From the Guidelines
Clavulanic acid, commonly found in the antibiotic combination Augmentin (amoxicillin-clavulanic acid), can cause several adverse effects, with the most common being gastrointestinal disturbances such as diarrhea, which occurs in approximately 25% of patients, as reported in a study by Hoberman et al 1.
Adverse Effects of Clavulanic Acid
The adverse effects of clavulanic acid can be categorized into common and less common effects. Common adverse effects include:
- Gastrointestinal disturbances such as diarrhea, nausea, vomiting, and abdominal pain, which are thought to occur due to the disruption of normal gut flora by clavulanic acid 1
- Headaches and dizziness
- Skin reactions like rash or itching Less common but more serious adverse effects include:
- Liver function abnormalities, which may present as jaundice, elevated liver enzymes, or hepatitis
- Allergic reactions ranging from mild skin rashes to severe anaphylaxis in susceptible individuals
- Secondary infections such as oral or vaginal candidiasis due to disruption of normal microbial balance
- Rarely, blood disorders like thrombocytopenia or neutropenia may occur
Mechanism and Clinical Implications
Clavulanic acid works by inhibiting beta-lactamase enzymes that would otherwise break down certain antibiotics, but this mechanism can also affect normal body processes, contributing to these side effects. The incidence of gastrointestinal side effects is significantly less with twice-a-day dosing compared to three times a day, as noted in a study published in the journal Otolaryngology--head and neck surgery 1. If severe reactions occur, discontinuation of the medication and medical attention are necessary. A clinical practice guideline update on adult sinusitis also highlights the potential increased gastrointestinal adverse effects with amoxicillin-clavulanate compared to other antibiotics 1.
From the FDA Drug Label
ADVERSE REACTIONS Amoxicillin and clavulanate potassium is generally well tolerated. The majority of side effects observed in clinical trials were of a mild and transient nature and less than 3% of patients discontinued therapy because of drug-related side effects The most frequently reported adverse effects were diarrhea/loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%) and vaginitis (1%). The following adverse reactions have been reported for ampicillin-class antibiotics: Gastrointestinal Diarrhea, nausea, vomiting, indigestion, gastritis, stomatitis, glossitis, black “hairy” tongue, mucocutaneous candidiasis, enterocolitis, and hemorrhagic/pseudomembranous colitis. Hypersensitivity Reactions Skin rashes, pruritus, urticaria, angioedema, serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever), erythema multiforme (rarely Stevens-Johnson syndrome), acute generalized exanthematous pustulosis, hypersensitivity vasculitis, and an occasional case of exfoliative dermatitis (including toxic epidermal necrolysis) have been reported.
The adverse effects of clavulanic acid (Augmentin) include:
- Gastrointestinal effects such as diarrhea, nausea, vomiting, and abdominal discomfort
- Hypersensitivity reactions including skin rashes, urticaria, and angioedema
- Hepatic effects such as a moderate rise in AST (SGOT) and/or ALT (SGPT) and hepatic dysfunction
- Renal effects such as interstitial nephritis and hematuria
- Hemic and Lymphatic Systems effects such as anemia, thrombocytopenia, and eosinophilia
- Central Nervous System effects such as agitation, anxiety, and convulsions 2
From the Research
Adverse Effects of Clavulanic Acid
The adverse effects of clavulanic acid, particularly when used in combination with amoxicillin (Augmentin), include:
- Gastrointestinal side effects, such as Clostridium difficile infection 3
- The combination of amoxicillin and clavulanic acid is more strongly associated with gastrointestinal side effects compared to amoxicillin alone 3
- Clavulanic acid is also associated with a higher risk of adverse reactions, such as diarrhea and nausea, due to its effect on the gut microbiome 3
Comparison with Other Studies
Other studies have reported that clavulanic acid is generally well-tolerated with mainly mild adverse reactions 4
- However, the exact nature and severity of these adverse effects may vary depending on the individual and the specific context in which the drug is used
Mechanism of Action
Clavulanic acid works by inhibiting bacterial beta-lactamases, which are enzymes that break down beta-lactam antibiotics like amoxicillin 5
- This mechanism of action can help to reduce the risk of antibiotic resistance, but it can also contribute to adverse effects like gastrointestinal disturbances 3