Pancrelipase (Creon, Pancreaze, Pertzye, Viokace, Zenpep) Form

Pancrelipase (Creon®, Pancreaze®, Pertzye®, Viokace®, Zenpep®) is a combination of porcine- derived lipases, proteases, and amylases. FDA Approved Indication(s) Creon, Pancreaze, Pertzye, and Zenpep are indicated for the treatment of exocrine pancreatic insufficiency in adult and pediatric patients. Viokace, in combination with a proton pump inhibitor, is indicated in adults for the treatment of exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatectomy. 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 Creon, Pancreaze, Pertzye, Viokace, and Zenpep are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Pancreatic Insufficiency (must meet all):

1. Diagnosis of exocrine pancreatic insufficiency;
   2. If request is for Pertzye or Viokace: Failure of Pancreaze, Creon, and Zenpep, unless clinically significant adverse effects are experienced or all are contraindicated;
2. If request is for Viokace, both of the following (a and b): a. Age ≥ 18 years; b. Viokace is prescribed concurrently with a proton pump inhibitor;

3. Dose does not exceed one of the following (a, b, or c): a. 2,500 lipase units/kg per meal; b. 10,000 lipase units/kg per day; c. 4,000 lipase units/g of fat ingested per day. Approval duration:
   HIM – 6 months Commercial – 12 months or duration of request, whichever is less Page 1 of 9

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

4. 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 and HIM.PA.33 for health insurance marketplace; 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 and HIM.PA.103 for health insurance marketplace; or
5. 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 and HIM.PA.154 for health insurance marketplace.
   II. Continued Therapy A. Pancreatic Insufficiency (must meet all):
6. 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. If request is for a dose increase, new dose does not exceed one of the following (a, b, or c): a. 2,500 lipase units/kg per meal; b. 10,000 lipase units/kg per day; c. 4,000 lipase units/g of fat ingested per day. Approval duration:
      HIM – 12 months Commercial – 12 months or duration of request, whichever is less
      B. Other diagnoses/indications (must meet 1 or 2):

7. 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 and HIM.PA.33 for health insurance marketplace; 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 and HIM.PA.103 for health insurance marketplace; or Page 2 of 9

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   Pancrelipase

8. 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 and HIM.PA.154 for health insurance marketplace.
   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 policies – CP.CPA.09 for commercial and HIM.PA.154 for health insurance marketplace or evidence of coverage documents.
   IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives Not applicable Appendix C: Contraindications/Boxed Warnings None reported V. Dosage and Administration Drug Name* Dosing Regimen Creon (pancrelipase) Infants (up to 12 months) • 3,000 lipase units (1 capsule) per 120 mL of formula or per breast-feeding. Do not mix capsule contents directly into formula or breast milk prior to administration. Children > 12 months and < 4 years • Begin with 1,000 lipase units/kg of body weight per meal to a maximum of 2,500 lipase units/kg of body weight per meal (or ≤ 10,000 lipase units/kg of body weight per day), or < 4,000 lipase units/g fat ingested per day. Children ≥ 4 years and Adults ≥ 18 years
   • Begin with 500 lipase units/kg of body weight per meal to a maximum of 2,500 lipase units/kg of body weight per meal (or ≤ 10,000 lipase units/kg of body weight per day), or < 4,000 lipase units/g fat ingested per day. Adult patients with chronic pancreatitis or pancreatectomy may require an initial starting dosage of 1,000 lipase units/kg of body weight per meal. Infants (up to 12 months) Page 3 of 9 Pancreaze (pancrelipase) Maximum Dose 2,500 lipase units/kg/meal, 10,000 lipase units/kg/day, or 4,000 lipase units/g of fat ingested/day Higher dosages may be administered if documented effective by fecal fat measures or improvement of malabsorption

   CLINICAL POLICY
   Pancrelipase Drug Name* Dosing Regimen Maximum Dose • 2,600 lipase units (1 capsule) per 120 mL of formula or per breast-feeding. Do not mix capsule contents directly into formula or breast milk prior to administration. Children > 12 months and < 4 years • Begin with 1,000 lipase units/kg of body weight per meal to a maximum of 2,500 lipase units/kg of body weight per meal (or ≤ 10,000 lipase units/kg of body weight per day), or < 4,000 lipase units/g fat ingested per day. Children ≥ 4 years and Adults ≥ 18 years
   • Begin with 500 lipase units/kg of body weight per meal to a maximum of 2,500 lipase units/kg of body weight per meal (or ≤ 10,000 lipase units/kg of body weight per day), or < 4,000 lipase units/g fat ingested per day. Infants (up to 12 months) • 4,000 lipase units (1 capsule) per 120 mL of formula or per breast-feeding. Do not mix capsule contents directly into formula or breast milk prior to administration. Children > 12 months and < 4 years • Begin with 1,000 lipase units/kg of body weight per meal to a maximum of 2,500 lipase units/kg of body weight per meal (or ≤ 10,000 lipase units/kg of body weight per day), or < 4,000 lipase units/g fat ingested per day. Children ≥ 4 years and Adults ≥ 18 years
   • Begin with 500 lipase units/kg of body weight per meal to a maximum of 2,500 lipase units/kg of body weight per meal (or ≤ 10,000 lipase units/kg of body weight per day), or < 4,000 lipase units/g fat ingested per day. Adults ≥ 18 years Begin with 500 lipase units/kg of body weight per meal to a maximum of 2,500 lipase units/kg of body weight per meal (or ≤ 10,000 lipase units/kg of body weight per day), or < 4,000 lipase units/g fat ingested per day. Infants (up to 12 months) • 3,000 lipase units (1 capsule) per 120 mL of formula or per breast-feeding. Do not mix capsule contents directly into formula or breast milk prior to administration. Page 4 of 9 Pertzye (pancrelipase) Viokace (pancrelipase) Zenpep (pancrelipase)

