Prior Auth Protocol

FDA Approved Indications:

Treatment of major depressive disorder (MDD)
(For Aplenzin only) Treatment of seasonal affective disorder (SAD)

Health Net Approved Indications and Usage Guidelines:

Diagnosis of depression

AND

Failure or clinically significant adverse reaction to TWO preferred antidepressants: Budeprion SR, bupropion, bupropion SR, bupropion XL, citalopram, escitalopram, fluoxetine, fluvoxamine, mirtazapine, paroxetine, sertraline, venlafaxine, venlafaxine XR

OR

The patient or a first degree relative of the patient has been successfully treated in the past with the requested agent

OR

(For Aplenzin only) Diagnosis of seasonal affective disorder (SAD)

AND

Failure or clinically significant adverse effects to generic bupropion extended release (generic Wellbutrin-XL)

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
Use of monamine oxidase inhibitor

General Information:

Desvenlafaxine fumarate extended release tablets is not a generic equivalent of Pristiq. (desvenlafaxine succinate extended release) or Khedezla (desvenlafaxine extended release) but is a new dosage form of existing agents for the same indication.
Failure of antidepressant therapy for major depressive disorder is defined as the inability to achieve minimal or partial response after 4 weeks of therapy at maximum tolerated doses.
Nefazodone requires prior authorization and is not included as a required agent; however, a prior trial of nefazodone will be sufficient for approval of a step therapy agent.
A first-degree relative is defined as a parent, sibling, or offspring.
In clinical trials, doses of Pristiq 50-400 mg/day were shown to be effective, although no additional benefit was demonstrated at doses greater than 50 mg/day and adverse events and discontinuations were more frequent at higher doses
Aplenzin and Forfivo are not FDA-approved for smoking cessation treatment.
Black box warning for Aplenzin, Forfivo, Pristiq, Desvenlafaxine and Viibryd includes that these agents are not approved for use in pediatric patients. Pooled analyses of short-term placebo-controlled studies of antidepressant drugs (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 monoamine oxidase inhibitors (MAOI) with Aplenzin, Pristiq, Forfivo, Desvenlafaxine or Viibryd 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 Aplenzin, Forfivo, Pristiq, Desvenlafaxine or Viibryd before starting an MAOI.

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
Selective Serotonin Reuptake Inhibitors citalopram (Celexa^R)	20 mg PO QD	40 mg/day
fluvoxamine (Luvox CR^R)	50-300 mg PO QD	300 mg/day
escitalopram (Lexapro^R)	10-20 mg PO QD	20 mg/day
fluoxetine (Prozac^R)	20 mg PO QD	80 mg/day
paroxetine (Paxil^R)	20 mg PO QD	50 mg/day
paroxetine controlled release (Paxil CR^R)	25 mg PO QD	62.5 mg/day
sertraline (Zoloft^R)	50 mg PO QD	200 mg/day
Dual-acting Antidepressants venlafaxine (Effexor^R)	75 mg/day PO in divided BID-TID	375 mg/day
venlafaxine extended release (Effexor XR^R)	75-225 mg PO QD	225 mg/day
mirtazapine (Remeron^R or Remeron^R SolTab)	15 mg PO QD	45 mg/day
Dopaminergic Agents bupropion (Wellbutrin^R, Budeprion^R)	100 mg PO TID	450 mg/day
bupropion sustained release (Wellbutrin SR^R, Budeprion SR^R)	150 mg PO BID	400 mg/day
bupropion sustained release 24 hour (Wellbutrin XL^R)	150-450 mg PO QD	450 mg/day

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Aplenzin	Major Depressive Disorder: Starting dose:174 mg PO QD, After 4 days, may increase to target dose of 348 mg PO QD Seasonal Affective Disorder: Initiate treatment in the autumn prior to onset of seasonal depressive symptoms. Starting dose: 174 mg PO QD (equivalent to 150 mg bupropion HCl). Usual target dose: 348 mg PO QD (equivalent to 300 mg bupropion HCl). After one week, may increase the dose to 348 mg PO QD. Continue treatment through the winter season.	Length of Benefit
Pristiq	50 mg PO QD	Length of Benefit
Khedezla	50 mg PO QD	Length of benefit
Desvenlafaxine Fumarate Extended-Release Tablets	50 mg PO QD	Length of Benefit
Viibryd	20 - 40 mg PO QD	Length of Benefit
Forfivo XL	450 mg PO QD Do not initiate treatment with Forfivo XL, use another bupropion formulation for initial dose titration. Patients currently treated with other bupropion products at 450 mg/day can be switched to equivalent dose of Forfivo XL.	Length of Benefit
Fetzima	40 mg PO QD for 2 days then increase to 40 mg QD Increase dose in increments of 40 mg at intervals of 2 or more days up to a maximum of 120 mg QD.	Length of Benefit
Trintellix	10 mg PO QD Increase to 20 mg/day as tolerated.	Length of Benefit

Product Availability:

Aplenzin extended-release tablets: 174 mg, 348 mg, 522 mg
Desvenlafaxine Fumarate Extended-Release Tablets: 50 mg, 100 mg
Fetzima extended-release capsules: 20 mg, 40 mg, 80 mg, 120 mg
Forfivo extended-release tablets: 450 mg
Khedezla extended release tablets 50 mg, 100 mg
Pristiq tablets: 25 mg, 50 mg, 100 mg
Trintellix immediate release tablets: 5 mg, 10 mg, 15 mg, 20 mg
Viibryd tablets: 10 mg, 20 mg, 40 mg

References:

Khedezla [Prescribing Information] Par Pharmaceutical Cos., Inc. Spring Valley, NY; September 2013.
Aplenzin [Prescribing Information] Bridgewaterm NJ: Sanofi-aventis; August 2012.
Pristiq [Prescribing Information] Philadelphia, PA: Wyeth Pharmaceuticals; December 2013.
Viibryd [Prescribing Information] St. Louis, MO: Forest Laboratories; April 2014.
Desvenlafaxine Fumarate Extended-Release Tablets [Prescribing Information] Teva Pharmaceuticals USA, Sellersville, PA, October 2013.
Forfivo [Prescribing Information] Austin, TX: Edgemont Pharmaceuticals; November 2011.
American Psychiatric Association: Practice guideline for the treatment of patients with major depressive disorder 3rd edition. Am J Psychiatry 2010;167(suppl):1-152.
Desvenlafaxine [Prescribing Information] Gujarat, India: Alembic Pharmaceuticals Limited; March 2013.
Fetzima [Prescribing Information] St. Louis, MO: Forest Pharmaceuticals. July 2014.
Trintellix [Prescribing Information] Deerfield, IL: Takeda Pharmaceuticals. May 2016.