The possibility of a prolonged bleeding time after oral treatment with a broad-spectrum drug like ampicillin should be borne in mind in patients receiving anticoagulants.
Hormonal contraceptives: A variety of broad-spectrum antibacterial have also been reported to decrease oral contraceptive efficacy. It is recommended that additional contraceptive precautions should be used while taking, and for 7 days after stopping, a short course of any broad-spectrum antibacterial. If these 7 days run into the last 7 days of the cycle, then the tablet-free interval (or the 7 inert tablets) should be omitted and the next cycle of tablets started immediately. If the course of antibacterial exceeds 3 weeks the intestinal flora develops resistance and additional precautions become unnecessary.
Methotrexate: Various penicillins have been reported to markedly decrease the clearance of methotrexate given intravenously for treatment of neoplasms. There have also been a few reports of penicillins possibly exacerbating the toxicity of low-dose methotrexate in patients being treated for psoriasis or rheumatoid arthritis, but a small study found that although flucloxacillin decreased methotrexate clearance slightly, this was not clinically significant.
Allopurinol: An increased frequency of skin rashes has been reported in patients receiving ampicillin or amoxicillin, with allopurinol.
Chloroquine: The absorption of ampicillin has been reduced in healthy subjects taking chloroquine.
Probenecid: Decreases the renal tubular secretion of ampicillin and sulbactam. This may result in increased blood level.