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7 Interactions found for:

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

Drug Interactions

Major
Neurontin + Tramadol

The following applies to the ingredients: Gabapentin (found in Neurontin) and Tramadol

GENERALLY AVOID: Concomitant use of opioids with gabapentinoids (e.g., gabapentin, pregabalin) may increase the risk of opioid overdose and serious adverse effects such as profound sedation, respiratory depression, syncope, and death due to potentially additive depressant effects on the central nervous system. Using administrative databases, investigators (Gomes T, et al.) conducted a matched case-control study among residents of Ontario, Canada, who received opioid analgesics for non-cancer pain (n=5875; 1256 cases who died of an opioid-related cause and 4619 matched controls) and found that concomitant gabapentin exposure was associated with a 49% higher risk of death from an opioid overdose after adjustment for potential confounders including opioid dose. Moreover, moderate-dose (900 to 1799 mg daily) and high-dose (>/=1800 mg daily) gabapentin use was associated with a nearly 60% increase in the odds of opioid-related death compared to no concomitant gabapentin use, and very high-dose (>/=2500 mg daily) gabapentin use was associated with a nearly 2-fold increase. Concomitant use of opioids has also been reported to increase the risk of gabapentinoid misuse or abuse, particularly in patients with a history of addiction. One retrospective cohort analysis of claims data for a commercially insured U.S. population found that among patients with prolonged gabapentin use (>/=120 days over a one year period), concomitant prolonged treatment with opioids increased the risk of misuse of one or both drugs by more than 6-fold. Data from several small studies suggest that in the United States and Europe, approximately 15% to 26% and 7% to 21% of patients with opioid use disorder also misused or abused gabapentin and pregabalin, respectively. Concurrent overuse of both opioids and gabapentin has been reported to quadruple the odds of an emergency department visit or hospital stay for respiratory depression.

Coadministration with opioids may increase the oral bioavailability of gabapentin. The precise mechanism has not been established but may involve increased gabapentin absorption due to delayed gastrointestinal transit induced by opioids. In 12 healthy male volunteers, single-dose administration of gabapentin 600 mg two hours following controlled-release morphine sulfate 60 mg increased gabapentin systemic exposure (AUC) by 44% and decreased apparent oral clearance and apparent renal clearance by 23% and 16%, respectively, compared to administration with placebo. The pharmacokinetics of morphine and its glucuronides were not altered. Gabapentin has also been reported to reduce the plasma concentrations of hydrocodone in a dose-dependent manner. The mechanism of this interaction is unknown. When immediate-release gabapentin 125 mg or 500 mg was coadministered with hydrocodone 10 mg, hydrocodone Cmax decreased by 3% and 21%, respectively, while AUC decreased by 4% and 22%, respectively. Gabapentin AUC was increased 14% by hydrocodone.

MANAGEMENT: Coadministration of opioids with gabapentinoids should be generally avoided, particularly in patients with additional risk factors for respiratory depression such as advanced age, renal insufficiency, or chronic lung disease. If concomitant use 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. Use of additional central nervous system depressants should be avoided if possible. 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. For patients who have been receiving extended therapy with both an opioid and a gabapentinoid (either for analgesia or seizure control) and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms and increased seizure risk.

