Factors that contribute to the extent of HPA axis suppression include steroid hormone potency (type of compound and route of administration), cumulative dose, duration of treatment and concomitant drug use. Any individual who has taken steroid hormones for 2+ weeks is at risk for developing HPA axis suppression. t Systemic methylprednisolone risk has been marked as moderate within the class of synthetic glucocorticoids.Consult with your physician prior to discontinuing methylprednisolone for any reason. Abrupt termination of the drug commonly causes transient non-specific symptoms such as loss of appetite, upset stomach, vomiting, drowsiness, confusion, headache, fever, joint and muscle pain, peeling skin, and weight loss. These symptoms can be attributed to steroid withdrawal syndrome, adrenal insufficiency or disease relapse. Those who have been taking methylprednisolone as a long-term treatment may be gradually be tapered off to minimize withdrawal symptoms and potential for relapse. If symptoms are exacerbated, temporarily increasing methylprednisolone dosage has shown clinical relevancy. Studies retesting patients upon methylprednisolone withdrawal, showed persistent adrenal insufficiency, with one study showing 15% after 3 years. However, there was a wide range of prevalence and lack of uniformity in the follow-up timeline. Drug interactions
Caution is advised when taking methylprednisolone concurrently with the medications described below. Enzyme inducers
All drugs that fall within the class of enzyme inducers increase the clearance and decrease the half-life of methylprednisolone when co-administered. Phenobarbital, phenytoin, rifampin, carbamazepine and barbiturates, increase hepatic enzymes and rate of elimination, thus reducing the immunosuppressive effect of methylprednisolone.
Dosage above 60–80 mg/day or 2 mg/kg/day is not recommended as it has not been shown to alter pulmonary function, rate of admission, or length of stay in the hospital compared to lower doses. Following ED discharge, it is advised to prescribed a five-day course of methylprednisolone to decrease the probability of relapse or withdrawal symptoms. Rheumatic diseases
Methylprednisolone is used to treat several rheumatic diseases, such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). Methylprednisolone dosage and administration for these diseases is highly variable due to varied pathophysiology between the diseases and within patients diagnosed with a given disease. In Lupus Nephritis, a common manifestation of SLE, patients are often prescribed methylprednisolone concomitantly with immunosuppressants. Severe manifestations are often treated with Cyclophosphamide or Rituximab and three doses of methylprednisolone IV-pulse treatment (as recommended by ACR guidelines) prior to switching to oral prednisolone and azathioprine for maintenance.Intra-articular corticosteroid injections (IACI) are a second line therapy to relieve joint pain resulting from  rheumatoid arthritis. It is most commonly injected into the joints of  the knees and shoulders. Although the injection is local, studies have shown systemic absorption as evidenced by beneficial effects on distant joints. In an attempt to minimize HPA suppression, FDA guidelines have restricted IACIs to three per year, with a minimum of 30 days in between injections. Primary or secondary adrenocortical insufficiency
Methylprednisolone is not typically recommended for primary or secondary adrenocortical insufficiency compared to other corticosteroids which have a higher affinity for mineralocorticoid receptor and salt retaining properties.