Liverpool HIV Interactions

Potential Interaction

Lopinavir/ritonavir (LPV/r)

Colchicine

Quality of Evidence: Very Low

Summary:

Coadministration is expected to increase colchicine concentrations. Ritonavir (100 mg twice daily) significantly increased colchicine Cmax (2.7-fold) and AUC (3.5-fold) when given with a single dose of colchicine (0.6 mg). Patients with renal or hepatic impairment should not be coadministered colchicine. A reduction in colchicine dosage or an interruption of colchicine treatment is recommended in patients with normal renal or hepatic function. When coadministered for treatment of gout flares, the recommended dosage is 0.6 mg (1 tablet) for 1 dose, followed by 0.3 mg (half tablet) 1 hour later. The dose is to be repeated no earlier than 3 days. When coadministered for prophylaxis of gout flares, if the original regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg once a day; if the original regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once every other day. When coadministered for treatment of familial Mediterranean fever (FMF) do not exceed a maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day).

Description:

Kaletra contains lopinavir and ritonavir, both of which are inhibitors of the P450 isoform CYP3A. Kaletra should not be co-administered with medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life threatening events. These medicinal products include colchicine. Life-threatening and fatal drug interactions have been reported in patients treated with colchicine and strong inhibitors of CYP3A like ritonavir. Concomitant administration with colchicine is contraindicated in patients with renal and/or hepatic impairment due to a potential increase of colchicine-related serious and/or life-threatening reactions such as neuromuscular toxicity (including rhabdomyolysis). A reduction in colchicine dosage or an interruption of colchicine treatment is recommended in patients with normal renal or hepatic function if treatment with Kaletra is required. Refer to colchicine prescribing information. Coadministration of a single dose of colchicine and ritonavir (200 mg twice daily) increased colchicine AUC by 3-fold and increased Cmax by 1.8-fold due to P-gp and/or CYP3A4 inhibition by ritonavir.
Kaletra Summary of Product Characteristics, AbbVie Ltd, January 2021.

Coadministration is expected to increase colchicine concentrations. Coadministration is contraindicated due to potential for serious and/or life-threatening reactions in patients with renal and/or hepatic impairment. For patient with normal or hepatic function dose as follows:
Treatment of gout flares - co-administration of colchicine in patients on Kaletra: 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (half tablet) 1 hour later. Dose to be repeated no earlier than 3 days.
Prophylaxis of gout flares - co-administration of colchicine in patients on Kaletra: If the original colchicine regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg once a day. If the original colchicine regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once every other day.
Treatment of familial Mediterranean fever (FMF) - co-administration of colchicine in patients on Kaletra: Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day).
Kaletra Prescribing Information, AbbVie Ltd, October 2020.

Coadministration of ritonavir (100 mg twice daily for 5 days) and colchicine (0.6 mg single dose) was studied in 18 subjects. Ritonavir significantly increased colchicine Cmax and AUC by 2.7-fold and 3.5-fold, respectively. Dosage adjustments of colchicine are required when given with CYP3A4 and/or P-gp inhibitors.
Novel evidence-based colchicine dose-reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome P450 3A4/P-glycoprotein inhibitors. Terkeltaub RA, Furst DE, Digiacinto JL, et al. Arthritis Rheum, 2011, 63(8): 2226-37.

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