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A complex called neuroleptic malignant syndrome (NMS) can occur in patients receiving phenothiazines. NMS consists of high body temperature, severe EPS, changes in consciousness and mental status, and increased heart rate with low or high blood pressure. NMS occurs more frequently in young men and in persons who are dehydrated.

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Excessive sedation may occur when promethazine is combined with other medications that depress the central nervous system (brain) and cause sedation. Such drugs include ethanol, barbiturates, anti-anxiety medications, sedatives, other phenothiazines, and narcotic pain medications.

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Concurrent use of promethazine with the dye used for myelography (x-rays of the spinal cord) can lower the threshold for seizures and thus increase the risk of seizures. Promethazine should be stopped at least 48 hours before myelography and not restarted until at least 24 hours after myelography.

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