Ampicillin is a broad-spectrum penicillin antibiotic, active against many Gram-positive and Gram-negative bacteria. It is used in respiratory, urinary, gastrointestinal infections and meningitis, among others. Like all penicillins, it can cause severe allergy (anaphylaxis) and skin rashes.
Also known as: Ampicilina, Amplital
Combining Ampicillin and Allopurinol increases the incidence of skin rashes.
The allopurinol label documents that "the following drugs may increase the risk of serious skin reactions: bendamustine, thiazide diuretics, ampicillin and amoxicillin" (section 7.1) and warns that "hypersensitivity reactions to allopurinol may be increased in patients with decreased kidney function receiving thiazide diuretics and allopurinol concurrently". The mechanism is not fully known, but ampicillin seems to increase skin reactivity during allopurinol therapy — possibly related to accumulation of the oxypurinol metabolite in the skin. The reaction is not a penicillin allergy but a maculopapular exanthema that can be severe (including hypersensitivity syndrome/DRESS). If a skin eruption appears when starting the combination, stop both and reassess; do not reintroduce allopurinol if the reaction was severe. In patients who need both, start separately, with weeks in between, and watch the skin.
Allopurinol + ampicillin: increased risk of severe skin reaction. Watch for skin rash; stop allopurinol at first sign.
Mechanism not fully established; increased cutaneous hypersensitivity reactivity when coadministered.
Skin status (eruption, extent, pruritus), signs of hypersensitivity.
Generalized rash, fever, mucosal involvement (hypersensitivity syndrome).
Watch for a rash; consider an alternative antibiotic or stop allopurinol if the eruption is extensive or pruritic; assess penicillin cross-reactivity.
DailyMed/FDA (NIH/NLM) — approved Ampicillin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=402e7cc7-5ae8-c113-e063-6394a90aa54a ; approved Allopurinol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b6c5b5c0-b1cb-44c0-a849-5d317e6fa300
Ampicillin (a broad-spectrum antibiotic) may potentiate the anticoagulant effect of Warfarin, raising the INR.
Ampicillin, like other broad-spectrum antibiotics, reduces the gut bacterial flora that synthesises vitamin K. Since warfarin inhibits vitamin K epoxide reductase, the lower availability of endogenous vitamin K translates into a higher INR and bleeding risk. The interaction is more relevant in patients with marginal nutrition, liver disease or prolonged antibiotic therapy. INR should be monitored during treatment and after its completion, with vigilance for bleeding signs; adjust the warfarin dose according to the INR.
Ampicillin can potentiate warfarin by reducing the gut flora that produces vitamin K. Monitor the INR during and after the antibiotic.
Reduction of vitamin-K-producing gut flora increases the response to the anticoagulant.
INR, signs of bleeding.
Unexplained bleeding, melena.
Monitor the INR when starting/stopping ampicillin; adjust the warfarin dose as needed.
DailyMed/FDA (NIH/NLM) — approved Ampicillin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=402e7cc7-5ae8-c113-e063-6394a90aa54a ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057
Estradiol + ampicillin: ampicillin interrupts the enterohepatic circulation of oestrogen, with possible reduced efficacy of oral contraceptives (QUADRO 2).
Broad-spectrum antibiotics, such as ampicillin, may alter the gut flora and reduce the hydrolysis of oestrogen conjugates, decreasing their reabsorption and, theoretically, contraceptive efficacy. QUADRO 2 of Annex 7 records this interaction in the oestrogen section. Although the evidence is limited and most women do not lose efficacy, caution is recommended: use a barrier method during antibiotic treatment and for up to 7 days after, especially in patients with diarrhoea or vomiting. Irregular bleeding may also occur. Inform the patient and reinforce adherence to the contraceptive.
Ampicillin + oestradiol: alteration of gut flora — possible reduced contraceptive efficacy; reinforce barrier method during treatment.
Broad-spectrum antibiotics (ampicillin) alter the gut flora and interrupt the enterohepatic circulation of oestrogen — possible reduced contraceptive efficacy (QUADRO 2, Oestrogens: "Ampicillin: interruption of the oestrogen enterohepatic circulation; possible reduced efficacy of oral contraceptives").
Alert the patient to the reduced contraceptive efficacy during antibiotics.
Unplanned pregnancy in a patient on an oral contraceptive + ampicillin.
Use an additional (barrier) contraceptive method during the antibiotic and the following week.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Oestrogens)
Tetracycline + Ampicillin: bacteriostatic drugs may interfere with the bactericidal action of penicillins; the combination should be avoided.
Bacteriostatic drugs, such as tetracycline, may interfere with the bactericidal action of penicillins (ampicillin), reducing the effectiveness of treatment for serious infections. The tetracycline label advises avoiding the combination with penicillins. In practice, the combination is sometimes used intentionally in mixed infections; in those cases, consider the potential antagonism and, whenever possible, choose an alternative or separate the regimen. Monitor the clinical response of the infection.
Tetracycline + ampicillin: avoid — the bacteriostatic effect of tetracycline may interfere with the bactericidal action of penicillin.
Tetracycline, being bacteriostatic, may interfere with the bactericidal action of ampicillin when used together.
Monitor therapeutic efficacy of the infection.
Therapeutic failure of the treated infection.
Avoid the combination; if needed, separate dosing and consider an alternative.
DailyMed/FDA (NIH/NLM) — approved Tetracycline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=02e88b4a-57ae-4ef6-ba48-97c657202b94 ; approved Ampicillin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3b683547-48ac-48ca-8fd4-6866fd17be34
Minocycline + Ampicillin: bacteriostatic drugs may interfere with the bactericidal action of penicillins; the combination should be avoided.
As a bacteriostatic drug of the tetracycline class, minocycline may interfere with the bactericidal action of penicillins, such as ampicillin. The minocycline label advises avoiding the combination with penicillins. In mixed infections where the combination is considered, weigh the potential antagonism and monitor the clinical response. Whenever possible, choose an alternative antibiotic or separate the therapeutic regimens.
Minocycline + ampicillin: avoid — the bacteriostatic effect may interfere with the bactericidal action of penicillin.
Minocycline, being bacteriostatic, may interfere with the bactericidal action of ampicillin when used together.
Monitor therapeutic efficacy of the infection.
Therapeutic failure of the treated infection.
Avoid the combination; if needed, separate dosing and consider an alternative.
DailyMed/FDA (NIH/NLM) — approved Minocycline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a5fc4d50-50b2-46e0-b722-4c6b2ec47d06 ; approved Ampicillin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3b683547-48ac-48ca-8fd4-6866fd17be34
Alcohol does not interact directly with ampicillin; caution is advised due to additive gastrointestinal effects.
Limit alcohol intake during treatment.
DailyMed/FDA (NIH/NLM) — approved Ampicillin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=402e7cc7-5ae8-c113-e063-6394a90aa54a
Food slightly reduces the absorption of oral ampicillin; taking it on an empty stomach maximises plasma levels.
Take ampicillin 1 hour before or 2 hours after meals.
DailyMed/FDA (NIH/NLM) — approved Ampicillin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=402e7cc7-5ae8-c113-e063-6394a90aa54a
Ampicillin frequently causes a maculopapular rash in patients with infectious mononucleosis.
Avoid ampicillin in mononucleosis; prefer an alternative when possible.
DailyMed/FDA (NIH/NLM) — approved Ampicillin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=402e7cc7-5ae8-c113-e063-6394a90aa54a
Ampicillin is a penicillin; it is contraindicated in patients with prior penicillin allergy (risk of anaphylaxis).
Contraindicated in penicillin allergy; choose an alternative from another class.
DailyMed/FDA (NIH/NLM) — approved Ampicillin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=402e7cc7-5ae8-c113-e063-6394a90aa54a
Reduce the dose in severe renal impairment; skin rashes more frequent.
Reduce the dose in severe renal impairment.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 4, Drugs and renal impairment: Reduce the dose in severe renal impairment; skin rashes more frequent.
Penicillins, including ampicillin, are generally safe in pregnancy and are first-line antibiotics when indicated.
May be used in pregnancy when indicated, at the usual doses.
Excreted into breast milk in small amounts; compatible with breastfeeding.
No specific additional contraception.
DailyMed/FDA (NIH/NLM) — approved Ampicillin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=402e7cc7-5ae8-c113-e063-6394a90aa54a ; Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 2, Drugs and Breastfeeding: Trace amounts in milk; safe at the usual dosage; monitor the infant.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Bactericidal beta-lactam antibiotic (inhibition of cell-wall synthesis during active multiplication), active against Gram-positives usually susceptible to penicillin G and against several Gram-negatives. In serum it is the least protein-bound penicillin (~20% vs 60-90% for others); a 500 mg oral dose produces a mean peak serum level of ~3.0 mcg/mL. Acid-stable.
Bactericidal action similar to penicillin G: binds penicillin-binding proteins (PBPs) and inhibits cell-wall transpeptidation, leading to bacterial lysis. Resistance is mediated mainly by beta-lactamases that cleave the beta-lactam ring.
Acid-stable and well absorbed from the gastrointestinal tract; oral absorption is incomplete (~40-60%) and delayed by food. Peak serum levels ~1-2 hours after oral dosing.
Largely excreted unchanged in urine (tubular secretion, delayed by probenecid); a small fraction is metabolised. Diffuses into most tissues and fluids; CSF and brain penetration occurs only with meningeal inflammation.
Elimination half-life of approximately 1 hour in patients with normal renal function (1.0-1.3 h); prolonged in renal impairment.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
