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Drug Interactions between Seroquel and tramadol

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

traMADol QUEtiapine

Applies to: tramadol and Seroquel (quetiapine)

GENERALLY AVOID: Concomitant use of opioids such as tramadol with other central nervous system (CNS) depressants such as quetiapine may result in hypotension, profound sedation, respiratory depression, coma, and death.

GENERALLY AVOID: There is some concern that quetiapine may have additive cardiovascular effects in combination with other drugs such as tramadol that are known to prolong the QT interval of the electrocardiogram. In clinical trials, quetiapine was not associated with a persistent increase in QT intervals, and there was no statistically significant difference between quetiapine and placebo in the proportions of patients experiencing potentially important changes in ECG parameters including QT, QTc, and PR intervals. However, QT prolongation and torsade de pointes have been reported during postmarketing use in cases of quetiapine overdose and in patients with risk factors such as underlying illness or concomitant use of drugs known to cause electrolyte imbalance or increase QT interval. The effect of tramadol on the QT interval was evaluated in a randomized, double-blind, 4-way crossover, placebo- and positive-controlled, multiple-dose ECG study of 62 healthy subjects. The maximum placebo-adjusted mean change from baseline in the Fridericia-corrected QT interval (QTcF) was 5.5 msec in the 400 mg/day treatment arm (100 mg every 6 hours on days 1 through 3 with a single 100 mg dose on day 4) and 6.5 msec in the 600 mg/day treatment arm (150 mg every 6 hours on days 1 through 3 with a single 150 mg dose on day 4), both occurring at the 8-hour time point. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). The extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: The use of tramadol in conjunction with quetiapine 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. Particular care should be exercised in patients suspected to be at an increased risk of torsade de pointes. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References (10)
  1. (2001) "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals
  2. Glassman AH, Bigger JT Jr (2001) "Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death." Am J Psychiatry, 158, p. 1774-82
  3. Sala M, Vicentini A, Brambilla P, et al. (2005) "QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy." Ann Gen Psychiatry, 4, p. 1
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  5. Vieweg WV, Schneider RK, Wood MA (2005) "Torsade de pointes in a patient with complex medical and psychiatric conditions receiving low-dose quetiapine." Acta Psychiatr Scand, 112, p. 318-22
  6. Vieweg WV (2003) "New generation antipsychotic drugs and QTc interval prolongation." Prim Care Companion J Clin Psychiatry, 5, p. 205-15
  7. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  8. Cerner Multum, Inc. "Australian Product Information."
  9. EMA. European Medicines Agency. European Union (2013) EMA - List of medicines under additional monitoring. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852
  10. US Food and Drug Administration (2016) 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

Drug and food/lifestyle interactions

Major

traMADol food/lifestyle

Applies to: 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 (18)
  1. (2017) "Product Information. Alfentanil Hydrochloride (alfentanil)." Akorn Inc
  2. (2024) "Product Information. TraMADol Hydrochloride (traMADol)." Advagen Pharma Ltd
  3. (2024) "Product Information. Jamp Tramadol (tramadol)." Jamp Pharma Corporation
  4. (2025) "Product Information. Tramadol (tramadol)." Sigma Pharmaceuticals Plc
  5. (2024) "Product Information. Tramedo (tRAMadol)." Alphapharm Pty Ltd
  6. (2022) "Product Information. Alfentanil (alfentanil)." Hameln Pharma Ltd
  7. (2024) "Product Information. Butorphanol Tartrate (butorphanol)." Apotex Corporation
  8. (2024) "Product Information. Codeine Sulfate (codeine)." Lannett Company Inc
  9. (2024) "Product Information. Meperidine Hydrochloride (meperidine)." Genus Lifesciences Inc.
  10. (2023) "Product Information. Dsuvia (SUFentanil)." AcelRx Pharmaceuticals
  11. (2024) "Product Information. Dzuveo (sufentanil)." Aguettant Ltd
  12. (2025) "Product Information. Pethidine (pethidine)." Martindale Pharmaceuticals Ltd
  13. (2023) "Product Information. Meperidine Hydrochloride (meperidine)." Sandoz Canada Incorporated
  14. (2024) "Product Information. Pethidine (Juno) (pethidine)." Juno Pharmaceuticals Pty Ltd
  15. Cherrier MM, Shen DD, Shireman L, et al. (2021) "Elevated customary alcohol consumption attenuates opioid effects." Pharmacol Biochem Behav, 4, p. 1-27
  16. Fuhr LM, Marok FZ, Fuhr U, Selzer D, Lehr T (2023) "Physiologically based pharmacokinetic modeling of bergamottin and 6,7-dihydroxybergamottin to describe CYP3A4 mediated grapefruit-drug interactions." Clin Pharmacol Ther, 114, p. 470-82
  17. (2025) "Product Information. TraMADol Hydrochloride ER (traMADol)." Trigen Laboratories Inc
  18. (2025) "Product Information. Codeine Contin (codeine)." Purdue Pharma
Moderate

