Phenobarbital Azoles

Barbiturates, especially phenobarbital Azoles, calcium channel blockers, propranolol, quinidine, steroids, wailarin, and many other drugs metabolized in the liver Increased deararx of the affected drugs due to enzyme induction, possibly leading to decreases in drug effectiveness... 

Drugs that might decrease plasma concentrations of lopinavir/ritonavir include rifampin, phenobarbital, carbamazepine, phenytoin, azole antifungals, delavirdine, rifabutin, St. John s wort, efavirenz, nevirapine, and corticosteroids. 

Drugs that may affect cyclosporine include allopurinol, amiodarone, androgens (eg, danazol, methyltestosterone), anticonvulsants (eg, carbamazepine, phenobarbital, phenytoin), azole antifungals (eg, fluconazole, ketoconazole), beta-blockers, bosentan, bromocriptine, calcium channel blockers, colchicine, oral contraceptives, corticosteroids, fluoroquinolones (eg, ciprofloxacin), foscarnet, HMG-CoA reductase inhibitors, imipenem-cilastatin, macrolide antibiotics, methotrexate, metoclopramide, nafcillin, nefazodone, orlistat, potassium-sparing diuretics, probucol, rifamycins (rifampin, rifabutin), serotonin reuptake inhibitors (SSRIs eg, fluoxetine, sertraline),... 

Cyclosporin is metabolised by the hepatic cytochrome P-450 enzyme system, and enzyme induction by phenobarbital, phenytoin, carbamazepine, or rifampicin will drastically increase the clearance of cyclosporin. Concurrent administration of these drugs has caused rejection of transplanted organs. Conversely, the use of enzyme inhibitors, such as erythromycin or the azole antifungal agents, e.g. ketoconazole, will increase the blood concentrations of cyclosporin leading to an increased risk of toxic side effects. 

Clinically important, potentially hazardous interactions with antihistamines, azole antifungals, benzodiazepines, carbamazepine, cimetidine, delavirdine, diazepam, erythromycin, HIV protease inhibitors, ketorolac, macrolide antibiotics, neuroleptics, phenobarbital, phenytoin, rifampin, ritonavir... 

Most abundant isoform wide substrate range inhibited by cimetidine, macrolides, azoles, and ethanol (acute) induced by general P450 inducers such as carbamazepine, phenobarbital, phenytoin, and rifampin and by ethanol (chronic). 

The serum levels of itraconazole 200 mg daily were very low (0.01 to 0.03 mg/L, therapeutic range 0.25 to 2 mg/L) in a patient taking phenobarbital. Two months after stopping the phenobarbital they were higher (0.15 mg/L), but still below the therapeutic range, apparently because carbamazepine had been recently started. For mention of two other patients who had very low itraconazole levels while taking both phenytoin and phenobarbital, see Phenytoin + Azoles , p.552. Some makers of itraconazole say that concurrent use of potent enzyme inducers such as phenobarbital is not recommended. ... 

Especially the inhibition or induction of cytochrome P450 subtype 3A4 (CYP 3A4) is clinically relevant, because a variety of active substances and food substances (e.g. grapefruit juice) are able to affect this enzyme. Substances inhibiting CYP 3A4 include ciclosporin, dihydropyridines, verapamil, midazolam, paclitaxel, simvastatin, lovastatin, atorvastatin, cimetidine, erythromycin, troleandomycin, ketoconazole (and other azoles). Substances inducing CYP 3A4 include steroids, rifampicin, phenobarbital and St John s wort. 

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