Antibiotic Allergy and Interactions


Specifically ask the patient as to the nature of 'allergy' as abdominal pain, nausea, vomiting, diarrhoea or dyspepsia does not constitute allergy. Document both the allergy and the nature of the allergy in the patient's medical notes and on HEPMA (or drug kardex if HEPMA has not been rolled out to your site).

Do not give penicillin, cephalosporin or other beta-lactam* antibiotic if patient has a history of anaphylaxis, urticaria, severe blistering rash, or rash immediately after penicillin administration. Adults with a history of a minor rash (e.g. non-confluent, non-pruritic rash restricted to a small area of the body), or a rash that occurs >3 days after starting an antibiotic course are unlikely to have an antibiotic allergy and therefore the antibiotic should not be withheld unnecessarily for serious infections. 

Penicillin allergy is reported by 10% of patients. Anaphylaxis (true penicillin allergy) occurs in <1% of treated patients. With co-trimoxazole a rash occurs in >1 in 100 patients prescribed it. If a rash occurs, discontinue co-trimoxazole immediately.

Be aware of the components of antibiotic co-formulations e.g. co-trimoxazole (trimethoprim and sulfamethoxazole), co-amoxiclav (amoxicillin and clavulanic acid), piperacillin with tazobactam.

For patients who have a low probability of type 1 or type 4 hypersensitivity reaction to penicillin, please consider penicillin allergy de-labelling (see the Penicillin Allergy guideline on the NHSGGC Clinical Directory as well as a Medicine Update blog article on this). Consider referral to OPAT. This pathway is not suitable for high risk patients (type 1 or type 4 hypersensitivity) and those with non-penicillin related allergy.

For further advice on antibiotic allergy contact the allergy service.

*Beta-lactam antibiotics include: amoxicillin; ampicillin; benzylpenicillin (Penicillin G); co-amoxiclav (Augmentin®); flucloxacillin; phenoxymethylpenicillin (Penicillin V); piperacillin / tazobactam (Tazocin®), pivmecillinam; temocillin; cefaclor; cefalexin; cefotaxime; ceftazidime; ceftazidime / avibactam (Zavicefta®); ceftaroline; ceftriaxone; ceftobiprole; ceftolozane / tazobactam (Zerbaxa®); cefuroxime; aztreonam; meropenem; meropenem / vaborbactam (Vaborem®); imipenem with cilastatin, ertapenem (see the BNF for more details).

Important Antibiotic Drug Interactions

Below is not a comprehensive list; for further information refer to a pharmacist or Appendix 1 of the BNF.

Table 1: Examples of antibiotic interactions
Drug Interaction


Absorption reduced by oral iron, calcium, magnesium, aluminium, zinc or sucralfate, and some nutritional supplements. Avoid / withhold these until doxycycline course is complete. If concomitant administration is necessary, give at least 2 hours before or after doxycycline.


(e.g. clarithromycin, azithromycin)

Numerous interactions (some potentially life-threatening) via:

  • Enzyme inhibition e.g. carbamazepine and simvastatin (see BNF Appendix 1).
  • QT prolongation e.g. citalopram, fluconazole, quinolones; seek advice from pharmacy. Consider other medical risk factors for QT prolongation. Also see Assessing Medicines on Admission in Acute Patients and Medicines Update Extra (MUE 08: Drug induced QT prolongation) at
  • Hydroxychloroquine - associated increased risk of CV events and mortality (see MHRA alert, Feb 2022).
Oral contraceptive pill No additional contraceptive precautions are now required when combined oral contraceptives are used with antibiotics which do not induce liver enzymes, unless diarrhoea or vomiting occur (see BNF for advice)


(e.g. ciprofloxacin, levofloxacin, ofloxacin)

  • QT prolongation (as for macrolides, see above)
  • Lower seizure threshold (see BNF Appendix 1).
  • Absorption reduced by oral iron, calcium, magnesium and some nutritional supplements. Follow above guidance for doxycycline.
Rifampicin Numerous interactions through enzyme induction (see BNF Appendix 1 for details). The interacting effect of rifampicin can persist for many days after stopping rifampicin therapy
Statins Avoid concomitant use with macrolides and sodium fusidate (consult BNF for details)
Warfarin INR may be altered by many antibiotics, particularly if a course is prolonged (check BNF Appendix 1)


Guideline reviewed March 2022

Page updated March 2022