Drug Interactions between Provigil and tramadol
This report displays the potential drug interactions for the following 2 drugs:
- Provigil (modafinil)
- tramadol
Interactions between your drugs
traMADol modafinil
Applies to: tramadol and Provigil (modafinil)
MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of tramadol, which is primarily metabolized by CYP450 3A4 and 2D6. Reduced opioid efficacy can occur, including opioid withdrawal in physically dependent patients. After discontinuing a CYP450 3A4 inducer, the tramadol plasma concentration will increase, which could increase and/or prolong opioid efficacy and adverse reactions, including seizures, serotonin syndrome, and respiratory depression. In addition, when two or more medications with similar adverse effect profiles are given concurrently, the likelihood of experiencing these adverse reactions may be increased. For example, coadministration with other agents that can prolong the QT interval (e.g., apalutamide, encorafenib, enzalutamide) may result in additive effects and an increased risk of ventricular arrhythmias like torsade de pointes.
MANAGEMENT: Caution is advised when tramadol is used with CYP450 3A4 inducers. Patients should be monitored for opioid efficacy and signs of withdrawal. If the CYP450 3A4 inducer also carries a risk of prolonging the QT interval, then obtaining more frequent electrocardiograms (ECGs) to monitor the QT interval may be advisable. Patients should be counseled to seek immediate medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, syncope, palpitations, irregular heartbeat, and/or shortness of breath. If a CYP450 3A4 inducer is discontinued, monitor for seizures, serotonin syndrome, sedation, and respiratory depression. The prescribing information for the concomitant CYP450 3A4 inducers should be consulted for specific recommendations.
References (1)
- (2022) "Product Information. Seglentis (celecoxib-tramadol)." Kowa Pharmaceuticals America (formerly ProEthic)
Drug and food/lifestyle interactions
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)
- (2017) "Product Information. Alfentanil Hydrochloride (alfentanil)." Akorn Inc
- (2024) "Product Information. TraMADol Hydrochloride (traMADol)." Advagen Pharma Ltd
- (2024) "Product Information. Jamp Tramadol (tramadol)." Jamp Pharma Corporation
- (2025) "Product Information. Tramadol (tramadol)." Sigma Pharmaceuticals Plc
- (2024) "Product Information. Tramedo (tRAMadol)." Alphapharm Pty Ltd
- (2022) "Product Information. Alfentanil (alfentanil)." Hameln Pharma Ltd
- (2024) "Product Information. Butorphanol Tartrate (butorphanol)." Apotex Corporation
- (2024) "Product Information. Codeine Sulfate (codeine)." Lannett Company Inc
- (2024) "Product Information. Meperidine Hydrochloride (meperidine)." Genus Lifesciences Inc.
- (2023) "Product Information. Dsuvia (SUFentanil)." AcelRx Pharmaceuticals
- (2024) "Product Information. Dzuveo (sufentanil)." Aguettant Ltd
- (2025) "Product Information. Pethidine (pethidine)." Martindale Pharmaceuticals Ltd
- (2023) "Product Information. Meperidine Hydrochloride (meperidine)." Sandoz Canada Incorporated
- (2024) "Product Information. Pethidine (Juno) (pethidine)." Juno Pharmaceuticals Pty Ltd
- Cherrier MM, Shen DD, Shireman L, et al. (2021) "Elevated customary alcohol consumption attenuates opioid effects." Pharmacol Biochem Behav, 4, p. 1-27
- 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
- (2025) "Product Information. TraMADol Hydrochloride ER (traMADol)." Trigen Laboratories Inc
- (2025) "Product Information. Codeine Contin (codeine)." Purdue Pharma
modafinil food/lifestyle
Applies to: Provigil (modafinil)
Administration with food may delay the absorption of modafinil (the racemate) and armodafinil (the R-enantiomer) without significantly affecting their overall bioavailability. According to the product labeling, modafinil's absorption may be delayed by approximately one hour if taken with food. Similarly, the time to reach peak plasma concentration (Tmax) of armodafinil may be delayed by approximately 2 to 4 hours in the fed state.
References (2)
- (2001) "Product Information. Provigil (modafinil)." Cephalon, Inc
- (2007) "Product Information. Nuvigil (armodafinil)." Cephalon Inc
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.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.