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7 Interactions found for:

Cymbalta and Flexeril
Interactions Summary
  • 3 Major
  • 2 Moderate
  • 2 Minor
  • Cymbalta
  • Flexeril

Drug Interactions

Major
Flexeril + Cymbalta

The following applies to the ingredients: Cyclobenzaprine (found in Flexeril) and Duloxetine (found in Cymbalta)

MONITOR CLOSELY: Concomitant use of agents with serotonergic activity such as serotonin reuptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, 5-HT1 receptor agonists, ergot alkaloids, cyclobenzaprine, lithium, St. John's wort, phenylpiperidine opioids, dextromethorphan, and tryptophan may potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MANAGEMENT: In general, the concomitant use of multiple serotonergic agents should be avoided if possible, or otherwise approached with caution if potential benefit is deemed to outweigh the risk. Patients should be closely monitored for symptoms of the serotonin syndrome during treatment. Particular caution is advised when increasing the dosages of these agents. The potential risk for serotonin syndrome should be considered even when administering serotonergic agents sequentially, as some agents may demonstrate a prolonged elimination half-life. For example, some experts suggest a 5-week washout period following use of fluoxetine and 3 weeks following the use of vortioxetine before administering another serotonergic agent. Individual product labeling for washout periods should be consulted for current recommendations. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary. Moderately ill patients may also benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures.

