Biovail Corporation has received an approvable letter from the US FDA for its New Drug Application (NDA) for Ralivia ER (tramadol hydrochloride) extended-release tablets, a once-daily oral controlled-release pain medication.

Biovail's NDA submission, which was accepted for review by the FDA in late February 2004, included clinical and safety data obtained from four original adequate and well-controlled trials involving more than 3,000 patients who received doses of up to 400mg of Ralivia ER once daily. The submission also included 12 definitive and five supportive pharmacokinetic studies which demonstrated that once-daily dosing of Ralivia ER delivers the equivalent amount of drug as Ultram (tramadol hydrochloride tablets) given three times (TID) or four times (QID) per day, the company says.

Ralivia ER has been developed by Biovail to provide effective pain control in appropriate patients over a 24-hour period, as an alternative to immediate-release formulations of tramadol. Subject to final FDA approval, Ralivia ER will be available in 100mg, 200mg and 300mg extended-release tablets, and will offer patients the convenience of a once-daily form of tramadol, as opposed to the current dosing regimen of up to six times per day for immediate release tramadol.

Ralivia ER uses Biovail's Smartcoat Technology, which is similar to that used in Biovail's Wellbutrin XL (bupropion HCl extended-release tablets) formulation. Biovail believes a considerable market opportunity exists for Ralivia ER in the United States analgesia market, where sales for the 12 months ended August 31, 2004 were $13.9 billion. Over the same period, tramadol-based products generated revenues of $419 million and 18.3 million prescriptions.

Tramadol is a centrally acting synthetic opioid analgesic, effective in the treatment of pain. Tramadol's minimal propensity to induce adverse effects is an advantage over morphine-like agents. Relative to morphine, tramadol causes less dependence and less respiratory depression. Tramadol is currently available under the brand name Ultram (a product of Ortho-McNeil, a division of Johnson and Johnson), and in several generic formulations. Branded and generic formulations of tramadol are indicated for the management of moderate to moderately severe pain, and may be dosed four to six times per day.