Hepatitis macrolides causing

Maximal plasma concentrations occur 2 to 3 hours after oral administration of reboxetine (178). Reboxetine has linear pharmacokinetics over its clinically relevant dosing range and a half-life of approximately 12 hours. For this latter reason, a twice a day, equally divided dosing schedule was used during clinical trial development. Its clearance is reduced and half-life becomes longer as a function of advanced age (mean = 81 years of age) and renal and hepatic impairment ( 178, 322, 323). Reboxetine is principally metabolized by CYP 3A3/4 such that its dose should be reduced when used in combination with drugs that are substantial inhibitors of CYP (e.g., certain azole antifungals, certain macrolide antibiotics). Reboxetine itself, however, does not cause detectable inhibition of CYP 3A3/4 based on formal in vivo pharmacokinetic interaction studies as well as its own linear pharmacokinetics. 

Quazepam (Doral) [C-IV] [Sedarive/Hypnoric/ Benzodiazepine] Uses Insonmia Action Benzodiazepine Dose 7.5-15 mg PO hs PRN X in elderly hepatic failure Caution [X, /-] NA glaucoma Contra PRG, sleep apnea Disp Tabs SE Sedation, hangover, somnolence, resp depression Interactions T Effects W/ azole antifungals, cimetidine, digoxin, clisulfiram, INH, levodopa, macrolides, neuroleptics, phenytoin, quinolones, SSRIs, verapamil, grapefruit juice, EtOH X effects W/ carbamazepine, rifampin, rifabutin, tobacco EMS Use caution w/ other benzodiazepines, antihistamines, opioids and verapamil, can T CNS depression concurrent EtOH and grapefruit juice use T CNS depression OD May cause profound CNS depression, confusion, bradycardia, hypotension, and altered reflexes flumazenil can be used as antidote activated charcoal may be effective... 

Erythromycin can cause acute carbamazepine intoxication, probably by inhibiting its hepatic metabolism (63). Erythromycin may also directly inhibit the conversion of carbamazepine to its epoxide. In a controlled study of the effects of eiythromycin on carbamazepine pharmacokinetics in healthy volunteers, the clearance of a single dose of carbamazepine was reduced by 19% during erythromycin treatment (64). In contrast, the single-dose pharmacokinetics of phenytoin were not affected by erythromycin (65,66). After withdrawal of the macrolide, carbamazepine concentrations quickly return to normal (67). If co-administration of erythromycin and carbamazepine cannot be avoided, a dosage reduction of... 

Erythromycin can cause two different types of liver damage (36,37), benign increases in serum transaminases, which may or may not recur on rechallenge, and cholestatic hepatitis. Reports of intrahepatic cholestasis with azithromycin (38), clarithromycin (39,40), and josamycin (41) suggest that the newer macrolides are not free of this adverse effect, although the relative risks compared with erythromycin are unclear. Similar involvement of the liver has been seen with the ester of triacetyloleandomycin, but not with the unesterified antibiotic. 

Macrolides such as josamycin, midecamycin, and spiramycin, which do not form stable complexes with cytochrome P450, rarely if ever cause cholestatic hepatitis. 

Adverse reactions Erythromycin can cause nausea, vomiting, diarrhea, and abdominal cramping. Gl intolerance due to erythromycin is due to direct stimulation of the motilin receptor, leading to increased Gl motility. This occurs with both the IV and PO formulation. Although rare, all macrolides can cause hepatotoxicity. The estolate formulation of erythromycin has been associated with cholestatic hepatitis in pregnant women. In high doses, all macrolides can cause tinnitus. All macrolides can cause QT prolongation and torsade de points... 

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