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Important Drug Interactions for the Antibiotic Clarithromycin

Worst Pills, Best Pills Newsletter article April, 2020

Patients taking the commonly prescribed antibiotic clarithromycin (BIAXIN XL) should be aware that it has clinically important interactions with many other prescription medications.

Initially approved by the FDA in 1991, clarithromycin is a macrolide antibiotic,[1] a family of drugs that also includes azithromycin (ZITHROMAX) and erythromycin (E.E.S., E.E.S. 400, ERY-TAB, ERYC, ERYPED). Clarithromycin is approved for treating a variety of mild-to-moderate bacterial infections,...

Patients taking the commonly prescribed antibiotic clarithromycin (BIAXIN XL) should be aware that it has clinically important interactions with many other prescription medications.

Initially approved by the FDA in 1991, clarithromycin is a macrolide antibiotic,[1] a family of drugs that also includes azithromycin (ZITHROMAX) and erythromycin (E.E.S., E.E.S. 400, ERY-TAB, ERYC, ERYPED). Clarithromycin is approved for treating a variety of mild-to-moderate bacterial infections, including acute (suddenonset) bacterial flare-ups of chronic bronchitis in adults, community acquired pneumonia, ear infections in children, acute maxillary sinusitis, skin infections and tonsillitis. It also is used in combination with other drugs to treat peptic ulcer disease caused by Helicobacter pylori bacteria.

Clarithromycin is available only in oral forms. Depending on the infection being treated, the drug typically is prescribed at dosages ranging from 250 to 500 milligrams twice daily for seven to 14 days.

Increased risk of fatal heart rhythm abnormalities[2],[3]

Like other macrolide antibiotics, clarithromycin has been linked to an increased risk of prolongation of the QT interval in the heart rhythm. QT prolongation is a change in the electrical activity of the heart that can lead to a potentially fatal heart rhythm disturbance called torsades de pointes, which can cause cardiac arrest and sudden death.

Numerous oral drugs, when used concomitantly (at the same time) with clarithromycin, further increase the risk of QT prolongation (see Table, below, for examples). The list of such drugs includes certain medications for treating abnormal heart rhythms, Alzheimer’s disease, bacterial infections, depression, fungal infections, HIV infection and overactive bladder, among others.

In some cases, the other interacting drug itself also causes QT prolongation. In addition, some of the interacting drugs can inhibit substances in the liver called enzymes that metabolize (break down or chemically modify) clarithromycin, which can lead to increased blood levels of clarithromycin, thereby further increasing the risk of QT prolongation. For some of these interacting drugs — including alfuzosin (UROXATRAL), citalopram (CELEXA), escitalopram (LEXAPRO), fluconazole (DIFLUCAN), ketoconazole (generic only), pimozide (generic only) and saquinavir (INVIRASE) — the risk of QT prolongation and potentially fatal abnormal heart rhythms is so high that clarithromycin should not be taken concomitantly with the interacting drugs. Table 1: Examples of Oral Drugs That Increase the Risk of QT Prolongation in the Heart When Taken Concomitantly with Clarithromycin

Generic Name Brand Name(s)† Drug Class
alfuzosin* UROXATRAL Benign prostate enlargement drug
amiodarone* PACERONE Abnormal heart rhythm drug
citalopram* CELEXA Antidepressant
disopyramide* NORPACE Abnormal heart rhythm drug
donepezil** ARICEPT Alzheimer’s disease drug
efavirenz SUSTIVA Antiviral drug for HIV infection
escitalopram* LEXAPRO Antidepressant
fluconazole DIFLUCAN Antifungal drug
fluoxetine PROZAC, SARAFEM, SELFEMRA Antidepressant
gemifloxacin** FACTIVE Antibiotic
hydroxychloroquine PLAQUENIL Drug for malaria, rheumatoid arthritis and lupus erythematosus
itraconazole*** ONMEL, SPORANOX, TOLSURA Antifungal drug
ketoconazole** generic only Antifungal drug
lofexidine LUCEMYRA Opioid withdrawal syndrome drug
nelfinavir VIRACEPT Antiviral drug for HIV infection
paroxetine BRISDELLE**, PAXIL*, PEXEVA* Drug for postmenopausal hot flashes (Brisdelle); antidepressant (Paxil, Pexeva)
pimozide generic only Tourette’s syndrome drug
posaconazole NOXAFIL Antifungal drug
quetiapine* SEROQUEL Antipsychotic
ritonavir NORVIR Antiviral drug for HIV infection
saquinavir INVIRASE Antiviral drug for HIV infection
thioridazine** generic only Antipsychotic
tolterodine* DETROL Overactive bladder drug
ziprasidone** GEODON Antipsychotic