References

  1. US Food and Drug Administration "FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR) When used with CNS depressants or in patients with lung problems. https://www.fda.gov/media/1336" (2020):
  2. Government of Canada "Summary Safety Review - Gabapentin - Assessing the Potential Risk of Serious Breathing Problems. https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/safety-reviews/summary-safety-review-gabapentin-assessing-potential-ri" (2020):
  3. Eckhardt K, Ammon S, Hofmann U, Riebe A, Gugeler N, Mikus G "Gabapentin enhances the analgesic effect of morphine in healthy volunteers." Anesth Analg 91 (2000): 185-91
  4. Eipe N, Penning J "Postoperative respiratory depression associated with pregabalin: a case series and a preoperative decision algorithm." Pain Res Manag 16 (2011): 353-6
  5. Smith RV, Havens JR, Walsh SL "Gabapentin misuse, abuse and diversion: a systematic review." Addiction 111 (2016): 1160-74
  6. Peckham AM, Evoy KE, Covvey JR, Ochs L, Fairman KA, Sclar DA "Predictors of gabapentin overuse with or without concomitant opioids in a commercially insured U.S. population." Pharmacotherapy 38 (2018): 436-43
  7. "Product Information. Acetaminophen-Tramadol Hydrochloride (acetaminophen-tramadol)." Amneal Pharmaceuticals (2024):
  8. "Product Information. Apo-Tramadol/Acet (acetaminophen-tramadol)." Apotex Incorporated (2022):
  9. "Product Information. Tramacet (paracetamol-tramadol)." Grunenthal Ltd (2024):
  10. "Product Information. Pregabalin (pregabalin)." Alembic Pharmaceuticals (2023):
  11. "Product Information. Gabapentin (gabapentin)." Cipla USA Inc. (2025):
  12. "Product Information. Gabapentin (gabapentin)." Rivopharm (UK) Ltd (2025):
  13. "Product Information. Alzain (pregabalin)." Dr Reddy's Laboratories (UK) Ltd (2024):
  14. "Product Information. Ach-Pregabalin (pregabalin)." Accord Healthcare Inc (2024):
  15. "Product Information. Pregabalin (WGR) (pregabalin)." GM Pharma International Pty Ltd (2024):
  16. "Product Information. Gabapentin (WP) (gabapentin)." MedTAS Pty Ltd (2023):
  17. "Product Information. Apo-Gabapentin (gabapentin)." Apotex Incorporated (2024):

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
Neurontin + Food

The following applies to the ingredients: Gabapentin (found in Neurontin)

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: Gabapentin (found in Neurontin)

Benefits should clearly outweigh risks

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

Risk Summary: There are no data on the developmental risks associated with use of this drug in pregnant women; in animal studies, developmental toxicity was observed at doses estimated to be similar or lower than those used clinically.

Comments:
-The risk of having a child with a congenital defect as a result of antiepileptic medication is far outweighed by the dangers to the mother and fetus of uncontrolled epilepsy; folic acid supplementation (5 mg) should be started 4 weeks prior to and continued for 12 weeks after conception.
-Women of childbearing potential should receive counseling on the risk of fetal abnormalities with use of antiepileptic drugs (AEDs) during pregnancy; AEDs should generally be continued during pregnancy utilizing monotherapy at the lowest effective dose as this has been shown to minimize risks of fetal abnormalities compared to combination AED therapy.
-A pregnancy exposure registry is available.

Animal studies have revealed evidence of developmental toxicity (increased fetal skeletal and visceral abnormalities, and increased embryofetal mortality) when administered at doses similar to, or lower than expected clinical doses. In rats, an increased incidence of hydroureter and/or hydronephrosis have been observed in offspring at all doses, the lowest dose being similar to the maximum recommended human dose on a mg/m2 basis. This drug crosses the human placenta. From the limited amount of data in human pregnancy, it is not possible to inform an associated increased risk of congenital malformations because epilepsy itself and the presence of concomitant antiepileptic medicinal products have their own risks. There are no controlled data in human pregnancy.

To provide information regarding the effects of in utero exposure to this drug, pregnant patients should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll-free number 1-888-233-2334 and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/.

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. Neurontin (gabapentin)." Parke-Davis 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. Horizant (gabapentin)." GlaxoSmithKline (2021):
  5. "Product Information. Gralise (gabapentin)." Depomed Inc (2021):

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: Gabapentin (found in Neurontin)

Benefits should clearly outweigh risks

Excreted into human milk: Yes

Comments:
-Breastfed infants should be monitored for drowsiness, adequate weight gain, and developmental milestones, especially when used in combination with other anticonvulsant or psychotropic drugs and in younger, exclusively breastfed infants.
-Some authorities suggest discontinuing nursing or discontinuing use of this drug while breastfeeding due to the potential for serious adverse reactions in the breastfed infant.

With maternal doses up to 2.1 g/day, estimated doses for fully breastfed infants are 0.2 to 1.3 mg/kg/day (equivalent to 1.3 to 3.8% of the maternal weight-adjusted dose). An expert panel has deemed this drug is an acceptable choice for refractory restless leg syndrome during lactation. Until more data becomes available, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for this drug and any potential adverse effects on the breastfed infant from this drug or from the underlying maternal condition.

References

  1. "Product Information. Neurontin (gabapentin)." Parke-Davis 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. Horizant (gabapentin)." GlaxoSmithKline (2021):
  6. "Product Information. Gralise (gabapentin)." Depomed Inc (2021):

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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