Drug Interactions between meloxicam / rizatriptan and pitolisant

MONITOR: Concomitant use of pitolisant with NSAIDs and/or corticosteroids may increase the risk of gastrointestinal adverse effects such as dyspepsia, abdominal pain or discomfort, and gastritis due to potential additive irritant effects on the gastrointestinal mucosa. Clinical studies with pitolisant reported gastric disorders caused by hyperacidity in 3.5% of patients. However, the effects were described as mostly mild to moderate in severity. Data are not available on the potential for serious gastrointestinal (GI) toxicity, including inflammation, bleeding, ulceration, and perforation.

MANAGEMENT: Caution is advised if pitolisant is used in combination with NSAIDs and/or corticosteroids, particularly in patients with a prior history of peptic ulcer disease or GI bleeding and in elderly or debilitated patients. If concomitant therapy is required, patients should be advised to report signs and symptoms of adverse GI effects, including abdominal pain or discomfort, dyspepsia, gastroesophageal reflux disease, gastritis, or the appearance of black, tarry stools.

Coadministration with rizatriptan may alter the plasma concentrations of drugs that are primarily metabolized by CYP450 2D6. Rizatriptan has been shown to be a competitive inhibitor of CYP450 2D6 in vitro, but only at high, clinically irrelevant concentrations and a clinically significant inhibitory effect on CYP450 2D6 has not been demonstrated in clinical drug interaction studies. Based on these observations, rizatriptan may be administered with CYP450 2D6 substrates without the need for increased clinical monitoring