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Hemophilia Products – Factor VIII/VWF Complex: Alphanate, Humate-P®, Wilate
Policy Number: PH-0345
Intravenous
Last Review Date: 06/04/2024
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, 06/2021, 06/2022, 06/2023, 01/2024, 06/2024
- Length of Authorization
Coverage is provided for 3 months and may be renewed thereafter, unless otherwise specified*.
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
- Dosing Limits
A, Quantity Limit (max daily dose) [NDC Unit]:
- N/A
B. 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
- Initial Approval Criteria 1-5,10,12
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:
Hemophilia A (congenital factor VIII deficiency) †
- Diagnosis of congenital factor VIII deficiency has been confirmed by blood coagulation testing; AND
- Used as treatment in one of the following:
- Treatment and control of acute bleeding episodes (episodic treatment of acute hemorrhage); OR
- Perioperative management (*Authorization is valid for 1 month); OR
- Routine prophylaxis to prevent or reduce the frequency of bleeding episodes; AND
- Used as primary prophylaxis in patients with severe factor VIII deficiency (factor VIII level of <1%); OR
- Used as secondary prophylaxis in patient with at least TWO documented episodes of spontaneous bleeding into joints
Hemophilia Management Program |
|
von Willebrand disease (vWD) † Ф
- Diagnosis of von Willebrand disease has been confirmed by blood coagulation and von Willebrand factor testing; AND
- Used as treatment in one of the following:
- Spontaneous and trauma-induced bleeding episodes; OR
- 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
- Spontaneous and trauma-induced bleeding episodes; OR
- 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) |
B. Wilate
Hemophilia A (congenital factor VIII deficiency) †
- Diagnosis of congenital factor VIII deficiency has been confirmed by blood coagulation testing; AND
- Used as treatment in one of the following:
- On-demand treatment and control of bleeding episodes; OR
- Routine prophylaxis to prevent or reduce the frequency of bleeding episodes; AND
- Used as primary prophylaxis in patients with severe factor VIII deficiency (factor VIII level of <1%); OR
- Used as secondary prophylaxis in patients with at least TWO documented episodes of spontaneous bleeding into joints
von Willebrand disease (vWD) † Ф
- Diagnosis of von Willebrand disease has been confirmed by blood coagulation and von Willebrand factor testing; AND
- Used as treatment in one of the following:
- Perioperative management of bleeding (*Authorization valid for 1 month); OR
- On-demand treatment and control of bleeding episodes in at least one of the following:
- Patients with severe vWD; OR
- Patients with mild or moderate vWD in whom the use of desmopressin is known or suspected to be ineffective or contraindicated; OR
- Routine prophylaxis to reduce the frequency of 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, then at every comprehensive care visit (yearly for the mild and moderate patients, semi-annually for the severe patients) |
† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug
- 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.
- Renewal Criteria 1-3,4,5,10
Coverage can be renewed based upon the following criteria:
- Patient continues to meet indication-specific relevant criteria identified in section III; AND
- Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: anaphylaxis and hypersensitivity reactions (e.g., angioedema, urticaria, tachycardia, chest tightness, hypotension, rash, nausea, vomiting, paresthesia, restlessness, wheezing, dyspnea, etc.), thromboembolic events (thromboembolism, pulmonary embolism), development of neutralizing antibodies (inhibitors), etc.; 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 and control 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
Perioperative management of surgical bleeding/Surgical bleeding prophylaxis
- Coverage may NOT be renewed
Routine prophylaxis to prevent or reduce the frequency of bleeding episodes
- Renewals will be approved for a 12 month authorization period; AND
- Patient has demonstrated a beneficial response to therapy (i.e., the frequency of bleeding episodes has decreased from pre-treatment baseline)
- Dosage/Administration 1-5
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:
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% of normal (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% of normal (40-50 IU FVIII/kg twice daily) for at least 3-5 days. 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 |
The expected in vivo peak increase in FVIII level expressed as IU/dL (or % normal) can be estimated using the following formulas:
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% of normal (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: 40-60 IU VWF:RCo/kg body weight at 8 to 12 hour intervals as clinically needed for 1-3 days. Pediatrics: 50-75 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: 40-60 IU VWF:RCo/kg body weight at 8 to 12 hour intervals as clinically needed for at least 3-7 days. Pediatrics: 50-75 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
Moderate
Major
|
Control and prevention of bleeding von Willebrand Disease (VWD) |
Administer 40-80 IU VWF:RCo intravenously (corresponding to 17 to 33 IU FVIII in Humate-P) per kg body weight every 8-12 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 (to be administered 1 to 2 hours before surgery) Major
Calculation of Loading Dose:
Minor
Calculation of Loading Dose:
Emergency
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 |
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Control of bleeding episodes von Willebrand Disease (VWD) |
Calculation of the required dose of VWF:RCo is based on the empirical finding that 1 IU VWF:RCo per kg body weight raises the plasma VWF activity by approximately 2% of normal activity or 2 IU/dL, using the following formula:
Adjust the dosage and frequency of administration to the clinical effectiveness in the individual patient. 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
Major
|
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Perioperative management of bleeding von Willebrand Disease (VWD) |
Calculation of the required dose of VWF:RCo is based on the empirical finding that 1 IU VWF:RCo per kg body weight raises the plasma VWF activity by approximately 2% of normal activity or 2 IU/dL, using the following formula:
Adjust the dosage and frequency of administration to the clinical effectiveness in the individual patient. Minor
Major
|
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Routine Prophylaxis von Willebrand Disease (VWD) |
Calculation of the required dose of VWF:RCo is based on the empirical finding that 1 IU VWF:RCo per kg body weight raises the plasma VWF activity by approximately 2% of normal activity or 2 IU/dL, using the following formula:
Adjust the dosage and frequency of administration to the clinical effectiveness in the individual patient.
