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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 12 of 12. This is the beginning of the thread.
Posted by janejj on July 31, 2002, at 14:04:39
Hey
I need to know if taking Prozac is going to Prevent the pain killing properties of Codiene ?
Something to do with cytochrome 2d6, especially cyp2d6 which is inhibited whilst taking an SSRI.
Thanks Janejj
Posted by ADD'er in SC on July 31, 2002, at 19:09:28
In reply to Prozac, Codeine, cyp2d6..CamW or anyone ?, posted by janejj on July 31, 2002, at 14:04:39
Seems that you may be onto something. My handy dandy epocrates on my handheld said that Prozac may decrease the efficacy of codeine....to use an alternative. I would look further into it. Have you noticed any decreased effect?
Posted by Cam W. on July 31, 2002, at 20:12:51
In reply to Prozac, Codeine, cyp2d6..CamW or anyone ?, posted by janejj on July 31, 2002, at 14:04:39
Jane - I was at a presentation about 5 years ago where the presenter had mentioned that Paxil (paroxetine), and to a lesser extent Prozac (fluoxetine) inhibited the conversion of codeine to morphine (the active metabolite of codeine - ie. codeine's main active constituent).
I have heard this interaction sporatically, butI have seen no hard evidence. Paxil's monograph used to contain a blurb on the inhibiton of the conversion, butI looked tonight and it's no longer there.
Codeine is not metabolized to any major extent by CYP-2D6, but is at least partially metabolized by one of those lesser known and weirder cytochrome enzymes. If memory serves me correctly, it is CYP-2C17 (or something like that). The CPS says that codeine's main excretable metabolite is glucuronide-conjugated morphine, and glucuronide-conjugation is done mainly by the cytochrome system, is also done in the blood stream.
So, is the Prozac/Paxil-codeine interaction a myth? I don't know. It seems to have all the ingredients of an urban legend (eg. [1] "a friend of a friend told me that the pain in his hip (back, knee - mostly likely = neck) came back when he started Prozac; [2] the story is believable enough that it "might" be true .... [3] the story changes to fit the times: Prozac was released first, thus the story began with it; the Paxil became the new wonder drug, so the story changed to reflect this.
It might have been a disgruntled competing drug rep &/or former employee that started this urban legend (urban legend sound so much better than rumor).
An explanation that I came to while typing this post is that the list of start-up side effects, as well as withdrawl symptoms, include various types of pain: flu-like symptoms, abdominal pain, myalgia, limp willy (oh, sorry .... that's just a pain in the ass), back pain, itching, etc. Also, other start-up side effects include anxiety and nervousness. Combine this with the pain and depression, of course you codeine isn't going to work any more.
The preceding is just a guess on my part, but like an urban legend, it sounds good.
;^)
- Cam
Posted by Sunnely on July 31, 2002, at 20:28:54
In reply to Prozac, Codeine, cyp2d6..CamW or anyone ?, posted by janejj on July 31, 2002, at 14:04:39
Yes, fluoxetine (Prozac) will prevent the pain-killing effects of codeine via inhibition of the CYP2D6 action.
Codeine is a "pro-drug." It is the parent compound but an inactive one. It needs to be converted into an active metabolite which possesses the pain-killing properties. This is achieved by breaking down codeine through the action of the enzyme called CYP2D6. If you combine codeine with Prozac, the conversion process is prevented because Prozac potently inhibits the action of CYP2D6, hence loss of pain-killing effects. BTW, the active metabolite which posseses the pain-killing properties that codeine is converted into is called morphine. An exactly similar event will occur if you combine codeine with paroxetine (Paxil) since Paxil is also a potent inhibitor of CYP2D6.
On a related note, tramadol (Ultram) will lose its pain-killing properties if combined with drugs that are inhibitors of CYP2D6 (e.g., Prozac, Paxil). Ultram is also a "pro-drug," i.e., it needs to be converted into an active metabolite to be an effective pain-killer. The active metabolite is called "M1." Another potential risks of hindering the conversion of tramadol to M1 by Prozac or Paxil is the possiblity of serotonin syndrome and seizure episode, although the latter appears to occur at higher dose of tramadol. It appears that the parent compound, tramadol, has serotonergic effect.
On another related note, some "pro-drugs" have been removed from the U.S. market because of deadly interactions with other drugs or beverages. Example of these drugs are terfenadine (Seldane) and astemizole (Hismanal). Both are nonsedating antihistamines (for hay fever). For example, terfenadine (inactive parent compound) needs to be converted to an active metabolite (fexofenadine) in order to be effective for hay fever. Terfenadine is metabolized via CYP3A4 and converted to the active metabolite, fexofenadine. Unfortunately, if terfenadine is combined with a drug or agent that inhibits the action of CYP3A4 (e.g., grapefruit juice), terfenadine accumulates in the system. In excess, terfenadine is harmful to the heart. Several sudden deaths were reported to the FDA because of these interactions. Subsequently, Seldane and Hismanal (and Propulsid) were removed from the U.S. market. As an offshoot, a safer version of Seldane, consisting mainly of the active metabolite (not harmful to the heart) was developed. It is better known as Allegra.
> Hey
>
> I need to know if taking Prozac is going to Prevent the pain killing properties of Codiene ?
>
> Something to do with cytochrome 2d6, especially cyp2d6 which is inhibited whilst taking an SSRI.
>
> Thanks Janejj
Posted by fairnymph on August 1, 2002, at 0:19:40
In reply to Prozac, Codeine, cyp2d6..CamW or anyone ?, posted by janejj on July 31, 2002, at 14:04:39
I have taken codeine many times while on prozac (40mg/day) and did not find that the codeine was any less effective for my pain.
