Both are potent inhibitors of CYP2D6 (which is also the chief enzyme responsible for their metabolism) and CYP2C19, and mild to moderate inhibitors of CYP2B6 and CYP2C9. In vivo, fluoxetine and norfluoxetine do not significantly affect the activity of CYP1A2 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 and hence P-glycoprotein substrates such as loperamide may have their central effects potentiated. This extensive effect on the bodys pathways for drug metabolism creates the potential for interactions with many commonly used drugs.Its use should also be avoided in those receiving other serotonergic drugs such as monoamine oxidase inhibitors, tricyclic antidepressants, methamphetamine, amphetamine, MDMA, triptans, buspirone, ginseng, dextromethorphan (DXM), linezolid, tramadol, serotonin–norepinephrine reuptake inhibitors, and other SSRIs due to the potential for serotonin syndrome to develop as a result.Fluoxetine may also increase the risk of opioid overdose in some instances, in part due to its inhibitory effect on cytochrome P-450. Similar to how fluoxetine can effect the metabolization of dextromethorphan, it may cause medications like oxycodone to not be metabolized at a normal rate, thus increasing the risk of serotonin syndrome as well as resulting in an increased concentration of oxycodone in the blood, which may lead to accidental overdose.
Sexual dysfunction
Sexual dysfunction, including loss of libido, erectile dysfunction, lack of vaginal lubrication, and anorgasmia, are some of the most commonly encountered adverse effects of treatment with fluoxetine and other SSRIs. While early clinical trials suggested a relatively low rate of sexual dysfunction, more recent studies in which the investigator actively inquires about sexual problems suggest that the incidence is >70%.On 11 June 2019, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency concluded that there is a possible causal association between SSRI use and long-lasting sexual dysfunction that persists despite discontinuation of SSRI, including fluoxetine, and that the labels of these drugs should be updated to include a warning. Antidepressant discontinuation syndrome
Fluoxetines longer half-life makes it less common to develop antidepressant discontinuation syndrome following cessation of therapy, especially when compared to antidepressants with shorter half-lives such as paroxetine. Although gradual dose reductions are recommended with antidepressants with shorter half-lives, tapering may not be necessary with fluoxetine. Pregnancy
Antidepressant exposure (including fluoxetine) is associated with shorter average duration of pregnancy (by three days), increased risk of preterm delivery (by 55%), lower birth weight (by 75 g), and lower Apgar scores (by <0.4 points). There is 30–36% increase in congenital heart defects among children whose mothers were prescribed fluoxetine during pregnancy, with fluoxetine use in the first trimester associated with 38–65% increase in septal heart defects. Suicide
In October 2004, the FDA added a black box warning to all antidepressant drugs regarding use in children. In 2006, the FDA included adults aged 25 or younger.