Age Limit Override (Codeine, Tramadol, Hydrocodone), HYDROCODONE, Hydrocodone Bitartrate HYDROCODONE TRAMADOL, Tramadol HCl CODEINE Form

Prior authorization is required for the following medications in the respective age groups due to FDA labeling of these medications: • Codeine-containing medications indicated for pain are contraindicated in pediatric patients younger than age 12 years and in patients less than 18 years to treat post-tonsillectomy and post-adenoidectomy pain; • Tramadol-containing medications are not indicated for pain in patients younger than age 18 years (use is contraindicated in pediatric patients younger than age 12 years and in patients less than 18 years to treat post-tonsillectomy and post-adenoidectomy pain); • Codeine- and hydrocodone-containing medications indicated for cough and cold are not indicated for use in pediatric patients younger than age 18 years. FDA Approved Indication(s) Codeine- and tramadol-containing medications are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.
Codeine- and hydrocodone-containing medications are indicated for relief of cough, nasal congestion, and other upper respiratory symptoms associated with allergies or cold.
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 codeine-, tramadol-, and hydrocodone-containing opioids are medically necessary for the following reasons:
I. Initial Approval Criteria
Please note: for HIM-Arkansas – if a member's covered prescription pain medication requires a prior authorization, then the prior authorization shall not be denied if the member has a terminal illness. A. Pain (must meet all):
*In addition to meeting these criteria, requests for all opioids are subject to the criteria outlined in the opioid analgesic policy for the relevant line of business.

1. Prescribed for pain management;

2. Prescribed agent is FDA-approved for pain management;
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   CLINICAL POLICY Age Limit Override for Codeine, Tramadol, Hydrocodone

   3. Member meets one of the following (a or b): a. Failure of at least two non-opioid ancillary treatments (e.g., non-steroidal anti- inflammatory drugs [NSAIDs], acetaminophen, anticonvulsants, antidepressants) at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated; b. For cancer, palliative care, or sickle cell disease: prescribed by or in consultation with an oncologist, hematologist, hospice provider, or pain specialist;
   4. Failure of at least two age-appropriate opioid analgesics (e.g., morphine, oxycodone), unless clinically significant adverse effects are experienced or all are contraindicated;
   5. Use is not for pain post-tonsillectomy or post-adenoidectomy;
3. Dose does not exceed health plan’s approved quantity limit. Approval duration:
   Non-cancer pain – 7 days
   Cancer, sickle cell, or palliative care – 12 months
   B. Cough (must meet all):
   
   1. Diagnosis of cough due to viral or bacterial infection;
4. Prescribed agent is FDA-approved for the treatment of cough;
5. Failure of at least two of the following agents at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated: dextromethorphan, benzonatate, guaifenesin;
   4. Member is concurrently receiving appropriate therapy for the underlying cause of the cough (e.g., antihistamines, decongestants, bronchodilators, oral and/or inhaled corticosteroids, antibiotics);
   5. Dose does not exceed the FDA-approved maximum recommended dose.
      Approval duration: health plan-specific duration of approval, not to exceed 7 days C. Other diagnoses/indications: Not applicable II. Continued Therapy Please note: for HIM-Arkansas – if a member's covered prescription pain medication requires a prior authorization, then the prior authorization shall not be denied if the member has a terminal illness. A. Cancer, Sickle Cell, or Palliative Care Pain (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);
6. Member is responding positively to therapy;

7. If request is for a dose increase, new dose does not exceed health plan’s approved quantity limit.
   Approval duration: 12 months Page 2 of 9

   CLINICAL POLICY Age Limit Override for Codeine, Tramadol, Hydrocodone
   B. All Other Indications in Section I (must meet all):
   Continued therapy for cough, or non-cancer, non-sickle cell or non-palliative care pain will not be authorized as the underlying causes of cough and pain must be treated with appropriate therapy. C. Other diagnoses/indications: Not applicable 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 MAOI: monoamine oxidase inhibitors NSAIDs: non-steroidal anti-inflammatory drugs REMS: Risk Evaluation and Mitigation Strategy 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 for all relevant lines of business and may require prior authorization.
   Drug Name Dosing Regimen Dose Limit/ Maximum Dose 75 mg/kg/day not to exceed 4 g/day acetaminophen (Tylenol®) Analgesia Weight-based pediatric dosing 10 – 15 mg/kg/dose PO Q4 – 6 hr PRN Age 6 to 11 years 325 mg PO Q4 – 6 hr PRN Age 12 years or older Immediate-release: 650 mg PO Q4 – 6 hr PRN or 1000 mg PO Q6 hr PRN Extended-release: 1300 mg PO Q8 hr PRN Neuropathic pain* Initial: 50 – 100 mg PO BID Maintenance: 100 – 200 mg PO Q4 – 6 hr Muscle spasm Age 15 years or older 5 – 10 mg PO TID Chronic musculoskeletal pain 30 mg PO QD for 1 week, then 60 mg PO QD
   1,200 mg/day 30 mg/day 60 mg/day carbamazepine (Tegretol®) cyclobenzaprine (Fexmid®) duloxetine (Cymbalta®) Page 3 of 9

