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use of Olanzapine as antiemetic in refractory nausea and vomiting in advanced ca
Posted by: Ms Shelagh O'Haire (IP Logged)
Date: February 09, 2005 10:26AM

Hi all, I recently read an article in Journal of Pain and Symptom Management regarding the successful use of Olanzapine (Zyprexa) in refractory N & V in two reported case studies. I was wondering if any or many of you out there are using same in the area of palliative care - if so, how successfully and in what form and dose? I include the reference for the article. Would be very interested to hear from you.
Srivastava et al 'Olanzapine as an antiemetic in refractory nausea and vomiting in advanced cancer'- Journal of Pain and Symptom Management (2003) 25 no.6 p578-582 - Shelagh

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advanced ca
Posted by: Doctor Mervyn Dean (IP Logged)
Date: February 09, 2005 12:00PM

I have used olanzapine several times since reading the JPSM article. I don't have the specific data to hand, but my recollection is that all the patients had extensive intra-abdominal malignancy, but not bowel obstruction. Response to standard anti-emetics was limited or ineffective. Olanzapine, starting at 2.5mg od, progressing to bid, and then 5mg bid if necessary was effective in, I would estimate, 80-85% of cases (but numbers are small - less than ten).

I still consider it a "last resort" anti-emetic, but it does seem to be very effective in many otherwise resistant cases. Formerly, I would have trialled methotrimaprazine (levopromazine), but the olanzapine is far less sedating. Hope this helps.

Mervyn

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advanced ca
Posted by: Doctor Zbigniew Zylicz (IP Logged)
Date: February 10, 2005 08:45AM

For resistant nausea and vomiting we usually choos for levomepromazine (methotrimeprazine) orally as drops. It workt good in low dose. But when the dose is going up, the anticholinergic effects may be significant. Than we change to olanzapine (I have also less than 10 cases). Olanzapine is just another wide spectrum antiemetic, with less anticholinergic effects, easy to be administered as a smelt-tablet (How would you call it in the UK?) on the tong. It is much more expensive so it is good to keep it as a last resort, although the drawback than is taht it is not available as injectable.
Adverse effects in dehydrated patients: mainly sleepiness.
Other uses: in delirium, when patients respond adversely to haloperidol.

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advanced ca
Posted by: Doctor paul howard (IP Logged)
Date: February 10, 2005 09:06AM

Dear Mervyn,

Had the people you mentioned already tried levomepromazine, or were you using olanzapine where you would previously have used levomepromazine?

Many thanks

Paul

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advanced ca
Posted by: Ms Sharon Wells (IP Logged)
Date: February 10, 2005 06:48PM

Here in the US we have had success with the following suppositories:
MetoCloPhen
Suppository ..............
Ingredient............... ....Amt Each.... ....Amt / 100....
Metoclopramide HCl 40 mg 4.000gms
Haloperidol powder 1 mg 100mgs
Dexamethasone powder 10 mg 2.10gms
Diphenhydramine powder 25 mg 2.50gms
Benztropine Mesylate powder 1 mg 100mgs
Silica Gel powder 20 mg 2.00gms
Fatty Base (MBK) 2.03gms 203gms

We do not have many of the medications you have in the UK, such as levomepromazine. I hope this is helpful. We have it compounded by a local pharmacy.

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advanced ca
Posted by: Doctor Alex Nicholson (IP Logged)
Date: February 11, 2005 01:33PM

I have used olanzapine several times over the last four years with, usually, a good response to refractory nausea and vomiting, but always after levomepromazine. The effect has been enhanced by the coadministration of a small dose of dexamethasone (2-4mg daily). It is now available in the UK as an injectable formulation - powder for reconstitution at a concentration of 5mg/ml - but I have not yet given it in this wa, preferring the orodispersible Velotabs.

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advanced ca
Posted by: Doctor Mervyn Dean (IP Logged)
Date: February 11, 2005 06:42PM

Hi, Paul,

Because the olanzapine is less sedating than the methotrimeprazine/ levopromazine I go straight to the olanzapine. They cover pretty much the same receptors (both cover anticholinergic, dopamine-2, and serotonin receptors; methotrimeprazine also covers H1) so I don't see the advantage of trialling one before the other. Of course, practice can disprove the theory, so if anyone has experience of using the two I'd be interested to know if response to one predicts (or not) the response to the other.

