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.
Another resistance mechanism employed by both C. albicans and C. glabrata is increasing the rate of efflux of the azole drug from the cell, by both ATP-binding cassette and major facilitator superfamily transporters. Other gene mutations are also known to contribute to development of resistance. C. glabrata develops resistance by up regulating CDR genes, and resistance in C. krusei is mediated by reduced sensitivity of the target enzyme to inhibition by the agent.The full spectrum of fungal susceptibility and resistance to fluconazole can be found in the TOKU-Es product data sheet. According to the United States Centers for Disease Control, fluconazole resistance among Candida strains in the U.S. is about 7%. Contraindications
Fluconazole is contraindicated in patients who:
Drink alcohol
have known hypersensitivity to other azole medicines such as ketoconazole;
are taking terfenadine, if 400 mg per day multidose of fluconazole is administered;
concomitant administration of fluconazole and quinidine, especially when fluconazole is administered in high dosages;
take SSRIs such as fluoxetine or sertraline. Side effects
Adverse drug reactions associated with fluconazole therapy include:
Common (≥1% of patients): rash, headache, dizziness, nausea, vomiting, abdominal pain, diarrhea, and/or elevated liver enzymes
Infrequent (0.1–1% of patients): anorexia, fatigue, constipation
Rare (<0.1% of patients): oliguria, hypokalaemia, paraesthesia, seizures, alopecia, Stevens–Johnson syndrome, thrombocytopenia, other blood dyscrasias, serious hepatotoxicity including liver failure, anaphylactic/anaphylactoid reactions
Very rare: prolonged QT interval, torsades de pointes
FDA is now saying treatment with chronic, high doses of fluconazole during the first trimester of pregnancy may be associated with a rare and distinct set of birth defects in infants.If taken during pregnancy it may result in harm.