Posted by Sunnely on July 25, 2000, at 1:00:50
In reply to CAM, need some info desperately, posted by Greg on July 24, 2000, at 20:33:56
> Was put on Tegretol and Despiramine today by my doc. After reading info on them at mentalhealth.com, it appears that there may be some potentially dangerous interactions between the two. Can you clear this up for me? I'm a little concerned. I was also told to continue the Prozac in tapering off mode for the next two weeks. Any danger there? You help would be greatly appreciated.
>
> GregPardon me for intruding. I hope you don't mind that I share my 2-cent opinion with you.
Tegretol, Desipramine, and Prozac can cause clinically significant drug-drug interactions. There are 2 kinds of drug-drug interactions which can happen: "pharmacodynamic" and "pharmacokinetic." Based on the "pharmacodynamic" interaction, Tegretol and desipramine taken together may cause increased emergent side effects such as drowsiness, dizziness, unsteadiness, confusion, and visual disturbances. Based on "pharmacokinetic" interaction, Tegretol can induce the liver metabolism of desipramine leading to decrease in desipramine's blood level and possibility of losing its therapeutic effect. However, inducing the metabolism via liver enzymes usually takes effect much longer (than inhibition of liver enzymes); the onset of decline in the desipramine's blood level may not take effect until after several days later. It may be necessary to increase the dose of desipramine (or other tricyclic antidepressant) if Tegretol is added. Checking the blood level of desipramine is also necessary to guide with the effective antidepressant dosing.
On the other hand, at least one case report documented Tegretol toxicity resulting from a doubling of the drug's blood level after the addition of desipramine to the patient's therapy. Desipramine does this by antagonizing or inhibiting the action of the liver enzymes that Tegretol depend on for metabolism. Symptoms of Tegretol toxicity may include dizziness, unsteadiness, nausea, vomiting, tremor, agitation, nystagmus (rapid eye movement). Heart rhythm irregularity and heart block have also been reported even at mildly elevated Tegretol blood levels. Therefore, it is clinically important to monitor both the Tegretol and desipramine blood levels when combined when these 2 drugs are used in combination. Whereas liver enzyme induction during drug-drug interaction occurs much later (several days to weeks), liver enzyme inhibition occurs much earlier (hours to a few days).
Prozac + Tegretol + Desipramine may spell trouble if not monitored closely. FYI, Prozac inhibits the action of several liver enzymes involved in the metabolism of drugs including the ones responsible for Tegretol and Desipramine. Prozac markedly inhibits the action of liver enzyme called CYP2D6; moderately inhibits CYP3A4, CYP2C9, and CYP2C19. Desipramine mainly depends on the liver enzyme CYP2D6 for its metabolism. Therefore, the combination of Prozac and desipramine will lead to increased in desipramine's blood level causing increased desipramine side effects. Heart rhythm irregularity and heart block has been reported with toxic level of desipramine (and other tricyclic antidepressants). On the same token, Prozac + Tegretol may lead to decreased (moderately) metabolism of Tegretol causing an increase in its blood level leading to potential Tegretol toxicity. In effect, both desipramine and Prozac are capable of raising the blood level of Tegretol.
Although your dose of Prozac is being tapered down, its inhibiting effect on the liver enzymes will continue until after about 5 weeks from the time it is stopped. This is due to its very long half-life (3 days for the parent compound and 5-15 days for its active metabolite). The pharmacokinetic interaction between Prozac + desipramine should be taken seriously. Toxic levels of desipramine (and other tricyclic antidepressants) can lead to a electrocardiogram abnormality called prolonged QTc which has the potential to generate an even more serious ECG abnormality called "torsades de pointes." "Torsades" usually is self-limiting and the only symptoms could be fainting and loss of consciousness and subsequently, the heart rhythm returns to normal. However, in some cases, it can generate into a serious arrhythmia called ventricular fibrillation and sudden cardiac death. Several sudden deaths attributed to serious heart rhythm irregularity (possibly "torsades") have been reported with the use of Seldane, Hismanal, and Propulsid. Aside from the tricyclic antidepressants, prolonged QTc, with potential for "torsades," have also been reported with thioridazine (Mellaril) and pimozide (Orap). Sertindole (Serlect), a promising atypical antipsychotic drug failed to make the US shores due to prolonged QTc. Ziprasidone (Zeldox) was on a holding pattern for FDA approval for awhile due to the same reason. (Zeldox, just recently received FDA approval.)
The bottom line here is, your ECG and blood levels of Tegretol and desipramine should be monitored periodically while you remain on this combination, especially if Prozac is to continue as part of the drug regimen. In fact, if you are over 40 or have pre-existing heart condition, you should have an ECG prior to the start of a tricyclic antidepressant therapy.
poster:Sunnely
thread:41333
URL: http://www.dr-bob.org/babble/20000717/msgs/41354.html