November 27, 2013

DynaMed EBM Journal Volume 8, Issue 48

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Physicians: .25 AMA PRA Category ICreditsTM

Family Physicians: .25 Prescribed credits

Nurse Practitioners: .25 Contact hours

Release Date: November 27, 2013

Expiration Date: November 27, 2014

Estimated Completion Time: 15 minutes

There is no fee for this activity.

To Receive Credit

In order to receive your certificate of participation, you should read the information about this activity, including the disclosure statements, review the entire activity, take the post-test, and complete the evaluation form. You may then follow the directions to print your certificate of participation. To begin, click the CME icon at the end of the article.

Program Overview

Learning Objectives

Upon successful completion of this educational program, the reader should be able to:
1. Discuss the significance of this article as it relates to your clinical practice.
2. Be able to apply this knowledge to your patient's diagnosis, treatment and management.

Faculty Information

Alan Ehrlich, MD - Assistant Clinical Professor in Family Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; Senior Deputy Editor, DynaMed, Ipswich, Massachusetts, USA

Michael Fleming, MD, FAAFP - Assistant Clinical Professor of Family Medicine and Comprehensive Care, LSU Health Science Center School of Medicine, Shreveport, Louisiana, USA; Assistant Clinical Professor of Family Medicine, Department of Family and Community Medicine, Tulane University Medical School, New Orleans, Louisiana, USA; Chief Medical Officer, Amedisys, Inc. & Antidote Education Company


Dr. Ehrlich, Dr. Fleming, DynaMed Editorial Team members, and the staff of Antidote Education Company have disclosed that they have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity.

No commercial support has been received for this activity.

Accreditation Statements

ACCME: This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Antidote EducationCompany and EBSCO Publishing. Antidote is accredited by the ACCME to provide continuing medical education for physicians. Antidote Education Company designates this enduring activity for a maximum of 0.25 AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

AAFP: Enduring Material activity, DynaMed EBM Focus, has been reviewed and is acceptable for up to 13 Prescribed credits by the American Academy of Family Physicians. AAFP certification begins March 7, 2012. Term of approval is for one year from this date with the option of yearly renewal. Each EBM Focus is worth .25 Prescribed credits. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AANP: This program is approved for 0.25 contact hour of continuing education by the American Academy of Nurse Practitioners.

Program ID: 1304159D


Last week 517 journal articles were evaluated via DynaMed's Systematic Literature Surveillance and summaries of 166 articles were added to DynaMed content.

Based on criteria for selecting "articles most likely to change clinical practice," one article was selected by the DynaMed Editorial Team.

Clarithromycin Might Increase All-Cause Mortality and Hospitalization for Acute Kidney Injury Compared to Azithromycin in Older Adults Receiving Calcium Channel Blocker
Reference: JAMA 2013 Dec 18;310(23):2544 (level 2 [mid-level] evidence)

Calcium-channel blockers are metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme. The macrolide antibiotic clarithromycin is an inhibitor of CYP3A4, potentially leading to a drug-drug interaction when coprescribed with calcium channel blockers, whereas azithromycin is not. In an observational study with elderly patients, coprescription of calcium channel blockers with either clarithromycin or erythromycin (also a CYP3A4 inhibitor) was associated with increased risk of hospitalization for hypotension but azithromycin did not significantly increase risk (CMAJ 2011 Feb 22;183(3):303). Hospitalization for hypotension soon after coadministration of a CYP3A4 inhibitor and a calcium-channel blocker has also been described in several case reports. Nevertheless, clarithromycin is often prescribed to patients who are chronically on calcium-channel blockers, despite a warning that serious adverse reactions may occur (clarithromycin prescribing information). Now, a new study has assessed the risk of mortality or hospitalization for acute kidney injury or hypotension in a large cohort of older adults when either clarithromycin or azithromycin was given to patients who were already being treated with calcium channel blockers.

A total of 190,309 older adults (mean age 76 years) receiving a calcium-channel blocker plus newly prescribed clarithromycin or azithromycin were retrospectively assessed for 30 days from the date of antibiotic prescription. Approximately 40% of clarithromycin prescriptions and 38% of azithromycin prescriptions were for treatment of respiratory infections. Calcium channel blockers evaluated in the study included amlodipine (53% of patients), diltiazem (22% of patients), nifedipine (17% of patients), verapamil (4% of patients), and felodipine (4% of patients). The study excluded patients who had been discharged from the hospital in the previous 2 days, those who had been prescribed potent CYP3A4 inhibitors (such as protease inhibitors or antifungals) in the previous 30 days, and those with a history of end-stage renal disease requiring chronic dialysis. Clinical outcomes for risk of acute kidney injury and hypotension were assessed by reviewing hospital-based diagnosis codes.

Clarithromycin was associated with an increased risk of all-cause mortality compared to azithromycin (1.02% vs. 0.59%, p < 0.05), with a number needed to harm (NNH) of 232. Clarithromycin was also associated with an increased risk of hospitalization for acute kidney injury (0.44% vs. 0.22%, p < 0.05, NNH 454), and hospitalization for hypotension (0.12% vs. 0.07%, p < 0.05, NNH 2,000). The risk of acute kidney injury was significantly greater in patients receiving nifedipine (NNH 160) compared to those receiving amlodipine (NNH 663).

It is worth noting that azithromycin is not without its own concerns. In March of 2013, the FDA issued a warning that azithromycin can cause abnormal changes in the electrical activity of the heart that may lead to a potentially fatal irregular heart rhythm. Patients at particular risk for developing this condition include those with known risk factors such as existing QT interval prolongation, hypophosphatemia or hypomagnesemia, bradycardia, or use of antiarrhythmic drugs (FDA MedWatch).

For more information, see the Clarithromycin topic in DynaMed.

Earn CME Credit for reading this e-Newsletter.
For more information on this educational activity, see the CME sidebar.

DynaMed Events

If you would like to meet with a DynaMed representative at an event, please contact us at

American Society of Hematology (ASH), December 7-10, 2013
Representatives will be attending the ASH conference, held at the Ernest N. Morial Convention Center in New Orleans, Louisiana. Stop by booth 3907 to discuss peer review, mobile access, and free trial information.

Visit the ASH website to learn more about the event and for registration information.

Call for Peer Reviews

We are currently seeking subspecialty reviewers for our Patient Education Resource Center (PERC). PERC provides fact sheets and discharge instructions for patients leaving the hospital or emergency room. These hand-outs fulfill the meaningful use requirements for the Medicare & Medicare Services Incentive Programs.

Click here to speak with us about becoming a peer reviewer.

DynaMed Careers

Looking for a change? The DynaMed editorial team is expanding and looking for talented and driven individuals. Visit the links below to learn about these exciting opportunities.

Deputy Editor of Cardiology
Deputy Editor of Oncology
Medical Writer
Medical Editor
Associate Editor