Chenodiol (Chenodal) Form

Chenodiol (Chenodal®) is a naturally occurring human bile acid. FDA Approved Indication(s) Chenodal is indicated for patients with radiolucent stones in well-opacifying gallbladders, in whom selective surgery would be undertaken except for the presence of increased surgical risk due to systemic disease or age. Limitation(s) of use: Safety of use beyond 24 months is not established. The likelihood of successful dissolution is far greater if the stones are floatable or small. For patients with non- floatable stones, dissolution is less likely and added weight should be given to the risk that more emergent surgery might result from a delay due to unsuccessful treatment. Safety of use beyond 24 months is not established. Chenodiol will not dissolve calcified (radiopaque) or radiolucent bile pigment stones. Chenodiol will not dissolve calcified (radiopaque) or radiolucent bile pigment stones. 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 Chenodal is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Radiolucent Gallstones (must meet all):

1. Presence of radiolucent stones in well-opacifying gallbladders;
   2. Age ≥ 18 years;
   3. Failure of a 6-month trial of ursodiol, unless contraindicated or clinically significant adverse effects are experienced;
2. Member is not a candidate for surgery (e.g., due to systemic disease or age);
   5. Dose does not exceed 18 mg per kg per day. Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):

3. 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): Page 1 of 6

   CLINICAL POLICY
   Chenodiol 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

4. 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. Radiolucent Gallstones (must meet all):
5. 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. Total treatment duration does not exceed 24 months;
   4. If request is for a dose increase, new dose does not exceed 18 mg per kg per day.
      Approval duration: 12 months (up to 24 months total treatment) B. Other diagnoses/indications (must meet 1 or 2):
6. 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

7. 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.
   Page 2 of 6

   CLINICAL POLICY
   Chenodiol 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, 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 FDA: Food and Drug Administration
   Appendix B: Therapeutic Alternatives This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent and may require prior authorization.
   Drug Name Dosing Regimen ursodiol (Actigall®) 8-10 mg/kg/day PO in 2-3 divided doses Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Dose Limit/ Maximum Dose Not available Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
   o Presence of known hepatocyte dysfunction or bile ductal abnormalities such as intrahepatic cholestasis, primary biliary cirrhosis or sclerosing cholangitis; a gallbladder confirmed as non-visualizing after two consecutive single doses of dye; radiopaque stones; gallstone complications or compelling reasons for gallbladder surgery (e.g., unremitting acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis, biliary gastrointestinal fistula). o Use in pregnancy or in women who can become pregnant. • Boxed warning(s): due to potential hepatotoxicity, poor response rate and increase rate of a need for cholecystectomy was seen in some Chenodiol treated patients therefore it is not an appropriate treatment for many patients with gallstones. Chenodiol should be reserved for carefully selected patients, accompanied with liver function alternations.
   Appendix D: General Information • Oral cholecystograms or ultrasonograms are recommended at 6 to 9 month intervals to monitor response. Complete dissolutions should be confirmed by a repeat test after 1 to 3 months continued administration of Chenodal. Most patients who eventually achieve complete dissolution will show partial (or complete) dissolution at the first on-treatment test. If partial dissolution is not seen by nine to 12 months, the likelihood of success of treating longer is greatly reduced. • Stone recurrence can be expected within 5 years in 50% of cases. After confirmed dissolution, treatment generally should be stopped. Serial cholecystograms or ultrasonograms are recommended to monitor for recurrence, keeping in mind that radiolucency and gallbladder function should be established before starting another course of Chenodal. Page 3 of 6

   CLINICAL POLICY
   Chenodiol V. Dosage and Administration Indication Treatment of cholelithiasis via the dissolution of radiolucent cholesterol gallstones Dosing Regimen The recommended range is 13 to 16 mg/kg/day PO in two divided doses, morning and night, starting with 250 mg BID the first two weeks and increasing by 250 mg/day each week thereafter until the recommended or maximum tolerated dose is reached. Chenodiol should be discontinued if there is no response by 18 months. Safety of use beyond 24 months is not established. Maximum Dose 18 mg/kg/day
   VI. Product Availability Tablet: 250 mg VII.