Liverpool HIV Interactions

Interaction Checker

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Potential Weak Interaction

Ritonavir (RTV)

Desipramine

Quality of Evidence: Very Low

Summary:

Coadministration of ritonavir (100 mg twice daily) and desipramine (50 mg single dose) increased desipramine AUC by 26%. No a priori dosage adjustment is recommended when ritonavir is used as a pharmacokinetic booster.

Description:

Coadministration of desipramine (100 mg single oral dose) and ritonavir (500 mg twice daily) increased desipramine AUC by 145% and Cmin by 22%. The AUC and Cmax of the 2-hydroxy metabolite were decreased 15 and 67%, respectively. Dosage reduction of desipramine is recommended when co-administered with ritonavir dosed as an antiretroviral agent.
Norvir Summary of Product Characteristics, AbbVie Ltd, September 2016.

Coadministration of ritonavir (500 mg every 12 hours for 12 days) with a single dose of desipramine (100 mg), in 14 subjects caused increases of 145% and 22% in desipramine AUC and Cmax, respectively, and decreases of 15% and 67% in 2-OH desipramine metabolite AUC and Cmax, respectively. Dosage reduction and concentration monitoring of desipramine is recommended.
Norvir Prescribing Information, AbbVie Inc, December 2016.

The effect of low-dose ritonavir (100 mg twice daily) on CYP2D6 was investigated in 13 HIV-negative subjects using single doses of desipramine (50 mg) as a probe substrate. Ritonavir had a modest inhibitory effect on the activity of CYP2D6 and increased desipramine AUC by 26%. It is expected that the effect of low-dose ritonavir on CYP2D6 will not require standard dose reductions for CYP2D6 substrates.
Effect of low-dose ritonavir (100 mg twice daily) on the activity of cytochrome P450 2D6 in healthy volunteers. Aarnoutse RE, Kleinnijenhuis J, Koopmans PP, et al. Clin Pharmacol Ther, 2005, 8(6): 664-74.

Coadministration of ritonavir (500 mg 12 hourly) and a single dose of desipramine (100 mg) was studied in 14 healthy volunteers. Desipramine AUC and Cmax increased by 145 and 22% respectively. The AUC and Cmax of 2-OH desipramine decreased by 15 and 67%, respectively. The pharmacokinetic changes are potentially significant given the narrow safety margin of desipramine.
Effect of ritonavir on the pharmacokinetics of desipramine. Bertz RJ, Cao G, Cavanaugh JH, et al. 11th International Conference on AIDS, 1996, abstract Mo.B.1201.

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