Trazodone manufacturers

The FDA published its final version of the class label for all antidepressants on January 26, 2005. The FDA applied the new label changes to all 34 antidepressants on the market, including older, more sedating antidepressants such as amoxapine (Asendin), trazodone (Desyrel), amitriptyline (Elavil), doxepin (Sinequan), and imipramine (Tofranil). The last-minute inclusion of the older antidepressant was an act of deference to the manufacturers of the newer antidepressants, in effect tarring all antidepressants with a brush meant only for the newer ones. 

The manufacturers of trazodone received 30 unpublished reports of seizures in patients, most of whom had evidence of seizure predisposition or concurrent contributory conditions. Two reports are detailed here (17,18). 

Trazodone can cause severe and persistent priapism. In a communication from the manufacturers in 1987, it was noted that there had been 136 reports of increased penile tumescence in patients taking trazodone. These included... 

In 6 patients taking trazodone 150 or 300 mg daily, the addition of ear-bamazepine 400 mg daily for 4 weeks deeieased the plasma levels of trazodone by 24%, and of the aetive metabolite of trazodone by 40%. However, the combination was considered clinically useful in three of the cases. In another study, when carbamazepine 400 mg daily was given with trazodone 100 to 300 mg daily, the plasma levels of trazodone and its active metabolite were reduced by 76% and 60%, respectively. The FDA in the US and the manufacturer of trazodone recommend that patients should be closely monitored and trazodone doses increased if necessary when both drugs are given. ... 

An isolated report describes a woman who developed marked and acute hypotension and weakness when desipramine, fluoxetine and venlafaxine were replaced by nefazodone. Isolated cases describe the serotonin syndrome in patients given nefazodone together, or sequentially, with another serotonei c drug (amitriptyline, paroxetine, St John s wort, or trazodone). The manufacturer recommended that nefazodone should not be used with an MAOI or within 14 days of discontinuing an MAOL Note that, due to adverse hepatic effects nefazodone was widely withdrawn from the market. 

The manufacturers of trazodone say that in vitro drug metabolism studies suggest that there is a potential for drug interactions when trazodone is given with a potent CYP3A4 inhibitor such as nefazodone. There may be substantial increases in trazodone levels, with the potential for adverse effects, and a lower dose oftrazodone should be considered. The UK manufacturer suggests avoidance of the combination where possible. ... 

Also note that the development of the serotonin syndrome has been attributed to the sequential use of an SSRI (fluoxetine, paroxetine, or sertraline) and venlafaxine. It has also occurred with concurrent use of venlafaxine and mirtazapine or trazodone. The manufacturers of venlafaxine caution its use with other drugs that affect serotonergic transmission, such as the SSRIs because of the potential risks of the serotonin syndrome. For more about the serotonin syndrome see Additive or synergistic interactions , (p.9). 

An in vitro study demonstrated that ketoconazole inhibited the metabolism of trazodone to its prineipal metabolite, meta-chlorophenylpipera-zine. Trazodone is a substrate for the eytochrome P450 isoenzyme CYP3A4 and inhibitors of this enzyme sueh as ketoconazole or itraconazole may inhibit its metabolism, leading to substantial inereases in trazodone plasma concentrations with the potential for adverse effects. " The FDA in the US and the manufacturers of trazodone recommend that a lower dose of trazodone should be considered if it is given with a potent CYP3A4 inhibitor such as ketoconazole or itraconazole. " However, the UK manufacturer also suggests that the combination should be avoided where possible. ... 

The FDA in the US and the manufacturers of trazodone recommend that a lower dose of trazodone should be considered if it is given with potent CYP3A4 inhibitors sueh as the protease inhibitors ritonavir and indina-vir. However, the UK manufaeturer also suggests that the eombination should be avoided where possible. ... 

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