High ( 50%) Restrictions

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1 MEDICATION COVERAGE POLICY PHARMACY AND THERAPEUTICS ADVISORY COMMITTEE POLICY: Cholesterol P&T DATE: 5/17/2016 THERAPEUTIC CLASS: Cardiovascular REVIEW HISTORY: 5/15, 5/14, 9/11, 5/11, LOB AFFECTED: Medi-Cal, SJHA (MONTH/YEAR) 2/10, 5/07, 3/07 PART 1 STATINS (HMG-COA REDUCTASE INHIBITORS) Per the 2013 American College of Cardiology/ American Heart Association Guidelines on cholesterol treatment, previous recommendations to lower LDL-C to pre-specified goals based on risk factors and co-morbidities are no longer considered the standard of care. The following document outlines current recommendations for appropriate statin therapy for risk reduction of atherosclerotic cardiovascular disease (ASCVD). Available Statin Agents based on ACC/AHA Clinical Guideline Recommendations LDL-C Reduction/Therapy Intensity Monthly Drug Atorvastatin (Lipitor) Low (<30%) Moderate (30-50%) High ( 50%) mg 40-80mg Restrictions Quantity Limit Notes Cost per 30 days $10.13 Rosuvastatin (Crestor) ⱡ Tablet splitting $ mg 20-40mg PA; TS ⱡ 15 ⱡ required. Reserved for treatment failure of Atorvastatin 40mg/day. Simvastatin (Zocor) 10mg 20-40mg $4.43 Pravastatin (Pravachol) 10-20mg 40-80mg $18.28 Lovastatin (Mevacor) 20mg 40mg -- 30* *40mg Tablet is $6.61 restricted to 2 tablets QL* per day (60 per month). Fluvastatin (Lescol) 20-40mg (BID) -- NF $$ 40mg Fluvastatin XL (Lescol -- 80mg -- NF $$ XL) Pitavastatin (Livalo) 1mg 2-4mg -- NF $$$ NF = Non-formulary, TS = Mandatory Tablet Splitting, PA = Prior Authorization Required. As reported by average cost per 30 days (5/2014-4/2015) Coverage Policy Cardiovascular -- Cholesterol Page 1

2 Clinical Justification: Choosing a Statin Agent: Members in the following categories are at high risk of ASCVD, and generally have the greatest net benefit from statin therapy. Generally, these members should be on the highest statin dose tolerated (High-intensity). Refer to the table below for additional guidance on intensity of therapy. Individuals with clinical ASCVD Individuals with primary elevations of LDL-C > 190 mg/dl Individuals 40 to 75 years of age with diabetes and LDL-C mg/dl Individuals without clinical ASCVD or diabetes who are 40 to 75 years of age with LDL-C mg/dl and an estimated 10-year ASCVD risk of 7.5% or higher Therapy Intensity Patient Benefit Group and Characteristics Primary Risk Reduction of ASCVD High-intensity >21 years of age and LDL-C >190 mg/dl years of age with diabetes mellitus and >7.5% 10-year ASCVD risk Adults years of age and >7.5% 10-year ASCVD risk Moderate-intensity Adults years of age with diabetes mellitus Adults years of age and 5-7.5% 10-year ASCVD risk Low-intensity Reserved for patients unable to tolerate moderate-intensity therapy Secondary Risk Reduction of ASCVD High-intensity Patients <75 years old with ASCVD Moderate-intensity Patients >75 years old with ASCVD Contraindication vs. Intolerance: Intolerance does NOT justify treatment discontinuation, but may suggest the need for an alternative statin or dose reduction. Contraindications should prompt discontinuation. Refer to the following (incomplete) list for examples: Contraindications ALT > 3 times ULN Active liver disease (defined as unexplained persistent elevations in transaminase levels.) Pregnancy or woman who may become pregnant Breast-feeding Intolerances Myopathy Rhabdomyolysis Elevation of aminotransferases < 3 times ULN Drug interactions Caveats: The American College of Cardiology/ American Heart Association Guidelines are limited to ASCVD risk reduction; therefore, do not apply to all patients presenting with lipid disorders. Patients with severely elevated triglycerides, > mg/dl, are at risk for acute pancreatitis and can be initiated on gemfibrozil or fenofibrate. Alternative therapy options for severe hypertriglyceridemia are niacin or omega-3 fatty acid (indicated for triglycerides >500 mg/dl). Please see the Non-Statin Lipid-Lowering-Agent Policy for guidance with these agents. Triage Information: Appropriate Diagnosis Most recent lipid panel Cholesterol medication trial history Reasons for respective treatment failure Coverage Policy Cardiovascular -- Cholesterol Page 2

