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7 Interactions found for:

tramadol and Xanax
Interactions Summary
  • 6 Major
  • 1 Moderate
  • 0 Minor
  • tramadol
  • Xanax

Drug Interactions

Major
Xanax + Tramadol

The following applies to the ingredients: Alprazolam (found in Xanax) and Tramadol

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
Tramadol + Food

The following applies to the ingredients: Tramadol

GENERALLY AVOID: Alcohol 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. In addition, alcohol may affect opioid release from sustained-release formulations.

GENERALLY AVOID: Grapefruit or grapefruit juice may increase the plasma concentrations of opioid analgesics by inhibiting CYP450 3A4-mediated metabolism of these agents, although the interaction has not been studied. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with opioid analgesics. Any history of alcohol or illicit drug use should be considered when prescribing an opioid analgesic, 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 opioid analgesics should preferably avoid the consumption of grapefruit and grapefruit juice.

References

  1. "Product Information. Alfentanil Hydrochloride (alfentanil)." Akorn Inc (2017):
  2. "Product Information. TraMADol Hydrochloride (traMADol)." Advagen Pharma Ltd (2024):
  3. "Product Information. Jamp Tramadol (tramadol)." Jamp Pharma Corporation (2024):
  4. "Product Information. Tramadol (tramadol)." Sigma Pharmaceuticals Plc (2025):
  5. "Product Information. Tramedo (tRAMadol)." Alphapharm Pty Ltd (2024):
  6. "Product Information. Alfentanil (alfentanil)." Hameln Pharma Ltd (2022):
  7. "Product Information. Butorphanol Tartrate (butorphanol)." Apotex Corporation (2024):
  8. "Product Information. Codeine Sulfate (codeine)." Lannett Company Inc (2024):
  9. "Product Information. Meperidine Hydrochloride (meperidine)." Genus Lifesciences Inc. (2024):
  10. "Product Information. Dsuvia (SUFentanil)." AcelRx Pharmaceuticals (2023):
  11. "Product Information. Dzuveo (sufentanil)." Aguettant Ltd (2024):
  12. "Product Information. Pethidine (pethidine)." Martindale Pharmaceuticals Ltd (2025):
  13. "Product Information. Meperidine Hydrochloride (meperidine)." Sandoz Canada Incorporated (2023):
  14. "Product Information. Pethidine (Juno) (pethidine)." Juno Pharmaceuticals Pty Ltd (2024):
  15. Cherrier MM, Shen DD, Shireman L, et al. "Elevated customary alcohol consumption attenuates opioid effects." Pharmacol Biochem Behav 4 (2021): 1-27
  16. 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
  17. "Product Information. TraMADol Hydrochloride ER (traMADol)." Trigen Laboratories Inc (2025):
  18. "Product Information. Codeine Contin (codeine)." Purdue Pharma (2025):

Moderate
Xanax + Food

The following applies to the ingredients: Alprazolam (found in Xanax)

GENERALLY AVOID: The pharmacologic activity of oral midazolam, triazolam, and alprazolam may be increased if taken after drinking grapefruit juice. The proposed mechanism is CYP450 3A4 enzyme inhibition. In addition, acute alcohol ingestion may potentiate CNS depression and other CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: The manufacturer recommends that grapefruit juice should not be taken with oral midazolam. Patients taking triazolam or alprazolam should be monitored for excessive sedation. Alternatively, the patient could consume orange juice which does not interact with these drugs. Patients should be advised to avoid alcohol during benzodiazepine therapy.

References

  1. "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn PROD (2002):
  2. "Product Information. Valium (diazepam)." Roche Laboratories PROD (2002):
  3. "Product Information. Halcion (triazolam)." Pharmacia and Upjohn PROD (2001):
  4. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  5. Kupferschmidt HHT, Ha HR, Ziegler WH, Meier PJ, Krahenbuhl S "Interaction between grapefruit juice and midazolam in humans." Clin Pharmacol Ther 58 (1995): 20-8
  6. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther 58 (1995): 127-31
  7. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77

Drug and Pregnancy Interactions

The following applies to the ingredients: Alprazolam (found in Xanax)

This drug is only recommended for use during pregnancy when there are no alternatives and the benefit outweighs the risk, especially during the first trimester of pregnancy.

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

Risk Summary: Use may be associated with an increased risk of congenital malformations. There are no adequate studies of this drug in pregnant women to inform a drug-related risk.

Comments:
-The child born to a mother taking benzodiazepines may be at risk for withdrawal symptoms.
-Benzodiazepines may cause fetal harm when administered during pregnancy.
-The patient should be warned of the potential risks to the fetus and instructed to discontinue the drug prior to becoming pregnant.
-A pregnancy exposure registry is available.

Several studies have suggested an increased risk of congenital malformations associated with the use of minor tranquilizers (i.e., chlordiazepoxide, diazepam, meprobamate) during the first trimester of pregnancy. There are no controlled data in human pregnancy.

To monitor maternal-fetal outcome of pregnant women exposed to antiepileptic drugs, the North American Antiepileptic Drug (NAAED) Pregnancy Registry has been established. Healthcare providers are encouraged to prospectively register patients. For additional information: http://www.aedpregnancyregistry.org/

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. Xanax (alprazolam)." Pharmacia and Upjohn PROD (2002):
  2. "Product Information. Niravam (alprazolam)." Schwarz Pharma (2005):
  3. "Product Information. Xanax XR (alprazolam)." Pfizer U.S. Pharmaceuticals Group (2005):
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  5. Cerner Multum, Inc. "Australian Product Information." O 0

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):

Drug and Breastfeeding Interactions

The following applies to the ingredients: Alprazolam (found in Xanax)

Use is not recommended.
-Some experts recommend: 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:
-The American Academy of Pediatrics considers this agent a drug for which the effect on nursing infants is unknown but may be of concern.
-Chronic administration of diazepam to nursing mothers has been reported to cause their infants to become lethargic and to lose weight.

References

  1. "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn PROD (2002):
  2. "Product Information. Niravam (alprazolam)." Schwarz Pharma (2005):
  3. "Product Information. Xanax XR (alprazolam)." Pfizer U.S. Pharmaceuticals Group (2005):
  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. Briggs GG, Freeman RK. "Drugs in Pregnancy and Lactation." Philadelphia, PA: Wolters Kluwer Health (2015):

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):

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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