Fluoxetine

Fluoxetine (Prozac) is given in the morning because of its potential for being activating and causing insomnia. Food does not affect its systemic bioavailability and may actually lessen the nausea reported by some patients. Fluoxetine is highly bound to serum proteins and may interact with other highly protein bound drugs. It is demethylated in the liver to form an active metabolite, norfluoxetine. Inactive metabolites are excreted by the kidney. Doses must be reduced in patients with liver disease.

The slow elimination of fluoxetine and norfluoxe-tine lead to special clinical concerns when adjusting doses and discontinuing this medication. Steady state is not reached until 4 to 6 weeks, and similarly, complete elimination takes 4 to 6 weeks after discontinuation of the medication. A 4- to 6-week waiting period should be permitted before starting a medication with potential for an interaction with fluoxetine, such as a monoamine oxidase inhibitor (MAOI). Additionally, fluoxetine is a potent inhibitor of cytochrome P450 2D6 and can significantly elevate levels of drugs metabolized by this route. Thus, coadministration of drugs with a narrow therapeutic index, such as TCAs and type 1C antiar-rhythmics, including flecainide and propafenone, are a particular concern.

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