Does clarithromycin cause diarrhoea?

Does Clarithromycin Cause Diarrhoea?

Yes, clarithromycin causes diarrhoea as a common gastrointestinal side effect, occurring in approximately 3-10% of patients, though it is generally mild and does not typically require treatment discontinuation. 1, 2, 3

Incidence and Clinical Significance

The FDA drug label explicitly warns patients that diarrhoea is a common problem caused by clarithromycin and other antibacterials. 2 The incidence varies across studies:

• Standard formulations: Diarrhoea occurs in approximately 3.0-3.8% of patients in large clinical trials 3
• Comparative data: The CDC and American Geriatrics Society note that gastrointestinal symptoms including diarrhoea are among the most common adverse effects, occurring in 9-11% of patients 1
• Formulation differences: The modified-release formulation may have lower rates of diarrhoea compared to immediate-release formulations (0% vs 4.8%, p=0.029 in one comparative trial) 4

Mechanism and Characteristics

Clarithromycin causes diarrhoea through two distinct mechanisms:

Direct gastrointestinal effects: The macrolide structure causes dose-related gastrointestinal irritation, typically presenting as mild, self-limited diarrhoea that resolves when the antibiotic is discontinued. 1, 2, 5

Clostridium difficile infection (CDI): Clarithromycin disrupts normal bowel microbiota, creating a niche for C. difficile overgrowth. 6 This is a serious complication that can occur even with long-term, low-dose therapy (as demonstrated in a case of CDI after 20 weeks of low-dose clarithromycin). 7 The FDA label specifically warns that watery and bloody stools with or without stomach cramps and fever can develop even 2 or more months after the last dose. 2

Risk Factors and High-Risk Populations

Patients at increased risk for clarithromycin-associated diarrhoea include:

• Elderly patients with low body weight: May require dose reduction to 250-500 mg/day to minimize gastrointestinal toxicity 8
• Patients with pre-existing gastrointestinal disorders: Higher baseline risk for developing diarrhoea 1
• Long-term users: Extended therapy (weeks to months) increases risk of both direct GI effects and CDI 7
• Higher doses: Doses >1000 mg/day are poorly tolerated and should be avoided 8

Clinical Management Algorithm

For mild diarrhoea (3-4 loose stools/day without systemic symptoms):

• Continue clarithromycin if clinically necessary, as this typically does not require discontinuation 6
• Counsel patients that this is expected and usually self-limited 1
• Consider switching to modified-release formulation if available 4

For moderate-severe diarrhoea or any bloody/watery diarrhoea:

• Immediately test for C. difficile toxin 2
• Discontinue clarithromycin pending results 6
• Do not attribute to "simple side effect" without excluding CDI, especially in children on long-term therapy 7

For patients requiring long-term macrolide therapy:

• The British Thoracic Society guidelines note that gastrointestinal side effects are slightly more common with macrolides but typically do not lead to treatment cessation 6
• Warn patients at initiation about the possibility of developing these effects 6
• Consider monitoring for antimicrobial resistance and using treatment breaks when clinical goals are achieved 6

Important Caveats

Do not dismiss persistent diarrhoea as a benign side effect: The case literature demonstrates that community-acquired CDI can be misdiagnosed as a simple medication side effect, leading to delayed diagnosis and unnecessary antibiotic exposure. 7 Any diarrhoea persisting beyond the treatment course or worsening in severity warrants C. difficile testing. 6, 2

Comparative context: While clarithromycin causes diarrhoea, the incidence is comparable to or less than other beta-lactams and macrolides used for similar indications. 3 Erythromycin causes gastrointestinal effects in up to 70% of patients, making clarithromycin relatively better tolerated within the macrolide class. 9