A. Brucato

D.H. Spodick

Y. Adler

AIR Universita degli studi di Milano

Letter Regarding Article by Imazio et al,
“Colchicine in Addition to Conventional Therapy
for Acute Pericarditis”
To the Editor:
We congratulate Imazio et al1 for their excellent article on
colchicine in acute pericarditis. We see 2 take-home messages in
this study: first, that colchicine is useful in the first attack, and
second, that corticosteroid therapy given in the first attack favors
the recurrence of pericarditis. This concept is in line with our
recent findings that pretreatment with steroids attenuates the
efficacy of colchicine in preventing recurrent pericarditis2 and
with animal experiments showing that corticosteroids may exac-
erbate virally induced pericardial injury. Thus, the results re-
ported by Imazio et al1 and those from our multicenter study
should strongly encourage clinicians not to use corticosteroids
except in extreme, very rare cases. Although their use may be
very gratifying in the short term, it will greatly complicate the
following course. On the other hand, a first episode of pericar-
ditis is often treated with antibiotics, and coadministration of
colchicine and macrolides may induce severe side effects,3 so
this drug combination should also be avoided.
Finally, Imazio et al excluded patients with current transami-
nase values 1.5 times the upper normal limit. In our cohort of
58 patients,4 we observed 5 patients (8.6%) with abnormal liver
test results in the first attack: 3 had alanine aminotransferase
elevations ranging from 87 to 1100 U/L, and 2 had alkaline
phosphatase elevations only, of 486 and 520 U/L. These abnor-
malities disappeared with resolution of the attacks. Therefore, we
propose not to negate this potentially useful therapy in patients
with abnormal liver test results. In the real world, colchicine
should be used more and steroids much less often.
Disclosures
None.
Antonio Brucato, MD
Department of Rheumatology and Internal Medicine
Ospedale Niguarda
Milano, Italy
Yehuda Adler, MD
Cardiac Rehabilitation Institute
Sheba Medical Center
Tel-Hashomer, Israel
David H. Spodick, MD
Cardiovascular Division
University of Massachusetts Medical School
Worcester, Mass
1. Imazio M, Bobbio M, Cecchi E, Demarie D, Demichelis B, Pomari F,
Moratti M, Gaschino G, Giammaria M, Ghisio A, Belli R, Trinchero R.
Colchicine in addition to conventional therapy for acute pericarditis.
Circulation. 2005;112:2012–2016.
2. Artom G, Koren-Morag N, Spodick DH, Brucato A, Guindo J, Bayes-
de-Luna A, Brambilla G, Finkelstein Y, Granel B, Bayes-Genis A,
Schwammenthal E, Adler Y. Pretreatment with corticosteroids attenuates
the efficacy of colchicine in preventing recurrent pericarditis: a multi-
center all-case analysis. Eur Heart J. 2005;26:723–727.
3. Rollot F, Pajot O, Chauvelot-Moachon L, Nazal EM, Kelaidi C, Blanche
P. Acute colchicine intoxication during clarithromycin administration.
Ann Pharmacother. 2004;38:2074–2077.
4. Brucato A, Brambilla G, Adler Y, Spodick DH, Canesi B. Therapy of
recurrent acute pericarditis: a rheumatological solution? Clin Exp
Rheumatol. 2006;24:45–50.
Response
We thank Drs Brucato, Adler, and Spodick for their interest and
remarks on our article.1 We agree with the main take-home messages.
However, caution should be recommended in the prescription
of colchicine for acute pericarditis. At present, this use is
unlabeled. The stronger evidence comes from a single, open-
label, randomized study (the COlchicine for acute PEricarditis
[COPE] trial). More evidence supports the use of colchicine in
recurrences after failure of conventional treatment,2 but the
precise proportion of responders is not exactly known because
appropriately randomized trials are lacking.3 Nevertheless, col-
chicine was given a class IIa indication for acute pericarditis in
the European guidelines.4
Although at low doses (0.5 to 1.2 mg/d) colchicine has been
found to be safe even when given continuously over decades,2 there
are other less common (1%) possible side effects to be considered
(eg, bone marrow suppression, hepatotoxicity, and myotoxicity)
beyond the well-known gastrointestinal side effects. Moderately
increased liver enzyme values were observed in 7% of patients in