Mervyn

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advanced ca
Posted by: Doctor Zbigniew Zylicz (IP Logged)
Date: February 12, 2005 09:06AM

Hi, Mervin,
Of course Olanzapine would work in most cases of N&V where levomepromazine is also active. But: levomepromazine can be used in drops (if you do not have drops, you can make them diluting 1 ml (25 mg) levomepromazine ampule with 9 ml water. Most patient respond to the dose as low as 1,25 mg (0,5 ml)per time. So if one ampule cost 1 euro (0,8 GBP) yo will use 0,15 Euro (0,12 GBP)/day. For Olanzapine the costs are about 2,8 Euro (2 GBP) per day. 20 times more expensive! You also probably very much overtreat patients. The dose could be much lower, but the tablets are going down only to 2,5 mg.
And it is not true that olanzapine and levomepromazine have the same activity. It is a mix of activities on the different receptors which makes that the drug is a good antiemetic or a good sedative. These mixes are different for all antipsychotics and when one drug (cheaper?) is not working enough you may switch it to the other. (more expensive?). In no means chepaer drugs are per definition better or worse than expensive ones (in this context).

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advanced ca
Posted by: Doctor Dean Blackburn (IP Logged)
Date: February 12, 2005 01:36PM

Hi, Can I just clarify about which receptor sites olanzapine works at, or more specifically which receptor sites it does not. From the above posts and a review of this site (drug information) it appears that it does NOT act at histamine or 5H3 receptors. Therefore if necessary good add in drugs would be cyclizine and ondansetron. Is this correct?
Finaly now we have it available as an injection, what about its use in a syringe driver? Is it compatible with the usually drugs? does it make skin sites sore?
Thanks

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advance
Posted by: Doctor ruth Todd (IP Logged)
Date: February 12, 2005 04:16PM

I have followed this thread with interest. I was not aware of olanzepine being used as an antiemetic but can appreciate why it would have this effect.However, we have a gentleman currently in the hospice (rectal ca with liver mets) who is taking olanzepine 10mg daily because of a recent episode of psychosis. When he developed problems with nausea and vomiting he seemed to respond well to the addition of levopromeprazine.

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advanced ca
Posted by: Doctor Mervyn Dean (IP Logged)
Date: February 14, 2005 03:17PM

Hi,

Re the receptor activity of olanzapine, I agree with Dean's comments on the information from the formulary on this site. My source was the paper from the June 2003 JPSM (Srivastava et al 2003;25:578-582), in which they give a referenced statement that olanzapine acts at dopamine recptors D1-4, serotonin receptors 5HT2A, 5HT2C, 5HT3 and 5HT6, alpha-1 adrenergic recptors, histamine H1 receptors, and ACh muscarinic receptors m1-4. They state that this coverage is very similar to that of methotrimeprazine (levomepromazine). I don't have the paper in front of me so cannot give you their references for this information.

The authors also comment that there is less potential for drug interaction as olanzapine does not inhibit the cytochrome P450 (CYP2D6) system.

I have asked the pharmacist here for any information on this topic for both olanzapine and methotrimeprazine/levomepromazine, and if she finds anything informative I'll pass it on.

Thanks, Ben, for the cost analysis - I'll keep it in mind, and also the "drops" technique.

Mervyn

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advanced ca
Posted by: Doctor Mervyn Dean (IP Logged)
Date: February 15, 2005 03:03PM

I said that when I heard more from my pharmacist, I'd pass on the information. The following is from Micromedex Health Series, Vol 123 (1974-2005):

Methotrimeprazine (levomepromazine) is antagonistic at the following receptors: dopamine D2; serotonin 5HT2; histamine H1; and muscarinic cholinergic.

Olanzapine is antagonistic at these receptors: dopamine D1, D2, and D4; serotonin 5HT2A and 5HT2C; histamine H1; alpha-1 adrenergic; and muscarinic M1. The monograph goes on to say that olanzapine at 5mg/day occupies over 90% of the 5HT2 recptors, but only 55% of the D2 receptors.

According to this, olanzapine covers a few more subgroups of receptors, but whether this is clinically significant (in comparison with methotrimeprazine/levomepromazine) I do not know. Does anyone? I am also uncertain how much more benefit there would be from adding a 5HT3 blocker. Input to the vomiting centre (5HT2) is mediated in some cases by 5HT3.

I think that this confuses the picture nicely. As ever, we need some trials.

Mervyn

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advanced ca
Posted by: Doctor lucy boyland (IP Logged)
Date: June 24, 2007 06:55PM

I followed this thread with great interest and have since used oral olanzapine with much success for refractory nausea and vomiting. I wondered if many others are now using the injectable form? We have been told it can only be given im and wondered if anyone has used it sc, or even in a syringe driver (though I imagine in view of its long half life a bolus injection should be adequate)?
Many thanks
Lucy

Editors note: Would be interested to hear about its parenteral use in palliative care. There are these cautions for the injection:

Fatalities from oversedation or cardiorespiratory depression have occurred after higher than licensed doses or concurrent use with benzodiazepines. Monitor blood pressure, heart rate, respiratory rate and level of consciousness for at least 4h after IM olanzapine, and do not give parenteral benzodiazepines within 1h of IM olanzapine.

