine the appropriate dose and dosing interval.
  • For members with a BMI ≥ 30, a half-life study should be performed to determine the appropriate dose and dosing interval.
  • For minimally treated patients (< 50 exposure days to factor products) previously receiving a different factor product, inhibitor testing is required at baseline, then at every comprehensive care visit (yearly for the mild and moderate patients, semi-annually for the severe patients)

von Willebrand disease (vWD) †

  • Diagnosis of von Willebrand disease has been confirmed by blood coagulation and von Willebrand factor testing; AND
    • Treatment of spontaneous and trauma-induced bleeding episodes; OR
      • Used as surgical bleeding prophylaxis during major or minor procedures in patients with vWD in whom desmopressin is either ineffective or contraindicated (*Authorization valid for 1 month) ; AND
  • Alphanate is not indicated for patients with severe (type 3) vWD undergoing major surgery OR treatment of spontaneous/trauma-induced bleeding episodes

Hemophilia Management Program

For minimally treated patients (< 50 exposure days to factor products) previously receiving a different factor product, inhibitor testing is required at baseline, then at every comprehensive care visit (yearly for the mild and moderate patients, semi-annually for the severe patients)

  1. Wilate

Hemophilia A (congenital factor VIII deficiency) †

  • Diagnosis of congenital factor VIII deficiency has been confirmed by blood coagulation testing; AND
  • Used as treatment for control and prevention of bleeding episodes (episodic treatment of acute hemorrhage); OR
  • Routine prophylaxis to prevent or reduce the frequency of bleeding episodes; AND
          • Patient must have severe hemophilia A (factor VIII level of <1%); OR
          • Patient has at least two documented episodes of spontaneous bleeding into joints

von Willebrand disease (vWD) †

  • Diagnosis of von Willebrand disease has been confirmed by blood coagulation and von Willebrand factor testing; AND
  • Used for perioperative management of bleeding(*Authorization valid for 1 month); OR
  • Used as treatment of spontaneous and trauma-induced bleeding episodes in at least one of the following:
  • Patients with severe vWD; OR
  • Patients mild or moderate vWD in whom the use of desmopressin is known or suspected to be ineffective or contraindicated

Hemophilia Management Program

For minimally treated patients (< 50 exposure days to factor products) previously receiving a different factor product, inhibitor testing is required at, then at every comprehensive care visit (yearly for the mild and moderate patients, semi-annually for the severe patients)

FDA Approved Indication(s)

  1. Dispensing Requirements for Rendering Providers (Hemophilia Management Program)
  • Prescriptions cannot be filled without an expressed need from the patient, caregiver or prescribing practitioner. Auto-filling is not allowed.
  • Monthly, rendering provider must submit for authorization of dispensing quantity before delivering factor product. Information submitted must include:
      • Original prescription information, requested amount to be dispensed, vial sizes available to be ordered from the manufacturer, and patient clinical history (including patient product inventory and bleed history)
      • Factor dose should not exceed +1% of the prescribed dose and a maximum of three vials may be dispensed per dose. If unable to provide factor dosing within the required threshold, below the required threshold, the lowest possible dose able to be achieved above +1% should be dispensed. Prescribed dose should not be increased to meet assay management requirements.
  • The cumulative amount of medication(s) the patient has on-hand should be taken into account when dispensing factor product. Patients should not have more than 5 extra doses on-hand for the treatment of acute bleeding episodes.
  • Dispensing requirements for renderings providers are a part of the hemophilia management program. This information is not meant to replace clinical decision making when initiating or modifying medication therapy and should only be used as a guide.
  1. Renewal Criteria 1-3,4,5,10

Coverage can be renewed based upon the following criteria:

