Hemin (Panhematin) Form

Hemin for injection (Panhematin®) is an enzyme inhibitor derived from processed red blood cells. FDA Approved Indication(s) Panhematin is indicated for amelioration of recurrent attacks of acute intermittent porphyria (AIP) temporally related to the menstrual cycle in susceptible women, after initial carbohydrate therapy is known or suspected to be inadequate. Limitation(s) of use:
• Before administering Panhematin, consider an appropriate period of carbohydrate loading (i.e., 400 g glucose/day for 1 to 2 days). • Attacks of porphyria may progress to a point where irreversible neuronal damage has occurred. Panhematin therapy is intended to prevent an attack from reaching the critical stage of neuronal degeneration. Panhematin is not effective in repairing neuronal damage.
Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Panhematin is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Acute Porphyria (must meet all):

1. Diagnosis of acute porphyria (i.e., AIP, variegate porphyria [VP], or hereditary coproporphyria [HCP]) confirmed by both of the following (a and b):
   a. Presence of clinical symptoms (e.g., abdominal pain, pain in chest, legs or back, peripheral neuropathy, hyponatremia, tachycardia, sweating, tremor, dysuria, incontinence, constipation, nausea, vomiting); b. History of at least a four-fold increase of 5-aminolevulinic acid (ALA) or porphobilinogen (PBG) using a random urine sample within the past year (see Appendix D);

   2. Age ≥ 16 years;
   3. Documentation of member’s current body weight (in kg);
   4. Dose does not exceed 6 mg/kg in any 24-hour period. Approval duration: 14 days Page 1 of 6

   CLINICAL POLICY Hemin B. Other diagnoses/indications (must meet 1 or 2):

2. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
3. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Acute Porphyria (must meet all):
4. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
   2. Member is responding positively to therapy;
   3. Documentation of member’s current body weight (in kg);
   4. If request is for a dose increase, new dose does not exceed 6 mg/kg in any 24-hour period. Approval duration: Up to 14 days B. Other diagnoses/indications (must meet 1 or 2):

5. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or Page 2 of 6

   CLINICAL POLICY Hemin

6. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   III. Diagnoses/Indications for which coverage is NOT authorized:
   A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policy – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key AIP: acute intermittent porphyria ALA: 5-aminolevulinic acid FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
   Not applicable HCP: hereditary coproporphyria PBG: prophobilinogen VP: variegate porphyria Appendix C: Contraindications/Boxed Warnings • Contraindication(s): known hypersensitivity to Panhematin • Boxed warning(s): none reported Appendix D: ALA and PBG Laboratory Testing Concentrations of ALA or PBG in a random urine sample greater than four times the upper limit of normal establish the diagnosis of AHP (Wang 2019). Variations in reference ranges and reporting (e.g., with or without creatinine correction) may differ across U.S. laboratories; however, four times the upper limit of normal based on a random urine sample remains an appropriate evaluative tool. Examples of laboratory reporting variations:ALA/PBG values below are chosen for demonstration purposes only and do not reflect actual required values. • Corrected for creatinine:Additional units applicable here include mg/mmol creatinine. o ALA = 38 mg/g creatinine (reference range 0-7 mg/g creatinine);
   o PBG = 85 mg/g creatinine (reference range 0-4 mg/g creatinine).
   See Wang et al (2019) for additional information. • Uncorrected for creatinine:Additional units applicable here include mcmol/L. o ALA = 40 mg/L (reference range 0.0-5.4 mg/L);
   o PBG = 90 mg/L (reference range 0.0-2.0 mg/L).
   See LabCorp (www.labcorp.com) and Mayo Medical Laboratories (www.mayoclinicalabs.com) testing information for additional information. __ Wang B, Rudnick S, Cengia B, Bonkovsky HL. Acute hepatic porphyrias: Review and recent progress. Hepatology Communications, 2019; 3(2): 193:206. Page 3 of 6

   CLINICAL POLICY Hemin V. Dosage and Administration
   Indication Amelioration of recurrent attacks of AIP
   Dosing Regimen 1 to 4 mg/kg/day IV for 3 to 14 days based on the clinical signs. The standard dose in clinical practice is 3 to 4 mg/kg/day. Maximum Dose 6 mg/kg in any 24- hour period. Repeat dose in more severe cases no earlier than every 12 hours. Do not exceed 6 mg/kg in any 24-hour period. VI. Product Availability
   Single-dose lyophilized powder vial: 350 mg VII.