Flucloxacillin Side Effects
Flucloxacillin is generally well-tolerated with an overall side effect incidence of approximately 9.5%, primarily involving gastrointestinal, hepatic, and hypersensitivity reactions. 1
Common Side Effects
Gastrointestinal Effects
- Nausea, dyspepsia, and vomiting are the most frequently reported adverse effects, occurring in 0.5-1.8% of patients 2
- These reactions are typically mild and reversible 3
Hepatic Reactions
- Mild transaminase elevations without clinical symptoms represent a class effect of beta-lactam antibiotics 3
- The overall incidence of flucloxacillin hepatotoxicity is comparable to that reported with amoxicillin-clavulanic acid 3
- While rare, significant hepatotoxicity has been documented in postmarketing surveillance 3
Hypersensitivity Reactions
- Immediate (IgE-mediated) hypersensitivity occurs more commonly than delayed reactions, with 82.5% of confirmed flucloxacillin allergies being immediate-type 4
- Among immediate reactions, 58% are classified as severe 4
- Skin reactions including rash, pruritus, and photosensitivity occur in 0.2-0.4% of patients 2
- Cross-sensitization to other penicillins appears in only 35% of patients with IgE-mediated allergy 4
Rare but Serious Side Effects
Central Nervous System Effects
- Neurological adverse effects including dizziness, insomnia, tremors, and headache occur in approximately 0.5% of patients 2
- These reactions are generally mild compared to fluoroquinolones 5
Drug Interactions
- Flucloxacillin is a weak inducer of CYP3A4, which can reduce efficacy of drugs metabolized by this pathway 6
- This may lead to clinically relevant interactions with narrow therapeutic range drugs such as warfarin, tacrolimus, voriconazole, and repaglinide 6
- The metabolic ratio of midazolam (a CYP3A4 substrate) decreases by approximately 25-28% after flucloxacillin treatment 6
Clinical Context and Safety Profile
Flucloxacillin is notably safer than many alternative antibiotics, with a success rate of 92% in skin infections and 84% in upper respiratory tract infections 1. The drug is specifically recommended as low-cost and not commonly associated with severe adverse events in diabetic foot infections 7. When used for infective endocarditis, gentamicin addition is not recommended due to lack of clinical benefit and increased renal toxicity 7.
Important Monitoring Considerations
- Patients should be monitored for signs of hepatotoxicity, particularly with prolonged use 3
- Hypersensitivity reactions require immediate discontinuation, with intradermal testing having an 86% negative predictive value for immediate reactions 4
- Consider potential drug interactions when prescribing flucloxacillin to patients on CYP3A4 substrates with narrow therapeutic indices 6