Notably, as ramelteon is metabolized by the CYP1A2 and CYP2C9 isoforms of cytochrome P450, the drug should not be used in combination with inhibitors of CYP1A2 (i.e., ciprofloxacin) or CYP2C9 (i.e., fluconazole), and it should be administered with caution in patients with hepatic insufficiency. This evidence concerns the gene CYP2C9 and Hepatic failure.