Psycho-Babble Medication Thread 652288

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Can someone explain this?

Posted by Sobriquet Style on June 3, 2006, at 8:44:55

"clonazepam and modafinil (minor Drug-Drug)

Description:
Coadministration with modafinil may decrease the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. Modafinil is a modest inducer of CYP450 3A4 in vitro, and pharmacokinetic studies suggest that its effects may be primarily intestinal rather than hepatic. Thus, clinically significant interactions would most likely be expected with drugs that have low oral bioavailability due to significant intestinal CYP450 3A4-mediated first-pass metabolism (e.g., buspirone, cyclosporine, felodipine, lovastatin, midazolam, nifedipine, nisoldipine, saquinavir, simvastatin, sirolimus, tacrolimus, triazolam, verapamil). However, the potential for interaction should be considered with any drug metabolized by CYP450 3A4, especially given the high degree of interpatient variability with respect to CYP450-mediated metabolism. Pharmacologic response to these drugs may be altered and should be monitored more closely whenever modafinil is added to or withdrawn from therapy. Dosage adjustments may be required if an interaction is suspected."

-

Vs.

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"diazepam and modafinil (moderate Drug-Drug)
Description:

MONITOR:
Based on in vitro inhibition data, coadministration with modafinil may increase the plasma concentrations of drugs that are substrates of the CYP450 2C9 and/or 2C19 isoenzymes. The mechanism is decreased clearance due to inhibition of CYP450 2C9/2C19 activities by modafinil. Pharmacologic response to these drugs may be altered, particularly if they have a narrow therapeutic range. For example, modafinil was implicated in a case of clozapine toxicity, characterized by dizziness, ataxia, and tachycardia. Clozapine serum levels increased from 761 ng/mL to 1400 ng/mL several weeks after concurrent modafinil therapy was initiated."

Can you describe what they are saying *basically* :-)

(source is from http://www.drugs.com/drug_interactions.html and is about interaction with either diazepam (valium) and clonazepam (klonopin) - interacting with Provigil.)

Thanks!

~

 

Re: Can someone explain this?

Posted by yxibow on June 3, 2006, at 12:10:43

In reply to Can someone explain this?, posted by Sobriquet Style on June 3, 2006, at 8:44:55

The first interaction is probably on the trivial level -- the second is modest. Almost all psychiatric drugs are metabolized through the liver, where a cytochrome system known as P450 governs how a drug in your body will affect other drugs.

In the second example, modafinil is an inhibitor at 2C9/2C19, meaning that it increases the time another drug that is also metabolized by 2C9/2C19 will stay in your body. In other words, it is conceivable a modest increase in your blood level of Valium will possibly occur and Valium should be down adjusted -- but modest usually means that rarely it is critical.


In the first example, which is most likely trivial, modafinil is an inducer, meaning that it will reduce the availability of a drug at 3A4 (eliminate it quicker), but that there is a great difference between patients. Thus, really no adjustment of the other drug is particularly necessary.

 

Re: Can someone explain this?

Posted by Caedmon on June 3, 2006, at 12:32:52

In reply to Can someone explain this?, posted by Sobriquet Style on June 3, 2006, at 8:44:55

Sounds like modafinil induces one type of isoenzyme but inhibits another. Subtle, yet complicated. :-P

- Chris

 

Re: Can someone explain this?

Posted by Phillipa on June 3, 2006, at 21:52:37

In reply to Re: Can someone explain this?, posted by Caedmon on June 3, 2006, at 12:32:52

Sounds like what luvox does with some meds it ups the concentration of them in your blood. If not taking luvox and take valium it won't be as stong. On valium it is stonger with luvox. My interpretation using different meds. Love Phillipa

 

Thanks! » yxibow

Posted by Sobriquet Style on June 5, 2006, at 7:12:22

In reply to Re: Can someone explain this?, posted by yxibow on June 3, 2006, at 12:10:43

Its interesting that even though diazepam and clonazepam full under the same class of drug - benzodiazepines, provigil will increase one and decrease the other, albeit very mild interaction(s)

I suspected the provigil interaction would be more or less the same for other benzo's aside from valium (I take valium ~ I don't take klonopin)

Very interesting...

Thanks

:-)

~


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