seroquel interfering with lorazepam?

[Wooster]

I'm going up on slurroquel, ladies and germs. Titrating up to 200 mg in the next few days if its tolerable.

The PI sheet for slurroquel says:

The mean oral clearance of lorazepam (2 mg, single dose) was reduced by 20% in the presence of quetiapine administered as 250 mg tid dosing.

Can someone please explain this to me in plain English?

Does this mean the lorazepam sticks around 20% longer than it did before?

Peace,

Wooster (still hangin' in there)

Edited to fix typos

[Silver]

Yes, you read that correctly.

But they were co-administering 250 mg of Seroquel three times per day.

[Wooster]

Thanks, Silver.

Golly gee you're swell.

Ok, pandering aside, what does that really mean?

Like possibly that I have to take less lorazepam because it's around 20% longer (like if it's usually around for 6 hrs, it might be around up to a little over 7 hours)?

Granted, yes, this is at less than 1/3 of the dosing they're talking about.

Just wondering....

Peace,

Wooster *whistling in the dark*

[Silver]

Yes, clearance refers to rate, and there's a decent explanation here.

If you are clearing the drug more slowly, and taking it on a regular basis, there's the possibility of building up a higher level over time.

Since you're taking a relatively short acting drug, with a relatively small increase in rate of clearance, and you're taking it on a sparing schedule, I don't see too much reason for concern.

I mean, make sure you're OK to go before you fly a jet plane or operate a cheese grater, but I suspect you'll notice a lot more sedation from the Seroquel than you would from the lorazepam.

Talk to your psyNP. The doses of both drugs are low enough that I suspect she'll tell you to just proceed as per normal, and give you the option of reducing your lorazepam by 0.25 mg per dose if it's bothering you.

And, of course, it's <1/3 the dose, yes. Doesn't really tell you much unless you know what the nature of the interaction is and then the level at which Drug A alters Process B which affects Drug C...

What's curious to me is that neither Stockley's nor Micromedex flag this as a significant interaction, and lorazepam is one of the cleaner choices for interactions, as it doesn't go through 3A4... I'd expect some other benzodiazepines to slow, but not lorazepam.

So it's a conjugation thing?... Anyway, I find a heap of articles that say they didn't find an interaction, and the PI sheet, which says that they did.

Sorry, rambling.

[CER]

I'm going up on slurroquel, ladies and germs. Titrating up to 200 mg in the next few days if its tolerable.

I like that, "slurroquel." I'll have to use that sometime.

Yes.

*heh heh*

[null0trooper]

What's curious to me is that neither Stockley's nor Micromedex flag this as a significant interaction, and lorazepam is one of the cleaner choices for interactions, as it doesn't go through 3A4... I'd expect some other benzodiazepines to slow, but not lorazepam.

So it's a conjugation thing?... Anyway, I find a heap of articles that say they didn't find an interaction, and the PI sheet, which says that they did.

No reaction in P450 system, probably.

NZ PI Sheet:

Glucuronidation to form lorazepam-glucuronide is the major pathway for metabolism. Minor metabolites include a hydroxylated derivative, a quinazolinone derivative and a quinazoline carboxylic acid. Seventy to seventy-five percent of the dose is excreted as the glucuronide in the urine. All the metabolites of lorazepam are inactive. There is no evidence for enzyme induction with lorazepam and it is not a substrate for the N-dealkylating enzymes of cytochrome P450.

I found this ACP 1999 article stating "None of all six atypical antipsychotic drugs are identified as significant inhibitors or inducers to any co-administered medication." So it's not surprising you didn't find much to support a specific interaction - they didn't either.

Looking for generally for articles on quetiapine and inhibition of gluconuridation pulls several articles suggesting that quetiapine grossly affects CBZ levels by inhibiting gluconuridation (or maybe it's just a more competitive substrate.) Since lorazepam is cleared through the same mechanism, there is probably a similar risk of reduced clearance.

[Wooster]

Yowza. *shakes brain around to see if there's any language comprehension going on... looks like a snow-globe*

Thanks for the info, nulltrooper and Silver.