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7 Interactions found for:

Flexeril and oxycodone
Interactions Summary
  • 4 Major
  • 1 Moderate
  • 2 Minor
  • Flexeril
  • oxycodone

Drug Interactions

Major
Oxycodone + Flexeril

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

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

MANAGEMENT: The use of opioids in conjunction with benzodiazepines or 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, with cautious titration and dosage adjustments when needed. 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. Cough medications containing opioids (e.g., codeine, hydrocodone) should not be prescribed to patients using benzodiazepines or other CNS depressants including alcohol. For patients who have been receiving extended therapy with both an opioid and a benzodiazepine and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms. Severe cases of benzodiazepine withdrawal, primarily in patients who have received excessive doses over a prolonged period, may result in numbness and tingling of extremities, hypersensitivity to light and noise, hallucinations, and epileptic seizures.

References

  1. 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

Major
Oxycodone + Food

The following applies to the ingredients: Oxycodone

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including oxycodone. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of oxycodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of oxycodone by certain compounds present in grapefruit, resulting in decreased formation of metabolites noroxycodone and noroxymorphone and increased formation of oxymorphone due to a presumed shifting of oxycodone metabolism towards the CYP450 2D6-mediated route. In 12 healthy, nonsmoking volunteers, administration of a single 10 mg oral dose of oxycodone hydrochloride on day 4 of a grapefruit juice treatment phase (200 mL three times a day for 5 days) increased mean oxycodone peak plasma concentration (Cmax), systemic exposure (AUC) and half-life by 48%, 67% and 17% (from 3.5 to 4.1 hours), respectively, compared to administration during an equivalent water treatment phase. Grapefruit juice also decreased the metabolite-to-parent AUC ratio of noroxycodone by 44% and that of noroxymorphone by 45%. In addition, oxymorphone Cmax and AUC increased by 32% and 56%, but the metabolite-to-parent AUC ratio remained unchanged. Pharmacodynamic changes were modest and only self-reported performance was significantly impaired after grapefruit juice. Analgesic effects were not affected.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with oxycodone. Any history of alcohol or illicit drug use should be considered when prescribing oxycodone, and therapy initiated at a lower dosage if necessary. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. Due to a high degree of interpatient variability with respect to grapefruit juice interactions, patients treated with oxycodone may also want to avoid or limit the consumption of grapefruit and grapefruit juice.

References

  1. Nieminen TH, Hagelberg NM, Saari TI, et al. "Grapefruit juice enhances the exposure to oral oxycodone." Basic Clin Pharmacol Toxicol 107 (2010): 782-8

The following applies to the ingredients: Oxycodone

GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.

