Evidence of Clinically Meaningful Drug–Drug Interaction With Concomitant Use of Colchicine and Clarithromycin

Villa‐Zapata, Lorenzo; Hansten, Philip D.; Horn, John R.; Boyce, Richard D.; Gephart, Sheila M.; Subbian, Vignesh; Romero, Andrew; Malone, Daniel C.

doi:10.1007/s40264-020-00930-7

Cited by 16 publications

(18 citation statements)

References 31 publications

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“…In a chart review of hospitalized patients treated with colchicine, among the 37 fatal cases, 17 had a CYP3A4 inhibitor drugs mentioned, including one individual with exposure to a macrolide [ 24 ]. An analysis of the FDA Adverse Event Reporting System (FAERS) found 58 reports mentioning colchicine and clarithromycin, including 13 (22%) reports of death [ 25 ]. A retrospective study reported that nine (10.2%) of the 88 patients who received clarithromycin and colchicine had expired [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Colchicine and macrolides: a cohort study of the risk of adverse outcomes associated with concomitant exposure

et al. 2022

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Colchicine is increasingly used as the number of potential indications expands. However, it also has a narrow therapeutic index that is associated with bothersome to severe side effects. When concomitantly use with medications inhibiting its metabolism, higher plasma levels will result and increase likelihood of colchicine toxicity. We conducted a cohort study using electronic health records comparing encounters with colchicine plus a macrolide and colchicine with an antibiotic non-macrolide. We assessed the relationship between the two groups using adjusted multivariate logistic regression models and the risk of rhabdomyolysis, pancytopenia, muscular weakness, heart failure, acute hepatic failure and death. 12670 patients on colchicine plus an antibiotic non-macrolide were compared to 2199 patients exposed to colchicine plus a macrolide. Patients exposed to colchicine and a macrolide were majority men ( n = 1329, 60.4%) and white ( n = 1485, 67.5%) in their late sixties (mean age in years 68.4, SD 15.6). Heart failure was more frequent in the colchicine plus a macrolide cohort ( n = 402, 18.3%) vs the colchicine non-macrolide one ( n = 1153, 9.1%) ( p < 0.0001) and also had a higher mortality rate [(85 (3.87%) vs 289 (2.28%), p < 0.0001 macrolides vs non-macrolides cohorts, respectively]. When the sample was limited to individuals exposed to either clarithromycin or erythromycin and colchicine, the adjusted OR for acute hepatic failure was 2.47 (95% CI 1.04–5.91) and 2.06 for death (95% CI 1.07–3.97). There is a significant increase in the risk of hepatic failure and mortality when colchicine is concomitantly administered with a macrolide. Colchicine should not be used concomitantly with these antibiotics or should be temporarily discontinued to avoid toxic levels of colchicine. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-022-05201-5.

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Section: Discussionmentioning

confidence: 99%

Colchicine and macrolides: a cohort study of the risk of adverse outcomes associated with concomitant exposure

et al. 2022

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“…So, we downloaded the data from the FAERS website from October 2015 to June 2021. The following reasons explain why the FAERS attracts our attention: collection of millions of spontaneous adverse events reports; public and easy access to raw data obtained in a format suitable for external researchers or consumers to look to signal detection of adverse drug events; published previous studies demonstrating great accuracy in detecting safety signals, especially for DDIs, and monitoring uncommon adverse events [20][21][22].…”

Section: Methodsmentioning

confidence: 99%

Musculoskeletal Adverse Events Associated with PCSK9 Inhibitors: Disproportionality Analysis of the FDA Adverse Event Reporting System

Ding

Chen

Yang

et al. 2022

Cardiovascular Therapeutics

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Background. Some studies suggest that potential safety issues about PCSK9 inhibitors have not been sufficiently explored in clinical trials, including musculoskeletal adverse events (MAEs). Objective. To examine the association between use of PCSK9 inhibitors with and without concurrent statins and risk of MAEs. Patients and Methods. FDA Adverse Event Reporting System (FAERS) dataset of PCSK9 inhibitors and statins from October 2015 to June 2021 was queried. The reporting odds ratio (ROR) with relevant 95% confidence interval (95% CI) was calculated as the index of disproportionality. Outcome of MAEs of different PCSK9 inhibitors regimens was also investigated. Results. 3,185 cases of PCSK9 inhibitor-associated MAEs were recorded. PCSK9 inhibitor class alone demonstrated a strong link to MAEs (ROR 5.92; 95% CI 5.70-6.15), and evolocumab was associated with more reports of MAEs than alirocumab. Concomitant use with statins leaded to an increased occurrence of MAEs (ROR 32.15 (25.55-40.46)), and the risk differed among different statins. The PCSK9 inhibitors were safer than statins in terms of hospitalization rate and death rate (15.64% vs. 36.83%; 0.72% vs. 3.53%). Conclusions. This pharmacovigilance investigation suggests that PCSK9 inhibitors are associated with MAEs. The risk significantly increases when combined with statins. Increased laboratory and clinical monitoring are required to timely diagnose and manage MAEs.

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“…These are summarized in Table 1 . Over 100 DDI cases of colchicine-related toxicity, many of them life-threatening or fatal, have been published in case reports, case series, and adverse reaction reporting systems [ 18 , 19 ]. A detailed analysis of colchicine DDI cases published in the medical literature is provided in the online Supplemental Table (see ESM).…”

Section: Colchicine Toxicitymentioning

confidence: 99%

Colchicine Drug Interaction Errors and Misunderstandings: Recommendations for Improved Evidence-Based Management

et al. 2022

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Colchicine is useful for the prevention and treatment of gout and a variety of other disorders. It is a substrate for CYP3A4 and P-glycoprotein (P-gp), and concomitant administration with CYP3A4/P-gp inhibitors can cause life-threatening drug–drug interactions (DDIs) such as pancytopenia, multiorgan failure, and cardiac arrhythmias. Colchicine can also cause myotoxicity, and coadministration with other myotoxic drugs may increase the risk of myopathy and rhabdomyolysis. Many sources of DDI information including journal publications, product labels, and online sources have errors or misleading statements regarding which drugs interact with colchicine, as well as suboptimal recommendations for managing the DDIs to minimize patient harm. Furthermore, assessment of the clinical importance of specific colchicine DDIs can vary dramatically from one source to another. In this paper we provide an evidence-based evaluation of which drugs can be expected to interact with colchicine, and which drugs have been stated to interact with colchicine but are unlikely to do so. Based on these evaluations we suggest management options for reducing the risk of potentially severe adverse outcomes from colchicine DDIs. The common recommendation to reduce the dose of colchicine when given with CYP3A4/P-gp inhibitors is likely to result in colchicine toxicity in some patients and therapeutic failure in others. A comprehensive evaluation of the almost 100 reported cases of colchicine DDIs is included in table form in the electronic supplementary material. Colchicine is a valuable drug, but improvements in the information about colchicine DDIs are needed in order to minimize the risk of serious adverse outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-022-01265-1.

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Evidence of Clinically Meaningful Drug–Drug Interaction With Concomitant Use of Colchicine and Clarithromycin

Cited by 16 publications

References 31 publications

Colchicine and macrolides: a cohort study of the risk of adverse outcomes associated with concomitant exposure

Colchicine and macrolides: a cohort study of the risk of adverse outcomes associated with concomitant exposure

Musculoskeletal Adverse Events Associated with PCSK9 Inhibitors: Disproportionality Analysis of the FDA Adverse Event Reporting System

Colchicine Drug Interaction Errors and Misunderstandings: Recommendations for Improved Evidence-Based Management

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