the Marburg Pericarditis Registry.5 Neuromyopathy with colchicine
can occur even during long-term administration of therapeutic low
doses. Chronic renal insufficiency leading to increased colchicine
levels appears to be the major risk factor for this disorder and other
possible negative interactions. Colchicine undergoes intensive he-
patic metabolism (CYP 3A4). Consequently, drugs (cyclosporine,
azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxy-
cycline, erythromycin, isoniazid, nicardipine, propofol, protease
inhibitors, quinidine, and verapamil) that interact with the cyto-
chrome P-450 system may interfere with colchicine, thereby in-
creasing the levels/effects of colchicine. Coadministration of colchi-
cine and macrolides may also impair colchicine elimination by
inhibition of P-glycoprotein, resulting in possible drug excess and
toxicity, particularly in the elderly and/or the renally compromised.6
At present, it seems reasonable to avoid use of the drug in
patients with hepatobiliary dysfunction, as well as those with
severe renal, hepatic, and gastrointestinal disorders and blood
dyscrasias. It is also prudent to reduce the maintenance/prophy-
lactic dose by 50% in individuals 70 years of age and in
patients with impaired renal function with glomerular filtration
rates50 mL/min. Although the safety profile of the drug seems
to be superior to that of corticosteroids and other immunosup-
pressive drugs, every patient should undergo careful monitoring
for possible side effects, including blood analyses (transami-
nases, serum creatinine, creatine kinase, and blood cell count).
In conclusion, although the findings of the COPE trial provide a
stronger evidence base for the use of colchicine in acute pericarditis,
they need to be confirmed in multicenter, possibly double-blind,
randomized trials before routine use can be recommended.
Disclosures
None.
Massimo Imazio, MD
Enrico Cecchi, MD
Daniela Demarie, MD
Brunella Demichelis, MD
Franco Pomari, MD
Mauro Moratti, MD
Gianni Gaschino, MD
Massimo Giammaria, MD
Aldo Ghisio, MD
Riccardo Belli, MD
Rita Trinchero, MD
Cardiology Department
Maria Vittoria Hospital and Amedeo di Savoia Hospital
Turin, Italy
e693
Correspondence
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Marco Bobbio, MD
Cardiology Medical School
University of Turin
Turin, Italy
1. Imazio M, Bobbio M, Cecchi E, Demarie D, Demichelis B, Pomari F,
Moratti M, Gaschino G, Giammaria M, Ghisio A, Belli R, Trinchero R.
Colchicine in addition to conventional therapy for acute pericarditis. Cir-
culation. 2005;112:2012–2016.
2. Adler Y, Finkelstein Y, Guindo J, Rodriguez de la Serna A, Shoenfeld Y,
Bayes-Genis A, Sagie A, Bayes de Luna A, Spodick DH. Colchicine
treatment for recurrent pericarditis: a decade of experience. Circulation.
1998;97:2183–2185.
3. Soler-Soler J, Sagrista-Sauleda J, Permanyer-Miralda G. Relapsing peri-
carditis. Heart. 2004;90:1364–1368.
4. Maisch B, Seferovic PM, Ristic AD, Erbel R, Rienmuller R, Adler Y,
Tomkowski WZ, Thiene G, Yacoub MH. Guidelines on the diagnosis and
management of pericardial diseases. Eur Heart J. 2004;25:587–610.
5. Maisch B. Recurrent pericarditis: mysterious or not so mysterious? Eur
Heart J. 2005;26:631–633.
6. Hung IFN, Wu AKL, Cheng VCC, Tang BSF, To KW, Yeung CK, Woo
PCY, Lau SKP, Cheung BMY, Yuen KY. Fatal interaction between
clarithromycin and colchicine in patients with renal insufficiency: a
retrospective study. Clin Infect Dis 2005;41:291–300.
e694 Correspondence
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Letter regarding article by Imazio et al, &quot;Colchicine in addition to conventional therapy for acute pericarditis&quot;

https://air.unimi.it/retrieve/handle/2434/630116/1182809/CIRCULATIONAHA.105.594481.pdf

Letter regarding article by Imazio et al, "Colchicine in addition to conventional therapy for acute pericarditis"

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AIR Universita degli studi di Milano

Letter regarding article by Imazio et al, &quot;Colchicine in addition to conventional therapy for acute pericarditis&quot;

Abstract

Similar works

Full text

Available Versions

AIR Universita degli studi di Milano

Letter regarding article by Imazio et al, "Colchicine in addition to conventional therapy for acute pericarditis"