What is the safest cough medication to use on a patient on xyrem?

Honey-based. Another choice would be to use one of the honey-based cough medications. A recent study indicated that honey was as effective as many other cough preparations. Because xyrem may cause some respiratory depression, honey-based products should not contribute to any potential adverse effects.
Cough. Robitussin dm (guaifenesin and dextromethorphan) as directed on bottle.