What are the adverse effects of clindamycin?

Side Effects of Clindamycin

Clindamycin's most serious adverse effect is Clostridioides difficile-associated diarrhea and pseudomembranous colitis, which can occur during or after treatment and may be fatal; gastrointestinal symptoms occur in approximately 20-30% of patients, with diarrhea in 13.5% and colitis in 1.9-2.5%. 1, 2

Gastrointestinal Adverse Effects

The most clinically significant category of clindamycin toxicity involves the gastrointestinal system:

• Clostridioides difficile colitis is the boxed warning adverse effect, with onset possible during or weeks after discontinuation of therapy 1
• Diarrhea occurs in 13.5-29.8% of patients depending on route and population studied 2, 3
• Pseudomembranous colitis develops in 1.9-2.5% of patients 2, 3
• Abdominal pain, nausea, vomiting are common gastrointestinal complaints 1
• Esophagitis and esophageal ulceration have been reported 1
• Unpleasant or metallic taste occurs after oral administration 1

Risk factors for increased diarrhea incidence include older age, parenteral administration, serious underlying illness, and abdominal/pelvic sepsis 2, 3. Notably, higher total dosage and concurrent aminoglycoside use did not increase diarrhea risk in one study 2.

C. difficile infection is more common after parenteral versus oral clindamycin exposure 4.

Hypersensitivity and Dermatologic Reactions

Skin reactions are the most frequently reported non-gastrointestinal adverse effects:

• Generalized morbilliform (maculopapular) rashes are the most common hypersensitivity manifestation 1
• Vesiculobullous rashes and urticaria occur during therapy 1
• Severe cutaneous adverse reactions (SCARs) including toxic epidermal necrolysis (some fatal), Stevens-Johnson syndrome-like presentations, and acute generalized exanthematous pustulosis (AGEP) have been documented 1
• Pruritus, angioedema, and rare exfoliative dermatitis are reported 1
• Anaphylactic shock and anaphylactic reactions can occur, though true incidence is very low at approximately 1 in 500,000 exposures 1, 4

The actual incidence of clindamycin hypersensitivity is much lower than historically reported, with adverse drug reactions occurring in less than 1% of administrations (0.47% in one tertiary care study) 5. Population-based data shows only 1 in 817,232 oral and 1 in 215,880 parenteral clindamycin exposures resulted in anaphylaxis 4.

Topical Clindamycin Adverse Effects

For topical formulations used in acne treatment:

• Erythema, peeling, dryness, burning are the most common local reactions 6
• Anaphylaxis remains a theoretical risk even with topical use 6
• Scaling, itching, stinging, nasopharyngitis occur with combination clindamycin-tretinoin products 6

Topical clindamycin should not be used with erythromycin-containing products due to antagonistic interactions 6, 7.

Hematologic and Hepatic Effects

• Transient neutropenia (leukopenia) and eosinophilia have been reported 1
• Agranulocytosis and thrombocytopenia cases exist, though direct causation is unclear 1
• Jaundice and abnormal liver function tests can occur during therapy 1

Other Serious Adverse Effects

• Acute kidney injury has been documented 1
• Drug reaction with eosinophilia and systemic symptoms (DRESS) cases reported 1
• Polyarthritis has been associated with clindamycin use 1

Special Populations and Contraindications

Absolute contraindications include:

• History of hypersensitivity to clindamycin or lincomycin 7, 1
• Regional enteritis, ulcerative colitis, or history of antibiotic-associated colitis 6, 8

For pregnant patients, clindamycin is Pregnancy Category B and can be used when indicated 7. Safety has not been established in children under 12 years for topical formulations 6, 7.

Critical Clinical Pitfalls

Avoid clindamycin monotherapy for extended periods in acne treatment, as this promotes antibiotic resistance; combination with benzoyl peroxide is strongly preferred 7, 8. Do not combine with neuromuscular blocking agents 6. Promptly discontinue if diarrhea develops and provide fluid support, as gastrointestinal effects are usually self-limited with early cessation 2.