{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:37:44Z","timestamp":1790347064179,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Reported here are the results of four rimegepant phase I studies, in healthy participants, aimed at determining the in\u00a0vivo potential of rimegepant (75\u2009mg) for cytochrome P450 (CYP) 3A4\u2010related drug\u2013drug interactions (DDIs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rimegepant orally disintegrating tablet (Pfizer Inc., New York, NY, USA) is a calcitonin gene\u2010related peptide receptor antagonist approved for acute treatment of migraine and preventive treatment of episodic migraine. People with migraine commonly use multiple drug treatments, with the potential for DDIs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Each study was an open\u2010label, single\u2010arm, single\u2010sequence, crossover study. Rimegepant was tested as a victim drug by separate co\u2010administration of itraconazole (a strong CYP3A4 inhibitor and P\u2010glycoprotein inhibitor) in Study 1, rifampin (a strong CYP3A4 inducer and moderate CYP2C9 inducer) in Study 2, and fluconazole (a strong CYP2C9 inhibitor and moderate CYP3A4 inhibitor) in Study 3, and as a perpetrator drug by co\u2010administration with midazolam (a CYP3A4 substrate) in Study 4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mean values of single\u2010dose rimegepant maximum concentration (C\n                      <jats:sub>max<\/jats:sub>\n                      ) and area under the curve from time 0 to infinity (AUC\n                      <jats:sub>0\u2013inf<\/jats:sub>\n                      ) increased with itraconazole co\u2010administration (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200922) by 1.42\u2010fold (90% confidence interval [CI] 1.25\u20131.61) and by 4.14\u2010fold (90% CI 3.87\u20134.44), respectively, and decreased with rifampin co\u2010administration (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200921) to 36% (90% CI 31.2\u201341.4%) and to 19% (90% CI 16.3\u201321.4%), respectively. Co\u2010administration with fluconazole (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200923) increased rimegepant mean AUC\n                      <jats:sub>0\u2013inf<\/jats:sub>\n                      by 1.80\u2010fold (90% CI 1.68\u20131.93), with no impact on C\n                      <jats:sub>max<\/jats:sub>\n                      (1.04\u2010fold; 90% CI 0.94\u20131.15). Co\u2010administration of rimegepant single dose (300\u2009mg;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200914) or multiple doses (150\u2009mg\/day;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200914) increased the mean C\n                      <jats:sub>max<\/jats:sub>\n                      of midazolam by 1.38\u2010fold (90% CI 1.13\u20131.67) and 1.53\u2010fold (90% CI 1.32\u20131.78), respectively, and the AUC\n                      <jats:sub>0\u2013inf<\/jats:sub>\n                      of midazolam by 1.86\u2010fold (90% CI 1.58\u20132.19) and 1.91\u2010fold (90% CI 1.63\u20132.25), respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Based on the magnitude of DDIs, these studies indicate the following: co\u2010administration of rimegepant with a strong CYP3A4 inhibitor should be avoided; during co\u2010administration with a moderate CYP3A4 inhibitor, another dose of rimegepant within 48\u2009h should be avoided; co\u2010administration of rimegepant with a strong or moderate CYP3A4 inducer should be avoided; CYP2C9 does not play a meaningful role in rimegepant metabolism; and there is no clinically meaningful CYP3A4 inhibition by rimegepant.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.14836","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T04:58:42Z","timestamp":1728017922000},"page":"291-302","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Characterization of rimegepant drug\u2013drug interactions using the cytochrome\n                    <scp>P450<\/scp>\n                    probe drugs, itraconazole, rifampin, fluconazole, and midazolam"],"prefix":"10.1111","volume":"65","author":[{"given":"Rajinder","family":"Bhardwaj","sequence":"first","affiliation":[{"name":"Certara USA  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Morris","sequence":"additional","affiliation":[{"name":"Biohaven Pharmaceuticals, Inc  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle T.","family":"Matschke","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Bertz","sequence":"additional","affiliation":[{"name":"Biohaven Pharmaceuticals, Inc  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Croop","sequence":"additional","affiliation":[{"name":"Biohaven Pharmaceuticals, Inc  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,4]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102417738202"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.14153"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/CON.0000000000000199"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-019-1010-3"},{"key":"e_1_2_12_6_1","volume-title":"National Library of Medicine (US), National Center for Biotechnology Information: PubChem Compound Summary for CID 51049968, 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