Ibuprofen and prednisone can be taken together only under a doctor's instruction due to the increased risk of gastrointestinal complications such as ulcers, internal bleeding, and stomach irritation. Both drugs can irritate the stomach lining, and their combination raises the risk of serious gastric problems. It is generally advised to take these medications with food to reduce stomach irritation, and in some cases, doctors may prescribe additional medication to protect the stomach. If any symptoms like severe stomach pain, bleeding, dizziness, or tarry stools occur, immediate medical attention is necessary. Taking ibuprofen and prednisone without medical supervision is not recommended due to these risks.

Additionally, both drugs can worsen swelling and water retention, so caution is needed, especially in patients with heart conditions. Doctors often recommend spacing the medications apart or choosing other pain relief options like acetaminophen if appropriate.