References

  1. Linnoila M, Hakkinen S "Effects of diazepam and codeine, alone and in combination with alcohol, on simulated driving." Clin Pharmacol Ther 15 (1974): 368-73
  2. Sturner WQ, Garriott JC "Deaths involving propoxyphene: a study of 41 cases over a two-year period." JAMA 223 (1973): 1125-30
  3. Girre C, Hirschhorn M, Bertaux L, et al. "Enhancement of propoxyphene bioavailability by ethanol: relation to psychomotor and cognitive function in healthy volunteers." Eur J Clin Pharmacol 41 (1991): 147-52
  4. Reece PA, Cozamanis I, Zacest R "Kinetics of hydralazine and its main metabolites in slow and fast acetylators." Clin Pharmacol Ther 28 (1980): 769-78
  5. Levine B, Saady J, Fierro M, Valentour J "A hydromorphone and ethanol fatality." J Forensic Sci 29 (1984): 655-9
  6. Sellers EM, Hamilton CA, Kaplan HL, Degani NC, Foltz RL "Pharmacokinetic interaction of propoxyphene with ethanol." Br J Clin Pharmacol 19 (1985): 398-401
  7. Carson DJ "Fatal dextropropoxyphene poisoning in Northern Ireland. Review of 30 cases." Lancet 1 (1977): 894-7
  8. Rosser WW "The interaction of propoxyphene with other drugs." Can Med Assoc J 122 (1980): 149-50
  9. Edwards C, Gard PR, Handley SL, Hunter M, Whittington RM "Distalgesic and ethanol-impaired function." Lancet 2 (1982): 384
  10. Kiplinger GF, Sokol G, Rodda BE "Effect of combined alcohol and propoxyphene on human performance." Arch Int Pharmacodyn Ther 212 (1974): 175-80
  11. "Product Information. Alfentanil Hydrochloride (alfentanil)." Akorn Inc (2017):
  12. "Product Information. Palexia SR (tAPENTadol)." Seqirus Pty Ltd (2022):
  13. "Product Information. Tapimio (tapentadol)." Neuraxpharm UK Ltd (2022):
  14. "Product Information. Nucynta (tapentadol)." Collegium Pharmaceutical, Inc. (2023):
  15. "Product Information. TraMADol Hydrochloride (traMADol)." Advagen Pharma Ltd (2024):
  16. "Product Information. Opium Deodorized (opium)." ANIP Acquisition Company (2018):
  17. "Product Information. Jamp Tramadol (tramadol)." Jamp Pharma Corporation (2024):
  18. "Product Information. Tramadol (tramadol)." Sigma Pharmaceuticals Plc (2025):
  19. "Product Information. Morphine Sulfate ER (morphine)." Actavis (formerly Abrika Pharmaceuticals LLP) (2024):
  20. "Product Information. Oxymorphone Hydrochloride (oxyMORphone)." Aurolife Pharma LLC (2024):
  21. "Product Information. Levorphanol Tartrate (levorphanol)." Virtus Pharmaceuticals LLC (2024):
  22. "Product Information. Nalbuphine Hydrochloride (nalbuphine)." Hospira Inc (2025):
  23. "Product Information. Remifentanil (remifentanil)." Wockhardt UK Ltd (2022):
  24. "Product Information. Naloxone HCl-Pentazocine HCl (naloxone-pentazocine)." Actavis U.S. (Amide Pharmaceutical Inc) (2024):
  25. "Product Information. Alfentanil (alfentanil)." Hameln Pharma Ltd (2022):
  26. "Product Information. Butorphanol Tartrate (butorphanol)." Apotex Corporation (2024):
  27. "Product Information. Codeine Sulfate (codeine)." Lannett Company Inc (2024):
  28. "Product Information. Cyclizine-Dipipanone (cyclizine-dipipanone)." Advanz Pharma (2024):
  29. "Product Information. Meperidine Hydrochloride (meperidine)." Genus Lifesciences Inc. (2024):
  30. "Product Information. Dsuvia (SUFentanil)." AcelRx Pharmaceuticals (2023):
  31. "Product Information. Dzuveo (sufentanil)." Aguettant Ltd (2024):
  32. "Product Information. Buprenorphine Hydrochloride (buprenorphine)." Advagen Pharma Limited (2024):
  33. "Product Information. Pethidine (pethidine)." Martindale Pharmaceuticals Ltd (2025):
  34. "Product Information. Meperidine Hydrochloride (meperidine)." Sandoz Canada Incorporated (2023):
  35. "Product Information. Actimorph (morphine)." Ethypharm UK Ltd (2025):
  36. "Product Information. Doloral Sirop (morphine)." Laboratoire Atlas Inc (2024):
  37. "Product Information. Morphine Sulfate (Medsurge) (morphine)." Medicianz Healthcare Pty Ltd (2024):
  38. "Product Information. Diacetylmorphine Hydrochloride (diamorphine)." Pharmascience Inc (2023):
  39. "Product Information. Pethidine (Juno) (pethidine)." Juno Pharmaceuticals Pty Ltd (2024):
  40. Cherrier MM, Shen DD, Shireman L, et al. "Elevated customary alcohol consumption attenuates opioid effects." Pharmacol Biochem Behav 4 (2021): 1-27
  41. Fuhr LM, Marok FZ, Fuhr U, Selzer D, Lehr T "Physiologically based pharmacokinetic modeling of bergamottin and 6,7-dihydroxybergamottin to describe CYP3A4 mediated grapefruit-drug interactions." Clin Pharmacol Ther 114 (2023): 470-82
  42. "Product Information. Nucynta Extended-Release (tapentadol)." Endo Operations, LTD. (2021):
  43. "Product Information. Oxymorphone Hydrochloride ER (oxyMORphone)." Amneal Pharmaceuticals LLC (2024):
  44. "Product Information. Morphine Sulfate (morphine)." BGP Pharma ULC (2025):
  45. "Product Information. Hysingla ER (HYDROcodone)." Purdue Pharma LP (2025):
  46. "Product Information. Covonia Dry Cough (pholcodine)." Thornton & Ross Ltd (2021):
  47. "Product Information. TUSCALMAN NIÑOS (noscapina)." DESMA LABORATORIO FARMACEUTICO, S.L. (2018):