3 APPROVAL CRITERIA / EXCEPTION CONSIDERATION Below are the coverage criteria and required information for each agent. These coverage criteria have been reviewed approved by the HPSJ Pharmacy & Therapeutics (P&T) Advisory Committee. For conditions not covered under this Coverage Policy, HPSJ will make the determination based on Medical Necessity as described in HSPJ Medical Review Guidelines (UM06). HMG-CoA Reductase Inhibitors ( Statins ) Atorvastatin (Lipitor), Simvastatin (Zocor), Pravastatin (Pravachol), Lovastatin (Mevacor) Coverage Criteria: None * (*Lovastatin is restricted to 2 tablets per day) Other Notes: The statin medications in this category are listed in order of potency (highest to lowest) at maximum doses, Atorvastatin is considered a high potency statin and should be used in most cases listed in the choosing a statin category above. Rosuvastatin (Crestor) Coverage Criteria: Rosuvastatin is reserved for patients who are intolerant to 2 (two) formulary first line statins, one of which must be dose optimized atorvastatin. Limits: All doses except 40mg daily require tablet splitting. (Maximum of 15 tablets per 30 days) Required Information for Approval: Chart notes documenting type and severity of reaction to 2 dose optimized statin treatments (including de-escalation of therapy) one statin must be Atorvastatin. Treatment notes must be corroborated by pharmacy fill history. Other Notes: Both Rosuvastatin and Atorvastatin are classified as High Intensity Statins per the ACC/AHA guidelines; there is no therapeutic difference between these agents at maximal doses. NEWLY APPROVED MEDICATIONS NOT ON FORMULARY None CRITERIA REVIEW FOR UNNECESSARY BARRIERS Current formulary restrictions are appropriate. GUIDELINE & LITERATURE REVIEW No updated guidelines have been released since last review. Coverage Policy Cardiovascular -- Cholesterol Page 3

4 PART 2 NON-STATIN LIPID LOWERING AGENTS Non-Statin medications are NOT proven to lower ASCVD risk, and should not be routinely used according to the ACC/AHA 2013 lipid guidelines. As such, they are not recommended as first line agents for cholesterol reduction. Though this is the case, some agents may have a role in reduction of hypertriglyceridemia, which can cause pancreatitis. Below is a table outlining use of these agents. Below is a table outlining use of these agents. Non-Statin Lipid Lowering Agents: Class Drug Therapy Benefits Form. Status Restriction Cost Per Rx Bile Acid Cholestyramine LDL-C levels ( 18%) F none $75.77 Sequestrants Colesevelam LDL-C levels ( 18%) Step therapy to intolerance of $ (Welchol) two formulary statins. Fibrates Fenofibrate (Multiple agents, Lofibra is preferred) LDL-C ( 20.6%), TC ( 18.7%), TG ( %)* Step therapy to statin treatment. (Lofibra is the preferred formulary agent) $47.31 (Lofibra) HDL-C ( 11%) F ⱡ, ST *likely higher with more severe elevations. Gemfibrozil (Lopid) TG ( 31-43%) * none $9.73 *likely higher with more severe F elevations. Niacin Omega 3 Fatty Acids Absorption Inhibitors PCSK9 Inhibitors Niacin (Niacor) Niacin ER (Niaspan) Omega-3 Fatty Acids (Lovaza) Omega-3 Fatty Acids (Vascepa) Ezetimibe (Zetia) Ezetimibe/Simvastatin (Vytorin) Alirocumab (Praluent) LDL-C ( 12%), Apo B ( 12%), TG levels ( 24-38%), HDL-C ( 20%) TG ( 20-30%), HDL ( 3%) LDL-C ( 18%), Apo B ( 16%), Non-HDL-C ( 16%) Additive effect to simvastatin monotherapy. NF NF Reserved for treatment failure of two formulary statins. $12.33(Niacin) $ (Niacin ER) TG>500mg/dL despite $ statin + fibrate therapy Non-Formulary $ Intolerance to two formulary 1st line statins despite step down to lower intensity statin dose or high risk of ASCVD with inability to tolerate the full recommended dose intensity of statin. Uncontrolled hyperlipidemia despite compliant use of doseoptimized atorvastatin or rosuvastatin. Non-Formulary $ $ $1344 Evolocumab (Repatha) LDL ( 50%) NF Non-Formulary $1300-$1950 *All therapy benefits refer to monotherapy. NOTE: Non-statin therapies have not shown reduction in ASCVD risk. ⱡ Brand Specific formulary restrictions. NF = Non-Formulary, F = Formulary, ST = Step therapy, PA = Prior Authorization required. based on claims data from 5/2015-4/2016. No Utilization data available. Based on AWP. Coverage Policy Cardiovascular -- Cholesterol Page 4