~fairnymph
Posted by Cam W. on August 1, 2002, at 10:45:26
In reply to Re: Prozac, Codeine, cyp2d6..CamW or anyone ? » janejj, posted by Sunnely on July 31, 2002, at 20:28:54
Sunnely - Out of curiosity, is the Prozac/codeine interaction clinically significant? more Many patients I have dealt with have had a traumatic incident (eg. car accident, fall a work, etc.) and subsequently have become depressed.
Docs in our area are fairly free with the Tylenol#3, but only use more potent anagesics short term (ie. at the time of the accident, and usually for 2 weeks afterward). If this interaction had any real effect on treatment, surely they would have listed it in the CPS (Canadian PDR) and is this interaction listed in the PDR.
Thanks for your time Sunnely - Cam
Also, do you know if the catalyst for the Prozac/codeine interaction in saturable. If it is, this could have clinical significance.
Posted by janejj on August 1, 2002, at 15:46:52
In reply to Re: Prozac, Codeine, cyp2d6..CamW or anyone ? » Sunnely, posted by Cam W. on August 1, 2002, at 10:45:26
Hi,
Thanks for your responses, although now I am a little confused ! I am having surgery 2morrow and have been prescribed Tylenol 3, just hoping that its going to work !!!
Thanks,
Janejj
Posted by katekite on August 1, 2002, at 19:10:10
In reply to Re: Prozac, Codeine, cyp2d6..CamW or anyone ? » janejj, posted by Cam W. on July 31, 2002, at 20:12:51
I'm on a big kick about effects of hormones lately and obsessive interest easily leads to far fetched ideas (well at least for me), so take this idea with a grain of salt, LOL.
Just was thinking that ssris will often normalize the HPA (adrenal) axis when they work. Since cortisol is an anti-inflammatory adrenal hormone that can be elevated or out of whack in general in depression, alcoholism and anxiety, normalizing (probably decreasing production) it might make you naturally start to feel pain more. More cortisol (like a cortisone shot) equals less pain, so maybe less cortisol would mean more pain.
An odd hypothesis of mine since headaches are painful and ssris are used in migraine prevention.
Many grains of salt.
kate
Posted by jazzdog on August 2, 2002, at 11:37:13
In reply to Re: Prozac, Codeine, cyp2d6..CamW or anyone ? » janejj, posted by Sunnely on July 31, 2002, at 20:28:54
Hi Sunnely -
I'm currently taking tylenol with codeine for hip bursitis, and am in week four of a Wellbutrin trial. Do you happen to know if Wellbutrin and codeine also act against one another?
Thanks, Jane
Posted by Sunnely on August 2, 2002, at 20:24:42
In reply to Re: Prozac, Codeine, cyp2d6..CamW or anyone ? » Sunnely, posted by jazzdog on August 2, 2002, at 11:37:13
Bupropion (Wellbutrin), like Prozac and Paxil although not as potent, inhibits the break down (metabolism) of codeine (pro-drug) to morphine (active compound) via CYP2D6. This could lessen the pain-killing (analgesic) effect of acetaminophen + codeine. The combination of acetaminophen + codeine is more popularly known as Tylenol # 2, Tylenol # 3, or Tylenol # 4.
Wellbutrin could also lessen the analgesic effect of oxycodone (pro-drug) as it inhibits oxycodone's break down to oxymorphine (active compound). This drug is more popularly known as Oxycontin.
Wellbutrin could also lessen the analgesic effect of hydrocodone (pro-drug) as it inhibits hydrocodone's break down to hydromorphone (active compound). The combination of acetaminophen + hydrocodone is more popularly known as Vicodin.
The following drugs inhibit the enzyme CYP2D6 and may lessen the analgesic effect of codeine:
Potent CYP2D6 inhibitors: cimetidine (Tagamet), fluoxetine (Prozac), paroxetine (Paxil), quinidine (Quinaglute), ritonavir (Norvir).
Less potent CYP2D6 inhibitors: amiodarone (Cordarone), cannabionoids, celecoxib (Celebrex), bupropion (Wellbutrin), desipramine (Norpramin), fluphenazine (Prolixin), haloperidol (Haldol), methylphenidate (Ritalin, Concerta, Focalin), moclobemide (Mannerix), propafenone (Rhythmol), ranitidine (Zantac), sertraline (Zoloft), thioridazine (Mellaril), ticlopidine (Ticlid), venlafaxine (Effexor), vinblastine (Velban). NOTE: Some of these drugs may not lead to clinically significant interaction with codeine.
It does not appear that codeine interferes with the break down of Wellbutrin.
> Hi Sunnely -
>
> I'm currently taking tylenol with codeine for hip bursitis, and am in week four of a Wellbutrin trial. Do you happen to know if Wellbutrin and codeine also act against one another?
>
> Thanks, Jane
Posted by janejj on August 3, 2002, at 12:33:02
In reply to Re: Prozac, Codeine, cyp2d6..CamW or anyone ? » Sunnely » jazzdog, posted by Sunnely on August 2, 2002, at 20:24:42
Hi,
Well I am now taking codeine to relieve my pain and it seems to be working, making me happy, hehehehe. I do wonder if it is working at its optimum though.
Janejj
Posted by bordendazed on August 5, 2002, at 13:27:06
In reply to Update , posted by janejj on August 3, 2002, at 12:33:02
Noticed that Darvocet seems to be less effective since upping Prozac dose to 40mg/day.
Also - this is a great tech thread, anyone have additional links to more data on 'pro-drug' opiates?
This is the end of the thread.
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