Date:  May 12, 2013
Title: Mac and CCBs (Macrolides and Calcium Channel Blockers)

Case Scenario: 67 year-old woman presents with a one week history of productive cough and no fever. She is a non-smoker and has no history of lung disease. Her past medical history is positive for hypertension and she is taking a calcium channel blocker. She has no allergies to medication. On exam she has no fever, oxygen saturation is 97% on room air, and has clear air entry. Xrays is reported as slight patchy infiltrate in right lower lobe possible early pneumonia.

Question:  Do macrolides cause serious hypotension in patients on CCBs?

Reference:  AJ Wright et al.  CMAJ, February 22, 2011;183(3)

  • Population: Patients 66+ years old admitted to hospital with a diagnosis of hypotension or shock (ICD-9 codes) while receiving a CCB (n=7,100) between 1994-2009. There was a almost 1 million patients who received single CCB during study period.
  • Intervention: Prescription of macrolide in the 7 days before admitted to hospital
  • Control: Each person served as there own control. Patients on CCBs were contrasted to exposure 7 days prior to admission with  7 d­day control period one month earlier.
  • Outcome: Hypotension or shock resulting in hospital admission

EBM: Case-crossover design was used in this study. These types of studies have some advantages over a randomized  longitudinal study. In crossover trials each patient serves as their own control reducing confounding influence of confounding covariates. The design is also more statistically efficient and so require fewer subjects.

“A case-control design involving only cases may be used when brief exposure causes a transient change in risk of a rare acute-onset disease.” Maclure Am J Epidemiol 1991

Results: 176 patients of the 7,100 had received a macrolide during either the risk or control intervals.

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Authors Conclusions: “In older patients receiving a calcium-channel blocker, use of erythromycin or clarithromycin was associated with an increased risk of hypotension or shock requiring admission to hospital. Preferential use of azithromycin should be considered when a macrolide antibiotic is required for patients already receiving a calcium-channel blocker.”

BEEM Comments: Calcium channel blockers (CCBs) are the ninth most commonly prescribed class of drugs in the USA with almost 90 million prescriptions in 2008. Macrolides are the most commonly prescribed class of antibiotics in the USA with over 66 million prescriptions in 2008. They both are effect the cytochrmome P450 system (specifically the isoenzyme 3A4). This raised the possibility of complications in addition to several case reports of such. This study of seniors from 1994 to 2009 identified almost one million patients who were prescribed a single CCB. During that time 7,100 patients were admitted to hospital for treatment of hypotension. There were 176 patients had also received a macrolide showing a strong association between erythromycin and clarithromycin use. No association was found with azithromycin (does not work through the same P450 system).

BEEM Bottom Line: If prescribing a macrolide antibiotic to a patient 66+ years old pick azithromycin or risk admitting them on your next shift for hypotension/shock.

Case Resolution: You diagnose the patient with community acquired pneumonia and prescribe a course of azythromycin. 

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