Clarithromycin with Colchicine Interaction Details

Brand Names Associated with Clarithromycin

Brand Names Associated with Colchicine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 08, 2023

Interaction Effect

Increased colchicine exposure and an increased risk of colchicine toxicity

Interaction Summary

Colchicine is a substrate of CYP3A4 and P-gp. Concomitant use of colchicine with dual strong CYP3A4 and P-gp inhibitors is contraindicated because life-threatening and fatal colchicine toxicity has been reported in these patients with colchicine taken in therapeutic doses. Also use of a dual CYP3A4 and P-gp inhibitor with colchicine is contraindicated in patients with renal or hepatic impairment. In patients with normal renal and hepatic function, a colchicine dosage adjustment is required . For gout flare, reduce colchicine dose to 1.2 mg for 1 dose, and give the repeat dose no earlier than 3 days later. For prophylaxis of gout flare, reduce the colchicine dose from an original dose of 0.6 mg twice daily to 0.6 mg/day, or from an original dose of 0.6 mg/day to 0.3 mg/day. In patients with familial Mediterranean fever, if concomitant use of colchicine and erythromycin is required, the maximum daily colchicine dose is 1.2 mg (may be given as 0.6 mg twice daily) . Colchicine and concomitant macrolide treatment was associated with a significantly higher incidence of heart failure and mortality compared with colchicine and a non-macrolide antibiotic .

Severity

Contraindicated

Onset

Delayed

Evidence

Established

How To Manage Interaction

Concomitant use of colchicine with dual strong CYP3A4 and P-glycoprotein (P-gp) inhibitors is contraindicated because life-threatening and fatal colchicine toxicity has been reported in these patients with colchicine taken in therapeutic doses. Also, use of colchicine with a dual CYP3A4 and P-gp inhibitor, such as clarithromycin, is contraindicated in patients with renal or hepatic impairment. A colchicine dosage adjustment is required  with concurrent or recent (last 14 days) use of clarithromycin in patients with normal renal and hepatic function. For the treatment of gout flare, reduce the colchicine dose to one 0.6 mg tablet for one dose followed by 0.3 mg (half tablet) 1 hour later, with the repeat dose to be given no earlier than 3 days. For the prophylaxis of gout flare, reduce the colchicine dose from an original dose of 0.6 mg twice daily to 0.3 mg once daily or from an original dose of 0.6 mg once daily to 0.3 mg once every other day. For the treatment of familial Mediterranean fever, the maximum daily colchicine dose should be no more than 0.6 mg (may be given as 0.3 mg twice daily) .

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism of colchicine; inhibition of P-gp-mediated efflux transport of colchicine

Literature Reports

A) In a retrospective cohort study (n=2199), colchicine and concomitant macrolide treatment (including clarithromycin) was associated with a significantly higher incidence of heart failure compared with colchicine and a non-macrolide antibiotic (n=12,670), 18.3% vs 9.1%, respectively (OR, 1.06; 95% CI, 0.67 to 1.67). A significantly higher mortality rate was also observed in the colchicine plus macrolide group compared with the colchicine plus non-macrolide antibiotic group (3.87% vs 2.28%; OR, 2.06; 95% CI, 1.07 to 3.97). There were no differences in the risk of rhabdomyolysis diagnosis, pancytopenia, muscle weakness, or acute hepatic failure .

B) Concomitant use of a 0.6 mg dose of colchicine and clarithromycin 250 mg twice daily for 7 days resulted in 227.2% and 281.5% increases in colchicine Cmax and AUC, respectively, from baseline in a study of 23 patients .

