Amlodipine/Atorvastatin (Caduet) Form

Amlodipine/atorvastatin (Caduet®) is a combination of amlodipine, a calcium channel blocker, and atorvastatin, an HMG CoA-reductase inhibitor. FDA Approved Indication(s) Caduet is indicated in patients for whom treatment with both amlodipine and atorvastatin is appropriate. Amlodipine is indicated for the treatment of: • Hypertension, to lower blood pressure • Coronary artery disease (CAD) o Symptomatic treatment of chronic stable angina o Treatment of confirmed or suspected vasospastic angina (Prinzmetal’s or variant angina) o Angiographically documented CAD
 To reduce the risk for hospitalization for angina and coronary revascularization procedure in patients with recently documented CAD by angiography and without heart failure or an ejection fraction < 40%
Atorvastatin is indicated as an adjunct therapy to diet for: • Prevention of cardiovascular disease: o Reduce the risk of myocardial infarction (MI), stroke, and revascularization procedures and angina in adult patients without clinically evident coronary heart disease (CHD), but with multiple risk factors for coronary heart disease (such as age, smoking, hypertension, low high-density lipoprotein cholesterol (HDL-C), or a family history of early coronary heart disease) o Reduce the risk of MI and stroke in patients with type 2 diabetes, and without clinically evident CHD, but with multiple risk factors (such as retinopathy, albuminuria, smoking, or hypertension) o Reduce the risk of non-fatal MI, fatal and non-fatal stroke, revascularization procedures, hospitalization for congestive heart failure (CHF), and reduce the risk of angina in patients with clinically evident CHD • Hyperlipidemia o Heterozygous familial and nonfamilial hypercholesterolemia, mixed dyslipidemia:  As an adjunct to diet to reduce elevated total-cholesterol (C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo B), and triglyceride (TG) levels and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson types IIa and IIb) Page 1 of 7

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Amlodipine/Atorvastatin o Elevated serum TG levels:  As an adjunct to diet for the treatment of patients with elevated serum TG levels (Fredrickson type IV) o Primary dysbetalipoproteinemia:  Treatment of patients with primary dysbetalipoproteinemia (Fredrickson type III) who do not respond adequately to diet
o Homozygous familial hypercholesterolemia:  Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable
o Pediatric patients:
 As an adjunct to diet to reduce total-C, LDL-C, and apo B levels in pediatric patients, 10 to 17 years of age, with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: • LDL-C remains ≥ 190 mg/dL or • LDL-C remains ≥ 160 mg/dL and: o There is a positive family history of premature cardiovascular disease or o Two or more other cardiovascular disease (CVD) risk factors are present in the pediatric patients Limitation(s) of use: Atorvastatin has not been studied in conditions where the major lipoprotein abnormality is elevation of chylomicrons (Fredrickson types I and V dyslipidemias). 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 Caduet is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. All FDA-Approved Indications (must meet all):

1. Diagnosis of one of the following (a, b, c, or d): a. Hypertension; b. Chronic stable angina; c. Confirmed or suspected vasospastic angina (Prinzmetal’s or variant angina); d. CAD documented by angiography and without heart failure or an ejection fraction < 40%;

   2. Diagnosis of hyperlipidemia or one of the diagnoses for which atorvastatin is FDA- approved;
   3. Member must instead use the individual components (atorvastatin and amlodipine) concurrently, unless contraindicated to excipients or clinically significant adverse effects are experienced;
   4. Failure to achieve National Cholesterol Education Program (NCEP) goals (see Appendix D) after a trial of at least one generic formulary statin (e.g., lovastatin, pravastatin, simvastatin, atorvastatin), followed by ezetimibe/simvastatin (Vytorin®) Page 2 of 7

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   Amlodipine/Atorvastatin or rosuvastatin (Crestor®), unless clinically significant adverse effects are experienced or all are contraindicated;

   5. Dose does not exceed (a and b): a. 80 mg per day of atorvastatin; b. 1 tablet per day. Approval duration:
      Medicaid – 12 months Commercial – 12 months or duration of request, whichever is less 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 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 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 and CP.PMN.53 for Medicaid.
      II. Continued Therapy A. All FDA-Approved Indications (must meet all):
2. 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);
3. Member is responding positively to therapy;

4. If request is for a dose increase, new dose does not exceed (a and b): a. 80 mg per day of atorvastatin; b. 1 tablet per day. Approval duration:
   Medicaid – 12 months Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):

   1. 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 3 of 7

   CLINICAL POLICY
   Amlodipine/Atorvastatin 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 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 and CP.PMN.16 for Medicaid; or

   2. 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 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 and CP.PMN.53 for Medicaid or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key apo B: apolipoprotein B CAD: coronary artery disease
      CHD: coronary heart disease CHF: congestive heart failure
      CVD: cardiovascular disease FDA: Food and Drug Administration HDL-C: high-density lipoprotein cholesterol
      LDL: low-density lipoprotein cholesterol
      MI: myocardial infarction NCEP: National Cholesterol Education Program TG: triglyceride 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 Dosing Regimen atorvastatin (Lipitor®)
      amlodipine (Norvasc®) lovastatin (Mevacor®)
      pravastatin (Pravachol®) 10 to 80 mg PO QD simvastatin (Zocor®) 10 to 80 mg PO QD 2.5 to 10 mg PO QD 10 to 80 mg PO QD or BID ezetimibe/simvastatin (Vytorin®) 5 to 40 mg PO QD (Note: coverage of the 80 mg strength requires PA) 10/10 mg to 10/80 mg PO QD (Note: coverage of the 10/80 mg strength requires PA) 5 to 40 mg PO QD
      rosuvastatin (Crestor®)
      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. 40 mg/day Dose Limit/ Maximum Dose 80 mg/day 10 mg/day 80 mg/day 80 mg/day 80 mg/day 10/80 mg/day Page 4 of 7

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   Amlodipine/Atorvastatin Appendix C: Contraindications/Boxed Warnings • Contraindication(s): o Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels o Pregnancy o Lactation • Boxed warning(s): none reported _ In July 2021, the FDA requested removal of the contraindication against use of statins in pregnant women. Because the benefits of statins may include prevention of serious or potentially fatal events in a small group of very high-risk pregnant patients, contraindicating these drugs in all pregnant women is not appropriate.
   https://www.fda.gov/safety/medical-product-safety-information/statins-drug-safety-communication-fda- requests-removal-strongest-warning-against-using-cholesterol Appendix D: NCEP Goals Risk Category CHD or CHD risk equivalents (10-year risk >20%) Multiple (2+) risk factors and 10-year risk ≤ 20% 0 to 1 risk factor Refer to Framingham point scores for 10-year risk % (https://www.nhlbi.nih.gov/files/docs/guidelines/atglance.pdf)
   LDL Goal
   < 100 mg/dL
   < 130 mg/dL < 160 mg/dL V. Dosage and Administration
   Indication For patients whom treatment with both amlodipine and atorvastatin is appropriate Dosing Regimen Initial Adults: 2.5/10 mg PO QD Pediatrics (age 10 to 17 years): 2.5/10 mg PO QD
   Maximum Dose Adult: 10/80 mg/day Pediatric: 5/20 mg/day VI. Product Availability Tablets: 2.5/10 mg, 2.5/20 mg, 2.5/40 mg, 5/10 mg, 5/20 mg, 5/40mg, 5/80 mg, 10/10 mg, 10/20 mg, 10/40 mg, 10/80 mg
   *Available as generic product only VII.