Colchicine is an old drug that is still commonly used to treat acute gout. While it has been shown to be effective in reducing pain and inflammation from gout attacks, its use can be complicated by drug interactions and safety concerns in patients with renal or hepatic impairment. The document discusses alternative treatment options like corticosteroids and interleukin inhibitors that are being studied, but notes more research is still needed. It provides revised dosing guidelines for using colchicine safely in patients with impaired kidney or liver function.

1. COLCHICINE;
AN OLD DRUG IN A NEW AGE -
IS TRADITION BESTING EVIDENCE?
IS TRADITION BESTING EVIDENCE?
IS TRADITION BESTING EVIDENCE?
An Evidence Based Review for the use of Colchicine in Acute Gout.
Reynder Hagen

2. Why Acute Gout?
• Common Ailment
• Increasing in prevalence
• 1969 = 0.5%
• 1996 = 1.7%
• Rarely occurs by itself
In Summary:
1.7% * 23 million Australians + Comorbidities
+ polypharmacy = Headache for Doctors

3. Colchicine:
A drug so old it makes the pyramids look
new
•Derived from Colchicum autumnale (aka autumn crocus)
•Used in management of acute gout + prophylactically
•First described for Rx of rheumatism by Egyptians around 1500BC
•Described in 1st century AD texts specifically for the use in Gout
•FDA approval on the 30th July 2009

4. The Case of Mr C:
PC:
• 81 yo caucasian male, Mareeba OPERA, rehab after
mechanical fall and #L NOH.
• during rehab Na+ = 133mmol/L
• 1L fluid restriction daily
• Had an acute attack of gout on L Big toe.
PmHx:
• HPTN
• CKD (eGFR = 42)
• Osteoarthritis
• Glaucoma
• Gout
• COPD
Surgical Hx:
• Bilateral inguinal hernia repair
Medications:
• Candesartan 8mg Mane
• Panadol Osteo 665mg two tablets tis
• Docusate-Senna 50mg-8mg PRN
• Indaceterol 150 mcg Nocte via Inhaler
• Oxycodone 5mg Tablets 1tablet q4h PRN
• Folic acid 5 mg weekly
• Colchicine 1.2 mg STAT followed 0.6mg 1hr later
Why is colchicine not ideal in this
patient?

5. Pharmokinetics of Colchicine:
Hepatically metabolised by:
•P-glycoprotein
•Cytochrome P450 (CYP) 3A4
Excreted:
•Predominantly through the biliary tract
•20% of the drug is excreted by the kidneys.
Contra-indications:
•Long-term regimens of oral colchicine are absolutely
contraindicated in patients with advanced renal failure
as it leads to colchicine toxicity.
A short list of drug interactions:
Anti-arrhythmics
Digoxin
Antibiotics
Clarithromycin, Erythromycin
Antifungals:
Fluconazole, Itraconazole, Ketoconazole
Antiretrovirals:
Amprenavir, Atazanavir, Fosamprenavir
Calcium-channel blockers
Diltiazem, Verapamil
Fibrates:
Fenofibrate, Gemfibrozil
Immunosuppresants:
Cyclosporin, Tacrolimus
Statins:
Atorvastatin, Fluvastatin, Simvastatin, Paravastatin
Statins:

6. Methodology:
Objectives:
To evaluate the efficacy and safety of colchicine for relief of the signs and symptoms of acute gouty arthritis,
compared to placebo and other treatment interventions.
Search methods:
‘colchicine’, ‘acute gout’, ‘interleukin inhibitor’, ‘NSAID*’ ‘glucocorticoid*’ ‘corticotrophin’
Search of the following Electronic Databases:
Cochrance Central Register of Controlled Trials (Central, Issue 1 2006)
Medline
EMBASE
CINAHL
Search of the following journals:
British Medical Journal
Annual Review of Medicine
Journal of Rheumatology
Selection Criteria:
Published randomised controlled trials (RCTs) and controlled clinical trials evaluating symptom relief and adverse
outcomes of colchicine therapy in acute gout were considered for this review. Pilot studies of alternative treatment
options to colchicine were included due to lack of literature.