References

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  9. Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics." J Clin Psychopharmacol 10 (1990): 48-50
  10. "Product Information. Zoloft (sertraline)." Roerig Division PROD (2001):
  11. "Product Information. Prozac (fluoxetine)." Dista Products Company PROD (2001):
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  17. "Product Information. Flexeril (cyclobenzaprine)." Merck & Co., Inc PROD (2001):
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  36. "Product Information. Celexa (citalopram)." Forest Pharmaceuticals PROD (2001):
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  40. Egberts AC, ter Borg J, Brodie-Meijer CC "Serotonin syndrome attributed to tramadol addition to paroxetine therapy." Int Clin Psychopharmacol 12 (1997): 181-2
  41. Weiner AL "Meperidine as a potential cause of serotonin syndrome in the emergency department." Acad Emerg Med 6 (1999): 156-8
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  46. "Product Information. Zyvox (linezolid)." Pharmacia and Upjohn PROD (2001):
  47. Perry NK "Venlafaxine-induced serotonin syndrome with relapse following amitriptyline." Postgrad Med J 76 (2000): 254-6
  48. Manos GH "Possible serotonin syndrome associated with buspirone added to fluoxetine." Ann Pharmacother 34 (2000): 871-4
  49. Nijhawan PK, Katz G, Winter S "Psychiatric illness and the serotonin syndrome: an emerging adverse drug effect leading to intensive care unit admission." Crit Care Med 24 (1996): 1086-9
  50. Laird LK "Issues in the monopharmacotherapy and polypharmacotherapy of obsessive-compulsive disorder." Psychopharmacol Bull 32 (1996): 569-78
  51. Margolese HC, Chouinard G "Serotonin syndrome from addition of low-dose trazodone to nefazodone." Am J Psychiatry 157 (2000): 1022
  52. Mackay FJ, Dunn NR, Mann RD "Antidepressants and the serotonin syndrome in general practice." Br J Gen Pract 49 (1999): 871-4
  53. Smith DL, Wenegrat BG "A case report of serotonin syndrome associated with combined nefazodone and fluoxetine." J Clin Psychiatry 61 (2000): 146
  54. Rosebraugh CJ, floxkhart DA, Yasuda SU, Woosley RL "Visual hallucination and tremor induced by sertraline and oxycodone in a bone marrow transplant patient." J Clin Pharmacol 41 (2001): 224-7
  55. Izzo AA, Ernst E "Interactions between herbal medicines and prescribed drugs: a systematic review." Drugs 61 (2001): 2163-75
  56. Duggal HS, Fetchko J "Serotonin syndrome and atypical antipsychotics." Am J Psychiatry 159 (2002): 672-3
  57. Wigen CL, Goetz MB "Serotonin syndrome and linezolid." Clin Infect Dis 34 (2002): 1651-2
  58. Hammerness P, Parada H, Abrams A "Linezolid: MAOI Activity and Potential Drug Interactions." Psychosomatics 43 (2002): 248-9
  59. "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals (2002):
  60. Dougherty JA, Young H, Shafi T "Serotonin syndrome induced by amitriptyline, meperidine, and venlafaxine." Ann Pharmacother 36 (2002): 1647-1648
  61. Turkel SB, Nadala JG, Wincor MZ "Possible serotonin syndrome in association with 5-HT3 antagonist agents." Psychosomatics 42 (2001): 258-60
  62. Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6
  63. Lavery S, Ravi H, McDaniel WW, Pushkin YR "Linezolid and serotonin syndrome." Psychosomatics 42 (2001): 432-4
  64. Lane R, Baldwin D "Selective serotonin reuptake inhibitor--induced serotonin syndrome: review." J Clin Psychopharmacol 17 (1997): 208-21
  65. Bernard L, Stern R, Lew D, Hoffmeyer P "Serotonin syndrome after concomitant treatment with linezolid and citalopram." Clin Infect Dis 36 (2003): 1197
  66. Dannawi M "Possible serotonin syndrome after combination of buspirone and St John's Wort." J Psychopharmacol 16 (2002): 401
  67. Tissot TA "Probable meperidine-induced serotonin syndrome in a patient with a history of fluoxetine use." Anesthesiology 98 (2003): 1511-1512
  68. Hachem RY, Hicks K, Huen A, Raad I "Myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients." Clin Infect Dis 37 (2003): E8-E11
  69. Gillman PK "Linezolid and serotonin toxicity." Clin Infect Dis 37 (2003): 1274-5
  70. Roy S, Fortier LP "Fentanyl-induced rigidity during emergence from general anesthesia potentiated by venlafexine." Can J Anaesth 50 (2003): 32-5
  71. Giese SY, Neborsky R "Serotonin syndrome: potential consequences of Meridia combined with Demerol or fentanyl." Plast Reconstr Surg 107 (2001): 293-4
  72. Jones SL, Athan E, O'Brien D "Serotonin syndrome due to co-administration of linezolid and venlafaxine." J Antimicrob Chemother 54 (2004): 289-90
  73. Tahir N "Serotonin syndrome as a consequence of drug-resistant infections: an interaction between linezolid and citalopram." J Am Med Dir Assoc 5 (2004): 111-3
  74. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company (2004):
  75. Thomas CR, Rosenberg M, Blythe V, Meyer WJ 3rd "Serotonin syndrome and linezolid." J Am Acad Child Adolesc Psychiatry 43 (2004): 790
  76. Boyer EW, Shannon M "The serotonin syndrome." N Engl J Med 352 (2005): 1112-20
  77. Bergeron L, Boule M, Perreault S "Serotonin toxicity associated with concomitant use of linezolid." Ann Pharmacother 39 (2005): 956-61
  78. Morales N, Vermette H "Serotonin syndrome associated with linezolid treatment after discontinuation of fluoxetine." Psychosomatics 46 (2005): 274-5
  79. Morales-Molina JA, Mateu-de Antonio J, Marin-Casino M, Grau S "Linezolid-associated serotonin syndrome: what we can learn from cases reported so far." J Antimicrob Chemother 56 (2005): 1176-8
  80. DeBellis RJ, Schaefer OP, Liquori M, Volturo GA "Linezolid-associated serotonin syndrome after concomitant treatment with citalopram and mirtazepine in a critically ill bone marrow transplant recipient." J Intensive Care Med 20 (2005): 351-3
  81. Hunter B, Kleinert MM, Osatnik J, Soria E "Serotonergic syndrome and abnormal ocular movements: worsening of rigidity by remifentanil?" Anesth Analg 102 (2006): 1589
  82. Taylor JJ, Wilson JW, Estes LL "Linezolid and serotonergic drug interactions: a retrospective survey." Clin Infect Dis 43 (2006): 180-7
  83. Strouse TB, Kerrihard TN, Forscher CA, Zakowski P "Serotonin syndrome precipitated by linezolid in a medically ill patient on duloxetine." J Clin Psychopharmacol 26 (2006): 681-683
  84. Keegan MT, Brown DR, Rabinstein AA "Serotonin syndrome from the interaction of cyclobenzaprine with other serotoninergic drugs." Anesth Analg 103 (2006): 1466-8
  85. Paruchuri P, Godkar D, Anandacoomarswamy D, Sheth K, Niranjan S "Rare case of serotonin syndrome with therapeutic doses of paroxetine." Am J Ther 13 (2006): 550-552
  86. Steinberg M, Morin AK "Mild serotonin syndrome associated with concurrent linezolid and fluoxetine." Am J Health Syst Pharm 64 (2007): 59-62
  87. Packer S, Berman SA "Serotonin syndrome precipitated by the monoamine oxidase inhibitor linezolid." Am J Psychiatry 164 (2007): 346-7
  88. Shapiro RE, Tepper SJ "The serotonin syndrome, triptans, and the potential for drug-drug interactions." Headache 47 (2007): 266-9
  89. Ailawadhi S, Sung KW, Carlson LA, Baer MR "Serotonin syndrome caused by interaction between citalopram and fentanyl." J Clin Pharm Ther 32 (2007): 199-202
  90. "Product Information. Pristiq (desvenlafaxine)." Wyeth Laboratories (2008):
  91. Rang ST, Field J, Irving C "Serotonin toxicity caused by an interaction between fentanyl and paroxetine." Can J Anaesth 55 (2008): 521-5
  92. "Product Information. Savella (milnacipran)." Forest Pharmaceuticals (2009):
  93. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):
  94. Lee J, Franz L, Goforth HW "Serotonin syndrome in a chronic-pain patient receiving concurrent methadone, ciprofloxacin, and venlafaxine." Psychosomatics 50 (2009): 638-9
  95. "Product Information. Viibryd (vilazodone)." Trovis Pharmaceuticals LLC (2011):
  96. Mugele J, Nanagas KA, Tormoehlen LM "Serotonin Syndrome Associated With MDPV Use: A Case Report." Ann Emerg Med (2012):
  97. "Product Information. Oleptro (trazodone)." Labopharm Inc (2012):
  98. "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals (2013):
  99. "Product Information. Brintellix (vortioxetine)." Takeda Pharmaceuticals America (2013):
  100. "Product Information. Exxua (gepirone)." Mission Pharmacal Company 1 (2023):

