Taking Vicodin (Hydrocodone/APAP) With Prozac (Fluoxetine)

In our latest question and answer, the pharmacist discusses the interaction between Vicodin (hydrocodone/acetaminophen) and Prozac (fluoxetine).


I take 300mg of lithium and 10mg of prozac a day. Can I take Vicodin for a toothache? Are there interactions?

Asked by Lis On Jan 05, 2018

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Jan 06, 2018

There is considered to be a minor interaction between Vicodin (hydrocodone/acetaminophen) and Prozac (fluoxetine). Taking Prozac along with hydrocodone may decrease the effectiveness of hydrocodone.

Hydocodone, an opioid analgesic, is metabolized in the body to two active metabolites, norhydrocodone and hydromorphone. While norhydrocodone is considered to be relatively inactive, it does appear to be responsible for some of the effects experienced in patients.

Hydrocodone is metabolized primarily by two liver metabolizing enzymes:

  • CYP3A4
  • CYP2D6

Prozac (fluoxetine) is a known inhibitor of the CYP2D6 metabolizing enzyme. This means that theoretically, hydrocodone will undergo slower metabolism due to CYP2D6 inhibition from Prozac. Slower metabolism will result in less of the active metabolites of hydrocodone being formed, potentially reducing the effectiveness of the drug.

This interaction is considered relatively minor as CYP2D6 isn't responsible for the majority of hydrocodone metabolism. You may notice slightly reduced benefit from taking hydrocodone with Prozac, but it most likely won't be significant.

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Dr. Brian Staiger Pharm.D

Dr. Brian Staiger is a licensed pharmacist in New York State and the founder of PharmacistAnswers.com. He graduated from the University At Buffalo with a Doctor of Pharmacy degree in 2010. He has been featured in numerous publications including the Huffington Post as well as a variety of health and pharmacy-related blogs. Please feel free to reach out to him directly if you have any inquiries or want to connect! He's answered thousands of medication and pharmacy-related questions and he's ready to answer yours! Brian.Staiger@PharmacistAnswers.com Office: 716-389-3076

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