Colchicine (Colcrys) Form

Colchicine (Colcrys®, Lodoco®) is an alkaloid. FDA Approved Indication(s) Colcrys is indicated: • For the prophylaxis and treatment of gout flares in adults • For the treatment of familial Mediterranean fever (FMF) in adults and children 4 years or older Lodoco is indicated to reduce the risk of myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease. 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 colchicine, Colcrys, and Lodoco are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Familial Mediterranean Fever (must meet all):

1. Diagnosis of FMF;
   2. Request is not for Lodoco;
   3. Age ≥ 4 years;
   4. Member must use generic colchicine tablets, unless contraindicated or clinically significant adverse effects are experienced;
2. Dose does not exceed both of the following (a and b): a. Total dosage of 2.4 mg per day; b. Health plan-approved quantity limits.
   Approval duration: 12 months B. Treatment of Acute Gout Attack (must meet all):

3. Diagnosis of acute gout attack;

   2. Request is not for Lodoco;
   3. Age ≥ 16 years;
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   CLINICAL POLICY Colchicine

4. Member must use generic colchicine tablets, unless contraindicated or clinically significant adverse effects are experienced;
5. Failure of a nonsteroidal anti-inflammatory drug (NSAID) (e.g., naproxen, indomethacin, sulindac) within the last 30 days, unless member has one of the following contraindications (a, b, c, d, or e): a. Heart failure or uncontrolled hypertension; b. Current use of an anticoagulant (e.g., aspirin, warfarin, low molecular weight heparin, direct thrombin inhibitors, factor Xa inhibitors, clopidogrel); c. Active duodenal or gastric ulcer (not gastroesophageal reflux disease [GERD]); d. Current use of corticosteroid;
   e. Chronic kidney disease with CrCl < 60 mL/min per 1.73 m2;
6. Dose does not exceed both of the following (a and b): a. Total dosage of 1.8 mg per day for the initial dose followed by 1.2 mg per day thereafter; b. Health plan-approved quantity limits.
   Approval duration: 2 weeks (no more than 30 tablets) C. Gout Anti-Inflammatory Prophylaxis (must meet all):
7. Diagnosis of gout;
   
   2. Request is not for Lodoco;
   3. Age ≥ 16 years;
   4. Member must use generic colchicine tablets, unless contraindicated or clinically significant adverse effects are experienced;
8. Member is currently taking or will be initiating a urate-lowering therapy (e.g., allopurinol, probenecid) within the next 6 months, unless contraindicated or clinically significant adverse effects are experienced;
9. Dose does not exceed both of the following (a and b): a. Total dosage of 1.2 mg per day; b. Health plan-approved quantity limits.
   Approval duration: 6 months D. Cardiovascular Event Prophylaxis (must meet all):
10. Member meets one of the following (a, b, c, d, or e, see Appendix D): a. History of myocardial infarction; b. History of stroke;
    c. History of coronary revascularization;
    d. Has multiple risk factors for cardiovascular disease; e. Diagnosis of stable coronary artery disease;
    
    2. Prescribed by or in consultation with a cardiologist;
    3. Age ≥ 18 years;
    4. Member must use generic colchicine 0.6 mg tablet, unless contraindicated or clinically significant adverse effects are experienced;

11. Documentation that member has been clinically stable for at least 6 months (see Appendix D); Page 2 of 11

    CLINICAL POLICY Colchicine

12. Prescriber attestation that member is concurrently receiving standard of care for one of the following (a or b, see Appendix D): a. Secondary prevention prophylaxis regimen for MI or stroke; b. Treatment for stable coronary artery disease;
13. Dose does not exceed 1 tablet per day. Approval duration: 12 months E. Pericarditis (off-label) (must meet all):
14. Diagnosis of pericarditis;
    
    2. Request is not for Lodoco;
    3. Prescribed by or in consultation with a cardiologist;
    4. Member must use generic colchicine tablets, unless contraindicated or clinically significant adverse effects are experienced;
15. Colchicine is prescribed concurrently with an NSAID or glucocorticoid;
    6. Dose does not exceed both of the following (a and b): a. Total dosage of 1.2 mg per day; b. Health plan-approved quantity limits.
       Approval duration: 6 months F. Other diagnoses/indications (must meet 1 or 2):
16. 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
17. 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. Familial Mediterranean Fever (must meet all):
    1. 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);

18. Request is not for Lodoco; Page 3 of 11

    CLINICAL POLICY Colchicine

19. Member is responding positively to therapy as evidenced by, including but not limited to, improvement in any of the following parameters: a. Reduction/normalization of C-reactive protein (CRP) or serum amyloid A (SAA) levels;
    b. Reduction of flare frequency, symptom severity, or duration;
20. Member must use generic colchicine tablets, unless contraindicated or clinically significant adverse effects are experienced;
21. Dose does not exceed both of the following (a and b): a. Total dosage of 2.4 mg per day; b. Health plan-approved quantity limits.
    Approval duration: 12 months B. Treatment of Acute Gout Attack
22. Re-authorization is not permitted. Member must meet the initial approval criteria. Approval duration: Not applicable C. Gout Anti-Inflammatory Prophylaxis (must meet all):
23. 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);
24. Request is not for Lodoco;
    3. Member is responding positively to therapy;
    4. Member must use generic colchicine tablets, unless contraindicated or clinically significant adverse effects are experienced;
25. Member is currently taking a urate-lowering therapy (e.g., allopurinol, probenecid) at up to maximally indicated doses, unless contraindicated;
26. Dose does not exceed both of the following (a and b): a. Total dosage of 1.2 mg per day; b. Health plan-approved quantity limits.
    Approval duration: 6 months D. Cardiovascular Event Prophylaxis (must meet all):
    
    1. 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);
27. Member is responding positively to therapy (e.g. no drug-related adverse events such as myotoxicity, rhabdomyolysis, abdominal pain, acute renal impairment);
    3. Member must use generic colchicine 0.6 mg tablet, unless contraindicated or clinically significant adverse effects are experienced;

28. If request is for a dose increase, new dose does not exceed 1 tablet per day. Page 4 of 11

    CLINICAL POLICY Colchicine Approval duration: 12 months E. Pericarditis (off-label) (must meet all):

29. 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);
30. Request is not for Lodoco;
    3. Member is responding positively to therapy;
    4. Member must use generic colchicine tablets, unless contraindicated or clinically significant adverse effects are experienced;
31. At least 4 weeks have passed since the last request for colchicine;
    6. Colchicine is prescribed concurrently with an NSAID or glucocorticoid;
    7. Dose does not exceed both of the following (a and b): a. Total dosage of 1.2 mg per day; b. Health plan-approved quantity limits.
       Approval duration: 6 months F. Other diagnoses/indications (must meet 1 or 2):
32. 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

33. 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 2 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 policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents. Page 5 of 11

    CLINICAL POLICY Colchicine IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ACC: American College of Cardiology AHA: American Heart Association ASCVD: atherosclerotic cardiovascular disease risk assessment CrCl: creatinine clearance CVD: cardiovascular disease FDA: Food and Drug Administration
    FMF: familial Mediterranean fever GERD: gastroesophageal reflux disease
    MI: myocardial infarction NSAID: nonsteroidal anti-inflammatory drug 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 Dose Limit/ Maximum Dose Naproxen: 1,500 mg/day
    Naproxen sodium: up to 1,650 mg/day 200 mg/day (IR capsules); 150 mg/day (SR capsules) 400 mg/day 800 mg/day naproxen (Naprosyn®) indomethacin (Indocin®) 250 mg PO every 8 hours 50 mg PO TID sulindac (Clinoril®) 200 mg PO BID allopurinol (Zyloprim®) 100 mg PO QD; may be increased by 100 mg every 2 to 4 weeks until serum urate concentration is ≤ 6 mg/dL or until maximum of 800 mg/day is reached 250 mg PO BID for the first week, then 500 mg PO BID
    probenecid 2 g/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. Appendix C: Contraindication/Boxed Warnings • Contraindication(s):
    o All agents: concurrent use of strong CYP3A4 inhibitors of P-gp inhibitors, including in patients with hepatic or renal impairment
    o Lodoco: Patients with pre-existing blood dyscrasias, renal failure, and severe hepatic impairment
    • Boxed warning(s): none reported Appendix D: General Information • Per the American College of Rheumatology 2012 guidelines for the management of gout, an inadequate response to therapy is defined as < 20% improvement in pain score within 24 hours or < 50% improvement in pain score at ≥ 50%.
    • Acute pericarditis is defined as new onset. Recurrent pericarditis is defined as recurring after a symptom-free interval of at least 4 weeks. Page 6 of 11

    CLINICAL POLICY Colchicine • Lodoco for cardiovascular event prophylaxis:
    o The Lodoco2 study inclusion criteria included patients that were clinically stable, defined as no cardiovascular related hospital admission in the prior 6 months. o Non-acute management of MI may include beta-blockers, long-term dual antiplatelet therapy with aspirin and a P2Y12 receptor blocker, high intensity statins, angiotensin converting enzyme inhibitors, aldosterone antagonist, and/or nitroglycerin. o Secondary prevention therapies for ischemic stroke may include antithrombotic therapy, antihypertensive therapy, and/or statins. o Chronic coronary syndrome treatment therapies include beta-blockers, calcium channel blockers, short-acting nitrates, and/or antiplatelet therapies.
    o Per American College of Cardiology (ACC) and American Heart Association (AHA), risk factors for cardiovascular disease include:  Overweight or obesity  Hypertension  Dyslipidemia  Hyperglycemia  Family history of premature ASCVD (males, age < 55 years; females, age <65 years)  Diabetes  Chronic kidney disease  Cigarette smoking  Dietary factors (diets with high glycemic index, low consumption of fruits and vegetables, high consumption of trans fatty acids, low consumption of fiber)  Chronic inflammatory conditions (e.g. psoriasis, RA, lupus, HIV/AIDS) V. Dosage and Administration Indication FMF Drug Name Colchicine (Colcrys) Prophylaxis of gout flares Treatment of gout flares Pericarditis (off-label) Cardiovascular event prophylaxis Colchicine (Lodoco) Dosing Regimen Age 4-6 years: 0.3 mg to 1.8 mg daily Age 6-12 years: 0.9 mg to 1.8 mg daily Age ≥ 12 years: 1.2 mg to 2.4 mg daily
    0.6 mg once or twice daily 1.2 mg at first sign of flare, followed by 0.6 mg one hour later Weight < 70 kg: 0.5 mg daily Weight ≥ 70 kg: 0.5 mg twice daily 0.5 mg PO once daily Maximum Dose 2.4 mg/day 1.2 mg/day 1.8 mg/treatment
    1 mg/day* 0.5 mg/day

    • This is the recommended dosing per the European Society of Cardiology guidelines.
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    CLINICAL POLICY Colchicine VI. Product Availability
    Drug Name Colchicine (Colcrys) Colchicine (Lodoco) Availability Tablet: 0.6 mg Tablet: 0.5 mg VII.