[4] The most frequent adverse events with saquinavir in either formulation are mild gastrointestinal symptoms, including diarrhoea, nausea, loose stools and abdominal discomfort.

[7] In the clinic, it was found that the oral bioavailability of saquinavir in both formulations significantly increases when patients also receive the PI ritonavir.

[medical citation needed] The mechanism behind this welcome observation was not directly known, but later it was determined that ritonavir inhibits the cytochrome P450 3A4 isozyme.

[11] Saquinavir was the sixth antiretroviral and the first protease inhibitor approved by the US Food and Drug Administration (FDA), leading ritonavir and indinavir by a few months.

[10][13] Roche requested and received approval of Invirase via the FDA's "Accelerated Approval" program—a process designed to speed drugs to market for the treatment of serious diseases—a decision that was controversial, as AIDS activists disagreed over the benefits of thorough testing versus early access to new drugs.

[14][better source needed] It was approved again on November 7, 1997, as Fortovase,[15] a soft gel capsule reformulated for improved bioavailability.