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  "documentTitle": "Harmony Biosciences (HRMY)",
  "authorId": "58_Scorpion_Capital",
  "authorName": "Scorpion Capital",
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  "presentationDate": "2023-03-28 00:00:00",
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      "text": "FDA pitolisant review documents",
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      "text": "Drug Interactions: Clinically important interactions with pitolisant can be expected with concomitant use of strong CYP2D6 inhibitors and inducers, Histamine 1 (H1) antagonists, drugs that prolong the QT interval, and sensitive CYP3A4 substrates.",
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      "text": "4.5 Interaction with other medicinal products and other forms of interaction Reviewer's Comment: This section of the labeling discusses several important potential drug-drug interactions between pitolisant and the following types of medications: tricyclic and tetracyclic antidepressants, antihistamines, QT interval-prolonging substances, CYP3A inducers, CYP2D6 inhibitors, substrates of CYP3A4 and CYP2D6, hormonal contraceptives, and substrates of OCT1.",
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      "text": "Both the FDA and EMA reviews list a broad range of potential interactions that can cause plasma levels to spike, SSRI’s in particular which the reviews state “are potent inhibitors of CYP2D6” and that “co-administration of pitolisant with inhibitors of CYP2D6 should be done with caution.” Our interviews with 20 prescribers indicate that virtually every patient is on multiple medications, especially SSRI’s which are extensively prescribed for narcolepsy as well as cataplexy – suggesting that a large percentage of pitolisant patients can be expected to have plasma levels at least double what’s stated as the average on the label.",
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      "text": "SSRIs are potent inhibitors of CYP2D6, pitolisant is a substrate and a weak inhibitor of CYP2D6. The inhibition of CYP2D6 by paroxetine could lead to 2-fold increase of pitolisant exposure. Given the safety profile of pitolisant from phase II and III trials, it can be concluded that co-administration of pitolisant with inhibitors of CYP2D6 should be done with caution.",
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      "text": "Source: https://www.ema.europa.eu/en/documents/assessment-report/wakix-epar-public-assessment-report_en.pdf; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/211150Orig2s000MedR.pdf; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211150Orig1s000OtherR.pdf",
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      "text": "CYP2D6 safety issues are triggered not only by genetics but by drug-drug interactions that inhibit CYP2D6 activity.",
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