Ampicillin: Drug Interactions

Major Interactions — Avoid or Monitor Closely

• ⚠Methotrexate — penicillins reduce renal tubular secretion of methotrexate, increasing toxicity risk; avoid or suspend penicillin before high-dose methotrexate
• ⚠Anticoagulants (warfarin) — high-dose IV penicillins may displace warfarin from protein binding and alter vitamin K-producing gut flora; monitor INR

Moderate Interactions — Use With Caution

• •Probenecid — blocks renal tubular secretion of penicillins, increasing plasma levels 2–4× (used therapeutically to extend effect)
• •Oral contraceptive pill — theoretical risk via reduction in enterohepatic recirculation of oestrogen (limited evidence for modern formulations)
• •Aminoglycosides (gentamicin) — synergistic bactericidal activity clinically; incompatible in same IV infusion (chemical inactivation)
• •Allopurinol — combined with amoxicillin/ampicillin increases risk of skin rash
• •Mycophenolate — penicillins reduce levels via gut flora alteration

Food & Drink Interactions

• •Food reduces absorption of some penicillins — take flucloxacillin and ampicillin on empty stomach; amoxicillin less affected by food
• •Dairy products — no significant interaction (unlike tetracyclines or fluoroquinolones)

Monitoring Requirements

Renal function in prolonged high-dose courses; electrolytes with high-dose IV benzylpenicillin (sodium loading); accurate penicillin allergy assessment before prescribing (>90% of labelled allergy patients can tolerate penicillin)