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Methadone drug interaction

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Methadone drug interaction

Post  drkamalika on Sun Sep 23, 2012 8:08 pm

A 18 yr old high school senior attends a "pharm party" and takes two pills of methadone, and later that evening he was found to have very shallow respiration, and was taken to ER. Which one of the following meds could have caused this reaction?

1. Lithium
2. Modafinil
3. Methylphenidate
4. Sertraline
5. Carbamazepine

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Re: Methadone drug interaction

Post  Admin on Mon Sep 24, 2012 7:51 pm

Interesting question. Looks like Opioid overdose/toxicity. Since methadone is a pure u opioid agonist, I think drug interaction resulted in high methadone level in this case.
Carbamazepine is universal P450 inducer, so it is responsible for low methadone levels, hence opioid withdrawal symptoms.
Modafinil is also responsible for lowering of methadone levels.
I don't think Lithium and Methylphenidate interacts with Methadone.

Only option left is Sertaline, and there is known interaction resulting in high Methadone levels and also serotonin syndrome in few patients.
so I will choose 4. Sertraline.

Good question.

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Re: Methadone drug interaction

Post  P450 on Mon Sep 24, 2012 8:18 pm

I agree that shallow respirations while on methadone would indicate opioid toxicity (increased serum concentration of methadone in this case). The only possible option is sertraline.

Methadone is a major substrate of cyp3A4 and minor substrate of cyp2B6. Sertraline has minimal cyp3A4 inhibition (if any). Sertraline is a known inhibitor of cyp2B6. Generally this should not affect methadone concentration as 3A4 should be able to metabolize the excess methadone. Although not considered polymorphisms, cyp3A4 has 10-30 fold variations in level of activity.

It is possible this patient had lower 3A4 levels, making him susceptible to this interaction. He may also have been taking a 3A4 inhibitor which his physicians were unaware of. Interestingly, although there is a marked variation in 3A4 activity, there is no 3A4 poor metabolizer genotype as having no 3A4 activity is thought to be incompatible with life.


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Re: Methadone drug interaction

Post  Admin on Mon Sep 24, 2012 8:22 pm

CYP450 polymorphism explains this clinical scenario.
I have few patient's on Methadone (as MMT) and Sertraline (commonly used antidepressant), and no toxicity or complaints noted so far.

Thanks. good learning.

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Re: Methadone drug interaction

Post  Admin on Mon Sep 24, 2012 8:26 pm

Information regarding Cytochrome P450 3A4


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Re: Methadone drug interaction

Post  drkamalika on Mon Sep 24, 2012 9:56 pm

Thanks for the chart. bravo.

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Re: Methadone drug interaction

Post  Admin on Mon Sep 24, 2012 10:06 pm

Thanks for posting this good question.

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