Headache is the most frequent adverse effect, and it may be severe and persistant. This occurs most frequently at the beginning of therapy. Usually a temporary reduction in dosage will control headache along with a concomitant administration of commonly used analgesics, or by administering the drug during meals. These headaches disappear within a week of continuous, uninterrupted therapy. Advise the patient they may occur and that isosorbide is important with regard to preventing of angina. Occasionally, drug and/or exfoliative dermatitis occur. Signs of cerebral ischemia associated with postural hypotension, such as weakness and transient episodes of dizziness, may occasionally develop. Cutaneous vasodilation with flushing may occur. Rarely, a marked sensitivity to the hypotensive effects of the drug can occur with a severe response (nausea, vomiting, restlessness, perspiration, and collapse); alcohol may enhance this effect. Isosorbide can antagonize the effects of histamine, acetylcholine, and similar agents.