Compositions comprised of olanzapine and a 5-HT3 receptor antagonist and a polyorthoester polymer are provided to provide extended release of the active agents. Also described are compositions comprising olanzapine and a polyorthoester. The compositions are effective for the prophylactic treatment or treatment of subjects at risk of or suffering from nausea and/or vomiting. The compositions are particularly useful for the prevention or treatment of acute, delayed, breakthrough or refractory chemotherapy induced nausea and vomiting (CINV). The CINV may result from, e.g., highly or moderately emetogenic cancer chemotherapy. The compositions are suitable for delivery via, e.g., intramuscular injection, intradermal injection, and subcutaneous injection.