QUEtiapine food/lifestyle

Applies to: Seroquel (quetiapine)

GENERALLY AVOID: Grapefruit juice and/or grapefruit may increase the plasma concentrations of quetiapine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for other CYP450 3A4 inhibitors. For example, in 12 healthy volunteers, administration of a single 25 mg dose of quetiapine with the potent CYP450 3A4 inhibitor ketoconazole (200 mg once daily for 4 days) increased mean quetiapine peak plasma concentration (Cmax) and systemic exposure (AUC) by 3.4- and 6.2-fold, respectively, and decreased mean oral clearance by 84%. In general, the effects of grapefruit products are concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit (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. High plasma levels of quetiapine may increase the risk and/or severity of serious adverse effects such as extrapyramidal symptoms, tardive dyskinesia, hyperglycemia, dyslipidemia, hyperprolactinemia, orthostatic hypotension, blood pressure increases (in children and adolescents), priapism, QT prolongation, cognitive and motor impairment, dysphagia, heat-related illnesses due to disruption of body temperature regulation, and symptoms of serotonin syndrome (e.g., 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).

Food may have varying effects on the absorption of quetiapine from immediate-release versus prolonged-release formulations. In a study examining the effects of food on the bioavailability of quetiapine, a high-fat meal was found to produce statistically significant increases in the quetiapine prolonged release Cmax and AUC of approximately 50% and 20%, respectively. It cannot be excluded that the effect of a high fat meal on the formulation may be larger. In comparison, a light meal had no significant effect on the Cmax or AUC of quetiapine.

Quetiapine may potentiate the cognitive and motor effects of alcohol. The mechanism is likely related to the primary central nervous system effects of quetiapine.

MANAGEMENT: According to the manufacturer, consumption of grapefruit juice should be avoided during treatment with quetiapine. Quetiapine immediate-release tablets may be taken with or without food. It is recommended that quetiapine prolonged release is taken once daily without food or with a light meal. Consumption of alcohol should be limited and used with caution while taking quetiapine.

References (10)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. Agencia Española de Medicamentos y Productos Sanitarios Healthcare (2008) Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html
  4. (2023) "Product Information. Aliquen (QUETIAPine)." Pharmacor Limited
  5. (2024) "Product Information. Mintreleq XL (quetiapine)." Aristo Pharma Ltd
  6. (2025) "Product Information. QUEtiapine Fumarate (QUEtiapine)." XLCare Pharmaceuticals, Inc
  7. (2024) "Product Information. QUEtiapine Fumarate ER (QUEtiapine)." ScieGen Pharmaceuticals, Inc.
  8. (2025) "Product Information. Apo-Quetiapine (quetiapine)." Apotex Inc
  9. Miyamatsu, Y., Tanizaki, R. (2021) "Serotonin syndrome triggered by increasing the dose of quetiapine" Clinical practice and cases in emergency medicine, 5, p. 365-366
  10. Kohen, I., Gordon, M.L., Manu, P. (2007) "Serotonin syndrome in elderly patients treated for psychotic depression with atypical antipsychotics and antidepressants: two case reports" CNS Spectr, 12, p. 596-8

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.


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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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.