CAUTION: Do not take Lexapro and Flexeril together...

Discussion in 'Fibromyalgia Main Forum' started by kjfms, Jul 30, 2006.

  1. kjfms

    kjfms Member

    Multi-Drug Interaction Checker

    Patient Regimen



    Moderate Interaction

    Lexapro Oral and Flexeril Oral may interact based on the potential interaction between SSRI'S; DULOXETINE and TRICYCLIC COMPOUNDS; TRAZODONE.

    Selective Serotonin Reuptake Inhibitors; Duloxetine/ Tricyclic Compounds; Trazodone

    This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.

    MONOGRAPH TITLE: Selective Serotonin Reuptake Inhibitors; Duloxetine/

    Tricyclic Compounds; Trazodone

    SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

    MECHANISM OF ACTION: Selective serotonin reuptake inhibitors and duloxetine impair oxidative hepatic metabolism. These agents may lead to a more rapid down regulation of postsynaptic beta-adrenergic receptors, thus possibly contributing to a faster onset of the antidepressant effect of other agents.

    CLINICAL EFFECTS: Concurrent administration of a selective serotonin reuptake inhibitor or duloxetine with a TCA or trazodone may result in an increase in serum levels, toxicities, and/or clinical effects of the TCA or trazodone.

    PREDISPOSING FACTORS: None determined.

    PATIENT MANAGEMENT: Patients should be observed for increased adverse effects and clinical effects of TCAs at the initiation of concurrent therapy with selective serotonin reuptake inhibitors or duloxetine. Plasma concentrations of the TCA should be monitored and the dosage adjusted accordingly.

    If selective serotonin reuptake inhibitor or duloxetine treatment is discontinued in a patient receiving TCA therapy, the dosage of the TCA may need to be adjusted.

    The effects of fluoxetine on hepatic metabolism may last for 5 weeks after fluoxetine discontinuation. A TCA started after the discontinuation of fluoxetine should be started a lower initial dosage.

    DISCUSSION: In a study, pretreatment with duloxetine (60 mg twice daily) increased the area-under-curve (AUC) of a single dose of desipramine (50 mg) by 3-fold.

    Case reports have shown that the addition of fluoxetine to TCA therapy can result in an increase of 100-300% in the TCA plasma concentration as well as an increase in adverse effects, including seizures and delirium.

    Fluvoxamine has been shown in an in vitro study to inhibit the metabolism of imipramine. Three case reports have shown increased serum levels of imipramine (32%, 198%, and 470% increases) and an increase in adverse effects (anticholinergic effects, confusion, and sedation) during concurrent administration with fluvoxamine. Two case reports of adverse effects (tonic-clonic seizure, tremors, dizziness, and confusion) and increased plasma desipramine levels (79% and 54% increases) with concurrent administration of fluvoxamine exist. Increased plasma levels of clomipramine (586%) and amitriptyline (100-150%) without signs of clinical toxicity were seen following the addition of fluvoxamine to TCA therapy.

    Sertraline has been shown to increase the maximum concentration (Cmax) and AUC of desipramine by 31% and 23%, respectively. There is one case report of serotonin syndrome during concurrent therapy with paroxetine and trazodone.

    The affinity of the different selective serotonin reuptake inhibitors for CYP P-450 may vary.


    1.Preskorn SH, Beber JH, Faul JC, Hirschfeld RM. Serious adverse effects of combining fluoxetine and tricyclic antidepressants. Am J Psychiatry 1990 Apr;147(4):532.

    2.Kahn DG. Increased plasma nortriptyline concentration in a patient cotreated with fluoxetine. J Clin Psychiatry 1990 Jan;51(1):36.

    3.Ciraulo DA, Shader RI. Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics. J Clin Psychopharmacol 1990 Feb; 10(1):48-50.

    4.Vaughan DA. Interaction of fluoxetine with tricyclic antidepressants. Am J Psychiatry 1988 Nov;145(11):1478.

    5.Bell IR, Cole JO. Fluoxetine induces elevation of desipramine level and exacerbation of geriatric nonpsychotic depression. J Clin Psychopharmacol 1988 Dec;8(6):447-8.

    6.Aranow AB, Hudson JI, Pope HG, Jr, Grady TA, Laage TA, Bell IR, Cole JO. Elevated antidepressant plasma levels after addition of fluoxetine. Am J Psychiatry 1989 Jul;146(7):911-3.

