Side Effects of Clotrimazole
Clotrimazole is generally very well tolerated with minimal side effects, primarily limited to local reactions when used topically, though oral formulations (rarely used now) can cause significant gastrointestinal and neurological adverse effects. 1
Topical Formulations (Vaginal and Cutaneous)
Common Local Reactions
- Local burning or irritation may occur but is generally mild 2
- Cutaneous hypersensitivity reactions including rash and pruritus can develop with short courses of topical therapy, though these are rare 2
- Local irritation has necessitated withdrawal of therapy in only a few cases historically 3
- In comparative studies, only 2 out of 65 patients experienced burning sensations with topical vaginal use 4
Safety Profile
- Topical agents cause essentially no systemic side effects 2
- The medication is very well-tolerated overall with few side effects reported 1
- No adverse reactions were noted in clotrimazole-treated patients in one comparative trial of 65 women 4
Oral Clotrimazole Troches (for Oropharyngeal Candidiasis)
Gastrointestinal Effects
- Patients may experience gastrointestinal upset with oral azole treatment 2
- Nausea and abdominal pain can occur occasionally 2
- Headache is another occasional side effect 2
Hepatotoxicity Considerations
- Patients treated for >7-10 days with azoles might experience hepatotoxicity 2
- If prolonged therapy is anticipated (>21 days), periodic monitoring of liver chemistry studies should be considered 2
- Therapy with oral azoles has been associated rarely with abnormal elevations of liver enzymes 2
Historical Oral Systemic Formulations (No Longer Commonly Used)
- A high incidence of gastrointestinal disturbances and neurological reactions limited oral clotrimazole therapy for systemic infections 3
- This formulation is not currently recommended or widely available 3
Drug Interactions
Clinically important interactions can occur when oral azoles are administered with other medications, including 2:
- Astemizole
- Calcium channel antagonists
- Cisapride
- Coumadin (warfarin)
- Cyclosporin A
- Oral hypoglycemic agents
- Phenytoin
- Protease inhibitors
- Tacrolimus
- Terfenadine
- Theophylline
- Trimetrexate
- Rifampin
Clinical Caveats
- Response to therapy is typically rapid, with improvement in signs and symptoms within 48-72 hours 2
- The excellent tolerability profile makes clotrimazole a preferred first-line topical agent for candidal infections 1
- Some drug resistance is appearing among immunocompromised patients, though this relates to efficacy rather than side effects 1