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MediGuard answeredOxymorphone (Opana) does have headache as a side effect. 6.8% of patients who received the immediate-release Opana reported headaches as a side effect. 3.8% of patients who took the extended-release Opana reported headaches. According to the prescribing information, 11.6% of patients who received Opana ER reported headaches during the titration period, which is the beginning of therapy usually. Once stabilized on Opana ER, only 2.9% of patients reported headaches. If your headaches continue or worsen, please contact your physician to discuss your symptoms.