Treatment with IFN beta usually is well tolerated. Side-effects depend partially on the dosage used and the route of administration. For all preparations mentioned, patients can experience flu-like reactions such as fever, myalgia, chills, and general discomfort for 24–48 hours after each injection, especially during the first months of treatment. These symptoms, however, generally are mild to moderate in severity and tend to decrease over time. Symptom management requires simple practical techniques such as dose escalation (some experts advocate giving a low dose of prednisone during the early weeks of initiating this agent), bedtime dosing, and the use of acetaminophen (paracetamol in Europe) or ibuprofen. The frequency of injection-site reactions (redness, tenderness, and swelling) is also initially high, almost exclusively in those patients who receive treatment by subcutaneous injection. Reactions can be managed by improving injection technique (e.g., warming the solution to room temperature, icing the injection site after each injection, and avoiding intradermal injections and excessive sun exposure) and maintaining site rotation. Injection-site necrosis occurs in about five percent of patients. In earlier studies, there was a suggestion that treatment with IFN beta could lead to depression or suicide attempts, but this was not supported by subsequent studies. Some people with MS report an initial worsening of symptoms during the first weeks of IFN therapy; an increase in spasticity has been reported in patients with primary and secondary progressive disease. IFN beta can also cause elevations in liver function tests, lymphopenia, or anemia. Some reports address the potential for severe autoimmune disease (thyroiditis, Grave’s disease, and hypothyroidism) after administration of IFN beta. Blood count and liver function are generally measured at baseline, then monthly for three months, and then every three months thereafter. The dose or frequency of administration in patients with elevated liver enzymes or neutropenia (rarely anaemia) is reduced, but treatment is usually not discontinued. There are isolated reports that IFN beta administration may be followed by myasthenia gravis, rheumatoid arthritis, systemic lupus erythematous, inflammatory arthritis, urticaria, Raynaud’s phenomenon, worsening of psoriasis, anaphylaxis, and intracerebral hemorrhage, but the association with IFN treatment often is unclear. Overall, the percentage of patients discontinuing treatment because of serious or intolerable side-effects is low.