Drug and Food Interactions

Moderate
Flexeril + Food

The following applies to the ingredients: Cyclobenzaprine (found in Flexeril)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
  3. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):

Moderate
Cymbalta + Food

The following applies to the ingredients: Duloxetine (found in Cymbalta)

GENERALLY AVOID: Use of duloxetine in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Duloxetine alone can increase serum transaminase levels. In clinical trials, 0.3% of patients discontinued duloxetine due to liver transaminase elevations. The median time to detection was about two months. Three duloxetine-treated patients had liver injury as manifested by transaminase and bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, which may have contributed to the abnormalities observed. Duloxetine does not appear to enhance the central nervous system effects of alcohol. When duloxetine and ethanol were administered several hours apart so that peak concentrations of each would coincide, duloxetine did not increase the impairment of mental and motor skills caused by alcohol.

MANAGEMENT: Due to the risk of liver injury, patients prescribed duloxetine should be counseled to avoid excessive use of alcohol. Duloxetine should generally not be prescribed to patients with substantial alcohol use.

References

  1. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company (2004):

Drug and Pregnancy Interactions

The following applies to the ingredients: Duloxetine (found in Cymbalta)

This drug should not be used during pregnancy unless the benefit outweighs the risk to the fetus.

AU TGA pregnancy category: B3
US FDA pregnancy category: Not assigned.

Risk summary: Observational study data have not produced clear drug-associated risks regarding adverse events or major birth defects.

Comments:
-A pregnancy exposure registry is available.
-Neonates exposed to this drug late in the third trimester may require respiratory support, tube feeding, and/or prolonged hospitalization.
-Exposed neonates should be monitored after delivery for direct toxic effects of this drug, drug discontinuation syndrome, and serotonin syndrome.
-Women who discontinued antidepressant use during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant use.

