Drug Interactions between amoxicillin / clarithromycin / vonoprazan and thiotepa

GENERALLY AVOID: Coadministration with strong CYP450 3A4 inhibitors may increase plasma concentrations of thiotepa, and decrease concentrations of its active metabolite triethylenephosphoramide (TEPA). Thiotepa is a prodrug that is primarily converted to TEPA by the isoenzyme. A pharmacokinetic study evaluating six breast cancer patients receiving high-dose chemotherapy (cyclophosphamide 1,500 mg/m2/day, thiotepa 120 mg/m2/day, and carboplatin AUC 5 mg min/mL/day) with the moderate CYP3A4 inhibitor aprepitant (125 mg one day before chemotherapy, then 80 mg daily during and for three days after) showed a 15% increase in total thiotepa exposure, a 33% decrease in TEPA formation, and 20% reduction in TEPA exposure. Although clinical evidence is limited, strong CYP450 3A4 inhibitors may more significantly increase thiotepa exposure and reduce TEPA exposure, potentially resulting in more thiotepa-related adverse effects and reduced efficacy.

MANAGEMENT: The use of thiotepa in combination with strong CYP450 3A4 inhibitors should generally be avoided. If concomitant use of a strong CYP450 3A4 inhibitor is required, it is recommended that patients be carefully monitored for reduced efficacy and thiotepa-related toxicities such as myelosuppression, cutaneous toxicity, and neurotoxicity.

MONITOR: Coadministration with CYP450 3A4 and/or 2B6 inhibitors may increase plasma concentrations of thiotepa and decrease concentrations of its active metabolite triethylenephosphoramide (TEPA). Thiotepa is a prodrug that is primarily converted to TEPA by these isoenzymes. A pharmacokinetic study evaluating six breast cancer patients receiving high-dose chemotherapy (cyclophosphamide 1,500 mg/m2/day, thiotepa 120 mg/m2/day, and carboplatin AUC 5 mg min/mL/day) with the moderate CYP3A4 inhibitor aprepitant (125 mg one day before chemotherapy, then 80 mg daily during and for three days after) showed a 15% increase in total thiotepa exposure, a 33% decrease in TEPA formation, and 20% reduction in TEPA exposure.

MANAGEMENT: Caution and closer monitoring for decreased efficacy and adverse effects are advised when thiotepa is used concurrently with CYP450 3A4 and/or 2B6 inhibitors. Patients should be more closely monitored for thiotepa-related toxicities such as myelosuppression, cutaneous toxicity, and neurotoxicity.

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.