Topical clindamycin for acne vulgaris: analysis of gastrointestinal events

Figures & data

Table 1. Safety and antibiotic resistance of clindamycin from US prescribing information.

	Oral clindamycin (9)	Topical clindamycin (6,8)
Adverse events	C. difficile-associated diarrhea, abdominal pain, pseudomembranous colitis, esophagitis, nausea, vomiting, diarrhea; hypersensitivity reactions; skin pruritis, vaginitis, angioedema, rare instances of exfoliative dermatitis; liver function abnormalities/jaundice; transient leukopenia/eosinophilia; acute kidney injury; drug reaction with eosinophilia and systemic symptoms; polyarthritis	Dermatitis/contact dermatitis/fungal dermatitis, folliculitis, photosensitivity reaction, pruritus, headache, application site reaction/burning/pruritis/dryness; stinging; eye pain
Warnings/precautions	C. difficile-associated diarrhea; anaphylactic/severe hypersensitivity reactions; nephrotoxicity; should not be used to treat meningitis; should be reserved for serious infections where less toxic antimicrobial agents are inappropriate; use with caution in atopic patients; use with caution in patients with a history of colitis/gastrointestinal disease; test liver enzymes in patients with severe liver disease	C. difficile-associated disease; diarrhea, bloody diarrhea, colitis (may be severe/fatal), pseudomembranous colitis; skin irritation; use with caution in atopic patients
Contraindications	History of hypersensitivity to clindamycin or lincomycin	History of irritable bowel disease or antibiotic-associated colitis, including regional enteritis, pseudomembranous colitis/ulcerative colitis; history of hypersensitivity to clindamycin or lincomycin
Drug-drug-interactions	Neuromuscular blocking agents; cytochrome P450 3A4 and 3A5 inhibitors	Neuromuscular blocking agents; erythromycin-containing agents; aminoglycoside agents
Use in pregnancy	Teratogenic: should not be used in pregnancy unless clearly needed	Teratogenicity unknown: should not be used in pregnancy unless clearly needed
Antibiotic resistance	Macrolide-induced resistance to clindamycin has occurred in some isolates of macrolide-resistant bacteria; cross-resistance with lincomycin/lincosamides, macrolides and streptogramin B	Associated with the development of antimicrobial resistance in C. acnes and other bacteria (e.g., Staphylococcus aureus, Streptococcus pyogenes); cross-resistance with erythromycin

Note: C. acnes: Cutibacterium acnes; C. difficile: Clostridioides difficile; US: United States.

Table 2. Adverse drug reactions of interest from post-marketing data sources of 141,265,758 patients (1 January 1900–31 December 2022).

	Serious events	Non-serious events
GI disorders (N = 64 patients)
Abdominal^a	5	21
Anal fissure	0	1
Colitis	3	7
Constipation	1	2
Diarrhea (includes hemorrhagic)	1	37
Dyspepsia	0	2
Flatulence	0	2
Frequent bowel movements	0	1
Hematochezia	1	1
Irritable bowel syndrome	0	2
Mucous in stools	0	1
Nausea	1	5
Proctalgia	1	0
Vomiting	1	7
Total events	14	89
Infections and infestations (N = 0 patients)
Clostridial infection	0	0
Clostridial colitis	0	0
C. difficile infection	0	0
C. difficile colitis	0	0
GI bacterial infection	0	0
GI infection	0	0
Pseudomembranous colitis	0	0
Total events	0	0
General disorders (N = 0 cases)
Drug resistance	0	0
Total events	0	0

Note: C. difficile: Clostridioides difficile; GI: gastrointestinal.

^aIncludes abdominal pain, pain upper, pain lower, discomfort, and distention.

Table 3. Colitis and IBS events in patients using topical clindamycin (January 1900–December 2022).

