Mibefradil Posicor

Mibefradil (POSICOR) Asymmetric hydrogenation of a-acylaminoacrylic acids with Stinson (1996)... 

Crameri et al. (1997) have reported an asymmetric hydrogenation constituting an important step in the production of a new calcium antagonist, Mibefradil (POSICOR) (of Hoffmann-LaRoche). Pilot-scale synthesis of (S)-2-(4-flurophenyl)-3-methylbutanoic acid by the asymmetric hydrogenation of 2-(4-fluorophenyl)-3-methyl but-2-enoic acid with a [Ru (/ )-MeOBIPHEP)(OAc)2]-catalyst has been described. The hydrogenation was performed in a continuous mode in a cascade stirred-tank reactor system at a pressure of 270 bar. A large reduction in total reactor volume compared to the batch mode was realized. 

Mibefradil Posicor Roche Laboratories Blood pressure, cardiovascular 6/20/1997 6/8/1998 1 year Drug interaction. Not available lowered heart rate in women ... 

Mibefradil (Posicor ) was launched in the United States in June 1997 by Roche, Switzerland. It was promoted as a unique calcium channel blocker (CCB) that affected both transient (T) and long (L) calcium channels. At the time of launch, it was projected to eventually provide 1-3% of Roche s sales. It was withdrawn from the market in June 1998. 

The calcium channel blocker mibefradil (Posicor ) was removed from the market in 1998. The headline for the Pink Sheets article describing this action was "Posicor Withdrawal Reflects Complexity of Interaction Profile" (59). Products identified as potentially dangerous in combination with mibefradil included cardiac drugs, such as amiodarone, flecainide, and propafenone oncologic products, such as tamoxifen, cyclophosphamide, etoposide, ifosfamide, and vinblastine and the immunosuppressant medications cyclosporine and tacrolimus. The sponsor s decision to withdraw mibefradil was based on the complexity of the drug interaction information that would have to be communicated to ensure safe usage. 

Mibefradil (Posicor) High blood pressure/ Chronic stable angina Drugdrug interactions Torsades de Pointes... 

Mechanism-based irreversible inhibition of P450 enzymes represents a serious flaw in any drug candidate because of the potential for clinical drug-drug interactions, as was demonstrated by the withdrawal of mibefradil (Posicor ) from the market. It is... 

Within several weeks of its launch, numerous serious adverse events involving mibefradil were being reported on a regular basis. These included severe bradycardia when used concomitantly with (5-blockers, cardiogenic shock when switching from Posicor to dihydropyridine CCBs (17), and rhabdomyolysis when used with HMG-CoA reductase inhibitors (18). 

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