No specific medications are available for the treatment of thalassemia intermedia. Most patients with severe disease are prone to developing megaloblastic anemia due to folate deficiency for several reasons, including poor absorption, low dietary intake, and, most importantly, the extreme demand of the very active bone marrow for folic acid. For this reason, most patients benefit from a low dose of folate.

Many patients with thalassemia intermedia ultimately require regular blood transfusions, usually about every 3-5 weeks. Similar to patients with thalassemia major, patients with thalassemia intermedia who receive regular transfusions are usually premedicated with an antipyretic, such as acetaminophen, and an antihistamine, such as diphenhydramine, 30 minutes before transfusion to prevent both febrile and allergic reactions