Cite Score:
0.73
ELSEVIER SCOPUS

Fatal Combination of Antibiotic and Calcium Channel Blocker Agents

AUTHORS

Masoud Mardani 1 , *

AUTHORS INFORMATION

1 Infectious Diseases and Tropical Medicine Research Center Shahid Beheshti University of Medical Sciences, Tehran, IR Iran

How to Cite: Mardani M. Fatal Combination of Antibiotic and Calcium Channel Blocker Agents, Arch Clin Infect Dis. 2013 ; 8(2):ee17840. doi: 10.5812/archcid.17840.

ARTICLE INFORMATION

Archives of Clinical Infectious Diseases: 8 (2); ee17840
Published Online: April 17, 2013
Article Type: Editorial
Received: February 20, 2013
Accepted: March 23, 2013
Crossmark

Crossmark

CHEKING

READ FULL TEXT

Keywords

Calcium Channel Blockers Kidney Anti-Bacterial Agents

Copyright © 2013, Infectious Diseases and Tropical Medicine Research Center. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

According to the new researches, clarithromycin prescribed for patients already taking antihypertensive calcium-channel blockers is associated with increased number of hospitalizations due to acute kidney injuries, hypotension, and death (1, 2). Clarithromycin is a cytochrome P453A4 inhibitor, which metabolizes calcium-channel blockers. Previous researches showed that the antibiotic can surge the blood calcium-channel blockers level to 500% of its normal level (1, 2). Gandhi et al. (3), from the London Health Sciences Centre and the University of Western Ontario, suggested that potentially hundreds of hospitalizations and deaths in our region may be associated with this largely preventable drug-drug interaction. This burden on the healthcare system, causing high costs on managing acute kidney injuries, might have been avoided (3).

A warning from the US Food and Drug Administration (4) states that "serious adverse reactions have been reported in patients taking clarithromycin concomitantly with CYP3A4 substrates, including hypotension with calcium-channel blockers metabolized by CYP3A4 (such as verapamil, amlodipine and diltiazem). The reasons for the continued use of the drugs, despite these warnings, still remain unclear (3). Since azithromycin is only a weak CYP34A inhibitor, the type of intensification of the calcium-channel blocker that occurs with clarithromycin is not estimated. The most common calcium-channel blocker - amlodipine - was prescribed for more than 50% of patients. In patients who take a calcium-channel blocker, the absolute risk of hospitalization for acute kidney injuries was higher, moreover, in patients taking clarithromycin this risk is greater than those taking azithromycin (0.44% vs. 0.22%; odds ratio [OR], 1.98). Patients taking clarithromycin also had a higher risk of hospitalization due to hypotension (OR, 1.60) and all-cause mortality rate (OR, 1.74). A subgroup analysis showed that dihydropyridines, particularly nifedipine, as the calcium-channel blockers, are associated with the highest risk acute kidney injury (OR, 5.33), with an absolute risk increase of 0.63%. The risk with nifedipine was followed by felodipine and amlodipine (3).

The researchers previously confirmed that there are no significant differences between clarithromycin and azithromycin regarding the rates of 30-day hospitalization rate of patients with acute kidney injuries, in the absence of other interacting medications. The use of calcium-channel blockers alone, 90 days prior to the antibiotic administration, did not affect the 30-day outcomes (3). Due to the role of kidneys in eliminating clarithromycin, the guidelines called to reduce the antibiotic dose for patients with chronic kidney disease, but the researches showed that this rarely occurs in routine practices (3). "Clarithromycin may be the top choice antibiotic in some cases, particularly in severely immunosuppressed patients, such as patients with AIDS, or in the treatment of extremely drug-resistant microbe, but in these cases, it is perfectly feasible to take the patient off the calcium-channel blockers. Drug-drug interactions are usually under-recognized by doctors, but newer electronic prescribing programs with specific interaction recognition software will significantly decrease this risk (5).

Acknowledgements

Footnotes

References

  • 1. Pai MP, Graci DM, Amsden GW. Macrolide drug interactions: an update. Ann Pharmacother. 2000; 34(4) : 495 -513 [PubMed]
  • 2. Westphal JF. Macrolide - induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycin. Br J Clin Pharmacol. 2000; 50(4) : 285 -95 [PubMed]
  • 3. Gandhi S, Fleet JL, Bailey DG, McArthur E, Wald R, Rehman F, et al. Calcium-channel blocker-clarithromycin drug interactions and acute kidney injury. JAMA. 2013; 310(23) : 2544 -53 [DOI][PubMed]
  • 4. Biaxin Filmtab (clarithromycin tablets, USP), Biaxin XL Filmtab (clarithromycin extended-release tablets), Biaxin Granules (clarithromycin for oral suspension, USP). 2013;
  • 5. Hunt WA, Perrone RD. Kidney Disease: A Guide for Living. 2011;
  • COMMENTS

    LEAVE A COMMENT HERE: