Excessive anti-cholinergic effects (described below) can occur when promethazine is used with other antihistamines, for example, diphenhydramine (Benadryl); some phenothiazines, for example, thioridazine (Mellaril); some tricyclic antidepressants, for example, amitriptyline (Elavil); clozapine (Clozaril), cyclobenzaprine (Flexeril), and disopyramide (Norpace).
Phenothiazines such as promethazine block dopamine receptors. This effect can lead to increases in blood levels of prolactin, a hormone involved in lactation (formation of breast milk). As a result, phenothiazines can cause the breast to produce fluid ("milk") even when a woman is not pregnant. Additionally, phenothiazines can cause missed menstrual periods, breast enlargement or tenderness, loss of sexual drive, impotence, inability to ejaculate, and priapism. Weight gain also may occur.
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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