(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. Increased dosages may be required to achieve desired effect of methylprednisolone. Cytochrome P450 (CYP) 3A4 inhibitors Troleandomycin, ketoconazole, and Clarithromycin inhibit metabolism; and may decrease rate of elimination and increase half-life of methylprednisolone. Dosages should be decreased accordingly to avoid side effects. Another CYP 3A4 inhibitor, grapefruit juice, prolongs half-life of oral methylprednisolone. Oral contraceptives Oral contraceptives inhibit oxidative processes, as highlighted by its ability to decrease methylprednisolone clearance. P-glycoprotein inhibitors Methylprednisolone is shown to be a substrate of P-glycoprotein; its inhibition is thought to increase methylprednisone absorption and distribution. No clinical relevance has been linked. Ciclosporin, tacrolimus, sirolimus (Rapamycin) Methylprednisolone and cyclosporin inhibit metabolism and therefore increase the likelihood of experiencing side effects associated with either of the individual drugs. In addition to known individual side effects, convulsions have been reported. Cox1 inhibitors Methylprednisolone may increase rate of elimination with chronic high dose aspirin. Patients are susceptible to increased salicylate serum levels or salicylate toxicity upon termination of methylprednisolone. Excessive caution should be taken when prescribing methylprednisolone