methylprednisolone
Sources réglementaires consultées
Indications approuvées
- Situations graves nécessitant un corticostéroïde immédiat ou empêchant la voie orale, notamment exacerbation de l’asthme, anaphylaxie ou hypersensibilité menaçant le pronostic vital, œdème cérébral, crise addisonienne et rejet aigu de greffe.
Contre-indications
Absolues
- Hors substitution ou urgence : ulcère gastroduodénal, ostéoporose sévère, troubles psychiatriques graves, glaucome, kératite herpétique et infections non contrôlées, selon le RCP.
- Hypersensibilité à la méthylprednisolone, aux autres glucocorticoïdes ou aux excipients.
Mises en garde cliniques
- Mise en garde majeure · Utiliser la dose minimale efficace et diminuer progressivement après un traitement prolongé ; un arrêt brutal peut provoquer une insuffisance surrénalienne. — CIMA/AEMPS, ficha técnica 71864
- Mise en garde majeure · Il peut accroître la sensibilité aux infections, réactiver des infections latentes et en masquer les signes. Éviter les vaccins vivants aux doses immunosuppressives. — CIMA/AEMPS, ficha técnica 71864
- Mise en garde majeure · Surveiller la glycémie, la pression artérielle, les électrolytes, la santé osseuse, les symptômes psychiatriques ainsi que les complications oculaires et gastro-intestinales pendant le traitement systémique. — CIMA/AEMPS, ficha técnica 71864
Interactions médicamenteuses
- ModéréeInhibiteurs ou inducteurs du CYP3A4
Mécanisme: Ils peuvent augmenter ou diminuer l’exposition systémique au glucocorticoïde.
Recommandation: Surveiller l’efficacité et la toxicité et n’ajuster que sous supervision clinique.
CIMA/AEMPS, ficha técnica 71864
- SévèreVaccins vivants
Mécanisme: L’immunosuppression peut favoriser une infection disséminée et réduire la réponse vaccinale.
Recommandation: Éviter les vaccins vivants pendant un traitement immunosuppresseur ; planifier la vaccination avec l’équipe soignante.
CIMA/AEMPS, ficha técnica 71864
- ModéréeAntidiabétiques, diurétiques et AINS
Mécanisme: Les glucocorticoïdes peuvent compromettre le contrôle glycémique, aggraver la perte de potassium et augmenter le risque gastro-intestinal.
Recommandation: Surveiller la glycémie et les électrolytes et envisager une gastroprotection ou des alternatives selon le risque.
CIMA/AEMPS, ficha técnica 71864
Effets indésirables
Rares mais graves
Anaphylaxie, arythmie ou collapsus lors d’une administration IV rapide, infection sévère et suppression surrénalienne
Grossesse et allaitement
Pendant la grossesse, n’utiliser que si le bénéfice attendu dépasse le risque et surveiller le nouveau-né après des doses élevées ou prolongées. Pendant l’allaitement, individualiser selon la dose et la durée.
Bibliographie récente (PubMed)
Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease (GD). Choice of treatment should be based on the assessment of clinical activity and severity of GO. Early referral to specialized centers is fundamental for most patients with GO. Risk factors include smoking, thyroid dysfunction, high serum level of thyrotropin receptor antibodies, radioactive iodine (RAI) treatment, and hypercholesterolemia. In mild and active GO, control of risk factors, local treatments, and selenium (selenium-deficient areas) are usually sufficient; if RAI treatment is selected to manage GD, low-dose oral prednisone prophylaxis is needed, especially if risk factors coexist. For both active moderate-to-severe and sight-threatening GO, antithyroid drugs are preferred when managing Graves' hyperthyroidism. In moderate-to-severe and active GO i.v. glucocorticoids are more effective and better tolerated than oral glucocorticoids. Based on current evidence and efficacy/safety profile, costs and reimbursement, drug availability, long-term effectiveness, and patient choice after extensive counseling, a combination of i.v. methylprednisolone and mycophenolate sodium is recommended as first-line treatment. A cumulative dose of 4.5 g of i.v. methylprednisolone in 12 weekly infusions is the optimal regimen. Alternatively, higher cumulative doses not exceeding 8 g can be used as monotherapy in most severe cases and constant/inconstant diplopia. Second-line treatments for moderate-to-severe and active GO include (a) the second course of i.v. methylprednisolone (7.5 g) subsequent to careful ophthalmic and biochemical evaluation, (b) oral prednisone/prednisolone combined with either cyclosporine or azathioprine; (c) orbital radiotherapy combined with oral or i.v. glucocorticoids, (d) teprotumumab; (e) rituximab and (f) tocilizumab. Sight-threatening GO is treated with several high single doses of i.v. methylprednisolone per week and, if unresponsive, with urgent orbital decom
Severe community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We hypothesized that downregulation of systemic and pulmonary inflammation with prolonged low-dose methylprednisolone treatment would accelerate pneumonia resolution and improve clinical outcomes. This double-blind, randomized, placebo-controlled clinical trial recruited adult patients within 72-96 h of hospital presentation. Patients were randomized in 1:1 ratio; an intravenous 40 mg loading bolus was followed by 40 mg/day through day 7 and progressive tapering during the 20-day treatment course. Randomization was stratified by site and need for mechanical ventilation (MV) at the time of randomization. Outcomes included a primary endpoint of 60-day all-cause mortality and secondary endpoints of morbidity and mortality up to 1 year of follow-up. Between January 2012 and April 2016, 586 patients from 42 Veterans Affairs Medical Centers were randomized, short of the 1420 target sample size because of low recruitment. 584 patients were included in the analysis. There was no significant difference in 60-day mortality between the methylprednisolone and placebo arms (16% vs. 18%; adjusted odds ratio 0.90, 95% CI 0.57-1.40). There were no significant differences in secondary outcomes or complications. In patients with severe CAP, prolonged low-dose methylprednisolone treatment did not significantly reduce 60-day mortality. Treatment was not associated with increased complications.
