A lot of isozymes of the cytochrome P450 system which realize Prozac metabolism are inhibited with medicine. Both Prozac and its active metabolite, norfluoxetine, greatly inhibit CYP2D6 (that enzyme plays the most important role for their metabolism) and mildly inhibit CYP1A2, CYP2B6, CYP2C9/2C19, and CYP3A4. They also inhibit the activity of P-glycoprotein, a type of membrane transport protein that plays an important role in drug transport and metabolism. Great possibility for interactions with many commonly used drugs is caused with those extensive pathways for metabolism of Prozac.

A rare but life-threatening adverse drug reaction known as serotonin syndrome can happen if Prozac is taken together with triptans, tramadol or other serotonergic agents