Use Fluoxetine's Long Half-Life to Your Advantage

0 Comments | Family Practice News, July 1, 2000 | by Betsy Bates

TUCSON, ARIZ. -- Fluoxetine's long half-life is both a blessing and a curse, Marilyn R. Semenchuk, Pharm.D., said at a psychopharmacology conference sponsored by the University of Arizona.

The savvy clinician can use its incredible staying power to stretch out dosages, with some patients doing well on 60 mg or 40 mg in a weekly dosage. Yet fluoxetine (Prozac) can trigger drug interactions long after a patient has tossed out the prescription bottle and replaced it with another on the medicine cabinet shelf.

A drug's half-life--the time taken for its blood concentration to decline by 50%--rises with age, illness, genetic factors, and interactions with other drugs, noted Dr. Semenchuk, an associate specialist in neurology at the university.

Fluoxetine's half-life is technically 48-72 hours--4-6 days after intense administration. But its active metabolite, norfluoxetine, sticks around for 4-16 days. Steady state is reached in 28-35 days.

Some physicians are cutting back on daily dosages of fluoxetine. A daily dosage of 20 mg is equally effective as a weekly dosage of 60 mg, she explained. Some patients need even less. "I've seen patients do well on 40 mg/week."

Fluoxetine's half-life can also seriously complicate changes in drug regimens, particularly since it can inhibit some cytochrome P-450 isoenzymes, especially CYP-2C, CYP-2C19, and CYP-2D6.

One patient who had been taking fluoxetine for a long period of time complained that it was no longer working. Since insomnia and anxiety were now complicating the picture, Dr. Semenchuk switched her right over to nefazodone. "After a few weeks, the patient started reporting increased anxiety, which at the time really did not make sense to me, since nefazodone is a really good drug for anxiety," she said.

The clinician's first impulse--to increase the dosage--would do no good, since fluoxetine metabolites still lingering in the patient's system were blocking breakdown of the 2D6 isoenzyme, preventing nefazodone from being fully effective.

"Sometimes these drug interactions can be extremely subtle," she said.