Drug Interactions??
 

So...in an attempt to try to manage my pain, my pain doctor is taking me off Lyrica and is putting me on Cymbalta. The pharmacy wouldn't fill the script initially because of "drug interactions" and they needed to check with the doctor. They have now filled the script...but I haven't started it yet.

I looked up the possible interactions and I am a little worried about starting these new meds (not to mention a little miffed that the doctor didn't mention this when she changed my meds so that I could talk to her about it). My biggest concern isn't the fact that there might be an interaction...my concern is that I wouldn't know if there was because all the symptoms for this possible interaction are what I already have...and it can be a fatal condition. So all my warning signs for this possibility are shot and the doctor only wants to see me once every two months.

Why do I just feel like I have the worst luck with doctors? Or is this sort of thing just normal? Am I probably just worrying over nothing? I'm going to discuss with my primary doctor Friday when I see her before I start the Cymbalta. Anyone have any experience with Cymbalta? The major interaction is between that and the Tramadol. They also say in the commercial that there are risks with Cymbalta and NSAIDS and I am taking NSAIDS...but I didn't see that listed under the drug interactions that I looked up.

If anyone has any information or experience with this, I'd love to hear about it. Thanks!

I dont think there is anything to worry about...
 

I know so many people that take cymbalta and lyrica at the same time inculding myself a few years back and I had no problems. The combination of Cymbata and lyrica/neurontin is a great combo for rsd. :) I take cymbalta an tramadol, and the pharmisist tells me that and i say i have been taken them for months with no problems. I wouldnt be afraid to take them. You will never know until you take them and the doctor wouldnt give them if he didnt feel that it was safe! :) I am no doctor, I just speak from experience from myself and others that are on those same meds with no problems!

Alot depends on the dose of Tramadol used. Tramadol has some serotonergic potential and can be additive with SSRIs. Cymbalta is a mixed SSRI + SSNI product.

Here is a drug checker:

http://www.drugs.com/drug_interactions.html

Another good resource is www.rxlist.com for details on most common drugs used today. Use Ultram for the search on tramadol there.

That's good to know that you take them both with no bad interactions. My big concern I guess is that if there was a problem, how would I or the doctor know since I already have all the serious symptoms that you are supposed to look for? But I guess we do have to trust that our doctors know what they are doing.

Thanks for the links!

How are you doing on the cymbalta? Did you get all of the drug interactions worked out?

Not so good...sad to say. The solution from the pharmacy was to NOT fill the Tramadol so I am off that now. And the cymbalta does NOT seem to agree with me AT ALL. I started taking it last Friday and 30-45 minutes after I take it I get violently sick. I was already having problems with vomitting but this hits me SO much worse and it is like clockwork. I have tried taking it with food, without food, with my other meds, seperately from the other meds...nothing seems to change the fact that I get violently ill. Today I actually started choking (lasted about 30 seconds) while I was sick so now I am actually scared. On top of which the pain is significantly worse than it was before...though not sure if that's because the meds don't work or because I can't keep them down. Either way...if it's the cymbalta making me sick then it doesn't matter.

Oh well...trial and error continues...

Hello again. Sorry to hear what you are going through. You say the "trial and error continues." Forgive me, but that seems about right.

In essence, I think you're being treated for fibromyalgia or a peripheral neuropathy, but not CRPS, whether you've been let in on this bit of information or not. If I may, the proper name for Cymbalta is Duloxetine. And if you run a PubMed search for "Tramadol Duloxetine," you'll get 34 hits, almost all of them dealing with fibromyalgia or peripheral neuropathies. And of the 34 articles, only four are freely available through "PubMed Central," and then only three are in English:

Fibromyalgia: presentation and management with a focus on pharmacological treatment, Sumpton JE, Moulin DE, Pain Res Manag. 2008 Nov-Dec; 13(6):477-83, ONLINE TEXT @ http://www.ncbi.nlm.nih.gov/pmc/arti...f/prm13477.pdf

