Long-term clinical safety of clindamycin and rifampicin combination for the treatment of hidradenitis suppurativa. A Critically Appraised Topic

Br J Dermatol. 2019 Apr;180(4):749-755. doi: 10.1111/bjd.17265. Epub 2018 Nov 25.

Abstract

Clinical question/scenario: Can therapy with clindamycin and rifampicin be safely continued long term beyond the recommended 10-week course?

Background: Clindamycin and rifampicin are used in combination to treat hidradenitis suppurativa (HS). There is no data on the efficacy and safety of clindamycin/rifampicin combination therapy for HS beyond 10 weeks.

Methods: We identified the following major concerns that still lack a proper evidenced-based analysis: for rifampicin, drug-induced liver injury, interstitial nephritis, drug interaction and hepatic p450 3A4 enzyme induction; for clindamycin, the concern was community-acquired Clostridium difficile infection (CA-CDI); and experience with long-term treatment. Data sources were used as appropriate to answer the question. Systematic searches were used to assess the risk of CA-CDI and experience with long-term treatment with clindamycin.

Results/identified evidence: The risk for rifampicin-induced liver injury is highest in the first 6 weeks of treatment, whereas interstitial nephritis is primarily observed during intermittent treatment. Enzyme induction due to rifampicin is usually complete after about 2 weeks of treatment and reduces clindamycin blood levels by about 90%. Three meta-analyses identified antibiotic use as a risk factor for CA-CDI. Two of them assigned the highest risk to clindamycin. None of them stratified by length of treatment. There is extensive experience with rifampicin, primarily for the treatment of tuberculosis. Long-term experience with clindamycin is limited.

Discussion and recommendation for clinical care: The analysed risks associated with a combination of clindamycin and rifampicin for hidradenitis suppurative cluster within the first 10 weeks. Treatment can be continued beyond 10 weeks, if clinically necessary.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / pharmacokinetics
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Chemical and Drug Induced Liver Injury / etiology
  • Clindamycin / administration & dosage
  • Clindamycin / adverse effects*
  • Clindamycin / pharmacokinetics
  • Cytochrome P-450 CYP3A / metabolism
  • Cytochrome P-450 CYP3A Inducers / administration & dosage
  • Cytochrome P-450 CYP3A Inducers / adverse effects*
  • Cytochrome P-450 CYP3A Inducers / pharmacokinetics
  • Drug Interactions
  • Drug Therapy, Combination / adverse effects
  • Drug Therapy, Combination / methods
  • Enterocolitis, Pseudomembranous / chemically induced
  • Enterocolitis, Pseudomembranous / epidemiology
  • Enterocolitis, Pseudomembranous / microbiology
  • Hidradenitis Suppurativa / drug therapy*
  • Humans
  • Meta-Analysis as Topic
  • Nephritis, Interstitial / chemically induced
  • Nephritis, Interstitial / epidemiology
  • Rifampin / administration & dosage
  • Rifampin / adverse effects*
  • Rifampin / pharmacokinetics
  • Risk Assessment
  • Systematic Reviews as Topic
  • Time Factors

Substances

  • Anti-Bacterial Agents
  • Cytochrome P-450 CYP3A Inducers
  • Clindamycin
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Rifampin