  • Patient continues to meet universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
  • Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include the following:  symptoms of allergic-anaphylactic reactions (anaphylaxis, dyspnea, rash); thromboembolic events (thromboembolism, pulmonary embolism); and development of neutralizing antibodies (inhibitors); AND
  • Any increases in dose must be supported by an acceptable clinical rationale (i.e. weight gain, half-life study results, increase in breakthrough bleeding when patient is fully adherent to therapy, etc.) ; AND
  • The cumulative amount of medication(s) the patient has on-hand will be taken into account when authorizing. The authorization will allow up to 5 doses on-hand for the treatment of acute bleeding episodes as needed for the duration of the authorization; AND

Treatment of acute bleeding episodes/Treatment of Spontaneous and trauma-induced bleeding episodes/On-demand treatment of bleeding episodes

  • Renewals will be approved for a 6 month authorization period

Prevention of acute bleeding episodes/Routine prophylaxis to prevent or reduce the frequency of bleeding episode

  • Renewals will be approved for a 12 month authorization period
  1. Dosage/Administration1-5

Alphanate

Indication

Dose

Control and prevention of bleeding Congenital Hemophilia A

The expected in vivo peak increase in FVIII level expressed as IU/dL (or % normal) can be estimated using the following formulas:

Dosage (units) = body weight (kg) x desired FVIII rise (IU/dL or % normal) x 0.5 (IU/kg per IU/dL) OR

IU/dL (or %of normal) = [Total Dose (IU)/body weight (kg)] x 2

Minor

FVIII:C levels should be brought to 30% of normal (15 IU FVIII/kg twice daily) until hemorrhage stops and healing has been achieved (1-2 days).

Moderate

FVIII:C levels should be brought to 50% (25 IU FVIII/kg twice daily) until healing has been achieved (2-7 days, on average).

Major

FVIII:C levels should be brought to 80-100% for at least 3-5 days (40-50 IU FVIII/kg twice daily). Following this treatment period, FVIII levels should be maintained at 50% (25 IU FVIII/kg twice daily) until healing has been achieved. Major hemorrhages may require treatment for up to 10 days. Intracranial hemorrhages may require prophylaxis therapy for up to 6 months.

Perioperative management Congenital Hemophilia A

Prior to surgery, the levels of FVIII:C should be brought to 80-100% of normal (40-50 IU FVIII/kg). For the next 7-10 days after surgery, or until healing has been achieved, the patient should be maintained at 60-100% FVIII levels (30-50 IU FVIII/kg twice daily).

Control and prevention of bleeding  and perioperative management von Willebrand Disease (VWD)

The ratio of VWF:RCo to FVIII in Alphanate varies by lot, so with each new lot, check the IU VWF:RCo/Vial to ensure accurate dosing.

Minor

Pre-operative/pre-procedure dose (Target FVIII:C Activity – 40-50 IU/dL):

Adults: 60 IU VWF:RCo/kg body weight.

Pediatrics: 75 IU VWF:RCo/kg body weight.

Maintenance dose (Target FVIII:C Activity – 40-50 IU/dL):

Adults: 40 to 60 IU VWF:RCo/kg body weight at 8 to 12 hour intervals as clinically needed for 1-3 days.

Pediatrics: 50 to 75 IU VWF:RCo/kg body weight at 8 to 12 hour intervals as clinically needed for 1-3 days.

Major

Pre-operative/pre-procedure dose (Target FVIII:C Activity – 100 IU/dL):

Adults: 60 IU VWF:RCo/kg body weight.

Pediatrics: 75 IU VWF:RCo/kg body weight.

Maintenance dose (Target FVIII:C Activity – 100 IU/dL):

Adults: 40 to 60 IU VWF:RCo/kg body weight at 8 to 12 hour intervals as clinically needed for at least 3-7 days.

Pediatrics: 50 to 75 IU VWF:RCo/kg body weight at 8 to 12 hour intervals as clinically needed for at least 3-7 days.

Humate-P

Indication

Dose

Control and prevention of bleeding Congenital Hemophilia A

One International Unit (IU) of Factor VIII (FVIII) activity per kg body weight will increase the circulating FVIII level by approximately 2.0 International Units (IU)/dL.

