Major Research Findings

Rolapitant is a selective, long-acting neurokinin-1 receptor antagonist approved in the United States and Europe for prevention of delayed chemotherapy-induced nausea and vomiting (CINV) in adults. 2

Intravenous rolapitant is not an inhibitor of CYP3A, CYP2C9, CYP2C19, or CYP1A2 but is a moderate inhibitor of CYP2D6. 2

Rolapitant is a selective and long-acting neurokinin-1 receptor antagonist approved in an oral formulation in combination with other antiemetic agents for the prevention of delayed CINV in adults. 3

Rolapitant, a selective, long-acting neurokinin-1 (NK-1) receptor antagonist, demonstrated efficacy in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly or moderately emetogenic chemotherapy. 11

Absolute bioavailability of oral rolapitant was determined to be ∼100%. Brain imaging by positron emission tomography showed that NK-1 receptor occupancy increased with escalating doses but was not dose-proportional. A 180-mg dose resulted in near-saturable binding to NK-1 receptors (mean ± standard deviation: 94% ± 9%). 11

Benefits and Risks

Benefit Summary

Rolapitant is a highly selective neurokinin-1 (NK-1) receptor antagonist with very good oral activity, central nervous system penetration and a long (180-hour) plasma half-life. 9

Unlike other available NK-1 receptor antagonists, rolapitant does not inhibit or induce cytochrome P450 (CYP) 3A4. 9

The bioavailability of rolapitant after oral administration is about 100%. 11

Rolapitant is a highly effective drug in preventing delayed chemotherapy-induced nausea and vomiting. 11

Risk Summary

Rolapitant is a moderate inhibitor of CYP2D6. Coadministration of rolapitant increased dextromethorphan exposure. 2

Infusion reactions following administration of intravenous rolapitant, such as anaphylaxis, anaphylactic shock, and other serious hypersensitivity reactions, have been reported. 6

Comparison between Studies

Similarities between Studies

Several studies have confirmed the effectiveness of rolapitant in preventing chemotherapy-induced nausea and vomiting. These studies consistently reported that rolapitant does not inhibit or induce CYP3A4 and has good penetration into the brain. 11 9

Differences between Studies

There are differences in research findings regarding the effects of rolapitant on drug-metabolizing enzymes such as CYP2D6. Some studies report that rolapitant is a moderate inhibitor of CYP2D6, while others found no effect on CYP2D6. 2

Severe hypersensitivity reactions such as anaphylaxis and anaphylactic shock have been reported following intravenous administration of rolapitant. This hypersensitivity reaction is not common to all patients and is thought to vary depending on individual constitution. 6

Consistency and Contradictions in Findings

While multiple studies have confirmed the efficacy of rolapitant in preventing chemotherapy-induced nausea and vomiting, research findings on the effect of rolapitant on drug-metabolizing enzymes such as CYP2D6 are inconsistent. Further research is needed to clarify this aspect. 2

Cautions for Application in Real Life

Rolapitant is widely used clinically as an effective drug for preventing chemotherapy-induced nausea and vomiting. However, it is important to note that patients taking CYP2D6 substrates may have an increased risk of side effects. Additionally, severe hypersensitivity reactions such as anaphylaxis and anaphylactic shock may occur following rolapitant administration. Consulting a doctor before taking rolapitant about patient history and medications is essential. 2 6

Limitations of Current Research

Clinical research on rolapitant has been conducted on a relatively small number of patients, making it impossible to assess the long-term safety of rolapitant. Further research is needed on the effects of rolapitant on drug-metabolizing enzymes such as CYP2D6. 2

Future Research Directions

Research is needed to evaluate the long-term safety of rolapitant. Further research is also needed to investigate the effects of rolapitant on drug-metabolizing enzymes such as CYP2D6 in detail. In addition, further research is needed on the potential for rolapitant to interact with other drugs. 2

Conclusion

Rolapitant is widely used clinically as an effective drug for preventing chemotherapy-induced nausea and vomiting. It is important to note that patients taking CYP2D6 substrates may have an increased risk of side effects. Additionally, severe hypersensitivity reactions such as anaphylaxis and anaphylactic shock may occur following rolapitant administration. Consulting a doctor before taking rolapitant about patient history and medications is essential. Further research is needed to evaluate the long-term safety of rolapitant and its effects on drug-metabolizing enzymes such as CYP2D6. 2 6