Mibefradil. drug interactions

Methylphenidate, effects at different ages, 31.6 Methylthiotetrazole, 11.226 Mibefradil, drug interactions, 23.210 Midazolam, 15.112 Midodrine, 26.159... 

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, a calcium channel blocker, is not toxic when used alone for cardiovascular treatment but on the market it was found to interact with at least 25 other drugs, resulting in increased plasma concentrations and consequently, toxicity. This example was one that increased regulatory focus on drug-drug interactions but only common interactions can be researched premarketing and the commonality of multiple polytherapy, for example in the elderly, cannot be fully legislated. 

Because of the large number of drug molecules metabolized by CYP3A4, potent inhibition, by whatever mechanism, can have a detrimental effect on a compound s marketability. This effect is exemplified by mibefradil, which was withdrawn from the market during its first year of sales because of its extensive CYP3A4 drug interactions (153-156). 

Roche, FDA announce new drug-interaction warnings for mibefradil. Am J Health Syst Pharm 1998 55 210. 

Krayenbuhl JC, Vozeh S, Kando-Ostreicher M, et al. Drug-drug interactions of new active substances mibefradil example. Eur J Clin Pharmacol 1999 55 559-565. 

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. 

Ocran KW, Plauth M, Mai I, Lochs H. Tacrolimus toxicity due to drug interaction with mibefradil in a patient after liver transplantation. Z Gastroenterol 1999 37 1025-1028. 

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... 

Mibefradil is a calcium-channel blocker that acts on the fast T-type calcium channel. It was withdrawn soon after it was launched because of identification of an increasing number of serious drug interactions caused... 

Mibefradil is a verapamil-like agent with a potentially attractive haemodynamic profile. It is a vasodilator, which also causes a reduction in heart rate, whereas it is devoid of negative inotropic activity. Some of its properties are attributed to its influence of calcium channels of the T- and N-types. Unfortunately, the compound has been withdrawn because of multiple interactions with various other drugs. 

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