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Macrolide antibiotics have been widely used over the past several decades to treat many illnesses caused by infectious organisms, such as strep throat, some types of pneumonia and chlamydia.
Erythromycin (ERYTHROCIN), the first macrolide, was discovered more than 50 years ago, followed much later by clarithromycin (BIAXIN) and, most recently, azithromycin (ZITHROMAX). All three macrolides have similar antibacterial effects, though one may be preferred over another in certain...
Macrolide antibiotics have been widely used over the past several decades to treat many illnesses caused by infectious organisms, such as strep throat, some types of pneumonia and chlamydia.
Erythromycin (ERYTHROCIN), the first macrolide, was discovered more than 50 years ago, followed much later by clarithromycin (BIAXIN) and, most recently, azithromycin (ZITHROMAX). All three macrolides have similar antibacterial effects, though one may be preferred over another in certain situations. However, two members of this class, erythromycin and clarithromycin, are involved in a larger variety of drug interactions than most other drug classes (see table below).
Why do these two macrolide antibiotics have so many drug interactions?
Both erythromycin and clarithromycin inhibit the most important enzyme for metabolizing other medications: CYP3A4. This enzyme metabolizes the majority of the medications that we take today.
Consequently, when a person is taking several medications, there is a good chance that erythromycin or clarithromycin would interact with one or more of the drugs he or she is taking. When erythromycin and clarithromycin inhibit the actions of the CYP3A4 enzyme, more of the drugs that would have been flushed out of the body by this enzyme stay in the bloodstream. This can result in drug toxicity due to the increased levels of these other drugs.
Another type of adverse interaction involving these macrolide drugs concerns other drugs that can speed up or slow down the body’s elimination of these antibiotics, making making them either less effective or toxic. Rifabutin (MYCOBUTIN) and rifampin (RIFADIN, RIMACTANE), for example, cause the macrolides to be eliminated too rapidly (thus causing lower blood levels), while ritonavir (KALETRA, NORVIR), causes them to be eliminated too slowly (thus higher blood levels).
An additional reason for the high risk of drug interactions with erythromycin and clarithromycin is their ability to inhibit another molecule called P-glycoprotein, a substance present in the intestine that prevents the absorption of foreign chemicals into the body. Of course, the body considers medications foreign substances, and P-glycoprotein pushes many medications back into the intestine to be eliminated in the stool. When a person takes erythromycin or clarithromycin, less medication is flushed away in the stool and more is absorbed into the body through the intestines. The result can be too much of the drug in the patient’s body.
How do the three macrolides differ in their drug interactions?
Azithromycin has very few drug interactions compared to erythromycin or clarithromycin. This is because azithromycin does not appear to inhibit CYP3A4 or P-glycoprotein.
How much do the drugs cost?
The following prices are based on 10 days of therapy (five for azithromycin). Of the three drugs, erythromycin is the least expensive, costing $19.20 for a course of therapy, according to data recently published in the Medical Letter. Generic clarithromycin costs $70.40 ($107 for brand name BIAXIN) for a course of therapy and generic azithromycin costs $39.06 ($55.02 for brand name ZITHROMAX).
As previously mentioned, azithromycin is least likely to react with other medications. For that reason, azithromycin is preferable for patients using any interacting drugs. However, patients who are not using any of the listed interacting drugs can use inexpensive erythromycin.
What You Can Do
Patients who are taking one of the drugs that interacts with erythromycin or clarithromycin listed in the accompanying table may be able to avoid the interaction by using azithromycin instead. Patients prescribed azithromycin should ask their doctor and/or pharmacist to give them the generic version instead of the more expensive Pfizer ZITHROMAX (also known as Z-PAC).
Drug Interactions with Clarithromycin and Erythromycin
The table lists the most important drug interactions for erythromycin and clarithromycin, but not all possible interactions of these macrolides. It is important, therefore, for patients to consult with their physician or pharmacist about drug interactions any time they take erythromycin or clarithromycin along with other medications.