Minor

Loading dose 15 IU FVIII:C/kg to achieve a FVIII:C plasma level of approximately 30% of normal; one infusion may be sufficient. If needed, half of the loading dose may be given once or twice daily for 1-2 days.

Moderate

Loading dose 25 IU FVIII:C/kg to achieve a FVIII:C plasma level of approximately 50% of normal, followed by 15 IU FVIII:C/kg every 8-12 hours for the first 1-2 days to maintain the FVIII:C plasma level at 30% of normal. Continue the same dose once or twice daily for up to 7 days or until adequate wound healing is achieved.

Major

Initially 40-50 IU FVIII:C/kg, followed by 20-25 IU FVIII:C/kg every 8 hours to maintain the FVIII:C plasma level at 80-100% of normal for 7 days. Continue the same dose once or twice daily for another 7 days to maintain the FVIII:C level at 30-50% of normal.

Control and prevention of bleeding  von Willebrand Disease (VWD)

Administer 40 to 80 International Units (IU) VWF:RCo (corresponding to 17 to 33 International Units (IU) FVIII in Humate-P) per kg body weight every 8 to 12 hours. Adjust the dosage based on the extent and location of bleeding. Administer repeat doses as long as needed based on monitoring of appropriate clinical and laboratory measures

Perioperative management von Willebrand Disease (VWD)

Loading Doses

Major

VWF:Rco Target Peak Plasma Level – 100 IU/dL

Target FVIII:C Activity – 80-100 IU/dL

((Target peak plasma VWF:RCo level – baseline plasma VWF:RCo level) x Body wt (kg)) /IVR (in vivo recovery)

If the IVR is not available, assume an IVR of 2.0 IU/dL per IU/kg and calculate the loading dose as follows: (100 – baseline plasma VWF:RCo) x BW (kg)/2.0

Minor

VWF:Rco Target Peak Plasma Level – 50-60 IU/dL

Target FVIII:C Activity – 40-50 IU/dL

((Target peak plasma VWF:RCo level – baseline plasma VWF:RCo level) x Body wt (kg)) /IVR (in vivo recovery)

Emergency

VWF:Rco Target Peak Plasma Level – 100 IU/dL

Target FVIII:C Activity – 80-100 IU/dL

Administer a dose of 50-60 IU VWF:RCo/kg body weight.

Maintenance Doses

The initial maintenance dose of Humate-P for the prevention of excessive bleeding during and after surgery should be half of the loading dose, irrespective of additional dosing required to meet FVIII:C targets. Subsequent maintenance doses should be based on the patient’s VWF:RCo and FVIII levels.

Wilate

Indication

Dose

Control of bleeding episodes VWD

The ratio between VWF:RCo and FVIII activities in Wilate is approximately 1:1. The dosage should be adjusted according to the extent and location of the bleeding.

Minor and Moderate

Loading dose: 20-40 IU/kg; Maintenance dose: 20-30 IU/kg every 12-24 hours until VWF:Rco and FVIII activity trough levels > 30%, for up to 3 days.

Major

Loading dose: 40-60 IU/kg; Maintenance dose: 20-40 IU/kg every 12-24 hours until VWF:Rco and FVIII activity trough levels > 50%, for up to 5-7 days.

Perioperative management of bleeding vWD

Minor

Loading dose: 30-60 IU/kg; Maintenance dose: 15-30 IU/kg or half of the loading dose every 12-24 hours until wound healing achieved, up to 3 days. VWF:Rco trough levels > 30% and peak levels 50%.

Major

Loading dose: 40-60 IU/kg; Maintenance dose: 20-40 IU/kg or half the loading dose every 12-24 hours (at least 2 doses within the first 24 hours after the start of surgery) until wound healing achieved, up to 6 days or more. VWF:Rco trough levels > 50% and peak levels 100%.

