Phenobarbital Dexamethasone

Drugs that may affect donepezil are CYP450 3A4 and 2D6 inhibitors (eg, ketoconazole, quinidine) and CYP450 3A4 and 2D6 inducers (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin). Drugs that may be affected by donepezil include anticholinergics, cholinometics/cholinesterase inhibitors, NSAIDs. 

Buspirone (BuSpar) [Anxiolytic] WARNING Closely monitor for worsening depression or emergence of suicidality Uses Short-term relief of anxiety Action Antianxiety antagonizes CNS serotonin receptors Dose Initial 7.5 mg PO bid T by 5 mg q2-3d to effect usual 20-30 mg/d max 60 mg/d Contra w/ MAOI Caution [B, /-] Avoid w/ severe hepatic/renal insuff Disp Tabs SE Drowsiness, dizziness, HA, N, EPS, serotonin synd, hostility, depression Notes No abuse potential or physical/psychologic d endence Interactions T Effects W/ erythromycin, clarithromycin, itraconazole, ketoconazole, diltiazem, verapamil, grapefruit juice effects W/ carbamazepine, rifampin, phenytoin, dexamethasone, phenobarbital, fluoxetine EMS T Sedation w/ concurrent EtOH use grapefruit juice may T risk of adverse effects OD May cause dizziness, miosis, N/V symptomatic and supportive... 

NA /D, abd pain, bleeding, fevCT, T QT Interactions t Effects W7 atazanavir, clarithromycin, CT5rthromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfi-navir, ritonavir, saquinavir, telithromycin X effects W7 antacids, carbamazqjine, dexamethasone, phenobarbital, phenytoin, rifampicin, St. John s wort EMS Drug contains lactose, may cause D/abd discomfort in pts w/ lactose intolerance OD Sxs unknown symptomatic and supportive... 

Drugs that are known to be substrates of P-gp include antihistamines (e.g. terfenadine), digoxin, ciclosporin, hydrocortisone and other steroids and drugs used in chemotherapy (e.g. paclitaxel, vinblastine). Ciclosporin, in addition to being a substrate of P-gp, is also an inhibitor of P-gp. Drugs known to induce P-gp include morphine, dexamethasone, phenobarbital, rifampin and St John s wort. Inhibitors of P-gp include amiodarone, amitriptyline, atorvastatin, chlorpromazine, ciclosporin, erythromycin, fluphenazine, haloperidol, quinidine, ritonavir and verapamil,... 

CYP2A6 <5 1-2 Acetaminophen Carbamazepi ne Cyclophosphamide Selegiline Flunitrazepam Nicotine Clotrimazole Isoniazid Methoxypsoralen Valproic acid Dexamethasone Phenobarbital Rifampin... 

The UK manufacturers point out that carbamazepine, dexamethasone, phenobarbital, phenytoin and rifampicin are all inducers of CYP3A4, an isoenzyme involved in the metabolism of sibutramine. These drugs might therefore increase the metabolism of sibutramine resulting in a fall in its serum levels. However, this has not been studied experimentally and, at the present time, the existence, the extent and the possible clinical relevance of any such interaction is unknown. 

No specific studies have been carried out with imatinib and other CYP3A4-inducing drugs, but the manufacturers suggest that carbamazepine, dexamethasone, phenobarbital, and phenytoin, may also reduce imatinib serum levels, and they have a possible case on file with phenytoin. The manufacturers therefore reasonably recommend caution, and suggest that concurrent use with these drugs should be avoided. However, if this is not possible it would be prudent to monitor the outcome of concurrent use, and increase the imatinib dose as necessary. 

P-gp (ABCB1) Verapamil, digoxin, mitoxantrone, vinblastine, doxorubicin, losartan, talinolol, cortisol, dexamethasone, colchicine, loperamide, domperidone, indinavir, erythromycin, tetracycline, itraconazole, cyclosporine, methotrexate, amitryptyline, phenobarbital, morphine, cimetidine, and others... 