C) In a retrospective study of 116 hospitalized patients, concurrent clarithromycin and colchicine administration was associated with non-significantly higher rates of mortality and pancytopenia compared with sequential therapy during the same hospital admission. Case-control comparisons were made between patients who received concomitant therapy with the 2 drugs (therapy overlap; n=88) and those who received sequential therapy (use of both medications within the same admission, n=28). In the concomitant group compared with the sequential group, there was a non-significantly higher rate of mortality (10.2% vs. 3.6%) and pancytopenia (10.2% vs 0%), but the small sample size may have contributed to the lack of statistical significance. A higher total dose of colchicine was significantly and independently associated with pancytopenia (relative risk (RR), 1.89; 95% CI, 1.23 to 2.89). Longer overlap therapy (RR, 2.16; 95% CI, 1.41 to 3.31), baseline renal impairment (RR, 9.1; 95% CI, 1.75 to 47.06) and development of pancytopenia (RR, 23.4; 95% CI, 4.48 to 122.7) were all significantly and independently associated with mortality. There was a 25-fold increase in the risk of death in patients who received concomitant therapy and developed pancytopenia .

D) In a case series of women with familial Mediterranean fever treated with colchicine (N=6), the initiation of clarithromycin for Helicobacter pylori gastric infection resulted in colchicine intoxication. The mean colchicine daily dose was 2 +/- 0.45 mg (range, 1.5 to 2.5 mg/day). Clarithromycin 500 mg twice daily with omeprazole 20 mg/day and amoxicillin 1 g twice daily was prescribed for 10 to 14 days. Symptoms of colchicine intoxication included abdominal pain, vomiting, diarrhea, general weakness, and myalgia. On admission, all patients had elevated creatinine phosphokinase and elevated liver enzymes; other lab abnormalities included hypokalemia (n=3), neutropenia (n=2), pancytopenia (n=1), and hyponatremia (n=1). Colchicine was immediately discontinued, and clarithromycin, omeprazole, and amoxicillin were discontinued in patients who had not completed the regimen. Colchicine was resumed 1 to 3 weeks after discontinuation with an initial dosage of 0.5 mg/day that was gradually increased to increased to full dose 6 to 12 weeks after reinitiation. Muscle pain was severe in most patients and required confinement to bed in a number of patients and use of a wheelchair in 1 patient. Symptoms eventually resolved in all patients, and laboratory abnormalities improved in approximately 10 days .

E) Acute colchicine toxicity occurred in a 76-year-old man after clarithromycin was added to a stable regimen of colchicine for familial Mediterranean fever. The patient had tolerated a long-term regimen of colchicine 1.5 mg daily prior to beginning a 7-day course of clarithromycin 1 g daily with amoxicillin and omeprazole to treat Helicobacter gastritis. Four days after beginning clarithromycin, the man presented with complaints of abdominal pain, nausea and vomiting, and bloody diarrhea; severe dehydration, pancytopenia, and hepatic cholestasis developed by day 8. On hospital day 13, the colchicine dose was reduced to 0.5 mg per day. He developed alopecia on day 14 but recovered without further treatment other than parenteral rehydration. Colchicine dose was restored 4 months later to pre-clarithromycin levels and tolerated thereafter .

Clarithromycin Overview

• Clarithromycin is used to treat certain bacterial infections, such as pneumonia (a lung infection), bronchitis (infection of the tubes leading to the lungs), and infections of the ears, sinuses, skin, and throat. It also is used to treat and prevent disseminated Mycobacterium avium complex (MAC) infection [a type of lung infection that often affects people with human immunodeficiency virus (HIV)]. It is used in combination with other medications to eliminate H. pylori, a bacterium that causes ulcers. Clarithromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as clarithromycin will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

Colchicine Overview

• Colchicine is used to prevent gout attacks (sudden, severe pain in one or more joints caused by abnormally high levels of a substance called uric acid in the blood) in adults. Colchicine (Colcrys) is also used to relieve the pain of gout attacks when they occur. Colchicine (Colcrys) is also used to treat familial Mediterranean fever (FMF; an inborn condition that causes episodes of fever, pain, and swelling of the stomach area, lungs, and joints) in adults and children 4 years of age and older. Colchicine is not a pain reliever and cannot be used to treat pain that is not caused by gout or FMF. Colchicine is in a class of medications called anti-gout agents. It works by stopping the natural processes that cause swelling and other symptoms of gout and FMF.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.