Drug Interactions

Duloxetine (Cymbaltaź) Interactions

Taking Duloxetine with:

Duloxetine Drug Interactions:

  • Alcohol: avoid, alcohol may increase hepatotoxic potential of duloxetine.
  • CYP1A2 inhibitors: (fluvoxamine, ketoconazole, norfloxacin, ciprofloxacin, ofloxacin, rofecoxib): may increase the levels of duloxetine.
  • CYP2D6 inhibitors: (chlorpromazine, delavirdine, miconazole, pergolide, quinidine, quinine, ritonavir, and ropinirole): may increase the levels of duloxetine.
  • Desipramine: duloxetine may increase desipramine levels.
  • MAO inhibitors: risk of serotonin syndrome. This combination is contraindicated. Wait 5 days after discontinuance of duloxetine before initiating MAO inhibitor; wait at least 2 weeks between discontinuance of MAO inhibitor and initiation of duloxetine.
  • SSRIs, SNRIs, Sibutramine, Serotonin agonists (eg, triptans, lithium): risk of serotonin syndrome.
  • Thioridazine: duloxetine may increase serum concentrations of thioridazine, which has been associated with the development of malignant ventricular arrhythmias; use caution.
  • Tricyclic antidepressants: serum levels may be increased by duloxetine.

Can you take Duloxetine and Amitriptyline together?

The use of duloxetine with the tricyclic antidepressant Amitriptyline may increase the risk of serotonin syndrome. The combination of duloxetine and amitriptyline should be used with caution. Monitor for antimuscarinic side effects (dry mouth, urinary retention, constipation).

Can you take Duloxetine and benzodiazepines at the same time?

No important interactions appear to occur between duloxetine and the benzodiazepines 1, 2 (e.g. alprazolam (Xanax), diazepam (Valium), lorazepam (Ativan), clonazepam (Klonopin), temazepam (Restoril)) or related medications such zolpidem (Ambien). Concurrent use of duloxetine and lorazepam2 and other benzodiazepines may increase sedation.

Can you take Duloxetine and Tramadol?

Duloxetine can be used along with tramadol, but caution should be undertaken. Possible risk of the serotonin syndrome.

Can you take Duloxetine and SSRIs?

Concurrent use of duloxetine with SSRIs (escitalopram, citalopram, fluoxetine, paroxetine, sertraline) should be undertaken with caution, because taking more than one serotonergic drug may result in serotonin syndrome.

Paroxetine (Paxil) is an inhibitor of the cytochrome P450 isoenzyme CYP2D68 and modestly increases duloxetine levels. Fluoxetine (Prozac) also can slightly increase duloxetine levels via CYP2D6 inhibitory effects.

Can you take Duloxetine with Pregabalin (Lyrica®)?

Concomitant use of duloxetine and pregabalin is acceptable. According to the clinical research the combination therapy is safe and well tolerated4.

Can you take Duloxetine with Gabapentin (Neurontin®)?

No clinically significant drug interactions expected between duloxetine and gabapentin1. The combination of duloxetine plus gabapentin is used when gabapentin alone provides insufficient pain relief5. This combination is safe and tolerable treatment for pain9.

Can you take Duloxetine and Olanzapine (Zyprexa®)?

Duloxetine can be safely used simultaneously with olanzapine. Research has shown that low-dose olanzapine can effectively reduce duloxetine-related nausea and vomiting3.

Can you take Duloxetine and Ibuprofen together?

No adverse drug interactions between duloxetine and ibuprofen. Animal study suggests that duloxetine and ibuprofen have synergistic efficacy in the treatment of persistent pain6.

Can you take Duloxetine and NSAIDs together?

Taking duloxetine along with NSAIDs is acceptable and generally safe1, 10.

Can you take Duloxetine and Aspirin together?

Taking duloxetine and aspirin at the same time is acceptable and generally safe1, 10.

Can you take Duloxetine and Aripiprazole (Abilify®)?

No adverse drug interactions7. Duloxetine may safely be used concomitantly with aripiprazole7.