    7.Goodnick PJ. Influence of fluoxetine on plasma levels of desipramine. Am J Psychiatry 1989 Apr;146(4):552.

    8.Schraml F, Benedetti G, Hoyle K, Clayton A. Fluoxetine and nortriptyline combination therapy. Am J Psychiatry 1989 Dec;146(12):1636-7.

    9.Downs JM, Downs AD, Rosenthal TL, Deal N, Akiskal HS. Increased plasma tricyclic antidepressant concentrations in two patients concurrently treated with fluoxetine. J Clin Psychiatry 1989 Jun;50(6):226-7.

    10.Downs JM, Dahmer SK. Fluoxetine and elevated plasma levels of tricyclic antidepressants. Am J Psychiatry 1990 Sep;147(9):1251.

    11.Westermeyer J. Fluoxetine-induced tricyclic toxicity: extent and duration J Clin Pharmacol 1991 Apr;31(4):388-92.

    12.Rosenstein DL, Takeshita J, Nelson JC. Fluoxetine-induced elevation and prolongation of tricyclic levels in overdose. Am J Psychiatry 1991 Jun; 148(6):807.

    13.Nierenberg AA, Cole JO, Glass L. Possible trazodone potentiation of fluoxetine: a case series. J Clin Psychiatry 1992 Mar;53(3):83-5.

    14.Bergstrom RF, Peyton AL, Lemberger L. Quantification and mechanism of the fluoxetine and tricyclic antidepressant interaction. Clin Pharmacol Ther 1992 Mar;51(3):239-48.

    15.Maskall DD, Lam RW. Increased plasma concentration of imipramine following augmentation with fluvoxamine. Am J Psychiatry 1993 Oct; 150(10):1566.

    16.Spino E, Campo GM, Avenoso A, Pollicino MA, Caputi AP. Interaction between fluvoxamine and imipramine/desipramine in four patients. Ther Drug Monit 1992 Jun;14(3):194-6.

    17.Bertschy G, Vandel S, Vandel B, Allers G, Volmat R. Fluvoxamine-tricyclic antidepressant interaction. An accidental finding. Eur J Clin Pharmacol 1991;40(1):119-20.

    18.Seifritz E, Holsboer-Trachsler E, Hemmeter U, Eap CB, Baumann P. Increased trimipramine plasma levels during fluvoxamine comedication. Eur Neuropsychopharmacol 1994 Mar;4(1):15-20.

    19.Skjelbo E, Brosen K. Inhibitors of imipramine metabolism by human liver microsomes. Br J Clin Pharmacol 1992 Sep;34(3):256-61.

    20.Preskorn SH, Alderman J, Chung M, Harrison W, Messig M, Harris S. Pharmacokinetics of desipramine coadministered with sertraline or fluoxetine. J Clin Psychopharmacol 1994 Apr;14(2):90-8.

    21.Reeves RR, Bullen JA. Serotonin syndrome produced by paroxetine and low-dose trazodone. Psychosomatics 1995 Mar-Apr;36(2):159-60.

    22.Cymbalta (duloxetine hydrochloride) US prescribing information. Eli Lilly and Company September 22, 2005.

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  2. dononagin

    dononagin New Member

    ya know.. my doc was giving me imitrex injections for migraines.. I found out they weren't compatible with cybalta by doing an online search and also that I couldn't take imitrex with my raynaulds.. We all really need to be aware of drug interactions before we take anything. Most of us are on multiple meds.. and some from different docs.. for instance, I see a dermie, a gastro, a rhumie and my gp.. I get scripts from all of them. I tell them all what I am taking but docs are fallible humans too and it is hard for them to remember everything.. we have to take the responsibility ourselves for doing the research!!

    Thanks! You may be saving someone a lot of grief!



    Flexeril and Ultram together.
  4. AbbeyMae

    AbbeyMae New Member

    According to my PSYCH., this is incorrect. He gave the explanation to this to me some time ago. I just did not write it down. I see him next week and will show him your Thread and see what he says. I consider him very intelligent.

    Does Flexeril contain duloxetine? Fluoxatine is not Flexeril.

    I did not see anything mentioned about Flexeril in any of the REFERANCES listed at the bottom of the pertaining article.