Control and prevention of bleeding/ Routine Prophylaxis Congenital Hemophilia A

Calculation of the required dose of Factor VIII is based on the empirical finding that 1 IU Factor VIII per kg body weight raises the plasma Factor VIII activity by approximately 2% of normal activity or 2 IU/dL when assessed using the one stage clotting assay. Use the following formula to determine the required dose:

  • Required IU = body weight (kg) x desired Factor VIII rise (%) (IU/dL) x 0.5 (IU/kg per IU/dL)
  • Expected Factor VIII rise (% of normal) = 2 x administered IU / body weight (kg)

Dose and duration of therapy depend on the patient’s weight, type and severity of hemorrhage, FVIII level, and presence of inhibitors. Titrate dose and frequency to the patient’s clinical response, individual needs, severity of deficiency, severity of hemorrhage, desired FVIII level, and presence of inhibitor, and the patient’s clinical condition. Patients may vary in their pharmacokinetic (e.g., half-life, in vivo recovery) and clinical responses to Wilate.

Routine Prophylaxis

A guide for dosing as routine prophylaxis to reduce the frequency of bleeding is provided below. Exact dosing should be defined by the patient’s clinical status and response.

Patients

Recommended Dose (IU/kg)

Frequency

Adolescents and adults

20-40 IU/kg

Every 2-3 days

Dosing for Hemorrhages

A guide for dosing in the treatment of major and minor hemorrhages is provided below. Exact dosing should be defined by the patient’s clinical status and response.

Hemorrhage Type

Recommended Dose (IU/kg)

Frequency

Frequency

Minor

30-40

Repeat every 12-24 hours

At least 1 day, until bleed stops

Moderate

30-40

Repeat every 12-24 hours

3+ days, until bleed stops

Major

35-50

Repeat every 12-24 hours

3+ days, until bleed stops

Life-Threatening

35-50

Repeat every 8-24 hours

Until threat has resolved

  1. Billing Code/Availability Information

Hemophilia products are covered under the prescription drug benefits of a member’s plan.  Claims for hemophilia products submitted for payment under any benefit section of the member’s plan (other than prescription drug benefits) will be denied as non-covered benefits.    The only exceptions to this are claims for hemophilia products used in an inpatient facility or for emergency use, accidents or surgery (Type Services A, S, or 2) in the following settings:

  • Outpatient Facility
  • Physician office

If home health nursing assistance is needed for drug administration, the hemophilia product should be accessed and paid through the member’s prescription benefit coverage. Nursing services should be billed only for the administration of the hemophilia product under the member’s home health benefits.

HCPCS code & NDC:

