Shares plunged 59.81% to US$2.15 each in US pre-market trading.
The FDA said in a complete response letter (CRL) that the safety database was suitable in a number of patients but required additional data on at least 50 patients. The health regulator also recommended changes to the directions of use.
"We believe the recommendations stated in the CRL are manageable and plan to fully cooperate with the FDA," said chief executive Vincent Angotti.
AcelRx plans to hold talks with the FDA on the CRL with the aim of resubmitting its new drug application.