What is the renal dosing for colchicine in hemodialysis patients being treated for pericarditis?

Comment by InpharmD Researcher

There are no recommended doses for colchicine for pericarditis in ESRD patients on dialysis, and European guidelines contraindicate colchicine in patients with ESRD. The dose for gout prophylaxis in patients undergoing dialysis is 0.3 mg twice weekly with close monitoring, while treatment in these patients is 0.6 mg x1 dose not to be repeated within two weeks.

Background

A 2019 expert analysis discusses randomized clinical trials which evaluated the use of colchicine in acute pericarditis and recurrent pericarditis. Of the available studies, none evaluated the safety or efficacy of colchicine specifically in a population of patients with renal impairment or end-stage renal disease. Additionally, the clinical trials did not analyze renal-specific baseline characteristics; therefore, it is unknown whether patients with end-stage renal disease were included. [1], [2], [3], [4], [5], [6]

A brief letter to the editor reports a case of ‘refractory uraemic pericarditis’ who ultimately responded to colchicine. A 48-year-old female with end-stage renal disease (ESRD) due to autosomal dominant polycystic kidney disease manifested tachycardia and deep heart tones without fever, dyspnoea, thoracic pain, or cough. The imaging revealed a large amount of pericardial effusion (anterior wall, 9 mm; posterior wall, 17 mm), diastolic dysfunction, and hypertrophy of the left ventricle, and the ejection fraction remained within a satisfactory range (65%). Despite intensive hemodialysis sessions (e.g., daily 3-hour hemodialysis sessions), pericardial effusion persisted and progressed, while remaining stable on ejection fraction. In addition to continued daily hemodialysis, methylprednisolone at a dose of 40 mg/day was added which resulted in a moderate reduction of the effusion a month later. Nonetheless, while the patient remained hemodynamically stable, pericardial effusion has progressed further despite another new course of steroids (1 mg/kg). Finally, colchicine, 2 mg per day for 5 weeks, followed by 1 mg and then 0.5 mg per day, for a total of 18 months was given. Steroids were gradually tapered and finally stopped after 6 weeks. Seven weeks after the initiation of colchicine, the pericardial effusion was diminished (anterior wall, 13.5 mm; posterior wall, 15 mm) and further reduced at 4 months (anterior wall, 7.6 mm; posterior wall, 9.7 mm). Approximately 6 months later, the remaining effusion did not exceed 5 to 6 mm, and the patient remained free of pericarditis 36 months later. This is a rare case of resistant pericarditis in which colchicine was utilized after the failure of intensive dialysis and steroids administered for an adequate time. [7]

A 2017 review states colchicine should generally be avoided in patients with advanced renal impairment. Colchicine is not cleared by dialysis and needs to be renally dose-adjusted during dialysis. It should only be used for short-term treatment. In the European Society of Cardiology guidelines on pericarditis, colchicine is contraindicated in end-stage renal disease (ESRD) patients; however, clinically used in small doses for a duration of up to 3 months. [8]

There is a general reluctance to use colchicine in renal impairment, even in conditions with relatively established indications. Some authors recommend complete avoidance of colchicine in patients with a creatine clearance less than 10 mL/min and patients undergoing hemodialysis but this is not based on firm evidence. Based on one study, the authors of a 2017 review state colchicine can be used safely in patients receiving hemodialysis when started on low doses and under close clinical surveillance. [9]

References:

[1] American College of Cardiology (ACC). The Use of Colchicine in Pericardial DIseases. Published December 5, 2019. Accessed June 9, 2022. https://www.acc.org/latest-in-cardiology/articles/2019/12/04/08/22/the-use-of-colchicine-in-pericardial-diseases
[2] Imazio M, Bobbio M, Cecchi E, et al. Colchicine in addition to conventional therapy for acute pericarditis: results of the COlchicine for acute PEricarditis (COPE) trial. Circulation. 2005;112(13):2012-2016. doi:10.1161/CIRCULATIONAHA.105.542738
[3] Imazio M, Brucato A, Cemin R, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013;369(16):1522-1528. doi:10.1056/NEJMoa1208536
[4] Imazio M, Bobbio M, Cecchi E, et al. Colchicine as first-choice therapy for recurrent pericarditis: results of the CORE (COlchicine for REcurrent pericarditis) trial. Arch Intern Med. 2005;165(17):1987-1991. doi:10.1001/archinte.165.17.1987
[5] Imazio M, Brucato A, Cemin R, et al. Colchicine for recurrent pericarditis (CORP): a randomized trial. Ann Intern Med. 2011;155(7):409-414. doi:10.7326/0003-4819-155-7-201110040-00359
[6] Imazio M, Belli R, Brucato A, et al. Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial. Lancet. 2014;383(9936):2232-2237. doi:10.1016/S0140-6736(13)62709-9
[7] Spaia S, Patsalas S, Agelou A, et al. Managing refractory uraemic pericarditis with colchicine. Nephrol Dial Transplant. 2004;19(9):2422-2423. doi:10.1093/ndt/gfh407
[8] Rehman KA, Betancor J, Xu B, et al. Uremic pericarditis, pericardial effusion, and constrictive pericarditis in end-stage renal disease: Insights and pathophysiology. Clin Cardiol. 2017;40(10):839-846.
[9] Solak Y, Siriopol D, Yildiz A, et al. Colchicine in Renal Medicine: New Virtues of an Ancient Friend. Blood Purif. 2017;43(1-3):125-135.

Relevant Prescribing Information

RENAL IMPAIRMENT:
Colchicine is significantly excreted in urine in healthy subjects. Clearance of colchicine is decreased in patients with impaired renal function. Total body clearance of colchicine was reduced by 75% in patients with end-stage renal disease undergoing dialysis.

CONTRAINDICATION:
Patients with renal or hepatic impairment should not be given colchicine, USP in conjunction with P-gp or strong CYP3A4 inhibitors.
In these patients, life-threatening and fatal colchicine, USP toxicity has been reported with colchicine, USP taken in therapeutic doses.

USE IN SPECIFIC POPULATION:
For patients undergoing dialysis, the total recommended dose for prophylaxis of gout flares should be 0.3 mg given twice a week with close monitoring. For treatment of gout flares, the total recommended dose should be reduced to 0.6 mg (one tablet) x 1 dose and the treatment course should not be repeated more than once every two weeks. For Familial Mediterranean fever (FMF), the starting dose should be 0.3 mg/day and dosing can be increased with close monitoring. [10]

References:

[10] Colcrys (colchicine). Prescribing Information. Takeda Pharmaceuticals America, Inc.; 2021.

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

What is the renal dosing for colchicine in hemodialysis patients being treated for pericarditis?

Level of evidence

D - Case reports or unreliable data  Read more→



Please see Table 1 for your response.


 

The case ∣ Multiple-organ failure in a dialysis patient with pericarditis

Design

Case report

Case Presentation

A 61-year-old man was admitted to the intensive care unit for hypotension and confusion. He had a history of kidney transplantation (24 years) and was on hemodialysis (started 2 months) prior to admission due to chronic allograft nephropathy. Medications included cyclosporine, prednisolone, and rosuvastatin.

The patient had been on colchicine 1 mg every other day for 7 days, but suddenly developed diarrhea, confusion, and hypotension. Multiple-organ failure soon developed, with leucopenia, acute liver failure, and rhabdomyolysis. Vasopressors, mechanical ventilation, and continuous venovenous hemofiltration were initiated.

The patient died 36 hours after admission from refractory shock. Postmortem examination revealed numerous mitotic arrests in the esophagus, small bowel, and bone marrow, a characteristic feature of colchicine poisoning.

Study Author Conclusion

Colchicine poisoning presents in three successive stages: initial gastrointestinal symptoms (day 1), followed by multiple-organ failure, associated with bone marrow suppression and myopathy (days 2–7), and potentially complete recovery within a few weeks.

Patients with renal failure and/or medications interfering with colchicine metabolism, such as potent inhibitors of P-glycoprotein 1 and CYP3A4 (cyclosporin in the present case), are at very high risk of poisoning.

 

References:

Cambier JF, Castanares-Zapatero D, Jacquet L, et al. The case ∣ Multiple-organ failure in a dialysis patient with pericarditis. Kidney Int. 2011;80(7):787-8.