   CLINICAL POLICY
   Pancrelipase Drug Name Dosing Regimen Maximum Dose Children > 12 months and < 4 years • Begin with 1,000 lipase units/kg of body weight per meal to a maximum of 2,500 lipase units/kg of body weight per meal (or ≤ 10,000 lipase units/kg of body weight per day), or < 4,000 lipase units/g fat ingested per day. Children ≥ 4 years and Adults ≥ 18 years
   • Begin with 500 lipase units/kg of body weight per meal to a maximum of 2,500 lipase units/kg of body weight per meal (or ≤ 10,000 lipase units/kg of body weight per day), or < 4,000 lipase units/g fat ingested per day. Each agent is not interchangeable with any other pancrelipase product VI. Product Availability Drug Name Creon (pancrelipase) Availability Delayed-release capsules: • 3,000 USP units of lipase; 9,500 USP units of protease; 15,000 USP units of amylase • 6,000 USP units of lipase; 19,000 USP units of protease; 30,000 USP units of amylase 12,000 USP units of lipase; 38,000 USP units of protease; 60,000 USP units of amylase • 24,000 USP units of lipase; 76,000 USP units of protease; 120,000 USP units of amylase • 36,000 USP units of lipase; 114,00 USP units of protease; 180,000 USP units of amylase Delayed-release capsules: • 2,600 USP units of lipase; 8,800 USP units of protease; 15,200 USP Pancreaze (pancrelipase) units of amylase • 4,200 USP units of lipase; 14,200 USP units of protease; 24,600 USP units of amylase • 10,500 USP units of lipase; 35,500 USP units of protease; 61,500 USP units of amylase • 16,800 USP units of lipase; 56,800 USP units of protease; 98,400 USP units of amylase • 21,000 USP units of lipase; 54,700 USP units of protease; 83,900 USP units of amylase • 37,000 USP units of lipase; 93,300 USP units of protease; 149,900 USP units of amylase Delayed-release capsules: • 4,000 USP units of lipase; 14,375 USP units of protease; 15,125 USP Pertzye (pancrelipase) units of amylase Page 5 of 9

   CLINICAL POLICY
   Pancrelipase Drug Name Availability • 8,000 USP units of lipase; 28,750 USP units of protease; 30,250 USP units of amylase • 16,000 USP units of lipase; 57,500 USP units of protease; 60,500 USP units of amylase • 24,000 USP units of lipase; 86,250 USP units of protease; 90,750 USP units of amylase Viokace (pancrelipase) Tablets:
   • 10,440 USP units of lipase; 39,150 USP units of protease; 39,150 USP Zenpep (pancrelipase) units of amylase • 20,880 USP units of lipase; 78,300 USP units of protease; 78,300 USP units of amylase Delayed-release capsules: • 3,000 USP units of lipase; 10,000 USP units of protease; 14,000 USP units of amylase. Capsules have a white opaque cap and white opaque body, red imprint with “APTALIS 3” • 5,000 USP units of lipase; 17,000 USP units of protease; 24,000 USP units of amylase. Capsules have a white opaque cap and white opaque body, blue imprint with “APTALIS 5” • 10,000 USP units of lipase; 32,000 USP units of protease; 42,000 USP units of amylase. Capsules have a yellow opaque cap and white opaque body, blue imprint with “APTALIS 10” • 15,000 USP units of lipase; 47,000 USP units of protease; 63,000 USP units of amylase. Capsules have a red opaque cap and white opaque body, blue imprint with “APTALIS 15” • 20,000 USP units of lipase; 63,000 USP units of protease; 84,000 USP units of amylase. Capsules have a green opaque cap and white opaque body, blue imprint with “APTALIS 20” • 25,000 USP units of lipase; 79,000 USP units of protease; 105,000 USP units of amylase. Capsules have a blue opaque cap and white opaque body, blue imprint with “APTALIS 25” • 40,000 USP units of lipase; 126,000 USP units of protease; 168,000 USP units of amylase. Capsules have an orange opaque cap and white opaque body, blue imprint with “APTALIS 40” • 60,000 USP units of lipase; 189,600 USP units of protease; 252,600 USP units of amylase. Capsules have a powder blue opaque cap with two black stripes and white opaque body, printed with “APTALIS 60” VII.