Prior Auth Protocol

FDA Approved Indications:

Management of fibromyalgia

Health Net Approved Indications and Usage Guidelines:

Fibromyalgia

Diagnosis of fibromyalgia

AND

Failure or clinically significant adverse effects to duloxetine

Depression

Failure or clinically significant adverse effects to TWO preferred antidepressants

Coverage is Not Authorized For:

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.
Pediatric patients
Use of monoamine oxidase inhibitors (MAOI) concomitantly or in close temporal proximity
Use in patients with uncontrolled narrow-angle glaucoma

General Information:

Class IIb recommendation in Micromedex for depression.
There are no head to head trials comparing Savella with Cymbalta or Lyrica for the management of fibromyalgia.
Sustained increases in blood pressure (increases of >15 mmHg in SBP) occurred more in the Savella-treated groups vs. placebo. However, relative to placebo, Cymbalta treatment was associated with mean increases in BP (up to 2.1 mmHg in SBP).
Black box warning for Savella includes that these agents are not approved for use in pediatric patients. Pooled analyses of short-term placebo-controlled studies of antidepressant drugs (selective serotonin reuptake inhibitors (SSRIs) and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with MDD and other psychiatric disorders.
Use of MAOI with Savella concomitantly is contraindicated due to the risk of serious, sometimes, fatal, drug interactions with serotonergic drugs. These interactions have been associated with symptoms that include tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome, seizures, rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. Allow at least 14 days after stopping an MAOI before starting Savella. Allow at least 5 days after stopping Savella before starting an MAOI.
Use of Savella in patients with uncontrolled narrow-angle glaucoma is contraindicated due to increased risk of mydriasis.

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
duloxetine (Cymbalta^R)	Fibromyalgia: 60 mg PO QD	60 mg/day
Lyrica^R (pregabalin) Tier/Prior Authorization requirement different for different regions	Fibromyalgia: 150-450 mg PO QD	450 mg/day

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Savella	The recommended dose of Savella is 100 mg/day (50 mg PO BID). Dosing should be titrated to 100 mg/day over a 1-week period: Day 1: 12.5 mg once PO Days 2-3: 25 mg/day (12.5 mg PO BID) Days 4-7: 50 mg/day (25 mg PO BID) After Day 7: 100 mg/day (50 mg PO BID) May be increased to 200 mg/day (100 mg PO BID) based on individual response. Doses above 200 mg/day have not been studied. For patients with severe renal impairment (indicated by an estimated creatinine clearance of 5-29mL/min), the maintenance dose should be reduced by 50% to 50 mg/day (25 mg PO BID). Savella is not recommended for patients with end-stage renal disease.	Length of benefit

Product Availability:

Tablets: 12.5 mg, 25 mg, 50 mg, 100 mg

References:

1. Savella [Prescribing Information] St. Louis, MO: Forest Laboratories; November 2013.

2. American Psychiatric Association: Practice guideline for the treatment of patients with major depressive disorder 3rd edition. Am J Psychiatry 2010;167(suppl):1-152.

3. Savella. ClinicalTrials.gov available at http://clinicaltrials.gov/ct2/show/study/NCT00797797. Accessed June 1, 2012.

4. American College of Rheumatology. Diagnostic Criteria for Fibromyalgia 2010. Available at: http://www.rheumatology.org/practice/clinical/classification/fibromyalgia/2010_preliminary_diagnostic_criteria.pdf. Accessed June 1, 2012.

5. Clauw DJ, Mease P, Plamer RH. Milnacipran for the treatment of fibromyalgia in adults: a 15-week, multicenter, randomized, double-blind, placebo-controlled, multiple-dose clinical trial. Clin Ther. 2008;30(11):1988-2004.

6. Micromedex^R Healthcare Series [Internet database]. Greenwood Villlage, Colo: Thomson Healthcare. Updated periodically. Accessed June 24, 2014.