Darunavir/ritonavir interaction with clarithromycin warrants caution
This was a 3-way crossover study investigating the steady-state pharmacokinetic interaction between darunavir/ritonavir (400/100 mg twice daily) and clarithromycin (500 mg twice daily) in 18 HIV- volunteers.
Coadministration of darunavir/ritonavir with clarithromycin resulted in a reduction in darunavir Cmax and AUC of 17% and 13% respectively. Ritonavir Cmax and AUC were unchanged. Clarithromycin Cmax and AUC increased by 26% and 57%, respectively; 14-OH clarithromycin concentrations were reduced to below the lower limit of quantification (50 ng/ml).
Although the authors indicate that neither clarithromycin nor darunavir/ritonavir dose adjustments are necessary when coadministered, caution is warranted and clinical monitoring recommended. The Prezista Summary of Product Characteristics and Prescribing Information recommend considering dose reduction when clarithromycin and darunavir/ritonavir are coadministered to patients with renal impairment.
Seker VJ et al. Darunavir/ritonavir pharmacokinetics following coadministration with clarithromycin in healthy volunteers. J Clin Pharmacol. 2008 Jan;48(1):60-5. http://www.ncbi.nlm.nih.gov/pubmed/18094220?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum