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7 Interactions found for:

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

Drug Interactions

Major
Flexeril + Tramadol

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

GENERALLY AVOID: Concomitant use of opioids with other central nervous system (CNS) depressants (e.g., benzodiazepines, sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may result in profound sedation, respiratory depression, coma, and death.

MANAGEMENT: The use of opioids in conjunction with other CNS depressants should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them.

GENERALLY AVOID: Concomitant use of phenylpiperidine opioids, tapentadol, or tramadol with each other or with other serotonergic agents 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. 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

  1. Nierenberg DW, Semprebon M "The central nervous system serotonin syndrome." Clin Pharmacol Ther 53 (1993): 84-8
  2. Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13
  3. Insel TR, Roy BF, Cohen RM, Murphy DL "Possible development of the serotonin syndrome in man." Am J Psychiatry 139 (1982): 954-5
  4. 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):
  5. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical PROD (2001):
  6. Mills KC "Serotonin syndrome: A clinical update." Crit Care Clin 13 (1997): 763
  7. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG "Serotonin syndrome resulting from drug interactions." Med J Aust 169 (1998): 523-5
  8. Weiner AL "Meperidine as a potential cause of serotonin syndrome in the emergency department." Acad Emerg Med 6 (1999): 156-8
  9. 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
  10. Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6
  11. Giese SY, Neborsky R "Serotonin syndrome: potential consequences of Meridia combined with Demerol or fentanyl." Plast Reconstr Surg 107 (2001): 293-4
  12. Boyer EW, Shannon M "The serotonin syndrome." N Engl J Med 352 (2005): 1112-20
  13. Keegan MT, Brown DR, Rabinstein AA "Serotonin syndrome from the interaction of cyclobenzaprine with other serotoninergic drugs." Anesth Analg 103 (2006): 1466-8
  14. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):
  15. US Food and Drug Administration "FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM518672.pdf" (2016):

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
Tramadol + Food

The following applies to the ingredients: Tramadol

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):

Drug and Pregnancy Interactions

The following applies to the ingredients: Tramadol

Use is not recommended

AU TGA pregnancy category: C
US FDA pregnancy category: Not Assigned

Risk Summary: There is insufficient data in humans to inform a drug-associated risk for major birth defects and miscarriage; prolonged use of opioids during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.

Comments:
-This drug is not recommended for obstetrical preoperative medication or for post-delivery analgesia in nursing mothers because its safety in infants and newborns has not been studied.

This drug has been shown to cross the placental barrier, with an umbilical vein to maternal vein serum concentration ratio of 0.83. Animal studies have shown at very high doses, this drug has an effect on organ development, bone growth, and mortality rate. Prolonged maternal use of opioid analgesics during pregnancy may result in respiratory depression and physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. There have been postmarketing reports of neonatal seizures, neonatal withdrawal syndrome, fetal death, and still births. There are no adequate and well-controlled studies in pregnant women.

Chronic use of opioids may cause reduced fertility; it is unknown whether these effects are reversible.

AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.

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. Ultram (tramadol)." McNeil Pharmaceutical PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. "Product Information. Ultram ER (tramadol)." PriCara Pharmaceuticals (2015):

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: Tramadol

Use is not recommended

Excreted into human milk: Yes

Comments:
-The US FDA recommends against the use of tramadol during breastfeeding due to risks of serious adverse reactions in breastfed infants; this drug is not recommended for obstetrical preoperative medication or for post-delivery analgesia in nursing mothers because its safety in infants and newborns has not been studied.
-If infants are exposed through breastmilk, they should be monitored for excess sedation and respiratory depression.

Serious adverse reactions in breastfed infants may include excess sleepiness, difficulty breastfeeding, or serious breathing problems that could result in death. Newborns have limited capacity to metabolize the active 0-desmethyltramadol.

A study in 75 mothers reported an average milk concentration of 748 mcg/L; this translates to an average infant dose of 112 mcg/kg and a maternal weight-adjusted dose of 2.24% and 0.64% for the drug and its metabolite, respectively. Reanalysis of the data using a population pharmacokinetic model showed a maternal weight adjusted dose of 2.2% for extensive metabolizers and 2.6% for poor metabolizers. The amount of drug present in breast milk represents a maximum of 2.6% of the proposed IV newborn dose. This drug can increase prolactin levels; however, the prolactin level in a mother with established lactation may not affect her ability to breastfeed.

References

  1. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical PROD (2001):
  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. "Product Information. Ultram ER (tramadol)." PriCara Pharmaceuticals (2015):
  6. US Food and Drug Administration (FDA) "FDA Drug Safety Communication: FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children; recommends against use in breastfeeding women. https://www.fda.gov/Drugs/DrugSafety/ucm549679.htm" (2017):

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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