   CLINICAL POLICY Age Limit Override for Codeine, Tramadol, Hydrocodone
   Drug Name Dosing Regimen gabapentin (Neurontin®) ibuprofen (Advil®, Motrin®) Neuropathic pain* 1,200 – 3,600 mg/day PO in 3 divided doses Analgesia Age 6 months to less than 12 years 4 – 10 mg/kg/dose PO Q6 – 8 hr PRN Dose Limit/ Maximum Dose 3,600 mg/day 40 mg/kg/day not to exceed 2,400 mg/day oxycodone (Roxicodone®, OxyContin®) morphine sulfate immediate-release Age 12 to 17 years 400 mg PO Q4 – 6 hr PRN Moderate-to-severe pain (immediate-release tablets) 0.1 – 0.2 mg/kg/dose (moderate pain) or 0.2 mg/kg/dose (severe pain) PO N/A Severe pain (extended-release tablets) Age 11 months or older Initial dose PO based on conversion from current opioid regimen dose
   Acute pain
   Age 6 months or younger 0.08 – 0.1 mg/kg/dose PO Q3 – 4 hr N/A Age greater than 6 months Weight < 50 kg: 0.2 – 0.5 mg/kg/dose PO Q3 – 4 hr PRN Weight ≥ 50 kg: 15 – 20 mg/kg PO Q3 – 4 hr PRN Cough (suppressant) Age 4 to 6 years (syrup) Immediate-release: 2.5 – 7.5 mg PO Q4 – 8 hr PRN Extended-release: 15 mg PO BID PRN Age 6 to less than 12 years Immediate-release: 5 – 10 mg PO Q4 hr PRN or 15 mg PO Q6 – 8 hr PRN Extended-release: 30 mg PO BID PRN Age 12 years or older Immediate-release: 10 – 20 mg PO Q4 hr PRN or 20 – 30 mg PO Q6 – 8 hr PRN Cough (expectorant) Age 2 to less than 4 years Liquid: 50 – 100 mg PO Q4 hr PRN
   Age 4 to 6 years: 30 mg/day Age 6 to 12 years: 60 mg/day Age ≥ 12 years: 120 mg/day Age 2 to < 6 years: 600 mg/day dextromethorphan (Delsym®, Robitussin®) guaifenesin (Mucinex®) Page 4 of 9

   CLINICAL POLICY Age Limit Override for Codeine, Tramadol, Hydrocodone
   Drug Name Dosing Regimen Age 4 to less than 6 years 50 – 100 mg PO Q4 hr PRN Age 6 to less than 12 years 100 – 200 mg PO Q4 hr PRN Age 12 years or older 200 – 400 mg PO Q4 hr PRN Cough Age greater than 10 years 100 – 200 mg PO TID PRN benzonatate (Tessalon Perles®) Dose Limit/ Maximum Dose Age 6 to < 12 years: 1,200 mg/day Age ≥ 12 years: 2,400 mg/day 600 mg/day albuterol nebulizer Bronchospasm Varies albuterol metered dose inhaler (ProAir®, Proventil®, Ventolin®) diphenhydramine (Benadryl®) oxymetazoline (Afrin® Nasal Spray) phenylephrine (Afrin® Childrens) Varies 150 mg/day Max 3 days use Max 3 days use Age 2 to less than 12 years Weight 10 – 15 kg: 0.63 – 1.25 mg PO TID or QID PRN Weight > 15 kg: 0.63 – 2.5 mg PO TID or QID PRN Age 12 years or older 2.5 mg PO TID or QID PRN Bronchospasm 2 inhalations Q4 – 6 hr PRN Cough Age 12 years or older 25 mg PO Q4 hr PRN Nasal congestion Age 6 years or older 2 – 3 sprays in each nostril BID for ≤ 3 days Nasal congestion Age 2 to less than 6 years 0.125% solution: 2 – 3 sprays in each nostril for no more than Q4 hrs for ≤ 3 days Age 6 to less than 12 years 0.25% solution: 2 – 3 sprays in each nostril for no more than Q4 hrs for ≤ 3 days Age 12 years or greater 0.25% to 1% solution: 2 – 3 sprays in each nostril for no more than Q4 hrs for ≤ 3 days Page 5 of 9