Please can colleagues using the injection report their palliative care experience of olanzapine (indication, dose, frequency)/any monitoring used/any caution regarding benzodiazepeines. Thank you.

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advance
Posted by: Doctor joel carter (IP Logged)
Date: June 24, 2007 10:59PM

I use sublinqual Olanzapine (zydis/zyprexa) very frequently for symptoms of nausea with success on most occasions in relevant clinical circumstances. Have use 2.5 - 5.0 mg sl/po q4-6h. I have found it a very good anxiolytic as alternative to lorazepam, with not as much sedation in older patients. It is also utilized as an appetite stimulant in our institution. Also, useful in regards to thought clarity issues/agitation. Overall, one of the most useful/versatile palliative meds in my tool kit...
Joel Carter MD/University of Minnesota

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advanced ca
Posted by: Miss inga andrew (IP Logged)
Date: June 27, 2007 10:24AM

We have used sub-cutaneous Olanzepine for nausea and vomiting recently in two patients with varying degrees of success. Before using it, we talked to Medical Information at Lilly who highlighted the cautions mentioned earlier and had no data on sub-cutaneous administration. However on discussion they could see no major problem with sub-cutaneous use.

Patient 1: Was using 2.5mg nocte sub cut in particular for nausea. She was started on it in the Hospice where she found it very beneficial and was discharged home on it. Unfortunately it was stopped at home on two different occasions and each time the nausea (and vomiting)came back but resolved when it was restarted. She suffered no adverse effects from it. In terms of concurrent benzodiazepine use, she was taking Lorazepam 0.5mg prn for anxiety/panic.

Patient 2: Was using 5mg nocte sub cut. Again started in the Hospice and discharged home on it. Nausea and vomiting definitely improved but unclear as to whether or not it was solely the Olanzepine as the dose of Metoclopramide via syringe driver did increase during the time. He had 10mg Midazolam in his syringe driver and again suffered no adverse effects.

Thanks

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advanced ca
Posted by: Miss inga andrew (IP Logged)
Date: June 28, 2007 08:52AM

Further to my previous message, yes both patients had tried Levomepromazine without success.
Thanks

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advance
Posted by: Doctor Ruth Brown (IP Logged)
Date: April 14, 2008 03:05PM

Probably a rather daft question but is there any evidence about the effect that Olanzepine may have on the "fit threshold" if used in a patient with brain mets?

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advanced ca
Posted by: Doctor Charlie Bond (IP Logged)
Role: Doctor
Organisation: Katharine House Hospice
Date: June 29, 2010 04:35PM

Can I re-vitalize this thread to ask if anyone has had further experience with use of Olanzapine SC ? (product literature noted and injectable comes with clear instructions only to initiate as inpatient). I have a patient with primary peritoneal CA, desperate to stay in the community. Metoclopramide and Levomepromazine caused distressing Parkinsonian tremor and cyclizine hasn't worked. We are trying Olanzapine oro-dispersible but may not be working due to high vomiting frequency. IV Ondansetron worked in hospital but she is in and out of functional bowel obstruction and I would rather not reduce bowel transit if I don't have to. We may have to use Granisetron and increase laxatives if there are no other options. (has also tried dexamethasone as co anti-emetic)

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advanced ca
Posted by: Mrs Judy Dobson (IP Logged)
Role: Nurse
Organisation: Hospice Seminars
Date: July 01, 2010 12:15AM

I was wondering about octreotide for this patient's problem???

Re: use of Olanzapine as antiemetic in refractory nausea and vomiting in advanced ca
Posted by: Doctor Scott King (IP Logged)
Role: Doctor
Organisation: Calvary Health Care Bethlehem
Date: July 01, 2010 02:01AM

I have used subcutaneous olanzapine for both intractable nausea and vomiting and agitated delirium. There is some limited evidence for its use in agitated delirium using 10mg 8 hourly PRN which was well tolerated, effective and no adverse skin reactions. I have had good results in both delirium and nausea. For nausea I start at 2.5mg BD or 5mg nocte. The main problematic side effect is sedation. The product information states that once the olanapine has been made in solution up it needs to be used in 1 hour, but as it has a long half life daily or BD doses work well in my experience.

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