Prior Auth Protocol

FDA Approved Indications:

To reduce elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and non-high-density lipoprotein cholesterol (non-HDL-C), and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary (heterozygous familial and non-familial) hyperlipidemia or mixed hyperlipidemia.
To reduce elevated total-C and LDL-C in patients with homozygous familial hypercholesterolemia (HoFH), as an adjunct to other lipid-lowering treatments.

Health Net Approved Indications and Usage Guidelines:

Patient has been taking 80 mg daily equivalent of simvastatin for 12 months or longer

Coverage is Not Authorized For:

Titration to or a new start of an 80 mg daily equivalent of simvastatin
Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature

General Information:

Vytorin is contraindicated with concomitant administration of:
- Strong CYP3A3 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, and cobicistat-containing products)
- Gemfibrozil, cyclosporine, or danazol.
Simvastatin is metabolized by the cytochrome P450 isoform 3A4. Certain drugs that inhibit this metabolic pathway can raise the plasma levels of the simvastatin component of Vytorin and may increase the risk of myopathy.
FDA recommends that healthcare professionals should:
- Maintain patients on simvastatin 80 mg only if they have been taking this dose for 12 or more months without evidence of muscle toxicity.
- Not start new patients on simvastatin 80 mg.
- Place patients who do not meet their LDL cholesterol (LDL-C) goal on simvastatin 40 mg on alternative LDL-C lowering treatment(s) that provides greater LDL-C lowering
Physicians with patients on an 80 mg daily equivalent of simvastatin for less than 12 months should consider a trial of Vytorin 10/40 mg or Crestor 20 mg or 40 mg.
In the SEARCH trial, there were two (0.03%) cases of myopathy in patients taking 20 mg simvastatin daily compared to 53 (0.9%) cases in the 80 mg group.
Relative LDL-lowering Efficacy of Statin and Statin-based Therapies: http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm

Therapeutic Alternatives:

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Vytorin	10/10 mg - 10/40 mg PO QD Use of the 10/80 mg dose of Vytorin should be restricted to patients who have been taking Vytorin 10/80 mg for 12 months or more without evidence of muscle toxicity	Length of Benefit

Product Availability:

Vytorin: 10/10, 10/20, 10/40, 10/80 mg tablet

References:

Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet 2010;376:1658-69.
Vytorin [Prescribing Information] Whitehouse Station, NJ: Merck & Co., Inc.; February 2015.
Micromedex^R Healthcare Series [Internet database]. Greenwood Village, CO: Thomson Healthcare. Updated periodically. Accessed June 22, 2015.
Clinical Pharmacology Web site. Available at: http://clinicalpharmacology-ip.com/default.aspx. Accessed June 22, 2015.
Ezetimibe. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 22, 2015.
Simvastatin. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 22, 2015.