   CLINICAL POLICY Age Limit Override for Codeine, Tramadol, Hydrocodone
   Drug Name Dosing Regimen phenylephrine (Sudafed PE® Childrens) Nasal congestion Age 4 to less than 6 years 2.5 mg PO Q4 hr PRN for ≤ 7 days Qvar® (beclomethasone) Age 6 to less than 12 years 5 mg PO Q4 hr PRN for ≤ 7 days Age 12 years or greater 10 mg PO Q4 hr PRN for ≤ 7 days Asthma Age 5 to 11 years 40 – 80 mcg inhaled BID Age 12 years or greater 40 – 320 mcg inhaled BID Dose Limit/ Maximum Dose Age 4 to < 6 years: 15 mg/day Age 6 to < 12 years: 30 mg/day Age ≥ 12 years: 60 mg/day Age 5 to 11 years: 80 mcg BID/day Age ≥ 12 years: 320 mcg BID/day 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. *Off-label Appendix C: Contraindications/Boxed Warnings • Contraindication(s): use in children younger than 12 years of age; postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy; significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment; concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days; known or suspected gastrointestinal obstruction, including paralytic ileus; hypersensitivity to the active ingredient. • Boxed warning(s): risks of misuse, abuse, addiction, overdose, death; serious or life- threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors; concomitant use with benzodiazepines or other central nervous system depressants; Risk Evaluation and Mitigation Strategy (REMS); ultra- rapid metabolism of codeine or tramadol and other risk factors for life-threatening respiratory depression in children. V. Dosage and Administration
   There are various codeine-, tramadol-, and hydrocodone-containing medications commercially available. Please refer to the respective package inserts for dosing and administration. VI. Product Availability
   Please refer to the respective package inserts for product availability. Page 6 of 9

   CLINICAL POLICY Age Limit Override for Codeine, Tramadol, Hydrocodone
   VII. References

8. Codeine Prescribing Information. Eatontown, NJ: West-Ward Pharmaceuticals Corp; March
9. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=010905f9- 3bcb-4b50-9fe8-a3ad0010f14c. Accessed January 11, 2023.
   2. Ultram Prescribing Information. Titusville, NJ: Janssen Pharmaceuticals, Inc.; September
   3. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/020281s049lbl.pdf. Accessed January 11, 2023.
   4. Tussionex Prescribing Information. Smyrna, GA: UCB, Inc.; January 2017. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=af2caf33-e587-4d80-9523- 44e1b565aae2. Accessed January 19, 2023.
   5. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2018. Available at: https://www.clinicalkey.com/pharmacology/login. Accessed January 11, 2023.
10. Food and Drug Administration. FDA Drug Safety Communication: FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children; recommends against use in breastfeeding women.
11. https://www.fda.gov/Drugs/DrugSafety/ucm549679.htm.
    6. Food and Drug Administration. FDA Drug Safety Communication: FDA requires labeling changes for prescription opioid cough and cold medicines to limit their use to adults 18 years and older. 2018. https://www.fda.gov/Drugs/DrugSafety/ucm590435.htm.
    7. Chang AB, Oppenheimer JJ, Weinberger MM, et al. Management of children with chronic wet cough and protracted bacterial bronchitis. Chest Journal. 2017;151(4):884-890.
    8. Malesker MA, Callahan-Lyon P, Ireland B, Irwin RS. Pharmacologic and nonpharmacologic treatment for acute cough associated with the common cold. CHEST Journal. 2017;152(5):1021-1037.
    9. World Health Organization (WHO). WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses. 2012. Available at http://apps.who.int/iris/bitstream/10665/44540/1/9789241548120_Guidelines.pdf.
    10. Dowell D, Ragan KR, Jones CM, Baldwin GT, and Chou R. CDC clinical practice guideline for prescribing opioids for pain – United States, 2022. MMWR Recomm Rep 2022;71(No. RR-3):1-95. Reviews, Revisions, and Approvals 2Q 2019 annual review: Updated the initial approval duration for cough to 7 days (or health plan-specific limit) to align with the treatment duration for pain.