Management of fibromyalgia syndrome--an interdisciplinary evidence-based guideline [Behandlung des Fibromyalgiesyndroms – eine interdisziplinäre S3-Leitlinie], Häuser W, Arnold B, Eich W, et al, Ger Med Sci. 2008 Dec 9; 6: Doc 14, ONLINE TEXT @ http://www.ncbi.nlm.nih.gov/pmc/arti.../GMS-06-14.pdf

Effects of treatments for symptoms of painful diabetic neuropathy: systematic review, Wong MC, Chung JW, Wong TK, BMJ 2007 Jul 14; 335(7610): 87, Epub 2007 Jun 11, ONLINE TEXT @ http://www.ncbi.nlm.nih.gov/pmc/arti...s-00087-el.pdf

And what do each of them suggest by way of pharmacological therapies? With minor variations it's (1) Duloxetine (Cymbalta) ("FDA-approved indication for fibromyalgia"), (2) Tramadol and (3) Gabapentin (Neurontin) or Pregabalin (Lyrica). Sound familiar?

What sticks out here is the universality of Tramadol, whereas RSD/CRPS patients are treated with a host of opioids, most of us blowing through Ultram (Tramadol) in a few weeks on our way to much harder sauces. And the funny thing is that Tramadol has a particularly bad rap with nausea. By way of example, if you compare the FDA approved Prescribing Information sheets for oxycodone and Ultram, you'll see that oxycodone is associated with nausea in less than 3% of those participating in trials, while nausea with is dose-dependent with Tramadol, ranging from 15.1 to 26.2%!!! Compare, http://pain-topics.org/pdf/PI/PI_Oxy...blets-30mg.pdf with, http://www.ortho-mcneil.com/ortho-mc...r.pdf#zoom=100.

In fact, there's a whole sub-industry devoted to combining Tramadol with Acetaminophen (Tylenol or Paracetamol in the U.K) just to cut down on the side-effects of Tramadol, primarily nausea. See, e.g., Tramadol/paracetamol combination tablet for postoperative pain following ambulatory hand surgery: a double-blind, double-dummy, randomized, parallel-group trial, Rawal N, Macquaire V, Catalá E et al, J Pain Res. 2011 Apr 8; 4:103-10, ONLINE TEXT @ http://www.ncbi.nlm.nih.gov/pubmed/21559356:

Adverse events (mainly nausea, dizziness, somnolence, vomiting, and increased sweating) occurred less frequently in patients under combination treatment (P = 0.004).

So if your doctors aren't going to give you oxycodone, why not cut the Tramadol with a little of your old friend, Tylenol? [In the U.S., the product is marketed under the trade-name Ultracet.] I would submit it's because they are slavishly adhering to the Groupthink on treating fibromyalgia and/or peripheral neuropathies. To the letter, thank you.

So, unless you have already done so, can't you please just get an ASAP consultation with Timothy Lubinow, MD at Rush, just in the name of a second opinion on CRPS? I'm on bended knee on this one, where all of the evidence suggests that no one's changes of going into permanent remission on ketamine improve over time, to put it mildly, but I think we've been over that ground before.

Please.

Mike

"why not cut the Tramadol with a little of your old friend, Tylenol? [In the U.S., the product is marketed under the trade-name Ultracet.]"

Hi, in what way does the tylenol enhance the tramadol?
cheers

In the US, historically Tylenol has been used in combination with other pain relievers.

Tylenol with Codeine
Tylenol with oxycodone (Percocet)
Tylenol with Darvon (Darvocet)

In OTC products Tylenol with just about EVERYTHING.

This is now changing as the US FDA is trying to cut Tylenol mixtures completely off the approval lists.

In the past Darvocet was released when the patent for Darvon expired. The same is true for Ultracet. It did not come on the market until Ultram went generic.

While it might be true that mixing Tylenol with tramadol results in more efficient pain relief, I think it is just basically a marketing ploy. Drug companies do this all the time with their drugs, even to the point of massaging data in studies to get the FDA to approve the new mixture.