    After, I see my PSYCH. this week, I will share his reasons why he says this is incorrect concerning the Flexeril, or possibly he may agree with this article. But, I highly doubt it. But I may be wrong, we'll see.

    Love and hugs,


    P.S. Flexeril is not a tricyclic antidepressant. Nor is it ever in that category.
  5. AbbeyMae

    AbbeyMae New Member


    Does anyone else have scientific proof of the "thread" Article. Would be nice to see if anyone has any feedback.

    I am confused.

    Love and hugs,

  6. kjfms

    kjfms Member

    The reason I brought this up is because I broke my number one rule when first taking a new medication. I did not check for interactions and subsequently became pretty ill and out of it for the first couple of days.

    I checked with Medscape's Medicine Interaction Checker and found the problem to be the Flexeril I was taking-this was after asking the physician if it was OK to take the two together. Physicians are not pharmacists and it is not their fault they simply can't be expected to remember everything...

    I am very susceptible to this type of thing and try to be careful but this one slip by me I was simply over drugged and quite frankly had I continued taking the Flexeril I feel I would have gone in to an overdose situation.

    I am sure each person reacts differently but even if one doesn't experience the over drugged feeling that I did-there is the strong chance of toxicity which is not good.

    Thanks to Fight, BEARANDBUGSMOM, dona, and AbbeyMae for reading and responding.

    Medscape is a very reliable source for medical and pharmaceutical information and is used by physicians, health professionals, and health information professionals throughout the country. I use it daily in my professional and personal related affairs and have for a number of years.


    Please discuss this with a pharmacist and your physician Flexeril is trycylic muscle relaxant and is very close chemically to tricylic antidepressants. This causes an increase effect of the Flexeril this is why I was feeling so drugged.

    I am glad you are having no problems with this combination and that it is working for you. The combination does not work for me and it was very scary. Best of luck to you :)

    Below I have copied and pasted some information from various sites and will include each site for reference. I will not post entire articles just highlights and you can go to the websites.

    This is about all I can give you as far as scientific proof (the chemical properties and drug warnings) a discussion with a pharmacist who is more qualified than I would give you the proof you are looking for if you need further evidence.

    DRUG INTERACTIONS: Cyclobenzaprine (Flexeril) is chemically related to the tricyclic class of antidepressants (e.g. amitriptyline, Elavil; nortriptyline, Pamelor). As such, it should not be taken with or within two weeks of any monoamine oxidase inhibitor, for example, isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate), and procarbazine (Matulane).

    High fever, convulsions and even death can occur when these drugs are used together. Additionally, cyclobenzaprine interacts with other medications and drugs that slow the brain's processes, such as alcohol, barbiturates, benzodiazepines (e.g. lorazepam, Ativan), and narcotics.

    Cyclobenzaprine hydrochloride is a white, crystalline tricyclic amine salt with the empirical formula C20H21N•HCl and a molecular weight of 311.9. It has a melting point of 217°C, and a pKa of 8.47 at 25°C. It is freely soluble in water and alcohol, sparingly soluble in isopropanol, and insoluble in hydrocarbon solvents. If aqueous solutions are made alkaline, the free base separates. Cyclobenzaprine HCl is designated chemically as 3-(5H-dibenzo[a,d] cyclohepten-5-ylidene)-N, N-dimethyl-1-propanamine hydrochloride, and has the following formula: HCCH2CH2N(CH3)2-HCL

    LEXAPRO™ (escitalopram oxalate) is an orally administered selective serotonin reuptake inhibitor (SSRI). Escitalopram is the pure S-enantiomer (single isomer) of the racemic bicyclic phthalane derivative citalopram. Escitalopram oxalate is designated S(+)-1-[3-(dimethyl-amino)propyl]-1-(p-fluorophenyl)- 5-phthalancarbonitrile.

    The molecular formula is C20H21FN2O • C2H2O4 and the molecular weight is 414.40

    Escitalopram oxalate occurs as a fine white to slightly yellow powder and is freely soluble in methanol and dimethyl sulfoxide (DMSO), soluble in isotonic saline solution, sparingly soluble in water and ethanol, slightly soluble in ethyl acetate, and insoluble in heptane.

    I hoped this has helped a little. I know it is a lot to take in. I would just discuss any concerns with a pharmacist.

