Dextromethorphan/quinidine: AVP 923, dextromethorphan/cytochrome P450-2D6 inhibitor, quinidine/dextromethorphan.

Avanir Pharmaceuticals in the US is developing a fixed-dose combination of dextromethorphan (30 mg), a weak NMDA antagonist/sigma 1 agonist, and quinidine (30 mg), a cytochrome P450-2D6 (CYP2D6) enzyme inhibitor [AVP 923, Neurodextrade mark]. Quinidine sustains therapeutic levels of dextromethorphan over a 12-hour dosing schedule by inhibiting oxidative first-pass metabolism of the drug, and is used in the combination product at 2.5-5.0% of its normal daily therapeutic dose. A rolling NDA for the treatment of emotional lability has been initiated, and phase II trials with dextromethorphan/quinidine for the treatment of neuropathic pain have been completed. Avanir is exploring partnering opportunities for dextromethorphan/quinidine in Europe and Japan. Prospective partners would carry out development and commercialisation in the licensed territory. Additionally, a co-promotion partner for the US is sought. Avanir Pharmaceuticals sublicensed this formulation of dextromethorphan from IriSys Research and Development. Avanir has exclusive rights to develop, manufacture and market dextromethorphan/quinidine for four potential indications: emotional lability, neuropathic pain, chronic cough and weaning drug-dependent patients from narcotics and antidepressants. Avanir will make milestone payments to Irisys upon US FDA acceptance of filing, marketing approval, and royalties based on product sales. Medison Pharma (Israel) has obtained development, marketing and distribution rights to the dextromethorphan/quinidine combination for the treatment of emotional lability in patients with multiple sclerosis in Israel. Avanir will fund all clinical development of the dextromethorphan/quinidine combination for the treatment of emotional lability. The phase II clinical trials with dextromethorphan/quinidine for the treatment of neuropathic pain have been completed. Results indicated that the combination significantly improved pain scores in patients with diabetic neuropathy. Phase III trials in this indication are expected to begin in 2005. Avanir has been issued with six patents in the US regarding dextromethorphan/quinidine and has a total of 14 pending applications, 12 of which are in Europe.