Codeine + Effexor (venlafaxine)

Got this from the wiki on codeine:

"Codeine has also been known to interact negatively with some psychiatric medications such as reboxetine and venlafaxine."

Pity the reference they gave was useless.

Have already nearly died from tramadol + effexor (SS) and don't want to risk it again yet use codeine daily.

Any further knowledge on this perceived containdiction?

On a side note: effexor is like the small kid at school who wants to fight everyone and even though most people are nice to him l(ike the opiate crew) and he just gets mad and kicks a fuss up; it doesn't mix well with... anything.

I'd double check w/ your pharmacist... or you can call up any random pharmacy to ask... theyll give u the answer w/o asking for info... also if you go to a chain pharmacy they should have a list of the meds your taking and its the pharmacist jobs to check for interactions before dispensing medications... if they dont have ur info on file (ie u went to another pharmacy) u can tell them that ur taking codeine for a bad cough n i was wondering if it interacted w/ my meds... also if u have ins n theyare paying for ur meds ur ins company will also check for interactions (as long as you use ur ins for meds [if applicable])

http://www.rxlist.com
http://www.drugs.com/drug_interactions.php

"codeine
Effexor (venlafaxine)
Interactions between your selected drugs

No results found - however, this does not necessarily mean no interactions exist. ALWAYS consult with your doctor or pharmacist."

I've heard of this too, but I doubt it. My sources don't reveal any interactions. Worst that will happen is probably an upset stomach or reduced analgesia.

I used to be on Effexor...was the wrong drug for me personally.

I took codeine on it fine
I took tramadol on it fine.

This doesn't mean it'll be the same for you though.

well the tramadol and venlafaxine interaction is obviously due to the possibility of seretonin syndrome as you unfortunately experienced (and both will elevate noradrenaline alot which may be a problem but not as bad as SS i would imagine) but codeine doesnt have seretonergic or noradrenergic interactions so that mechanism is atleast not a possibility

my educated guess at this possible interaction is due to the enzymes responisible for their metabolism in the liver. Both Venlafaxine and reboxetine are metabolised by CYP3A4 enzyme. Codeine is converted to morphine by CYP2D6 but the morphine is broken down by the CYP3A4 and if it is busy metabolising venlafaxine or reboxetine for example levels of morphine would be increased/prolonged.

So basically imo it is a enzyme related precaution that is nowhere near as imperative as the seretonergic tramadol to venlafaxine or SSRI interaction

I dont know about codeine and effexor but recently I was prescribed tramadol from my doctor but the pharmacy call him up and told him that he needed to change that drug to another since you can get a seisure from mixing tramadol and effexor

jachung said:

I dont know about codeine and effexor but recently I was prescribed tramadol from my doctor but the pharmacy call him up and told him that he needed to change that drug to another since you can get a seisure from mixing tramadol and effexor

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That sounds like it could be a bigger problem then I thought. Usually pharmacies don't pull rank like that over doctors unless there's a good chance of dangerous reactions or interactions with other drugs.

I might have just been lucky with the effexor + tramadol. Now that I think of it I was probably also on codeine as well I would have done this combo at least a few times and no problems (this doesn't mean it's safe though!)

Doses:
Effexor 225mg
Tramadol - 100mg x 2 (slow release if I remember right)
Codeine - 300mg

If anyone has any experience with mixing these please post asap. These drugs are pretty common and I'd imagine a fair few people would be mixing them..if there's a high risk of seizure it's important people know.

good post mcwally

I take Effexor and I have nothing but praise for the drug. It has completely changed my life in a positive way.

I pick up a box of Nurofen+ every time I renew my script for Effexor and the pharmacist has never mentioned anything about a negative interaction between the two. I have taken the two together many, many times and have never felt any indication that they may interact negatively.

Thanks for the replies, as I mentioned have not have had a problem after prolonged combined use of the two but didn't want some nasty surprise. Much appreciated.

Just quickly: never mix effexor and tramadol! Have been trying to preach this on these forums and it shocks me how many people casually take the two. This is a deadly combination in even low doses. I was on life support after taking 75mg venlafaxine and a single tramadol pill in India. The cause was deemed serotonin syndrome; was not breathing for many minutes, heart kept on failing, needed resuscitation, anatropes to keep curculation running and I was like the people on this board that didn't know how dangerous it is. Just read the booklet that comes in the effexor packet or do a simple Google search, many people die of taking the two and as a harm minimisation group I'm shocked it isn't more well known.

The reason I got to this situation was that the pharmacist giving me tramadol for a hangover in Thailand did not enquire as to any SNRIs I was on and my stupid trusting Australian mind thought I would be fine. To the poster that had a doctor who prescribed tramadol and effexor simultaneously, buy a box of chocolates for your pharmacist b/c they probably saved your life with their knowledge and get rid of that retarded, negligent doctor who did such a thing. That is seriously bordering on malpractice and even a simple search of MIMS on the computer comes up with a red box signifying a definite contraindiction. I'm not even joking, that is seriously poor and disturbing general practice on their behalf.