Can you take Duloxetine and Risperidone (Risperdal®)?

No adverse drug interactions. Duloxetine may be used with risperidone7.

When you should NOT take Duloxetine?

  • Uncontrolled narrow-angle glaucoma
  • MAOI therapy
  • Hypersensitivity to duloxetine
  • Renal dysfunction: Not recommended for patients with a CrCl < 30ml/min.
  • Hepatotoxicity: Duloxetine should not be given to patients who drink alcohol heavily or who has chronic liver disease. May markedly increase serum transaminase levels (> 20 times the upper limit of normal).

Duloxetine during Pregnancy & Lactation

Pregnancy category C
Neonates exposed to duloxetine late in the third trimester may develop complications requiring prolonged hospitalization, respiratory support, and tube feeding.

Nursing mothers
Duloxetine enters breast milk; not recommended.


  • 1. U.S. FDA Duloxetine Prescribing Information
  • 2. Chalon S, Vandenhende F, Ertle S. Combined administration of duloxetineand lorazepam: a pharmacokinetic and pharmacodynamic study. Clin Pharmacol Ther (2005) 77, p.65.
  • 3. Zhong Z, Zhang Y, Han H, Huang Z, Wang J, Chen M, Zhang J. Effects of low-dose olanzapine on duloxetine-related nausea and vomiting for the treatment of major depressive disorder. J Clin Psychopharmacol. 2014 Aug;34(4):495-8. PubMed
  • 4. Tesfaye S, Wilhelm S, Lledo A, Schacht A, Tölle T, Bouhassira D, Cruccu G, Skljarevski V, Freynhagen R. Duloxetine and pregabalin: high-dose monotherapy or their combination? Pain. 2013 Dec;154(12):2616-25. PubMed
  • 5. Tanenberg RJ, Irving GA, Risser RC, Ahl J, Robinson MJ, Skljarevski V, Malcolm SK. Duloxetine, pregabalin, and duloxetine plus gabapentin for diabetic peripheral neuropathic pain management in patients with inadequate pain response to gabapentin: an open-label, randomized, noninferiority comparison. Mayo Clin Proc. 2011 Jul;86(7):615-26. PubMed
  • 6. Jones CK, Peters SC, Shannon HE. Synergistic interactions between the dual serotonergic, noradrenergic reuptake inhibitor duloxetine and the non-steroidal anti-inflammatory drug ibuprofen in inflammatory pain in rodents. Eur J Pain. 2007 Feb;11(2):208-15. PubMed
  • 7. Hendset M, Molden E, Enoksen TB, Refsum H, Hermann M. The effect of coadministration of duloxetine on steady-state serum concentration of risperidone and aripiprazole: a study based on therapeutic drug monitoring data. Ther Drug Monit. 2010 Dec;32(6):787-90. PubMed
  • 8. Skinner MH, Kuan HY, Pan A, Sathirakul K, Knadler MP, Gonzales CR, Yeo KP, Reddy S, Lim M, Ayan-Oshodi M, Wise SD. Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers. Clin Pharmacol Ther. 2003 Mar;73(3):170-7. PubMed
  • 9. Irving G, Tanenberg RJ, Raskin J, Risser RC, Malcolm S. Comparative safety and tolerability of duloxetine vs. pregabalin vs. duloxetine plus gabapentin in patients with diabetic peripheral neuropathic pain. Int J Clin Pract. 2014 Sep;68(9):1130-40. PubMed
  • 10. Li H, Cheng Y, Ahl J, Skljarevski V. Observational study of upper gastrointestinal tract bleeding events in patients taking duloxetine and nonsteroidal anti-inflammatory drugs: a case-control analysis. Drug Healthc Patient Saf. 2014 Oct 29;6:167-74. PubMed

By HealthyStock Research Group, September 2009
Medical resources reviewed: August 2018

Contact Us

Copyright © 2009-2018 All rights reserved.
All information on is intended for general knowledge only.
For medical advice consult with your physician.