CYP3A4 inducers

Conversely buprenorphine metabolism could by increased by carbamazepine, phenytoin, St. John s wort, efavirenz, and nevirapine, or any other CYP3A4 inducer the effects may be less than expected may need to increase buprenorphine dose. 

This HIV drug is a CYP3A4 inducer efavirenz decreases... 

Nervirapine is an HIV drug that is a CYP3A4 inducer in a small sample, nevirapine caused a 50% reduction in methadone blood levels, resulting in complaints of methadone withdrawal symptoms in patients receiving methadone maintenance may need to increase methadone dose in patients who have nevirapine added to their drug regimen. 

No clear SAR emerges for induction, nor are any particular groups or functions implicated as shown by the diverse structures of the known CYP3A4 inducers (Figure 8.29). Structures are diverse but most are lipophilic as defined by a positive calculated log P value. 

Tab. 8.3 Dose, total and free plasma concentrations for clinical CYP3A4 inducers.

Fig. 8.29 Structures of known clinical CYP3A4 inducers nevirapine (A), troglitazone (B), phenobarbitone (C), efavirenz (D), probenicid (E), phenytoin (F), moricizine (G), felbamate (H), rifampicin (I) and carba-mazepine (J).

P450 system In vitro drug metabolism studies have shown that solifenacin is a substrate of CYP3A4. Inducers or inhibitors of CYP3A4 may alter solifenacin pharmacokinetics. 

Drugs that may interact with buprenorphine hydrochloride include barbiturate anesthetics, benzodiazepines, CNS depressants, CYP3A4 inducers and inhibitors, and MAOIs. 

Drugs that may affect aprepitant include CYP 3A4 inhibitors (eg, clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin), CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin), and paroxetine. 

Concomitant use with potential CYP3A4 inducers - When a potential CYP3A4 inducer such as carbamazepine is added to aripiprazole therapy, double the... 

Drugs that induce CYP3A4 CYP3A4 is a minor metabolizing enzyme of zaleplon. The CYP3A4-inducer rifampin reduced zaleplon C ax AUC by approximately... 

Drugs that may interact with eszopiclone include CYP3A4 inducers, CYP3A4 inhibitors, and ethanol. 

The following drug interactions were reported for metronidazole, a chemically related nitroimidazole. Therefore, these drug interactions may occur with tinidazole. Drugs that may affect tinidazole include cholestyramine, CYP3A4 inducers and inhibitors and oxytetracycline. Drugs that may be affected by tinidazole include alcohols, anticoagulants, cyclosporine, tacrolimus, disulfiram, fluorouracil, hydantoins, and lithium. 

Monitoring Monitor whole blood sirolimus concentrations in patients receiving concentration-controlled sirolimus. Monitoring is also necessary in patients likely to have altered drug metabolism, in patients at least 13 years of age who weigh less than 40 kg, in patients with hepatic impairment, and during coadministration of potent CYP3A4 inducers and inhibitors. 

El-Sankary, W Gibson, G.G., Ayrton, A. and Plant, N. (2001) Use ofa reporter gene assay to predict and rank the potency and efficacy of CYP3A4 inducers. Drug Metabolism and Disposition The Biological Fate of Chemicals, 29, 1499-1504. 

St. Johns wort (a CYP3A4 inducer) caused a small (about 30%) decrease in eplerenone AUC... 

Buspirone Mechanism uncertain Partial agonist at 5-HT receptors but affinity for D2 receptors also possible Slow onset (1-2 weeks) of anxiolytic effects t minimal psychomotor impairment—no additive CNS depression with sedative-hypnotic drugs Generalized anxiety states Oral activity forms active metabolite short half-life Toxicity Tachycardia paresthesias t gastrointestinal distress Interactions CYP3A4 inducers and inhibitors... 

Thus, in patients taking digitoxin, who then start therapy with phenobarbital, (CYP3A4 inducer), the blood level of digitoxin decreases by about half. The dose would then need to be raised to compensate, but if the phenobarbital was stopped, the induction would decline and toxicity would ensue if there was no readjustment of the dose. 

Sunirinib (Sutent) [Kinase Inhibitor] Uses Advanced GI stromal tumor refractory/intolerant of imatinib advanced RCC Action Kinase inhibitor Dose Adults. 50 mg PO daily x 4 wk, followed by 2 wk holiday = 1 cycle 4- to 37.5 mg w/ CYP3A4 inhibitors (Table VI-8), to T 87.5 mg w/ CYP3A4 inducers Contra w/ atazanavir Caution [D, -] Multiple interactions require dose modification (eg, St. John s wort) Disp Caps SE -l WBC pit, bleeding, T BP, -l ejection fraction, T QT interval, pancreatitis, DVT, Sz, adrenal insuff, N/V/D, skin discoloration, oral ulcers, taste perversion, hypothyroidism Interactions Multiple interactions require dose modification (eg, St. John s wort) EMS Monitor ECG for T QT interval grapefruit juice may T adverse effects may affect potassium level (hypo-/hyperkalemia) monitor for S/Sxs of heart failure drug can 4- ejection fraction OD May cause abd pain, muscle weakness, and chills symptomatic and supportive... 

---