    I have a background in chemistry and can read this material and understand it for my own use but will be the first to admit I have never done very well at explaining chemistry...

    and my background is not pharmaceutical chemistry it is environmental chemistry (I performed heavy metal analysis on water, coal, plant material, and waste water material for over 7 years in the coal industry) but it helps me enough to know what is going on.

    So a pharmacist or someone with that type of background can explain this much better than I.

    More reading material:

    Here is the site where your physician can enter all of your medications and check for any interactions he may find this of some use he can enter up to 20 drugs.

    I personally think every physician should use it. It is quick and would save them time and would save patients a lot of grief:

    I am just trying to save anyone the grief I went through when I started Lexapro while taking Lexapro and I should change the title of my thread to read Caution: When taking Lexapro and Flexeril I guess.

    I feel based on what I have read and the fact that Flexeril is a trycylic muscle relaxant that they should not be taken with Lexapro as advised in all of the articles and references which I have pasted in this thread.

    I do apologize to everyone for this being so long. I know for many of you it is difficult to read I tried to space it out.

    Thanks again to all,

    Karen :)

    [This Message was Edited on 07/31/2006]
    [This Message was Edited on 07/31/2006]
  7. kjfms

    kjfms Member

  8. kjfms

    kjfms Member

    for AbbeyMae.
  9. AbbeyMae

    AbbeyMae New Member

    I can't believe that I accidentally deleted what I just wrote. I'll write back later, because I'm too tired to rewrite everything at this time. Sorry. I don't even know what key that I hit for that to happen.

    Love and hugs,

  10. kjfms

    kjfms Member

    No problem. Get some rest and take care of you.


    Karen :)
  11. AbbeyMae

    AbbeyMae New Member


    I did read that they were a moderate risk for interactions.
    I see my Psych. tomorrow. I am curious to see what he has to say.

    Of course, I am very sensitive to antidepressants, especially tricyclics. I am surprised the Flexeril did not give me the horrible reactions. I take 20mg. at bedtime and have weaned off the one during the day except on really painful days. Actually, I am down to 1 and 1/2 tablets, (15mg) at bedtime now.

    Also, the highest strength of Lexapro I have taken is 3mg. I took only 1mg. last night. I dissolve a 5mg.(1/2 of tab) in 5 ounces of water. Last night I only drank one ounce. I hope that I can continue this. Sometimes new regimens work at first only to disappoint later on. I do not get real excited too much anymore when something is working to make me feel like a recovery.

    If I still feel better down the line, I will share my protocol. I went to see a Naturopathic Dr., he is also a Master Herbalist, and Vital Hematologist. He observed my blood under a microscope and was able to identify a lot, even mycoplasmas, which he called Stealth Pathogens.

    I am taking supplements that I haven't heard of before except a few. The sad part is my review for SSDI will come up and I will need that Psych. So I'll take 1 ounce for awhile. He claims he has other PT.'s that are sensitive and they are also Rx.d small dosages.

    He is also intelligent with alternatives/supplements. I was taking St. John's Wort a few years ago and was able to tell me that,that is what was why I was having dizziness. He is also knowledgeable about SAMe, L-Tyrosine, GABA, and others.

    My other Doc's don't have a clue. So even before I took the Lexapro, my Psych. still consulted me with interactions of Rx.d meds and supplements. I had gone to him some years ago and my S.S. Atty. told me to go and continue to see him because we would need him and his statement for SSDI. I had suffered PTSD and depression when I saw him before, and still do.

    I want to try the SAMe again. The only problem is that it is expensive and I may be losing my health benefits, except for Medicare alone because my Ex-husband went back to work and IL DES is garnishing his wages for back arrears of child support. That money is always owed, so deadbeat dads are still responsible for the $ owed for child support.

    Thank you for the thread. I'll have the Doc write down if he has the time, if he still agrees with what he said.

    Love and hugs,

  12. kjfms

    kjfms Member

    It sounds like you have an excellent psychiatrist that is great.

    I am taking 10 mg of Lexapro q.d. (once a day) and before I stopped Flexeril was taking 10 mg t.i.d. p.r.n. (three times a day as needed) it really knock me for a loop I don't even remember much about the first two I started taking Lexapro. I was not even taking Flexeril t.i.d. I was only taking it q.d.

    Well I got to go to bed have to work tomorrow.

    Have a good visit with your psychiatrist and let me know what he says.

    Talk to you later,

    Karen :)

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