Spinal cord injury (SCI) is a major cause of morbidity and mortality, posing a significant financial burden on patients and the healthcare system. While little can be done to reverse the primary mechanical insult, minimizing secondary injury due to ischemia and inflammation and avoiding complications that adversely affect neurologic outcome represent major goals of management. This article reviews important considerations in the acute critical care management of SCI to improve outcomes. Neuroprotective agents, such as riluzole, may allow for improved neurologic recovery but require further investigation at this time. Various forms of neuromodulation, such as transcranial magnetic stimulation, are currently under investigation. Early decompression and stabilization of SCI is recommended within 24 h of injury when indicated. Spinal cord perfusion may be optimized with a mean arterial pressure goal from a lower limit of 75-80 to an upper limit of 90-95 mmHg for 3-7 days after injury. The use of corticosteroids remains controversial; however, initiation of a 24-h infusion of methylprednisolone 5.4 mg/kg/hour within 8 h of injury has been found to improve motor scores. Attentive pulmonary and urologic care along with early mobilization can reduce in-hospital complications.
The effect of glucocorticoids on major kidney outcomes and adverse events in IgA nephropathy has been uncertain. To evaluate the efficacy and adverse effects of methylprednisolone in patients with IgA nephropathy at high risk of kidney function decline. An international, multicenter, double-blind, randomized clinical trial that enrolled 503 participants with IgA nephropathy, proteinuria greater than or equal to 1 g per day, and estimated glomerular filtration rate (eGFR) of 20 to 120 mL/min/1.73 m2 after at least 3 months of optimized background care from 67 centers in Australia, Canada, China, India, and Malaysia between May 2012 and November 2019, with follow-up until June 2021. Participants were randomized in a 1:1 ratio to receive oral methylprednisolone (initially 0.6-0.8 mg/kg/d, maximum 48 mg/d, weaning by 8 mg/d/mo; n = 136) or placebo (n = 126). After 262 participants were randomized, an excess of serious infections was identified, leading to dose reduction (0.4 mg/kg/d, maximum 32 mg/d, weaning by 4 mg/d/mo) and addition of antibiotic prophylaxis for pneumocystis pneumonia for subsequent participants (121 in the oral methylprednisolone group and 120 in the placebo group). The primary end point was a composite of 40% decline in eGFR, kidney failure (dialysis, transplant), or death due to kidney disease. There were 11 secondary outcomes, including kidney failure. Among 503 randomized patients (mean age, 38 years; 198 [39%] women; mean eGFR, 61.5 mL/min/1.73 m2; mean proteinuria, 2.46 g/d), 493 (98%) completed the trial. Over a mean of 4.2 years of follow-up, the primary outcome occurred in 74 participants (28.8%) in the methylprednisolone group compared with 106 (43.1%) in the placebo group (hazard ratio [HR], 0.53 [95% CI, 0.39-0.72]; P < .001; absolute annual event rate difference, -4.8% per year [95% CI, -8.0% to -1.6%]). The effect on the primary outcome was seen across each dose compared with the relevant participants in the placebo group recruited to e
Despite the increasing efficacy of chemotherapy, permanently unresectable colorectal liver metastases are associated with poor long-term survival. We aimed to assess whether liver transplantation plus chemotherapy could improve overall survival. TransMet was a multicentre, open-label, prospective, randomised controlled trial done in 20 tertiary centres in Europe. Patients aged 18-65 years, with Eastern Cooperative Oncology Group performance score 0-1, permanently unresectable colorectal liver metastases from resected BRAF-non-mutated colorectal cancer responsive to systemic chemotherapy (≥3 months, ≤3 lines), and no extrahepatic disease, were eligible for enrolment. Patients were randomised (1:1) to liver transplantation plus chemotherapy or chemotherapy alone, using block randomisation. The liver transplantation plus chemotherapy group underwent liver transplantation for 2 months or less after the last chemotherapy cycle. At randomisation, the liver transplantation plus chemotherapy group received a median of 21·0 chemotherapy cycles (IQR 18·0-29·0) versus 17·0 cycles (12·0-24·0) in the chemotherapy alone group, in up to three lines of chemotherapy. During first-line chemotherapy, 64 (68%) of 94 patients had received doublet chemotherapy and 30 (32%) of 94 patients had received triplet regimens; 76 (80%) of 94 patients had targeted therapy. Transplanted patients received tailored immunosuppression (methylprednisolone 10 mg/kg intravenously on day 0; tacrolimus 0·1 mg/kg via gastric tube on day 0, 6-10 ng/mL days 1-14; mycophenolate mofetil 10 mg/kg intravenously day 0 to <2 months and switch to everolimus 5-8 ng/mL), and postoperative chemotherapy, and the chemotherapy group had continued chemotherapy. The primary endpoint was 5-year overall survival analysed in the intention to treat and per-protocol population. Safety events were assessed in the as-treated population. The study is registered with ClinicalTrials.gov (NCT02597348), and accrual is complete. Between