5 Clinical Justification: Clinical Pearls: ACC/AHA guidelines do not provide guidance on the treatment of hypertriglyceridemia. Providers should refer to ATP III for guidance. Generally pancreatitis is seen at triglyceride levels >1000 mg/dl, but is treated at >500 mg/dl. Combination of statins with fibrates (especially gemfibrozil) can increase risks of rhabdomyolysis. Patient should be monitored for generalized body weakness or fatigue that is not attributable to a known cause. Niacin flushing, a common reason for niacin intolerance, can be pretreated by administering aspirin 81mg (or any NSAID) 30 minutes prior to niacin administration. Lifestyle modification can play a big part in triglyceride reduction, especially fatty food intake. Triage: Appropriate diagnosis Current lipid panel Previous lipid lowering drugs used History of lipid lowering drug intolerances. APPROVAL CRITERIA/ EXCEPTION CONSIDERATION Below are the coverage criteria and required information for each agent. These coverage criteria have been reviewed approved by the HPSJ Pharmacy & Therapeutics (P&T) Advisory Committee. For conditions not covered under this Coverage Policy, HPSJ will make the determination based on Medical Necessity as described in HSPJ Medical Review Guidelines (UM06). Bile Acid Sequestrants Cholestyramine Coverage Criteria: None Colesevelam (Welchol) Coverage Criteria: Welchol is reserved for patients who are intolerant to 2 formulary statins. Required Information for Approval: Chart notes documenting treatment failure and reaction severity/nature. Pharmacy fill history indicating prescription fills for 2 formulary statins. Fibrates Gemfibrozil (Lopid) Coverage Criteria: None Other Notes: Gemfibrozil should not be used in conjunction with a statin, due to increased risk of rhabdomyolysis. Fenofibrate (Lofibra) Coverage Criteria: Fenofibrate (Formulary strengths of 54mg, 67mg, 134mg, 160mg and 200mg) are restricted to patients with contraindication or intolerance to 2 (two) formulary 1st line statins (despite step down approach), high risk for ASCVD with suboptimal response to dose-optimized statin therapy or unable to tolerate full recommended dose intensity of statin. Other Notes: Claims for generic Lofibra (Fenofibrate 54mg, 67mg, 134mg, 160mg and 200mg) will automatically process if the patient is concurrently on a statin and compliant with therapy. Coverage Policy Cardiovascular -- Cholesterol Page 5

