Antihistamines and hyoscine have similar adverse effects, including sedation, dry mouth, blurred vision, urinary retention and constipation, although these do not normally cause problems at the low doses and over the short periods used.

They should be avoided by patients suffering from glaucoma or prostatic hypertrophy, and should in general be used with caution in the elderly and in patients with epilepsy or cardiac or cardiovascular disease.

Paradoxical CNS stimulation may occur with antihistamines in children, resulting in insomnia and excitement and, rarely, nightmares, hallucinations and even convulsions. Photosensitivity reactions have been reported with promethazine. Alcohol should be avoided when taking any preparation for motion sickness. Although no link has been established between antihistamines or hyoscine and congenital malformations, use under medical supervision and only when absolutely necessary is advised for travel-sickness medicines during pregnancy.

Antihistamines and hyoscine interact with other drugs that cause sedation or have antimuscarinic effects, including tricyclic antidepressants, monoamine oxidase inhibitors, phenothiazines, hypnotics, nefopam, amantadine and disopyramide. Dry mouth caused by the antimuscarinic effects of antihistamines and hyoscine may reduce the effect of sublingual nitrates.