Methylprednisolone adverse effects

The incidence and severity of adverse reactions to glucocorticoids depend on the dose and duration of treatment. Even the very high single doses of glucocorticoids, such as methylprednisolone, which are sometimes used, do not cause serious adverse effects, whereas an equivalent dose given over a long period of time can cause many long-term effects. 

Tornatore KM, Biocevich DM, Reed K, Tousley K, Singh JP, Venuto RC. Methylprednisolone pharmacokinetics, cortisol response, and adverse effects in black and white renal transplant recipients. Transplantation 1995 59(5) 729-36. 

Infusion-related adverse effects of gemtuzumab ozogamicin can be treated with a brief course of an intravenous glucocorticoid. Of 143 patients with refractory myeloid leukemia treated with gemtuzumab ozogamicin, 110 received paracetamol 650 mg orally with diphenhydramine 50 mg intravenously and 33 received the same premeditations plus methylprednisolone sodium succinate 50 mg intravenously before the infusion and repeated 1 hour later (1). There were grade 2 or worse infusion-related adverse events in 32 (29%) of the former, but in only one of the latter (3%). 

In an open study in six adults with mild to moderate asthma, clarithromycin significantly reduced methylprednisolone clearance, thereby increasing the risk of steroid-induced adverse effects (160). In contrast, prednisolone clearance and mean prednisolone plasma concentrations were unaffected. Frank psychosis due to combined therapy with prednisone and clarithromycin has been reported (161). 

An effective carboplatin desensitization protocol has been reported in a child with hypersensitivity, allowing additional months of carboplatin treatment (248). After premedication with diphenhydramine, ranitidine, and methylprednisolone, eight dilutions of carboplatin (0.01-50.0 mg) were given intravenously at 15-minute intervals at a rate of 1 mg/minute. Subsequently, carboplatin 600 mg was given as a continuous infusion over 3 hours without adverse effects. Whether desensitization is generally suitable for overcoming allergic adverse events should be tested prospectively (249). 

Corticosteroids also may be delivered by injection. The intramuscular route is preferable in patients with compliance problems, since a depot effect is achieved. Depot forms of corticosteroids include triamcinolone acetonide, triamcinolone hexacetonide, and methylprednisolone acetate. This provides the patient with 2 to 8 weeks of symptomatic control. The depot effect provides a physiologic taper, avoiding withdrawal reaction associated with hypothalamic-pituitary axis suppression. It should be noted that the onset of effect via this route may be delayed by several days. Intravenous corticosteroids may be used to provide the patient with large amounts of drug during a steroid burst to control severe symptoms. Intra-articular injections of depot forms of corticosteroids can be useful in treating synovitis and pain when a small number of joints are affected. The onset and duration of symptomatic relief are similar to those of intramuscular injection. The intra-articular route often is preferred because it is associated with the fewest number of systemic adverse effects. If efficacious, intra-articular injections may be repeated every 3 months. No one joint should be injected more than two to three times per year because of the risk of accelerated joint destruction and atrophy of tendons. Soft tissues such as tendons and bursae also may be injected. This may help control the pain and inflammation associated... 

Information about the interaction between diltiazem and methylprednisolone seems limited to these two studies, but the effect of concurrent use is clear. However, the clinical significance of the raised methylprednisolone levels has not been established. Monitoring for an increase in the adverse effects of methylprednisolone, as suggested by one of the authors, seems a prudent measure. ... 

It is established that the pharmacokineties of some corticosteroids are affected by oral contraceptives, but the elinical importance of any such changes is not known. The therapeutie and adverse effects would be expected to be increased but there appear to be no clinical reports of adverse reactions arising from concurrent use. In fact the authors of one study concluded that women can be dosed similarly with methylprednisolone irrespective of oral contraceptive use. 

Troleandomycin and, to a lesser extent, clarithromycin and erythromycin can reduce the clearance of methylprednisolone, thereby increasing both its therapeutic and adverse effects. A patient receiving long-term clarithromycin developed Cushing s syndrome after starting treatment with inhaled budesonide. There appears to be no pharmacokinetic interaction between erythromycin and inhaled ciclesonide. Similarly, prednisolone appears not to be affected by macrolides, except possibly in those also taking enzyme-inducers such as phenobarbital. Isolated case reports describe the development of acute mania and psychosis in two patients, apparently due to an interaction between prednisone and clarithromycin. 

Information about the clarithromycin or erythromycin interactions with methylprednisolone is much more limited than with the interaction between troleandomycin and methylprednisolone, but they all appear to be established and of clinical importance. The effect should be taken into account during concurrent use and appropriate dosage reductions made to avoid the development of corticosteroid adverse effects. The authors of one study suggest that this reduction should be empirical, based primarily on clinical symptomatology. Another group found that a 68% reduction in methylprednisolone dosage was possible within 2 weeks. Troleandomycin appears to have a greater effect than erythromycin or clarithromycin. 

An adverse effect of the hydrocortisone acetate enemas in this case cannot be either confirmed or excluded. Since the concentration of methylprednisolone or its metabolites in the blood was not measured, the relation between adrenal insufficiency in the child and maternal exposure to methylprednisolone was not unequivocal. 

The most commonly used corticosteroids are methylpred-nisolone (IV and oral) and prednisone (oral), although prednisolone and dexamethasone also have been shown to be effective for organ transplantation. Corticosteroid doses vary by center-specific protocols, organ type, and patient characteristics. A typical taper would include an IV 100 to 500 mg bolus of methylprednisolone at the time of transplant and then a taper over 5 to 7 days to a maintenance dose of prednisone 20 mg/day or complete cessation.2,7 It is important for practitioners to know that approximately 4 mg methylprednisolone is equivalent to 5 mg prednisone and 0.75 mg dexamethasone.11 At most transplant centers, therapeutic drug monitoring of corticosteroids is not employed. Corticosteroids are associated with a variety of acute and chronic toxicides. The most common adverse events have been summarized in Table 52-5. 

Chlorpromazine, prochlorperazine, promethazine, methylprednisolone, lorazepam, metoclopramide, dexamethasone, or dronabinol may be used for adult patients. Around the clock dosing should be considered. The choice of specific agent should based on patient specific factors, including potential for adverse drug reactions, and cost. SSRIs are effective for breakthrough nausea and vomiting but they are not superior to the less expensive antiemetics above. 

---