We are seeing a change in the US about this trend with Tylenol. And in fact it may even result with some OTC brands including Tylenol Extra strength 500mg tabs being removed from the OTC market in the future and becoming RX only.

Ultram was a huge money maker for McNeil when it came out. Going generic really was painful for them. Adding their own Tylenol to make a new product restored a lucrative situation to their balance sheets!

As far as the nausea issue...all opiates cause nausea. I received far more complaints about nausea side effects than I ever did regarding Tramadol (which was never). Opiate nausea may occur when doses are too high for that particular patient, and dose adjustments often take care of them.

The nausea of Tramadol is different IMO and more connected to the serotonin actions of this drug. SSRIs are also reported high in nausea when first starting them.

And it is correct that Tramadol is recommended for Fibro patients specifically. This is because some studies show that the pain receptors for opiates are blocked by high endogenous endorphins in this disorder. I saw this mentioned at a chronic pain seminar during the Fibro portion. Opiates are no longer being recommended for Fibro patients for this reason. Also opiates have a checkered past for not working well for peripheral neuropathies.

When I was given Tramadol last year, I had one brief episode of nausea at the 50mg dose level, that lasted briefly...about 30 minutes. I haven't had any recurrance of that since. I don't take Tramadol every day, and only use it on very bad nights in fact with no further problem.

I worked many years in night shifts and never once had a nausea question regarding Tramadol. But nausea with opiates? Very very common.

I had been taking the Tramadol with Tylenol (1000mg of Tylenol with each 100mg of Tramadol). But now they have me off Tramadol completely and the pain is through the roof...though even before it wasn't doing very much to control the pain. And if they're not really treating me for CRPS then it would make sense that they haven't been able to get the pain under control.

I want to go to Rush...but I can't afford it. I know that sucks and it's my decision...but it's just not covered by my insurance and work comp isn't doing ANYTHING while my case is in appeal (THEY appealed it, not me). So, I am doing the best I can for now with what I can afford. When all the "legal" stuff gets taken care of then I will most likely be able to go to Rush...but I just can't right now. When you deal with work comp, you're stuck with going to doctors that are referred by other doctors and then waiting for approval. When you go through regular insurance, you're stuch with what's either in network or what you can afford. There are even some places that won't let me make an appointment at all since it is a work related injury and work comp isn't going to approve ANYTHING until the appeal is done (which could take years if they take it all the way to the end..don't think they will since they have absolutely no evidence for anything since even THEIR doctors agree with what mine said)...but work comp won't comply with what the doctor's offices require in order to run it through my regular insurance. It's frustrating...cause I just want to get better and focus on my health...but it just isn't going to work out that way for me.

Anyway...have a call out to my doctor to see what they can do about this now because I cannot continue with the Cymbalta given how violently ill I get. I still am dizzy and nauseous all the time and vomit several times a day besides what happens with the Cymbalta, but I think that other stuff is my reaction to the pain because I have always been one to throw up when I am in a lot of pain and these past few months have been worse than anything I remember in the past.

I wonder if some of your unpleasant symptoms are from suddenly discontinuing the Tramadol?

This drug is known to cause habituation in patients. Even though it is not a controlled substance, it does need to be tapered off, in a similar way, antidepressants (SSRIs) do. We are seeing with all the new drugs from the last 20 yrs, that those affecting neurotransmitter receptors, need careful tapering when being discontinued whether they are controls or not.

[QUOTE=catra121;777549]

Please seek immediate evaluation for withdrawal from Tramadol. I was only on Tramadol for about six months and was told by three doctors that it is not particularly difficult to come off of. I tapered for a little over a week and then had the exact same violently ill symptoms that you have described.

I went to the emergency room and was told that Tramadol is every bit as addictive as heroin, and that many physicians who prescribe it don't know the facts. I continued to experience severe symptoms for the two weeks following my ER visit bur was given medication to ease the vomiting etc.