Drug

Manufacturer

J-Code

1 Billable Unit Equiv.

Vial Size

NDC

Alphanate

Grifols Biologicals Inc

J7186

1 IU

250 units

  • 68516-4601
  • 68516-4611

500 units

  • 68516-4602
  • 68516-4612

1000 units

  • 68516-4603
  • 68516-4613

1500 units

  • 68516-4604
  • 68516-4614

2000 units

  • 68516-4609
  • 68516-4615

Humate-P

CSL Behring LLC

J7187

1 IU

600 units

63833-0615

1200 units

63833-0616

2400 units

63833-0617

Wilate

Octapharma USA

J7183

1 IU VWF:RCO

500 units

68982-0182

1000 units

  1. References
  1. Alphanate [package insert]. Los Angeles, CA; Grifols Biologicals Inc.; June 2018.  Accessed January 2020.
  2. Humate-P [package insert]. Kankakee, IL; CSL Behring LLC; September 2017. Accessed January 2020.
  3. Wilate [package insert].  Hoboken, NJ; Octapharma USA; September 2019. Accessed January 2020.
  4. CONCERNING PRODUCTS LICENSED FOR THE TREATMENT OF HEMOPHILIA AND OTHER BLEEDING DISORDERS.  2016 National Hemophilia Foundation.  MASAC Document #249; October 2016.  Available at: http://www.hemophilia.org.   Accessed January 2019.
  5. Guidelines for the Management of Hemophilia. 2nd Edition. World Federation of Hemophilia. 2013. Available at: https://www1.wfh.org/publication/files/pdf-1472.pdf.  Accessed January 2019.
  6. Annual Review of Factor Replacement Products. Oklahoma Health Care Authority Review Board. Updated April 2016. Access January 2019.
  7. Graham A1, Jaworski K. Pharmacokinetic analysis of anti-hemophilic factor in the obese patient. Haemophilia. 2014 Mar;20(2):226-9.
  8. Croteau SE1, Neufeld EJ. Transition considerations for extended half-life factor products. Haemophilia. 2015 May;21(3):285-8.
  9. Mingot-Castellano, et al. Application of Pharmacokinetics Programs in Optimization of Haemostatic Treatment in Severe Hemophilia a Patients: Changes in Consumption, Clinical Outcomes and Quality of Life. Blood. 2014 December; 124 (21).
  10. MASAC RECOMMENDATION CONCERNING PROPHYLAXIS. 2016 National Hemophilia Foundation.  MASAC Document #241; February 2016.  Available at: http://www.hemophilia.org.   Accessed January 2019.
  11. First Coast Service Options, Inc. Local Coverage Article: Hemophilia Clotting Factors (A56482). Centers for Medicare & Medicaid Services Inc. Updated on 12/06/2019 with effective date 07/01/2019. Accessed January 2020.
  12. Palmetto GBA. Local Coverage Article: Billing and Coding: Guidance for Anti-Inhibitor Coagulant Complex (AICC) National Coverage Determination (NCD) 110.3 (A56065). Centers for Medicare & Medicaid Services Inc. Updated on 10/24/2019 with effective date 10/31/2019. Accessed January 2020.
  13. Novitas Solutions, Inc. Local Coverage Article: Billing and Coding: Hemophilia Factor Products (A56433). Centers for Medicare & Medicaid Services Inc. Updated on 11/08/2019 with effective date 11/14/2019. Accessed January 2020.

Appendix 1 – Covered Diagnosis Codes

ICD-10

ICD-10 Description

D66

Hereditary factor VIII deficiency

D68.0

Von Willebrand's disease

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD) and Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. They can be found at: http://www.cms.gov/medicare-coverage-database/search/advanced-search.aspx. Additional indications may be covered at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD):

Jurisdiction(s): N

NCD/LCD Document (s): A56482

https://www.cms.gov/medicare-coverage-database/search/article-date-search.aspx?DocID=A56482&bc=gAAAAAAAAAAA

Jurisdiction(s): J,M

NCD/LCD Document (s): A56065

https://www.cms.gov/medicare-coverage-database/search/article-date-search.aspx?DocID=A56065&bc=gAAAAAAAAAAA

Jurisdiction(s): H,L

NCD/LCD Document (s): A56433

https://www.cms.gov/medicare-coverage-database/search/article-date-search.aspx?DocID=A56433&bc=gAAAAAAAAAAA

Medicare Part B Administrative Contractor (MAC) Jurisdictions

Jurisdiction

Applicable State/US Territory

Contractor

E (1)

CA, HI, NV, AS, GU, CNMI

Noridian Healthcare Solutions, LLC

F (2 & 3)

AK, WA, OR, ID, ND, SD, MT, WY, UT, AZ

Noridian Healthcare Solutions, LLC

5

KS, NE, IA, MO

Wisconsin Physicians Service Insurance Corp (WPS)

6

MN, WI, IL

National Government Services, Inc. (NGS)

H (4 & 7)

LA, AR, MS, TX, OK, CO, NM

Novitas Solutions, Inc.

8

MI, IN

Wisconsin Physicians Service Insurance Corp (WPS)

N (9)

FL, PR, VI

First Coast Service Options, Inc.

J (10)

TN, GA, AL

Palmetto GBA, LLC

M (11)

NC, SC, WV, VA (excluding below)

Palmetto GBA, LLC

L (12)

DE, MD, PA, NJ, DC (includes Arlington & Fairfax counties and the city of Alexandria in VA)

Novitas Solutions, Inc.

K (13 & 14)

NY, CT, MA, RI, VT, ME, NH

National Government Services, Inc. (NGS)

15

KY, OH

CGS Administrators, LLC