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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:
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.
Treatment of Hemorrhages A guide for dosing in the treatment of hemorrhages is provided below. Exact dosing should be defined by the patient’s clinical status and response.
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- 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:
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(s) & NDC(s):
Drug |
Manufacturer |
J-Code |
1 Billable Unit Equiv. |
Vial Size |
NDC |
Alphanate |
Grifols Biologicals LLC |
J7186 |
1 IU |
250 units |
68516-4616-xx 68516-4611-xx |
500 units |
68516-4617-xx 68516-4612-xx |
||||
1000 units |
68516-4618-xx 68516-4613-xx |
||||
1500 units |
68516-4619-xx 68516-4614-xx |
||||
2000 units |
68516-4620-xx 68516-4615-xx |
||||
Humate-P |
CSL Behring LLC |
J7187 |
1 IU VWF:RCO |
600 units |
63833-0615-xx |
1200 units |
63833-0616-xx |
||||
2400 units |
63833-0617-xx |
||||
Wilate |
Octapharma USA Inc. |
J7183 |
1 IU VWF:RCO |
500 units |
68982-0182-xx |
1000 units |
- References
- Alphanate [package insert]. Los Angeles, CA; Grifols Biologicals LLC.; November 2022. Accessed May 2024.
- Humate-P [package insert]. Kankakee, IL; CSL Behring LLC; June 2020. Accessed May 2024.
- Wilate [package insert]. Paramus, NJ; Octapharma USA Inc.; March 2024. Accessed May 2024.
- MASAC Recommendations Concerning Products Licensed For The Treatment Of Hemophilia And Selected Disorders of the Coagulation System. Revised April 11, 2024. National Hemophilia Foundation. MASAC Document #284; April 2024. Available at: http://www.bleeding.org/. Accessed May 2024.
- Guidelines for the Management of Hemophilia 3rd Edition. World Federation of Hemophilia 2020. Available at: https://www1.wfh.org/publications/files/pdf-1863.pdf. Accessed May 2024.
- Annual Review of Factor Replacement Products. Oklahoma Health Care Authority Review Board. Updated April 2016. Accessed May 2024.
- Graham A1, Jaworski K. Pharmacokinetic analysis of anti-hemophilic factor in the obese patient. Haemophilia. 2014 Mar;20(2):226-9.
- Croteau SE1, Neufeld EJ. Transition considerations for extended half-life factor products. Haemophilia. 2015 May;21(3):285-8.
- 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).
- MASAC Recommendation Concerning Prophylaxis for Hemophilia A and B with and without Inhibitors. Revised April 27, 2022. National Hemophilia Foundation. MASAC Document #267; April 2022. Available at: http://www.bleeding.org/. Accessed May 2024.
- Connell NT, Flood VH, Brignardello-Petersen R, et al. ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease. Blood Advances, Volume 5, Issue 1, 2021, Pages 301-325, https://doi.org/10.1182/bloodadvances.2020003264.
- Hoots, WK. (2024). Hemophilia A and B: Routine management including prophylaxis. In Leung LLK, Tirnauer JS (Eds.), UptoDate. Last updated: April 16, 2024. Accessed May 13, 2024. Available from https://www.uptodate.com/contents/hemophilia-a-and-b-routine-management-including-prophylaxis?search=hemophilia%20a&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2#H978189854
- First Coast Service Options, Inc. Local Coverage Article: Billing and Coding: Hemophilia Factor Products (A56482). Centers for Medicare & Medicaid Services Inc. Updated on 09/29/2023 with effective date 10/01/2023. Accessed May 2024.
- 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 11/14/2022 with effective date 11/24/2022. Accessed May 2024.
- Novitas Solutions, Inc. Local Coverage Article: Billing and Coding: Hemophilia Factor Products (A56433). Centers for Medicare & Medicaid Services Inc. Updated on 09/29/2023 with effective date 10/01/2023. Accessed May 2024.
Appendix 1 – Covered Diagnosis Codes
ICD-10 |
ICD-10 Description |
D66 |
Hereditary factor VIII deficiency |
D68.01 |
Von Willebrand disease, type 1 |
D68.020 |
Von Willebrand disease, type 2A |
D68.021 |
Von Willebrand disease, type 2B |
D68.022 |
Von Willebrand disease, type 2M |
D68.023 |
Von Willebrand disease, type 2N |
D68.03 |
Von Willebrand disease, type 3 |
D68.04 |
Acquired von Willebrand disease |
D68.09 |
Other von Willebrand disease |
Appendix 2 – Centers for Medicare and Medicaid Services (CMS)
The preceding information is intended for non-Medicare coverage determinations. 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 Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.
Medicare Part B Covered Diagnosis Codes |
||
Jurisdiction |
NCD/LCA/LCD Document (s) |
Contractor |
N |
A56482 |
First Coast Service Options, Inc. |
J, M |
A56065 |
Palmetto GBA |
H,L |
A56433 |
Novitas Solutions, Inc. |
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 |
M (11) |
NC, SC, WV, VA (excluding below) |
Palmetto GBA |
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 |
VWF_VIII COMPLEX_HEMOPHILIA PRODUCTS - Prior Auth Criteria |
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