My psychiatrist prescribes me effexor and tramadol. He said that the chance of serotonin syndrome was possible but extremely rare. Are you 100% sure what you had was serotonin syndrome KingConvenience? I know that tramadol itself causes an allergic reaction in some people, perhaps that was it?

mcwally said:

my educated guess at this possible interaction is due to the enzymes responisible for their metabolism in the liver. Both Venlafaxine and reboxetine are metabolised by CYP3A4 enzyme. Codeine is converted to morphine by CYP2D6 but the morphine is broken down by the CYP3A4 and if it is busy metabolising venlafaxine or reboxetine for example levels of morphine would be increased/prolonged.

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That's a good point, I never considered that. I was basically working from the opposite assumption (i.e. reduced analgesia). Seeing as numerous SSRIs inhibit CYP2D6 and thus inhibit the conversion of codeine to morphine. Going by what you said, it may increase analgesia and consequently euphoria too.

This could help explain why I (as someone who takes 300mg of venlafaxine a day) find codiene extremely pleasant.

vanth said:

My psychiatrist prescribes me effexor and tramadol. He said that the chance of serotonin syndrome was possible but extremely rare. Are you 100% sure what you had was serotonin syndrome KingConvenience? I know that tramadol itself causes an allergic reaction in some people, perhaps that was it?

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Yah am sure, the extreme end of serotonin syndrome, confirmed by at least 3 docs. Some of them told me effexor and tramadol was extremely dangerous together and quite easy to die from (Read the pamphlet inside the Effexor box it states you should NEVER take the 2 together). Someone on this board recently died from exactly this and at small doses.

As I said, only 75mg venlafaxine and one or two tramadol tablets. Thing is that I had had the combo before and it was fine.

The mitigating factor was that I was in India and quite run-down body wise, most likely dehydrated and all that.

But if I was you I would most surely check with your doc. Don't have time right now to find the thread about the guy who died but there's a pic of him in the darkside thread on drug related deaths. Another doctor friend says that a decent amount of emergency admissions are from taking these together aswell.

Most likely the combo won't kill you but every time you take it your are treading a very fine line.

I wouldn't be writing all this if I wasn't trying to make a point, even if you manage to survive SS you sort of wish it had killed you. Not very fun.

Put is this way, I have taken just about every drug on the planet in quite stupid amounts and even stupider combos and this is the only thing that has ever tripped me up, and came close to killing me (well it did but was revived).

PS: I am quite partial to codeine as well

I would stick to that instead of tramadol considering it doesn't seem to conflict with effexor.

Well I was prescribed tramadol for my back pain because I am actually addicted to codiene It was suggested to me by both a regular gp and my psychiatrist who both knew I take effexor, I was just told to keep it under 400mg/day. You have definitely given me a scare though, I will have to look into this more. Thanks for the information.

Well I talked to my psychiatrist today and he said in all his time working at a pain clinic he's never seen anyone develop serotonin syndrome from mixing effexor and tramadol, though it is theoretically possible, and that it does happen very very occasionally.

I had been taking it for a while already and apparently if I was going to develop serotonin syndrome by now I would have, so I'm going to continue taking it.

had another look at the enzymes here, (dabbling in some tramadol myself atm) effexor is actually predominantly metabolised by CYP2D6 (not 3A4 like I said above), but it is also a relatively weak inhibitor of CYD2D6 and CYP3A4.

so back to the interactions when on venlafaxine (ignoring SS/seizures affects):

codeine: less efficient conversion to morphine due to load on 2D6 and its inhibition, of what actually gets converted (to morphine) atleast its metabolism is weakly inhibited.

tramadol: CYP2D6 converts tramadol to O-desmethyl-tramadol (M1) and CYP3A4/CYP2B6 converts to N-desmethyl-tramadol (M2). So basically I would imagine the effects of tramadol are even more screwed than codeine not only because both active metabolites' (M1/M2) are reduced due to venlafaxines inhibition of 2D6 and 3A4, but M1 is the stronger and it would be more inhibited.

So that would be a better explanation of effexor/codeine/tramadol enzyme interactions from my small research. So imo analgesia and buzz reduced from codeine and tramadol if on venlafaxine. Obviously other stuff like dose timing, dose levels, persons natural variance of CYP2D6 enzyme availability etc.

I havent looked into what part causes the seretonergic/noradrenergic effects of tramadol anyone know bout that?

But yeh Vanth your not getting SS, seizures and I presume enough analgeisa? its all apples despite the above

Effexor And Tramadol Combined

I am currently going through the issue of stopping the use of effexor and tramadol. I had been asking my doctor for months about the "twitching" that was going on with my body. Thank God I really pushed the issue with him last Wednesday. I am now totally off tramadol but have continued the use of Vicodan. Can anyone tell me how long the continued effects will last? I'm down to only a couple a night but they're stronger than the previous ones. Hopefully tonight will be a "twitch" free night. Any help would greatly be appreciated. Looks like I got off the combination in the nick of time.