7. Colchicine (aka the least favourite drug to
study)
• 1986 Australian RCT compared colchicine Rx with placebo
• 43 Participants used, split roughly 50-50 into the 2 groups
• Diagnosis of gout confirmed
• Study group received 1mg followed 2 hourly with 0.5mg until treated or got toxicity.
• No NSAIDs were allowed
• Pain was measured on a 100 point visual analogue scale.
• Results: Colchicine improved scores by 34pts, placebo = 3.6pts
((95% CI, -50.33 to -17.67) and -3.60 (95% CI, -5.32 to -1.88) )
• RR of Colchicine vs placebo for a 50% reduction in pain = 2.00
(95% CI, 1.09 to 3.68)
• NNT = 3
• Results = Statistically significant

8. Canakinumab
• Fully humanised anti-IL-1B monoclonal antibody
• 2013; 2 phase III studies showed efficacy in treating
acute gout
• 12 weeks long with a 12 week extension
• 150mg canakinumab vs 40gm tricinolone
• @72hrs canakinumab reduced pain more than
triamcinolone. (p<0.0001).
• Canakinumab had more adverse outcomes (66%)
compared to 53%.
• Criticism of study; Why use triamcinolone?
• Other Studies have been focussing on interleukin
modulation in mice models.
• Pilot studies have shown benefit but participation
has been low. (2 studies have only used 10 patients
as a sample)

9. Corticosteroids
•Body of evidence for intraarticular corticosteroids and ACTH is very limited
Prospective trial
•systemic corticosteroid treatment given
•Improvement within 12-48 hours.
•13 consecutive patients with 15 episodes of acute gout were treated with systemic
corticosteroids.
•Eight of 12 patients had MSU crystal-proven gout. 20-50mg dosage showed 84% of pts with,
complete resolution
•Comparison of different administration regimens had not been done.
2 RCTs, placebo controlled.
•Trial I evaluating prednisolone 30 mg daily
•Trial 2 evaluating prednisolone 35 mg daily,
•Both trials demonstrated equivalence to relatively standard regimens of NSAIDs
(indomethacin and naproxen, respectively)
Frustratingly although these trials did display promising results in the management of acute
gout, they were not compared to colchicine.

10. Summary;
Where does all this leave
us?Therapeutic Intent:
•Acute therapy is directed toward reducing inflammation rather than eliminating crystals.
Conventional therapies of acute gout include:
•NSAIDs, commonly naproxen, with the aim of reducing the swelling in the joint.
•Colchicine, which According to Australian Guidelines is given 1mg STAT and then 0.5mg an hour later.
•Glucocorticoids can be used if NSAIDs and colchicine and either contra-indicated or inappropriate to use in the patient.
Can be injected directly into the affected joint or they can be given as pills or by intramuscular injection.
People who have multiple affected joints or who cannot take NSAIDs or colchicine give oral
steroids.
FDA
•Warns that concomitant use of P-glycoprotein or strong cytochrome P 450 isoenzyme 3A4 inhibitors is contraindicated
in patients with renal or hepatic impairment receiving therapy.
•Dose reductions or interruption of colchicine therapy should be considered in patients with normal renal and hepatic
function who require concomitant treatment with a P-glycoprotein or strong cytochrome P 450 isoenzyme 3A4
inhibitor.
Other Therapies:
•More research required. Most promising is Interleukin 1Beta modulators.

11. Colchicine in the impaired patient
Revised dosing recommendations and use in renal and hepatic impairment:
Consider colchicine for acute gout when nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are
contraindicated or not tolerated.
Colchicine prescribing considerations:
To reduce the risk of serious drug interactions
In patients with normal renal or hepatic function, colchicine therapy should be stopped, or the dose reduced, when a
strong CYP3A4 inhibitor or P-gp inhibitor is prescribed.
Renal Impairment
Gout prophylaxis/flares:
Mild (CrCl 50-80 mL/min) and moderate (CrCl 30-50 mL/min): Dosage adjustment not required; monitor
patients for adverse effects
Severe (CrCl <30 mL/min): Dose adjustment not needed; do not repeat more frequently than q2Wks
Hepatic Impairment
Gout propylaxis/flares:
Mild to moderate: Dosage adjustment not required; monitor patients for adverse effects
Severe: Dose adjustment not needed; do not repeat more frequently than q2Wks; consider alternative
therapy if requiring repeated courses