| Drugs | Potential Effect of Interaction |
|---|---|
| Alfentanil (ALFENTA) | Increased risk of alfentanil toxicity, such as excessive sedation and respiratory depression |
| Alfuzosin (UROXATRAL)b | Increased risk of alfuzosin toxicity, such as dizziness and hypotension |
| Alprazolam (XANAX)c | Increased risk of excessive alprazolam-induced sedation |
| Atorvastatin (LIPITOR) | Increased risk of atorvastatin-induced muscle damage; symptoms include muscle pain, muscle weakness and dark urine |
| Buspirone (BUSPAR) | Increased risk of excessive buspirone-induced sedation |
| Carbamazepine(TEGRETOL) | Avoid combination if possible; frequent carbamazepine toxicity, such as nausea, vomiting, dizziness, headache and visual problems |
| Cilostazol (PLETAL) | Increased risk of cilostazol toxicity, such as headache, diarrhea and vasodilation |
| Clonazepam (KLONOPIN) | Increased risk of excessive clonazepam-induced sedation |
| Clozapine (CLOZARIL)e | Possible increased risk of clozapine toxicity; risk of clozapine seizures may be increased, but based on limited data |
| Colchicine | Dangerous combination; avoid concurrent use; severe colchicine toxicity may occur with decreased white blood cells |
| Conivaptan (VAPRISOL) | Avoid combination if possible; increased risk of conivaptan toxicity |
| Cyclosporine (NEORAL) | Increased risk of cyclosporine toxicity, which can result in kidney damage |
| Digoxin | Increased risk of digoxin toxicity, such as nausea, lethargy, visual changes and disorientation |
| Diltiazem (CARDIZEM) | Avoid combination if possible; increased risk of heart arrhythmias |
| Disopyramide (NORPACE) | Avoid combination if possible; increased risk of disopyramide toxicity, such as heart arrhythmias or hypoglycemia |
| Docetaxel (TAXOTERE) |
Possible increased risk of docetaxel toxicity, such as reduced white blood cells or numbness and tingling in extremities |
| Eletriptan (RELPAX)b | Increased risk of eletriptan toxicity such as dizziness, nausea and excessive vasoconstriction |
| Ergotamine | Avoid combination if possible; increased ergotamine toxicity such as reduced blood flow to extremities (cold, pain, tenderness, bluish color) |
| Felodipine (PLENDIL) | Increased risk of felodipine toxicity, such as low blood pressure and headache |
| Lovastatin (MEVACOR) | Increased risk of lovastatin-induced muscle damage; symptoms include muscle pain, muscle weakness and dark urine |
| Methylprednisolone (MEDROL) | Increased risk of methylprednisolone toxicity, such as edema (swelling), diabetes, hypertension, etc. |
| Midazolam (VERSED) | Increased risk of midazolam toxicity, such as excessive sedation; risk higher with oral midazolam |
| Paclitaxel (TAXOL) | Increased risk of paclitaxel toxicity, such as inflammation of the mucous membranes (e.g., in the mouth) and reduced white blood cells |
| Pimozide (ORAP) | Avoid concurrent use; increased risk of heart arrhythmias |
| Quetiapine (SEROQUEL) | Increased risk of quetiapine toxicity, such as dizziness, sedation, dry mouth and low blood pressure |
| Quinidine | Increased risk of quinidine toxicity; may need to monitor electrocardiogram |
| Ranolazine (RANEXA) | Increased risk of ranolazine toxicity, such as nausea, headache and dizziness |
| Rifabutin (MYCOBUTIN) | Avoid concurrent use; increased risk of rifabutin toxicity, such as eye problems, muscle damage and reduced white blood cells; also macrolides blood levels may be decreased |
| Rifampin (RIFADIN, RIMACTANE) | Avoid combination if possible; marked decrease in blood levels of macrolides likely to reduce antibiotic effect |
| Ritonavir (KALETRA, NORVIR) | Blood levels of both drugs may increase, resulting in ritonavir toxicity and/or macrolide toxicity |
| Sildenafil (VIAGRA) | Increased risk of sildenafil toxicity, such as flushing, headache or visual problems |
| Simvastatin (ZOCOR) | Increased risk of simvastatin-induced muscle damage; symptoms include muscle pain, muscle weakness and dark urine |
| Sirolimus (RAPAMUNE) | Increased risk of sirolimus toxicity, which can result in kidney damage |
| Tacrolimus (PROGRAF) | Increased risk of tacrolimus toxicity, which can result in kidney damage |
| Tadalafil (CIALIS)d | Increased risk of tadalafil toxicity, such as flushing, headache or visual problems |
| Tamoxifen (NOLVADEX) | Possible increased risk of tamoxifen toxicity |
| Theophylline | Increased risk of theophylline toxicity, such as nausea, diarrhea, restlessness and irritability |
| Tolterodine (DETROL) | Increased risk of tolterodine toxicity in some patients; symptoms may include dry mouth, blurred vision, urinary retention and constipation |
| Triazolam (HALCION)f | Increased risk of triazolam toxicity, such as excessive sedation |
| Vardenafil (LEVITRA)d | Increased risk of vardenafil toxicity, such as flushing, headache or visual problems |
| Verapamil (CALAN) | Avoid combination if possible due to increased risk of heart arrhythmias |
| Vinblastine (VELBAN) | Increased risk of vinblastine toxicity, such as reduced white blood cells |
| Vincristine (ONCOVIN) | Increased risk of vincristine toxicity, such as numbness and tingling in extremities and severe constipation |
| Warfarin (COUMADIN) | Possible increased warfarin effect with increased risk of bleeding in some patients; in most people warfarin is only slightly affected |
| Zafirlukast (ACCOLATE)f | Possible decreased zafirlukast effect |
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Legend a. Interactions based on isolated case reports or interactions that are otherwise poorly documented are not included in the table. b. Do Not Use until 2010 in Worst Pills, Best Pills c. Do Not Use (except for panic disorder) in Worst Pills, Best Pills d. Do Not Use until 2011 in Worst Pills, Best Pills e. Last Choice drug in Worst Pills, Best Pills f. Do Not Use in Worst Pills, Best Pills |
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