The US Food and Drug Administration (FDA) has added new information to the package insert for the latest protease inhibitor (PI) atazanavir (Reyataz), which warns of recently-discovered pharmacokinetic interactions between atazanavir and the non-nucleotide tenofovir (Viread), as well as between atazanavir and PDE5 inhibitors used to treat erectile dysfunction, including sildenafil (Viagra), tadalafil (Cialis) and vardenafil (Levitra).
Tenofovir’s effect on atazanavir
The FDA states:
“Tenofovir decreases the AUC (area under the curve) and Cmin (minimum concentration) of atazanavir.
“When co-administered with tenofovir, it is recommended that atazanavir 300mg is given with ritonavir 100mg and tenofovir 300mg (all as a single daily dose with food). Atazanavir without ritonavir should not be co-administered with tenofovir."
Atazanavir’s effect on tenofovir
The FDA states:
“Atazanavir increases tenofovir concentrations. The mechanism of this interaction is unknown. Higher tenofovir concentrations could potentiate [make more likely] tenofovir-associated adverse events, including renal [kidney] disorders. Patients receiving atazanavir and tenofovir should be monitored for tenofovir-associated adverse events.
“When co-administered with tenofovir, it is recommended that atazanavir 300mg is given with ritonavir 100mg and tenofovir 300mg (all as a single daily dose with food). Atazanavir without ritonavir should not be co-administered with tenofovir.”
Atazanavir and PDE5 inhibitors
The FDA has added the following to the 'Warnings and Precautions' section:
“Co-administration with atazanavir has not been studied but may result in an increase in PDE5 inhibitor-associated adverse events, including hypotension [low blood pressure], visual changes, and priapism [long-lasting, painful erections].
“Use sildenafil with caution at reduced doses of 25mg every 48 hours with increased monitoring for adverse events. Use tadalafil with caution at reduced doses of 10mg every 72 hours with increased monitoring for adverse events. Use vardenafil with caution at reduced doses of no more than 2.5mg every 72 hours with increased monitoring for adverse events.”
It should be noted that in the US, atazanavir is approved as a single, unboosted PI, taken as two 200mg capsules once daily. This is not the case in the EU and UK: here, two 150mg capsules of atazanavir taken once daily must always be boosted by an additional 100mg dose of ritonavir.
Further information on this website
Atazanavir: positive opinion in EU, but only for treatment-experienced and only when boosted - news story
Warning on atazanavir and tenofovir combination - news story
Atazanavir - overview