Event	Drug	Indication	Event severity	Relation to drug	Concomitant antibiotics	Other concomitant medications
Colitis	Clindamycin/BPO	Acne	Serious	Unlikely	Clarithromycin; topical erythromycin/BPO; minocycline; topical clindamycin phosphate (2 formulations); topical sodium sulfacetamide	Topical adapalene; topical BPO
Colitis	Clindamycin/BPO	Acne	Serious	Unlikely^a	NR	NR
Colitis	Clindamycin/tretinoin	Papule	Serious	Unlikely	NR	Levothyroxine sodium; levonorgestrel/ethinyl estradiol
Colitis	Clindamycin/BPO	Cystic acne	Non-serious	Highly probable	Minocycline hydrochloride	NR
Colitis	Clindamycin/BPO	Folliculitis^b	Non-serious	Possible	NR	NR
Colitis	Clindamycin/BPO	Acne	Non-serious	Possible^a	NR	Topical tretinoin; vitamins E and B; magnesium; norethisterone acetate/ethinyl estradiol; valsartan
Colitis	Clindamycin/BPO	Acne	Non-serious	Possible	Possible oral antibiotic^c	NR
Colitis	Clindamycin/tretinoin	Acne	Non-serious	Possible	NR	NR
Colitis	Clindamycin/BPO^d	Acne	Non-serious (2 events)	Unknown (2)	NR	NR
IBS	Clindamycin/BPO	Acne	Non-serious	Unlikely	NR	Cystic fibrosis medications^c; diabetes medications^c
IBS	Clindamycin/BPO + metronidazole	Acne; infection prophylaxis	Non-serious	Unlikely	Metronidazole	NR

Note: BPO: benzoyl peroxide; IBS: irritable bowel syndrome; NR: not reported.

^aPatient had previous medical history of colitis.

^bNoted as an unapproved indication.

^cDrug(s) not specified.

^dTwo separate instances reported in the same patient.

Table 4. Acne vulgaris patients with or without IBD prescribed topical clindamycin within one year of first acne vulgaris diagnosis (1 January 2011–31 January 2019).

IBD history	Total patients	Patients prescribed topical clindamycin, n (%)
None	70,151	14,495 (20.7%)
IBD^a	515	98 (19.0%)
Crohn’s disease	301	55 (18.3%)
Ulcerative colitis	262	52 (19.8%)

Note: IBD: inflammatory bowel disease (Crohn’s or ulcerative colitis). Demographic characteristics: patients without IBD: mean age 32.7 years, 72% females, 80% White; patients with IBD: mean age 40.1 years, 67% females, 85% White.

^aSome patients had diagnoses for both Crohn’s disease and ulcerative colitis.

Table 5. Incidence of pseudomembranous colitis within 30 days of initial prescription for acne vulgaris treatment.

Treatment	Total patients	IBD history, n (%)	Pseudomembranous colitis diagnosis^a, n (%)	95% CI	Incidence^b (95% CI)
Topical monotherapy
Clindamycin	5977	66 (1.1%)	0 (0%)	0, 0.06	0 (0, 0.6)
Tretinoin	10,307	93 (0.90%)	0 (0%)	0, 0.04	0 (0, 0.4)
Topical combination
Clindamycin + tretinoin OR benzoyl peroxide	12,001	94 (0.78%)	2 (0.02%)^d	0.005, 0.06	0.2 (0.05, 0.6)
Systemic monotherapy
Clindamycin	84	1 (1.2%)	0 (0%)	0, 4.4^c	0 (0, 44)^c
Systemic + topical
Clindamycin + clindamycin	34	0 (0%)	1 (2.9%)^d	0.5, 14.9^c	29 (5, 149)^c
Clindamycin + tretinoin	19	0 (0%)	0 (0%)	0, 16.8^c	0 (0, 168)^c

Note: CI: confidence interval; IBD: inflammatory bowel disease (Crohn’s or ulcerative colitis). Patient demographic characteristics: range: mean age 25–33 years, 65%–78% females, 70%–77% White.

^aWithin the past 30 days.

^bPer 1000 patients.

^cEstimates based on small sample sizes are imprecise and should be interpreted with caution.

^dNo history of IBD.

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Data availability statement

The data that support the findings of this study are available from the corresponding author, GH, upon reasonable request.