The present invention relates to compositions comprising an antiemetic, particularly including 5-HT3 antagonist and/or NK-1 antagonist antiemetics, in combination with a choline esterase inhibitor such as an acetylcholine esterase inhibitor and/or a butyrylcholine esterase inhibitor, and methods of using the composition to provide improved protection of subjects at risk of organophosphorus poisoning, or, for the treatment, prevention, or alleviation/reduction of toxicity from an organophosphorus compound, by enabling the use of a highly protective daily dose of the choline esterase inhibitor without the typical adverse effects.