Ritonavir

Colchicine

Modification of dose and/or administration time necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

Ritonavir can inhibit the CYP 3A4 and P-gp and increase the plasma concentration of Colchicine.

Ritonavir

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Colchicine

Pharmacodynamic effects

Increase of adverse effects.

Recommendations

Decrease dosage. See comments.

The administration of colchicine, combined with a potent CYP3A4 inhibitor, is contraindicated in patients with renal or hepatic impairement.

Monitor closely clinical efficacy and appearance of adverse effects.

In patients already being treated with this combination and tolerating it, if deemed appropriate, keep actual treatment and exercise close monitoring of adverse effects.

Alternative solution(s)

Monitor

Symptoms of colchicine toxicity: nausea, vomiting, diarrhea and abdominal pain are the first signs of an overdose. Rare: pancytopenia, neuromyopathy, rhabdomyolysis, marrow depression, renal or hepatic impairment, rash,azoospermia, polyvisceral failure, respiratory depression, cardiovascular collapse, etc.

Tests

Blood count

Pharmacokinetic parameters
Parameters
Reference number
# patients
HIV
Dose
Frequency
Duration (days)
Cmax
AUC
Ritonavir
2753
24
-
400 mg
QD
4
 
 
Colchicine
2753
24
-
0.6 mg
 
 
+ 170%
+ 245%
Comment

Symptoms of colchicine intoxication can be gastrointestinal disturbances (including severe diarrhea), myopathy (muscular pain or weakness, possibly leading to a rhabdomyolysis), neuropathy, marrow depression, renal or hepatic impairment

Treatment of gout flares: 0.6 mg (1 tablet) x dose, followed by 0.3 mg (1/2-co) an hour later.

Do not repeat this cycle of treatment for three days.

Prophylaxis of gout: If the initial treatment was 0.6 mg BID, adjust the treatment to 0.3 mg QD. If the initial treatment was 0.6 mg QD or 0.3 BID, adjust the treatment to 0.3 mg once every other day.

Treatment of familial Mediterranean fever: Maximum daily dose of 0.6 mg (may be given at 0.3 mg BID).

Ref # 2816: An FDA advice was issued in 2009 to the fact that cases of colchicine toxicity including fatal ones have been reported in the literature with concomitant use of inhibitors of CYP3A4 and P-gp especially in patients with renal or hepatic impairement.

Ref #2817 to 2822: Indeed, cases of deaths have been associated with the use of colchicine and strong CYP3A4 inhibitors, particularly in patients with hepatic or renal impairment.

Colchicine intoxication appears during the first hours by gastroenteritis-like symptoms (nausea, vomiting, diarrhea, and abdominal pain). Cases of severe intoxication refer to myopathy and blood dyscrasia.

The administration of colchicine, combined with a potent CYP3A4 inhibitor, is contraindicated in patients with renal or hepatic impairement.

See Ritonavir and Colchicine.

Reference
  • 2572
    Ritonavir (Norvir), Corporation AbbVie, Quebec, Canada, 25 septembre 2018.
  • 2753
    Wason S, DiGiacinto JL and Davis MW. Clinically significant pharmacokinetic interaction between colchicine and ritonavir in healthy volunteers. Clinical Medicine Insights: Therapeutics 2013; 5: 25-32.
  • 2816
    U.S. Food and Drug Administration (FDA). Information for Healthcare Professionals: New Safety Information for Colchicine (marketed as Colcrys). Disponible: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm174315.htm. Publié le 30 juillet 2009. Consulté en août 2013.
  • 2817
    Hung IF, Wu AK, Cheng VC et al. Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study. Clin Infect Dis. 2005 Aug 1; 41(3): 291-300.
  • 2818
    Finkelstein Y, Aks SE, Hutson JR, Juurlink DN et al. Colchicine poisoning: the dark side of an ancient drug. Clin Toxicol (Phila). 2010 Jun; 48(5): 407-14.
  • 2819
    Todd BA, Billups SJ, Delate T et al. Assessment of the association between colchicine therapy and serious adverse events. Pharmacotherapy. 2012 Nov; 32(11): 974-80.
  • 2820
    Caraco Y, Putterman C, Rahamimov R, Ben-Chetrit E. Acute colchicine intoxication—possible role of erythromycin administration. J Rheumatol 1992; 19: 494-6.
  • 2821
    Dogukan A, Oymak FS, Taskapan H, Guven M, Tokgoz B, Utas C. Acute fatal colchicine intoxication in a patient on continuous ambulatory peritoneal dialysis (CAPD). Possible role of clarithromycin administration. Clin Nephrol 2001; 55: 181-2.
  • 2822
    Borron SW, Scherrmann JM, Baud FJ. Markedly altered colchicine kinetics in a fatal intoxication: examination of contributing factors. Hum Exp Toxicol 1996; 15: 885-90.
  • 3113
    Colchicine, Sandoz, Québec, Canada, 8 décembre 2017.