6 Niacin Niacin (Niacor), Niacin ER (Niaspan) Coverage Criteria: Prior Authorization Required. Restricted to patients with contraindication or intolerance to 2 (two) formulary 1st line statins (despite step down approach). Consider Gemfibrozil in isolated hypertriglyceridemia. Required Information for Approval: Pharmacy fill history and chart note documentation of a trial of two statin medications, with attempted dose reductions and continued intolerance. Notes: Pretreat with aspirin to reduce flushing side effects. Omega-3 Fatty Acids Omega-3 Fatty Acids (Lovaza) Coverage Criteria: Lovaza is reserved for patients with elevated triglycerides >500 mg/dl despite dose-optimized treatment with both a statin AND fenofibrate. Required Information for Approval: Laboratory results indicating uncontrolled triglycerides, greater than 500 mg/dl after 6-8 weeks of dose optimized statin and fibrate therapy, as evidenced by pharmacy fill history. Absorption Inhibitors Ezetimibe (Zetia) Coverage Criteria: Zetia is reserved for patients with contraindication or intolerance to 2 (two) formulary 1st line statins (despite step down to lower intensity statin dose) or high risk for ASCVD with suboptimal response to dose optimized statin, or unable to tolerate the full recommended dose intensity of statin. Required Information for Approval: Pharmacy fill history for two formulary first line statins, with appropriate dose stepdown. Chart notes documenting the type/severity and nature of intolerance or contraindication to two formulary first line statins, despite dose de-escalation. Ezetimibe/Simvastatin (Vytorin) Coverage Criteria: It is reserved for uncontrolled hyperlipidemia despite compliant use of (or intolerance to) dose optimized Atorvastatin (Lipitor) AND Rosuvastatin (Crestor). Required Information for Approval: Pharmacy fill history of both Atorvastatin and Rosuvastatin. Coverage Policy Cardiovascular -- Cholesterol Page 6

7 CRITERIA REVIEW FOR UNNECESSARY BARRIERS Current formulary restrictions are appropriate. GUIDELINE & LITERATURE REVIEW No new guidelines have been released since the last review. Due to lack of efficacy data in combination with statins, Advicor and Simcor have recently lost their FDA approval. These drugs have been pulled from the market. Neither of these drugs are on HPSJ s formulary. Niaspan and Trilipix have also lost indications for use in conjunction with statins, but remain on the market for other indications. Fibrates and niacin remain on HPSJs formulary for use in patients with Hypertriglyceridemia. These agents remain useful in patients with very high triglycerides due to the risk of pancreatitis. However, these medications are step therapy to dose-optimized statin therapy, which can also help to lower triglycerides, 10-20%, but with proven mortality benefits. REFERENCES ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults 2. ATP III (NCEP) Expert Panel on Detection, Evaluation, and Treatment 3. AbbVie Inc. et al; Withdrawal of Approval of Indications Related to the Coadministration With Statins in Applications for Niacin Extended-Release Tablets and Fenofibric Acid Delayed-Release Capsules. Food and Drug Administration. 81 FR AbbVie Inc.; Withdrawal of Approval of New Drug Applications for ADVICOR and SIMCOR. Food and Drug Administration. 81 FR REVIEW & EDIT HISTORY Document Changes Reference Date P&T Chairman Creation of Policy Lipid- Lowering Class Review- Statins 3-3/2007 Allen Shek PharmD BCPS 07.doc Update to Policy Potential Generics 2007 and 2008.doc 5/2007 Allen Shek PharmD BCPS Update to Policy Statins class review 5-07.doc 5/2007 Allen Shek PharmD BCPS Update to Policy Formulary realignment xlsx 2/2010 Allen Shek PharmD BCPS Update to Policy Formulary Realignment 5-11.xlsx 5/2011 Allen Shek PharmD BCPS Update to Policy Statin Realignment docx 9/2011 Allen Shek PharmD BCPS Update to Policy Cholesterol Therapy Review /2014 Jonathan Szkotak, PharmD BCACP 29.docx Update to Policy PCSK9 Inhibitors docx 5/2015 Johnathan Szkotak, PharmD BCACP Update to Policy HPSJ Coverage Policy Cardiovascular Cholesterol docx 6/2015 Johnathan Yeh, PharmD Note: All changes are approved by the HPSJ P&T Committee before incorporation into the utilization policy Coverage Policy Cardiovascular -- Cholesterol Page 7