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Other Medications That Can Cause Fatigue Common FDAapproved medications that may cause tiredness include: Antihistamines such as diphenhydramine (Benadryl) and hydroxyzine Antidepressants and antianxiety medications Muscle relaxers like cyclobenzaprine (Flexeril) Certain blood pressure medications, including metoprolol and verapamil Seizure and migraine medications Opioid pain medications like oxycodone and hydrocodone How to Manage Fatigue While Taking Amoxicillin It is important to complete the full course of antibiotics prescribed