Calcium Channel Blockers Make Dangerous Combination with Most Macrolide Antibiotics

Calcium Channel Blockers Make Dangerous Combination with Most Macrolide Antibiotics

(Dr. Guru Prasad Mohanta, Professor, Department of Pharmacy, Annamalai University, Annamalai Nagar – 608 002, Tamil Nadu, E. mail: gpmohanta@hotmail.com)

Calcium channel blockers like amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nisoldipine and verapamil are primarily used to treat high blood pressure and chest pain caused by coronary artery disease. They are metabolized by cytochrome p4503A4 (CYP3A4) in the liver. The inhibition of the metabolizing enzyme can cause accumulation of dangerously high levels of these high blood pressure treating medicines.

The macrolide group of antibiotics: clarithromycin, erythromycin, azithromycin and telithromycin are used for treatment of a variety of infections in sore throat, sinusitis, acute bronchitis, and community acquired pneumonia. Clarithromycin is also part of regimen used to eradicate H. pylori infection in peptic ulcer treatment. The three macrolides: erythromycin, clarithromycin and telithromycin are known potent inhibitor of the metabolizing enzyme CYP3A4. But azithromycin is not a inhibitor of CYP3A4 thus does not show the dangerous effect associated with calcium channel blockers. The grape fruit juice is also known inhibitor of cytochrome p450 3A4. The grape fruit juice has similar effects on calcium channel blockers as clarithromycin or erythromycin.

The various well designed population based studies have reported that amlodipine, diltiazem, felodipine, nifedipine and verapamil when received along with erythromycin or clarithromycin caused hospitalization due to hypotension and acute kidney injury. This even led to deaths. The comparative study of calcium channel blockers and clarithromycin Vs calcium channel blockers and azithromycin showed an increased risk of being hospitalization with acute kidney injury in former. There is an increased absolute risk of 0.22 percent for clarithromycin treated patients and a two-fold relative increase risk.   Similarly, the studies have shown higher risks of both being hospitalised with hypotension and dying with clarithromycin treated patients.  The risk analysis puts the medicines in the following decreasing order: nifedipine, felodipine and amlodipine. Statistical significant increased risk was not observed in patients treated with diltiazem or verapamil with clarithromycin.

The calcium channel blockers and clarithromycin form a dangerous combination leading to serious adverse effects like hypotension, acute kidney injury and death. The acute kidney injury is attributed to the drop in blood pressure due to excess concentration of calcium channel blockers. This leads to decrease in blood supply to kidney. In our country, the possibility of such combination is high as medicines are freely available even without prescription and there is rampant practice of polypharmacy as well. The clinicians, clinical pharmacists and other pharmacy professionals involved in patient care should take care to avoid such combinations. While the patients are with calcium channel blockers for blood pressure treatment, macrolide antibiotics need to be avoided. If the infection demands the use of macrolide, then azithromycin is a safe choice. The patients too need to be educated not to self medicate with antibiotics in the greater public health interest and to safe-guard themselves from adverse effects of drug-drug interactions.