According to the ASHP drug shortage bulletin, 40 and 125 mg vials of methylprednisolone are in short supply. Pfizer appears to be experiencing a manufacturing delay, and Fresenius Kabi states the reason for the shortage is increased demand.
This isn’t the first time we’ve faced a shortage of methylprednisolone. In 2011 and 2014 similar problems occurred.
Can an equivalent dose of another corticosteroid be substituted? Dexamethasone is probably the steroid most similar to methylprednisolone.
Compared to methylprednisone, dexamethasone also has no mineralcorticoid activity but is a bit longer acting. Finding a steroid equivalency chart is the easy part. In this episode I’ll review the evidence behind some alternative corticosteroids.
For patients with a COPD exacerbation, methylprednisolone was compared to dexamethasone:
There was an obvious improvement in symptoms after 1-3 days in all 71 patients in the MP group, with their wheezing being distinctly reduced or disappearing entirely. The maximum benefit that occurred in the MP group (90.14%) was considerably higher than that of the DXM group (25.35%), P < 0.05. The predicted FEV1% in the MP group increased from 46.7 +/- 10.6 to 67.5 +/- 12.4, compared with an increase in the DXM group from 50.1 +/- 7.6 to 58.9 +/- 10.8. The difference between the two groups was significant (P < 0.05).
An adequate and tapering dose of MP used in acute exacerbations of COPD can relieve the inflammatory reaction in airways and reduce airway spasm more promptly than DXM.
Methylprednisolone has also been compared to hydrocortisone in patients with COPD:
Baseline characteristics were comparable. Mortality, need for mechanical ventilation and acute exacerbation within 2 weeks of discharge were not significantly different between the two groups. However, at 2 weeks, Group B showed significant improvement over Group A in FEV(1) and PEF.
This study suggests that in AECOPD, IV MP followed by oral MP produced greater improvement in FEV(1) and PEF than IV HC followed by oral prednisolone, although there were no differences in need for ventilator support or in recurrence of exacerbation.
Most IV methylprednisolone use for COPD can probably be converted to an oral corticosteroid. A Cochrane review from 2014 concluded that there is no difference between oral and intravenous corticosteroid use in patients with COPD.
Asthma treatment guidelines make no differentiation between prednisone, prednisolone, and methylprednisolone. For patients unable to take oral corticosteroids it appears that hydrocortisone in adults and dexamethasone in pediatric patients is acceptable.
Fifty-two adults with severe acute asthma were treated with either IV hydrocortisone or prednisolone. There was no difference in their peak flow measurements 24 h after admission.
In children, a single dose of dexamethasone 0.6 mg/kg (maximum 18 mg) was found to be equivalent to prednisolone 2 mg/kg/d in two divided doses for 5 days in terms of symptoms resolution.
Pulse dose steroids
I was surprised to find out that for “high dose” / “pulse dose” corticosteroids there is some evidence for using dexamethasone for many conditions.
According to ASHP the large 1 gram vials of methylprednisolone are not currently affected by the shortage. If the shortage of the smaller vials persists though, I’d be on the lookout for the larger vials to go into short supply as well.
The National MS Society says:
Although the steroid most often used to treat relapses is IVMP, other options may also be appropriate. For example, comparable doses of IV dexamethasone could be substituted for IVMP. Although comparative trials have not been done, dexamethasone is a reasonable alternative if MP is unavailable, or for other reasons such as a previous allergic reaction to MP. Patients on dexamethasone may experience fewer overall side effects due to its relative lack of mineralocorticosteroid effects and consequently lower sodium retention than seen with other steroids.
If needed, the dose of oral dexamethasone is 176 mg/day for an exacerbation according to the National MS Society.
Immune thrombocytopenia (ITP)
High dose dexamethasone for ITP can be considered 40 mg daily, although this has not been compared to IV methylprednisolone in patients who are actively bleeding.
Prospective evidence for alternative IV steroids in lupus nephritis is non-existent, but countries such as India that do not have access to methylprednisolone suggest that dexamethasone is an appropriate alternative.
In summary, COPD exacerbations appear to be the condition where substituting another corticosteroid may be least desirable.
With supplies of IV methylprednisolone low, I’d conserve use for patients with COPD who are unable to take oral steroids. If I run out of methylprednisolone completely, I’d substitute hydrocortisone 200 mg IV every 6 hours for the standard regimen of methylprednisolone 40 mg IV every 6 hours.
If you have an alternative to methylprednisolone for another indication, please add it to the comments below!
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