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):

Drug and Pregnancy Interactions

The following applies to the ingredients: Oxycodone

Use is not recommended.
-Some authorities recommend avoiding use, unless it is clearly needed.

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

Risk Summary: Based on animal data, may cause fetal harm; prolonged maternal use of opioids during pregnancy may cause neonatal opioid withdrawal syndrome.

Comments:
-Prolonged use of opioids during pregnancy can result in physical dependence in the neonate; women should be advised of the risk of neonatal abstinence syndrome and ensure that appropriate treatment will be available.
-Opioid analgesics, can prolong labor by temporarily reducing the strength, duration, and frequency of uterine contractions. These agents are not recommended during or immediately prior to labor.
-Monitor neonates exposed to opioid analgesics for signs of excess sedation and respiratory depression.

Opioid analgesics cross the placenta. The use of this drug during labor may cause respiratory depression in the newborn infant. Prolonged use of opioids during pregnancy can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. The onset, duration, and severity of the condition will vary based on use (duration of use, timing, and amount of last maternal use) and rate of elimination in the newborn. There are no controlled data in human pregnancy.

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. Percocet (acetaminophen-oxycodone)." DuPont Pharmaceuticals PROD (2001):
  2. "Product Information. Tylox (acetaminophen-oxycodone)." McNeil Pharmaceutical PROD (2001):
  3. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company PROD (2001):
  4. Koren G, Pastuszak A, Ito S "Drugs in pregnancy." N Engl J Med 338 (1998): 1128-37
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. "Product Information. Xtampza ER (oxyCODONE)." Patheon SUPPL-21 (2023):

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: Oxycodone

Avoid during breastfeeding.

Excreted into human milk: Yes

Comments:
-Maternal use of oral opioids during breastfeeding can cause excess sedation and respiratory depression in the infant. In some cases, it may progress to rare but severe central nervous system depression.
-In breastfeeding patients, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of this drug.
-If used, monitor breastfed infants closely for excess sedation, adequate weight gain, and respiratory depression.
-Withdrawal symptoms may occur in breastfed infants when maternal administration of an opioid is stopped or when breast-feeding is stopped.

Maternal use of opioids during breastfeeding can cause infant drowsiness, central nervous system depression, and even death. Infant sedation is common with maternal use of this drug. Newborn infants are particularly sensitive to the effects of even small dosages of opioid analgesics. When possible, pain control should be with a non opioid analgesic. However, if needed, use should be limited to the immediate-release products with a maximum dosage of 30 mg per day. Infants should be monitored closely for drowsiness, adequate weight gain, and developmental milestones, especially younger, exclusively breastfed infants.

References

  1. "Product Information. Percocet (acetaminophen-oxycodone)." DuPont Pharmaceuticals PROD (2001):
  2. "Product Information. Tylox (acetaminophen-oxycodone)." McNeil Pharmaceutical PROD (2001):
  3. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company PROD (2001):
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  5. Cerner Multum, Inc. "Australian Product Information." O 0
  6. United States National Library of Medicine "Toxnet. Toxicology Data Network. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT" (2013):
  7. "Product Information. Xtampza ER (oxyCODONE)." Patheon SUPPL-21 (2023):

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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