Take Care!!!!!!

mrsD -

I inadvertently posted the link to only the abstract of Tramadol/paracetamol combination tablet for postoperative pain following ambulatory hand surgery: a double-blind, double-dummy, randomized, parallel-group trial, Rawal N, Macquaire V, Catalá E et al, J Pain Res. 2011 Apr 8; 4:103-10, ONLINE TEXT @ http://www.ncbi.nlm.nih.gov/pmc/arti.../jpr-4-103.pdf, however that abstract included its own link to the full text article, which does a very good job of explaining the mechanism of 325 mg. of Acetaminophen/Tylenol/Paracetamol in supplementing the analgesic effect of 37.5 mg. of Tramadol, which has significantly fewer side effects than the analgesia equivalent ("monotherapy") dose of 50 mg. of Tramadol, although both were significantly higher than what could have been acheived by using oxycodone alone:

Nausea was the most common event in both groups (25.8%
for tramadol/paracetamol vs 36.4% for tramadol) followed
by dizziness (15.9% vs 18.6%) and somnolence (9.1% vs 14%).

At 108.

But I found the comparisons between the Prescribing Information sheets for Oxycodone and Tramadol the most instructive, however you didn't comment on that information as such.

Nevertheless, I think the most important point of clarification is that we cannot lump opioids - such as Oxycodone - and true opiates together in looking at their profiles for side effects. See, e.g., Epidural oxycodone or morphine following Ggynaecological surgery, Yanagidate F, Dohi S, Br J Anaesth. 2004 Sep;93(3):362-7, 366, Epub 2004 Jun 25, ONLINE TEXT @ http://bja.oxfordjournals.org/content/93/3/362.full.pdf:

Undesirable side-effects such as pruritus and nausea are common with epidural morphine and are believed to be caused via mu-opioid receptor stimulation at the supraspinal level.23–25 It is not clear why the need for anti-emetics was significantly less in those who received epidural oxycodone 12 mg day−1 in our study. Since patient characteristics were similar between the three groups, it may be that oxycodone, when administered in the epidural space, is less emetogenic than morphine. Although oxycodone has effects at both mu- and kappa-opioid receptors, the affinity of oxycodone for the mu-opioid receptor has been reported to be one-tenth that of morphine.26 This may account for the fewer side-effects and less analgesia when compared with the same dose of epidural morphine.

Notes
23 Gustafsson LL, Schildt B, Jacobsen K. Adverse effects of extradural
and intrathecal opiates; report of a nationwide survey in Sweden.
Br J Anaesth 1982; 54: 479–86.
24 Martin WR. Clinical evidence for different narcotic receptors and
relevance for the clinician. Ann Emerg Med 1986; 15: 1026–9.
25 Yaksh TL. Opioid receptor systems and the endorphins: a review of
their spinal organization. J Neurosurg 1987; 67: 157–76.
26 Kalso E, Vainio A, Mattila MJ, Rosenberg PH, Seppala T. Morphine
and oxycodone in the management of cancer pain: plasma levels
determined by chemical and radioreceptor assays. Pharmacol
Toxicol 1990; 67: 322–8.

I spent most of last night looking for any published study showing that Tramadol had a dose equivalent level of nausea less than or equal to that of Oxycodone, when all the evidence I saw was to thew contrary. If you or anyone else knows of such studies, I would be most appreciative.

Mike

[QUOTE=ballerina;777570]Catra,

Please google "patient reviews of Tramadol" for reports of severe reactions lasting weeks when not tapered off very slowly.

That looks like alot of effort, you put in to this discussion.

I only look at studies when I have no personal experience in an area, or when an area is "new" or rare.

For 40 yrs I've dealt with patients who complain or worry about their medications. Who have negative experiences, or who are not getting what they expected, etc.

Prescribing data, and data off the drug insert is typically taken off short lived studies. Post operative pain, is rather unique and short lived for most patients. Also it can be subject to fraud as we learned about Pfizer and Celebrex, and Dr. Reuben:
http://www.theday.com/article/201001...100119833/1047
I tend to think these post operative studies are drug company funded to give them leverage with sales/marketing etc.

Insert reports do not often include post marketing data, unless it is extreme and dangerous, and getting that added may take a decade or more in some cases. Nausea? not like aplastic anemia or metabolic acidosis. The latter two might get added more quickly.

Basically when people get discharged home, with meds, and it is late at night and they cannot call their doctors, etc, they call me. I've had many many opiate side effects including Sphincter of Oddi attacks which are alarming in the extreme.

But nausea, is a biggie and more common with codeine, and morphine. Oxycodone and hydrocodone may cause nausea in high doses, and also severe itching spells at moderate doses.

But I never had an Ultram/tramadol call! These would be emergency calls. Over the long haul people may call their doctors the next day and ask for another medicine. But I did not see many discharged surgical patients on Ultram at all in fact. It is more of a chronic long term intervention. People coming to me with trauma and other painful things in the night, always had Vicodin at least. Maybe Percocet. Sometimes Darvocet, which is no longer available finally.
Many people with trauma are given Toradol (an NSAID) injection in the ER or hospital, to augment the narcotic given. Ultram? Seems like a foolish choice for acute or severe issues.

I forgot to list Hydrocodone +Tylenol = Lortab and Vicodin, Norco etc.
In this case, I believe the tylenol was added to prevent abuse of the hydrocodone portion which when used alone is a CII narcotic.

The Tylenol also functions in the other mixes as an abuse deterent but for determined abusers really isn't effective and just becomes a poison to the liver instead.

Let's look at Ultracet:
This drug is 37.5mg of tramadol and 325mg of Tylenol. The typical starting dose of tramadol plain is 50mg. But many people use 100.

Why 37.5mg tramadol? This is a trick used by drug companies so the doctor cannot give regular 50mg tramadol and tell the person to take a tylenol with it. It forces the dosing to use TWO tablets to give 75mg of tramadol to get a therapeutic dose + 650mg of Tylenol. TWO tablets for a response that maybe one tablet of plain tramadol 50mg would accomplish for many situations.

This is a frequent thing, drug companies do to sell more product.
In the case of tramadol, it also protects the patent, because any generic company would be forced to spend $$ to provide studies for the new 37.5mg dose.

Here is another example of manipulation of doses, with a well known brand name: Soma:
http://www.soma250.com/
This product really bombed because the insurance companies refused to pay for it. Generic Soma 350mg has been on the market almost for 20 yrs! I read about the launch of this bomb on Cafepharma.com and it was very amusing and enlightening!

So while I don't dispute the PubMed articles you found, empirically, they don't often reflect real life situations.
Today, unfortunately, if a drug company does something we need to look very carefully at the result, because often it is for THEIR edification, and not for the patient at all. I keep hoping we are turning a corner in this regard, but I have yet to see much improvement!

Ah...so much information that my head is spinning...

I have my attorney working towards getting work comp to approve me seeing Timothy Lubenow at Rush. My fingers are crossed, and I am praying that he is successful, but only time will tell. I really sense that my current doctors are just way out of their comfort zones when it comes to CRPS and seeing someone more specialized with it will be a giant relief. Last visit my current pain doctor even said that she just didn't know what to do and was just percribing stuff for generalized pain.

The nurse from my doctor's office called back (finally) and told be to stop taking the Cymbalta. Not sure what the doctor wants me to do beyond just stopping the Cymbalta.

I think my body may be going through some shock with just coming off the Tramadol suddenly...possibly the Lyrica too since that didn't get tapered off either and I was just told to stop taking it and take the Cymbalta instead. At this point I almost wonder if I should just go off everything and start from scratch since I am just not getting any sort of decent relief from any of it. Even the Lyrica which used to help when I was first put on it (last year) barely was making a dent now (though it DID make a difference that I could notice even if it wasn't much).

Guess I'll find out soon enough and in the mean time...well...I'll survive...