Animal studies have revealed increased perinatal toxicity and fetotoxicity at doses potentially correlated with maternal toxicity. There are no controlled data in human pregnancy.

Some neonates exposed to SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors), or SSRIs (Selective Serotonin Reuptake Inhibitors) late in the third trimester had clinical findings including respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. This clinical picture is consistent with either direct toxic effect of SSRIs and SNRIs, drug discontinuation syndrome, or serotonin syndrome.

A less than 2-fold increase in postpartum hemorrhage was determined by observational data in patients exposed to the drug within 1 month before birth.

A study of women with a history of major depression who were euthymic at the beginning of pregnancy, showed women who discontinued antidepressant medication during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant medication.

To monitor maternal-fetal outcomes of pregnant women exposed to antidepressant therapy, a National Pregnancy Registry for Antidepressants has been established. Healthcare providers are encouraged to prospectively register patients. For additional information: https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/

Healthcare providers are encouraged to register patients receiving Cymbalta by calling the Cymbalta Pregnancy Registry at 1-866-814-6975 or by visiting www.cymbaltapregnancyregistry.com.

AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

References

  1. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company (2004):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0

The following applies to the ingredients: Cyclobenzaprine (found in Flexeril)

This drug should be used during pregnancy only if clearly needed.

US FDA pregnancy category: B

Embryofetal development in rats and rabbits given approximately 3 and 15 times, respectively, the maximum recommended human dose (MRHD) was not adversely effected. Dams receiving this drug at doses 3 times or more the MRHD during pregnancy and lactation, had pups with decreased body weight and survival. There are no adequate and controlled studies in pregnant women.

US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.
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References

  1. "Product Information. Flexeril (cyclobenzaprine)." Merck & Co., Inc PROD (2001):
  2. "Product Information. Amrix (cyclobenzaprine)." A-S Medication Solutions (2016):

Drug and Breastfeeding Interactions

The following applies to the ingredients: Duloxetine (found in Cymbalta)

Use is not recommended and a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

Excreted into human milk: Yes

Comments:
-Some experts state that a more thoroughly studied alternative agent (e.g., nortriptyline, paroxetine, sertraline) may be preferred while breastfeeding premature or neonates.
-The American Academy of Pediatrics classifies other antidepressants as agents for which the effect on nursing infants is unknown but may be of concern.
-Exposed infants should be monitored for developmental milestones, feeding, sedation, weight gain, especially in younger infants who are exclusively breastfed and/or when breastfed infants are exposed to multiple antipsychotropic agents.

The estimated neonatal dose is approximately 0.1% to 0.3% of the maternal dose.

References

  1. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company (2004):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. United States National Library of Medicine "Toxnet. Toxicology Data Network. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT" (2013):
  5. Briggs GG, Freeman RK. "Drugs in Pregnancy and Lactation." Philadelphia, PA: Wolters Kluwer Health (2015):
  6. National Library of Medicine (US) "Drugs and Lactation Database (LactMed) https://www.ncbi.nlm.nih.gov/books/NBK501922/" (2019):

The following applies to the ingredients: Cyclobenzaprine (found in Flexeril)

Caution is recommended.

Excreted into human milk: Unknown
Excreted into animal milk: Yes

The effects in the nursing infant are unknown.

This drug has been shown to be excreted in rat milk and achieve concentrations in the milk which are 50% of those in the rat maternal plasma. As this drug is closely related to the tricyclic antidepressants, some of which are known to be excreted in human milk, use caution especially when other drugs that cause sedation are used simultaneously.

References

  1. Hucker HB, Stauffer SC, Balletto AJ, White SD, Zacchei AG, Arison BH "Physiological disposition and metabolism of cyclobenzaprine in the rat, dog, rhesus monkey, and man." Drug Metab Dispos 6 (1978): 659-72
  2. "Product Information. Flexeril (cyclobenzaprine)." Merck & Co., Inc PROD (2001):
  3. "Product Information. Amrix (cyclobenzaprine)." A-S Medication Solutions (2016):

Therapeutic Duplication Warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

Switch to: Consumer Interactions

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

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