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).

Jan 05, 2018

Lis asked

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

Answer

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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