Note: this interaction was studied using a darunavir/ritonavir dose lower than that licensed. Coadministration increases atorvastatin concentrations. Coadministration of atorvastatin (10 mg once daily) and darunavir/ritonavir (300/100 mg twice daily) resulted in atorvastatin exposure that was only 15% lower than that obtained with atorvastatin 40 mg once daily alone. When coadministered it is recommended to start with atorvastatin 10 mg once daily. A gradual dose increase may be tailored to the clinical response. A daily dose of 40 mg atorvastatin should not be exceeded with careful safety monitoring. (Note, the US product label for Prezista states not to exceed atorvastatin 20 mg/day.)

Pitavastatin is metabolised by UGTs 1A3 and 2B7 with minimal metabolism by CYPs 2C9 and 2C8. Data from pharmacokinetic studies suggest no clinically significant interaction between darunavir/ritonavir and pravastatin. Coadministration of darunavir/ritonavir (800/100 mg once daily) and pitavastatin (2 or 4 mg once daily) was investigated in two studies in HIV-negative subjects. Coadministration with 2 mg pitavastatin decreased pitavastatin AUC and Cmax by 9% and 7% (n=10) and increased darunavir AUC and Cmax by 8% and 3% (n=14). Coadministration with 4 mg pitavastatin decreased pitavastatin AUC and Cmax by 26% and 4% (n=27) and increased darunavir and ritonavir exposure (darunavir AUC and Cmax increased by 3% and 6%; ritonavir AUC and Cmax increased by 8% and 2%).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pyridoxine is absorbed from the GI tract and is converted to the active form pyridoxal phosphate. It is excreted in the urine as 4-pyridoxic acid.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zinc is poorly absorbed from the gastro-intestinal tract. It is widely distributed throughout the body and is excreted in the faeces with traces appearing in the urine. Darunavir/ritonavir is metabolized by CYP3A4.