Harm Reduction Who's used new sleep med lemborexant (dayvigo) especially same time as methadone?

[Echotango]

Its been prescribed for sleep starting 2020 as a new mode of action medication.

Its a CYP2B6 inducer the main way methadone metabolizes I'm unsure if taking it for sleep at night will make methadone taken in morning feel weaker or not? If anyone has a opinion about this it'd be helpful.

 

[deficiT]

Its been prescribed for sleep starting 2020 as a new mode of action medication.

Its a CYP2B6 inducer the main way methadone metabolizes I'm unsure if taking it for sleep at night will make methadone taken in morning feel weaker or not? If anyone has a opinion about this it'd be helpful.

This is the first thing I found about an interaction from Medscape:

"methadone will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.

lemborexant, methadone. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects."

It was in the "Monitor Closely" category, one step below "severe find alternative "

 

[Echotango]

@deficiT Methadone inhibits CYP2D6 not CYP3A4 iirc so that doesn't make sense.

This link says how it decreases bupropion via CYP2B6 metabolism.

Evaluation of the CYP3A and CYP2B6 Drug-Drug Interaction Potential of Lemborexant - PubMed

Lemborexant is approved for treating insomnia and is under investigation for treating irregular sleep-wake rhythm disorder. Based on in vitro drug-drug interaction (DDI) characteristics, phase 1, open-label DDI studies were conducted to evaluate lemborexant's cytochrome P450 3A (CYP3A) and...

pubmed.ncbi.nlm.nih.gov

I'm not sure if the half-life matters for lemborexant as I will be taking it roughly 10-12 hours apart from Methadone BTW in case that makes a difference.

This is another link regarding Methadone being metabolized by CYP2B6 in case anyone finds it interesting. https://pubmed.ncbi.nlm.nih.gov/33455055/

 

[Skorpio]

@deficiT Methadone inhibits CYP2D6 not CYP3A4 iirc so that doesn't make sense.

This link says how it decreases bupropion via CYP2B6 metabolism.

Evaluation of the CYP3A and CYP2B6 Drug-Drug Interaction Potential of Lemborexant - PubMed

Lemborexant is approved for treating insomnia and is under investigation for treating irregular sleep-wake rhythm disorder. Based on in vitro drug-drug interaction (DDI) characteristics, phase 1, open-label DDI studies were conducted to evaluate lemborexant's cytochrome P450 3A (CYP3A) and...

pubmed.ncbi.nlm.nih.gov

I'm not sure if the half-life matters for lemborexant as I will be taking it roughly 10-12 hours apart from Methadone BTW in case that makes a difference.

This is another link regarding Methadone being metabolized by CYP2B6 in case anyone finds it interesting. https://pubmed.ncbi.nlm.nih.gov/33455055/

Looked at articles citing this, and not much newer has been written.

From the study, it talks about a 50% area under the curve of buproprion, so I would definately be prepared for up to that decrease. It is also metabolized by CYP3A4 and that may reduce the decrease in AUC.

The CYP2B6 induction occurs through increases in gene expression which occurs through steroid receptor signaling (hypothesized to be CAR receptors), which take from hours to days fo fully transudce their signals. This means it's not as much an effect of having the drug in your system as it is an effect of using the drug.

This may be a good thing to bring up to staff at the clinic or the doctor in case you begin to slip into precipitated withdrawals.

From Evaluation of the CYP3A and CYP2B6 Drug-Drug Interaction Potential of Lemborexant

.Lemborexant resulted in approximate 0.5-fold decreases in the Cmax and AUC0-inf of S-bupropion, a sensitive CYP2B6 substrate. Whereas this level of decrease in exposure may not be clinically relevant, concomitant use of lemborexant may lead to a decrease in the efficacy of CYP2B6 substrates and therefore would need to be monitored. The finding that lemborexant did not have an inductive effect on midazolam, but had a small effect on bupropion, likely reflects the understanding that induction of CYP2B6 is regulated not only by the pregnane X receptor (PXR), but also by the constitutive androstane receptor (CAR).7, 8 PXR activators induce CYP2B6 as well as CYP3A4. CAR activators also induce CYP2B6 and show greater activation of CYP2B6 gene expression than PXR activators.8 Considering the outcomes of our DDI studies with midazolam and bupropion, lemborexant may have a greater activation effect on CAR than PXR.