Dexamethasone, the macrolide antibiotic triacetylo-leandromycin, and phenobarbital are all well established inducers of the CYP3A subfamily, and can increase microsomal 4-hydroxylation of RA in rat liver. To what extent this is also the case for humans is not completely clear. 

Aflatoxin Bl, bupropion, cyclophosphamide, dexamethasone, etoposide, ifosfamide, midazolam, phenobarbital, propofol, rifampin, teitiposide, thiotepa, vitamin D, xenobiotics Amitriptyhne, carisoprodol,... 

Although specific drug or food interactions with mifepristone have not been studied, on the basis of this drug s metabolism by CYP3A4, it is possible that ketoconazole, itraconazole, erythromycin, and grapefruit juice may inhibit its metabolism (increasing serum levels of mifepristone). Furthermore, rifampin, dexamethasone, St. John s wort, and certain anticonvulsants (e.g., phenytoin, phenobarbital, and carbamazepine) may induce mifepristone metabolism (lowering serum levels of mifepristone)... 

Rifampicin and pregnenolone-16a-carbonitrile (PCN) induce members of the CYP3A family and represent a third type of inducer, in that the substrate specificity of the microsomes from treated animals differs from that of the microsomes from either phenobarbital-treated or TCDD-treated animals. Inducing substrates of this class include endogenous and synthetic glucocorticoids (e.g., dexamethasone), pregnane... 

Increased P450 synthesis requires enhanced transcription and translation. A cytoplasmic receptor (termed AhR) for polycyclic aromatic hydrocarbons (eg, benzo[a]pyrene, dioxin) has been identified, and the translocation of the inducer-receptor complex into the nucleus and subsequent activation of regulatory elements of genes have been documented. A pregnane X receptor (PXR), a member of the steroid-retinoid-thyroid hormone receptor family, has recently been shown to mediate CYP3 A induction by various chemicals (dexamethasone, rifampin) in the liver and intestinal mucosa. A similar receptor, the constitutive androstane receptor (CAR) has been identified for the phenobarbital class of inducers (Sueyoshi, 2001 Willson, 2002). 

Delavirdine is extensively metabolized to inactive metabolites by the CYP3A and CYP2D6 enzymes. However, it also inhibits CYP3 A and thus inhibits its own metabolism. In addition to its interactions with other antiretroviral agents (see Table 49 1), delavirdine will result in increased levels of numerous agents (Table 49-3). Dose reduction of indinavir and saquinavir should be considered if they are administered concurrently with delavirdine. Delavirdine plasma concentrations are reduced in the presence of antacids, phenytoin, phenobarbital, carbamazepine, rifabutin, and rifampin concentrations are increased during coadministration with clarithromycin, fluoxetine, dexamethasone, and ketoconazole. 

Since indinavir is a substrate as well as an inhibitor of CYP3 A4, numerous and complex drug interactions can occur as described above. Indinavir levels decrease with concurrent use of rifabutin, fluconazole, St. John s wort, and rifampin. Caution is advised with other 3 A4 inducers also, including phenobarbital, phenytoin, carbamezepine, and dexamethasone. Dose reduction of indinavir should be considered if coadministered with delavirdine, ketoconazole, or itraconazole, while an increase in the dose of indinavir is indicated if the drug is coadministered with efavirenz or rifabutin. 

Figure 3 Northern blot analysis of CYP3A and CYP2B mRNAs in rat hepatocytes cultured on Matrigel. Cells were incubated in the presence of 10-pM dexamethasone or 50-pM phenobarbital for 48 hours. Source From Ref. 12.

If a drug is a substrate of CYP3A, coadministration with St. John s wort, a CYP3A inducer, can decrease the systemic exposure and effectiveness. St. John s wort may be listed in the labeling along with other known inducers, such as rifampin, rifabutin, rifapentin, dexamethasone, phenytoin, carbamazepine, or phenobarbital, as possibly decreasing plasma levels. 

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