†Brand-name combination products were excluded.
*Designated as Limited Use
**Designated as Do Not Use
***Designated as Do Not Use except for serious fungal infections

Inhibition of the breakdown of other drugs[4]

Clarithromycin also can inhibit liver enzymes involved in the breakdown of many other drugs. Additionally, it can block other processes involved in the removal of certain drugs from the body. As a result, concomitant use of clarithromycin and these interacting drugs can increase the blood levels of the other drugs, potentially leading to serious drug toxicity (see Table 2, below, for examples). The list of such drugs includes certain blood-pressure-lowering calcium channel blockers, cholesterol-lowering statins and migraine headache drugs, among others. Table 2: Examples of Oral Drugs That Can Reach Toxic Levels in the Blood When Taken Concomitantly with Clarithromycin

Generic Name Brand Name(s)† Drug Class
amlodipine* KATERZIA, NORVASC Calcium channel blocker, hypertension drug
atorvastatin LIPITOR Cholesterol-lowering statin
colchicine COLCRYS, GLOPERBA, MITIGARE Gout drug
digoxin LANOXIN Drug for heart failure, atrial fibrillation
dihydroergotamine MIGRANAL Migraine headache drug
diltiazem* CARDIZEM, CARTIA XT, DILTZAC, TAZTIA XT, TIAZAC Calcium channel blocker, hypertension drug
ergotamine ERGOMAR Migraine headache drug
felodipine generic only Calcium channel blocker, hypertension drug
fentanyl* ACTIQ, FENTORA, SUBSYS Opioid analgesic
lovastatin ALTOPREV Cholesterol-lowering statin
lurasidone LATUDA Antipsychotic
nifedipine ADALAT CC*, PROCARDIA**, PROCARDIA XL* Calcium channel blocker, hypertension drug
rivaroxaban** XARELTO Anticoagulant (blood thinner)
silodosin* RAPAFLO Benign prostate enlargement drug
simvastatin*** FLOLIPID, ZOCOR Cholesterol-lowering statin
verapamil CALAN SR, VERELAN Calcium channel blocker, hypertension drug

†Brand-name combination products were excluded.
*Designated as Limited Use
**Designated as Do Not Use
***The 80-milligram dose of simvastatin is designated as Do Not Use.



For example, concomitant use of clarithromycin and the gout drug colchicine (COLCRYS, GLOPERBA, MITIGARE) can increase blood levels of colchicine by more than threefold, which may result in fatal colchicine toxicity. Therefore, concomitant use of these two drugs should be avoided.

Likewise, clarithromycin can interfere with the breakdown of several cholesterol-lowering statins, including simvastatin (FLOLIPID, ZOCOR) and atorvastatin (LIPITOR). This interaction increases the risk of statin-induced myopathy (muscle damage). In severe cases, this condition can progress to rhabdomyolysis, a life-threatening, muscle-destroying condition that can lead to sudden kidney failure and death.

Other important drug interactions[5]

Concomitant use of clarithromycin and the anticoagulant (blood thinner) warfarin (COUMADIN, JANTOVEN) can increase the anticoagulant effects of warfarin. This can increase the risk of bleeding complications. Ideally, concomitant use of these two drugs should be avoided. If such use is unavoidable, more frequent monitoring of warfarin levels should occur, especially during initiation and discontinuation of clarithromycin.

What You Can Do

If you need treatment with clarithromycin, review all your other medications with your doctor to assess for potentially significant drug interactions. If you are taking certain medications that interact with clarithromycin, you may need a lower dose of the interacting drug, or your doctor may advise you to stop the interacting drug. Be aware that many other drugs not listed in this article also may have dangerous interactions with clarithromycin.
 



References

[1] Sandoz Inc. Label: clarithromycin. October 2019. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b98b02bb-2609-49a0-b29f-e5911aa0cbc1&type=display. Accessed February 4, 2020.

[2] Ibid.

[3] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “clarithromycin.” Accessed February 4, 2020.

[4] Ibid.

[5] Ibid.