Drug Interactions between amoxicillin / clarithromycin / omeprazole and butorphanol

MONITOR CLOSELY: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of butorphanol according to the product labeling. However, pharmacokinetic data are not available. Increased butorphanol concentrations could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. Conversely, discontinuation of a CYP450 3A4 inhibitor could decrease butorphanol plasma concentrations, decrease opioid efficacy, and possibly even lead to a withdrawal syndrome in patients who had developed physical dependence to butorphanol.

MANAGEMENT: Patients receiving butorphanol with potent or moderate CYP450 3A4 inhibitors should be carefully monitored, and dosage adjustments made accordingly as needed. This is particularly important when an inhibitor is added after a stable dose of butorphanol has been achieved. Patients and/or their caregivers should be advised to seek medical attention if potential signs and symptoms of toxicity occur, such as dizziness, confusion, fainting, extreme sedation, unresponsiveness, bradycardia, slow or difficult breathing, and shortness of breath. When discontinuing CYP450 3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur.

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

Clarithromycin may increase and prolong the omeprazole plasma concentration. The mechanism may be related to clarithromycin inhibition of hepatic cytochrome P450 enzymes responsible for omeprazole metabolism. Coadministration of omeprazole may result in an increase in clarithromycin and 14-(R)-hydroxyclarithromycin plasma concentrations. These increases may be due to the effect of omeprazole on gastric pH.