The drug is metabolized by CYPs 1A2 and 2D6. It is not a substrate of, and thus not an inducer of or an inhibitor of CYP 3A4. There are therefore no non-clinical findings suggesting porphyrogenicity, nor are there any reports of interference with CYP3A4-metabolism of other drugs. There is one published report of duloxetine and an acute attack of porphyria variagata, but the clinical data question the causality of this observation.

(+)-(S)-N-Methyl-γ-(1-naphthyloxy)-2-thiophenepropylamine hydrochloride. M =333.9. There are no chemical moieties within the drug pointing to capacity for action as CYP suicide substrate.

Duloxetine is a combined serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor (SNRI), which weakly inhibits dopamine reuptake. The common side effects may mimic symptoms of acute porphyria, i.e. tachycardia, agitation, abdominal pain, nausea, vomiting, obstipation, musculoskeletal pain, paraesthesias. Should these occur, for sake of safety PBG excretion should be monitored for a few days, or (perhaps preferably) the patient should be instructed to initially observe the color of urine and without delay report reddish discoloration.

With a daily peroral dose of 60 mg there is significant hepatic exposure, i.e > 1 micromolar.

Duloxetine is extensively metabolised, primarily by the liver. The bioavailability is 32-80 percent. Duloxetine is metabolised by CYP 1A2 and CYP 2D6, it moderatly inhibits CYP 2D6, it does not affect the CYP 3A4 isoenzyme (European public assessment report, 2005). Large difference in exposure between women and men, with women having twice as large exposure to the drug.

No published information.

There is one published report of duloxetine and an acute attack of porphyria variagata. The symptoms which the patient had experienced such as painful and ulcerating red rash, severe abdominal pain with constipation and vomiting, paresthesias, and worsening depression and anxiety, along with hallucinations, paranoia and suicidality ( Loper T et al. 2007 ) are all side effects of duloxetine ( Marindale ). But in the case report the side effects of duloxetine were suspected to be the symptoms of acute porphyria. Since this case report lacks biochemical evidence such as measurements of PBG excretion for a couple of days etc., the causality could not be established.

1 report of uneventful use in acute porphyria.