Tamoxifen Carbamazepine

A4 Acetaminophen, alfentanil, amiodarone, astemizole, cocaine, cortisol, cyclosporine, dapsone, diazepam, dihydroergotamine, dihydropyridines, diltiazem, ethinyl estradiol, gestodene, indinavir, lidocaine, lovastatin, macrolides, methadone, miconazole, midazolam, mifepristone (RU 486), paclitaxel, progesterone, quinidine, rapamycin, ritonavir, saquinavir, spironolactone, sulfamethoxazole, sufentanil, tacrolimus, tamoxifen, terfenadine, testosterone, tetrahydro-cannabinol, triazolam, troleandomycin, verapamil Barbiturates, carbamazepine, macrolides, glucocorticoids, pioglitazone, phenytoin, rifampin Erythromycin, 613-hydroxy cortisol... 

TAMOXIFEN ANTIEPILEPTICS -CARBAMAZEPINE, PHENYTOIN, PHENOBARBITAL i plasma concentrations of tamoxifen and risk of inadequate therapeutic response Due to induction of metabolism of tamoxifen by the CYP3A isoenzymes by phenytoin Avoid concurrent use if possible. Otherwise monitor for clinical efficacy of tamoxifen by t dose of tamoxifen... 

Acetaminophen, aldrin, alfentanil, amiodarone, aminopyrine, amitriptyline, amprenavir, androstenedione,antipyrine, astemizole, benzphetamine, budesonide, carbamazepine, celecoxib, chlorpromazine, chlorzoxazone, cisapride, clarithromycin, clozapine, cocaine, codeine, cortisol, cyclophosphamide,cyclosporin, dapsone, delavirdine, dextromethorphan, digitoxin, diltiazem, diazepam, erythromycin, 17j3-estradiol, ethinylestradiol, etoposide, felbamate, fentanyl, flutamide, hydroxyarginine, ifosphamide, imipramine, indinavir, ketoconazole, lansoprazole, loratidine, losartan, lovastatin, (iS)"mephen3d in, methadone, mianserin, miconazole, mifepristone, nelfinavir, nevirapine, nicardipine, nifedipine, odansetron, omeprazole, orphenadrine, proguanil, propafenone, quinidine, quinine, rapamycin, retinoic acid, ritonavir, saquinavir, selegiline, serindole, sufentanil, sulfinpyrazone, tacrolimus, tamoxifen, tamsulosin, taxol, teniposide, terfenadine, tetrahydrocannabinol, theophylline, toremifene, triazolam, trimethadone, trimethoprim, troleandomycin, verapamil, warfarin, zatosetron, Zolpidem, zonisamide... 

CYP2B6 <5 1-2 Bupropion Carbamazepi ne Cyclophosphamide Selegiline Flunitrazepam Meperidine Bupropion Selegiline Ethinylestradiol Phencyclidine Tamoxifen Ticlopidine Clotrimazole Carbamazepine Phenobarbital Phenytoin Pioglitazone Rifampin Troglitazone Valproic acid Ritonavir... 

Figure 7.11. 8-Methoxypsoralen (8-MOP) is oxidized to an epoxide, and either the epoxide or a ring-opened product derived from it is responsible for inactivation of P450. The structures of two drugs, tamoxifen and carbamazepine (CBZ), that inactivate P450 by unknown mechanisms are also shown.

A4 Barbiturates, carbamazepine, corticosteroids, efavirenz, phenytoin, rifampin, troglitazone Antiarrhythmics, antidepressants, azole antifungals, benzc iazepines, calcium channel blockers, cyclosporine, delavirdine, doxorubicin, efavirenz, erythromycin, estrogens, HIV protease inhibitors, nefazodone, paclitaxel, proton pump inhibitors, HMG-CoA reductase inhibitors, rifabutin, rifampin, sildenafil, SSRIs, tamoxifen, trazodone, vinca anticancer agents... 

Avoid co-administration of carbamazepine with azoles (consider using fluconazole), epierenone, irinotecan (if not able to avoid, t dose of irinotecan by 50%) or tamoxifen. Avoid co-administration of telithromycin for up to... 

CYPs are good at epoxidizing aikenes and alkynes as well, which is probably one reason why more drugs don t contain these groups. Then again, just because a reaction can happen doesn t mean that it will. For carbamazepine (Figure 9.18), epoxidation followed by diol formation is the major metabolic route, but for tamoxifen, metabohc epoxidation of the central double bond hardly happens, and other CYP-catalyzed reactions, including arene epoxidation and N-demethylation (discussed in a later section) are much more in evidence. 

Figure 9.18 Relative contribution of CYP3A4-catalyzed double bond epoxidation to drug metabolism. For carbamazepine, this represents the major metabolic route, while for tamoxifen CYP3A4-catalyzed epoxidation of the alkene is negligible and the enzyme instead Y-demethylates it.

In vitro studies found quinupristin/dalfopristin inhibited the cytochrome P450 isoenzyme CYP3A4-mediated metabolism of docetaxel, tamoxifen, and terfenadine. Quinupristin/dalfopristin is predicted to raise the levels of other drugs ineluding antiarrhythmics (disopyramide, lidocaine, quinidine), antiretrovirals (such as delavirdine, indinavir, nevirapine, ritonavir), astemizole, carbamazepine, cisapride, methyl-prednisolone, paclitaxel, statins (but see Lipid regulating drugs , (p.l086)), and vinca alkaloids. More study is needed. 

---