Too strange that it takes an attorney to get an appointment with a doctor. But then the whole CRPS experience is strange as well. (You too can have an illness at the cutting edge of neuroscience and immunology.) And if you'll excuse a digression on strangeness, you might appreciate the video and/or reading an article that appeared in the NY Times a few days ago, "Venezuela's Prison Paradise: On the outside, the San Antonio prison on Margarita Island looks like any other Venezuelan penitentiary. But venture inside and you'll see how far the rabbit hole goes. . . ." Video: http://video.nytimes.com/video/2011/...l?ref=americas Article: http://www.nytimes.com/2011/06/04/wo...s/04venez.html

Silliness aside, I would strongly suggest that you NOT go off Lyrica without talking to your doctor(s) first, however inept s/he/they may be.

Once upon a time, I had been taking Trileptal (Oxcarbazepine, an anticonvulsant that works by decreasing abnormal electrical activity in the brain). It was a great drug but it can have a nasty side-effect of causing serum sodium levels to plummet without warning, leading to irreversible nerve damage. So after 18 months and frequent if uneventful blood tests, just before I was going into the hospital in Philadelphia for a week-long Lidocaine infusion - so it could fail on the record and my insurance company would then let me move onto ketamine - I was being worked up for an apparently unrelated blood condition at the Mayo Clinic, which Dr. Schwartzman wanted done before I went into his hospital. Out of nowhere, my neurologist called me from LA: the blood work drawn a week earlier was back, sodium levels had dropped 50% in 6 weeks, and I was to discontinued Trileptal at once. Except that no one ramped me up on a replacement med where I was moving about on the fly. By the time I was being wheeled onto the plane to Philadelphia, a week or so later, I was having scalp cramps!

I used to say that someone hadn't lived until they tried scalp cramps, but I'm not sure it's your thing.

Mike

Yeah...no thanks. If that's what it takes to 'live' then count me out...lol!

But seriously...it was the doctor who took me off the Lyrica in favor of the Cymbalta (which clearly didn't work out). I don't have any more refills on the Lyrica either so it's not like I can go back on it now. Which may be causing some of the other problems, increase in pain, etc. But things are so bad these days that I don't know what are symptoms of what's wrong with me, what are side effects from medications, what are side effects from withdrawal from the medications...it's so confused now that I'm not really shocked that the doctors can't sort it out either. I just wish someone would really take the reins and hopefully that will come soon.

And...yeah...I hate that I even have to have an attorney to be an advocate for me when it comes to work comp...I wish they would just do what they are supposed to and not play games...but then again there are a lot of things I wish that just aren't a reality and I have to deal with that is rather than what isn't.

In more positive news, my primary care doctor ordered at home physical therapy and for the first time I am feeling optimistic about a treatment. I'm still worried about how far I can push with the pain as bad as it is...but then again it's so bad already that what's a little more in a good cause (the good cause being working towards getting me walking again...even a little). So I am pumped about that. Would feel better if we were able to get the pain even moderately under control...but I need to just keep working on that as a seperate issue and focus on what I can control. And what I can control is going at this physical therapy with a focused and determined attitude, do my exercises every day, and maybe it will even help with the pain a little. You know...trying to get out of the cycle of not using it, the pain gets worse, I use it less, so the pain gets even worse...I'm thinking long term and that the pain I feel now after doing the physical therapy is going to get me in a better place in the future.

Wow... sudden d/c of Trileptal? That can cause seizures!

There is a poster here who was suddenly d/c'd from Tegretol (similar drug).

You might want to look at his experience:
http://neurotalk.psychcentral.com/thread112178.html

Hyponatremia, can be additive with opiates too. Taking both together may be an issue for some. Even SSRI's are now known to cause hyponatremia in some patients.

Interesting but odd thread there.

From what I understand, in light of the results of my blood work, gradually discontinuing Trileptal would have put me at greater actual risk than going cold turkey. I only regret that my local neurologist didn't suggested at the time that one of my Mayo Clinic doctors write me script for Neurontin by way of replacement, even if it had to be phased in gradually.

Mike