Finalized: 8/5/2013 Prior Authorization Guidelines

TCA with fluoxetine (strong 2D6 inhibitor) TCA with paroxetine (strong 2D6 inhibitor) TCA with bupropion (moderate 2D6 inhibitor) TCA with duloxetine (moderate 2D6 inhibitor) TCA with sertraline (moderate-weak 2D6 inhibitor) Clomipramine with fluvoxamine (strong 1A2 inhibitor) Background: Tricyclic antidepressants (TCAs) continue to be utilized as a treatment option for depression. The pharmacokinetics of TCAs are characterized by substantial presystemic first-pass metabolism, a large volume of distribution, extensive protein binding, and an elimination half-life averaging about 1-3 days. Metabolic clearance of tricyclics is dependent primarily on hepatic Cytochrome P450 (CYP) oxidative enzymes. The activities of some P450 isoenzymes may be influenced by the concomitant use of other medications. Patient variables, such as gender, ethnicity and age, also affect TCA metabolism. Metabolism of TCAs, especially their hydroxylation, results in the formation of active metabolites, which contribute to both the therapeutic and the adverse effects of these compounds. SSRIs vary in their ability to cause clinically significant drug interactions based upon the inhibition of the liver Cytochrome P450 (CYP) isoenzymes. When a drug, that is a potent inhibitor of one or more of the CYP isoenzymes, is combined with a narrow therapeutic index medication, toxicity may result. As stated above, tricyclic antidepressants (TCAs) are dependent upon CYP2D6 for metabolism; clomipramine is dependent upon CYP1A2. Serious, life threatening side effects may occur very rapidly when TCAs are combined with potent inhibitors of these enzymes. It is of the utmost importance that Providers are knowledgeable of the interaction potential. The monitoring requirements for these drugs are critical to safe prescribing. For these reasons, Providers must submit a Prior Authorization Request for drugs prescribed in the combinations that are listed above