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Methylprednisolone Sodium Succinate Injection

[18 August 2014]

Products Affected - Description

Methylprednisolone sodium succinate injection, Fresenius Kabi
40 mg single dose vial (NDC 63323-0255-03)
125 mg single dose vial (NDC 63323-0258-03)
1 gram single dose vial (NDC 63323-0265-30)

Reason for the Shortage

  • Hospira discontinued all methylprednisolone sodium succinate products in January 2013 due to raw material issues.1
  • Bedford discontinued methylprednisolone in May, 2011 to concentrate on the manufacturing of other products.2
  • Pfizer had Solu-Medrol on shortage due to manufacturing delays.3
  • Fresenius Kabi (formerly APP) has methylprednisolone sodium succinate on shortage due to priority of other medications.4

Available Products

Solu-Medrol injection, Pfizer3
40 mg single dose Act-O-vial (NDC 00009-0039-28)
125 mg single dose Act-O-vial (NDC 00009-0047-22)
40 mg single dose Novaplus Act-O-vial (NDC 00009-0039-32)
125 mg single dose Novaplus Act-O-vial (NDC 00009-0047-26)
500 mg single dose vial (NDC 00009-0758-01)
500 mg single dose Act-O-vial (NDC 00009-0003-02)
1 gram single dose vial (NDC 00009-0698-01)
1 gram single dose Act-O-vial (NDC 00009-0018-20)
2 gram single dose vial (NDC 00009-0796-01)

Estimated Resupply Dates

Fresenius Kabi has methylprednisolone sodium succinate 40 mg vials and125 mg vials on back order and the company estimates a release date of early-September 2014 for the 40 mg vials and late-September to early-October 2014 for the125 mg vials. The 1 gram vials are on intermittent back order and the company is releasing product as it becomes available.4

Implications for Patient Care

Methylprednisolone is labeled for a variety of conditions including endocrine disorders, rheumatic disorders, collagen diseases, dermatologic diseases, allergic states, ophthalmic diseases, gastrointestinal diseases, respiratory diseases, hematologic disorders, neoplastic diseases, edematous states, acute exacerbations of multiple sclerosis, tuberculosis meningitis, and trichinosis with myocardial or neurologic involvement.5 Methylprednisolone may also be used to prevent adverse reactions in patients receiving monoclonal antibodies or other agents.5,6

Hydrocortisone possesses both mineralocorticoid and glucocorticoid activity and is generally considered the first-line agent for adrenocortical insufficiency. Because other corticosteroids primarily have glucocorticoid activity (see Table 1), concomitant mineralocorticoid supplementation with fludrocortisone may be required in these patients.7,8 In neonates, hydrocortisone is the preferred agent because of concerns about possible detrimental effects of dexamethasone on neurologic development and because dexamethasone injection contains benzyl alcohol.9-13

  • Oral methylprednisolone and hydrocortisone are as effective as the injectable products.14 However, the oral route may not be practical for all patients or for clinical situations requiring high-dose parenteral therapy.

Alternative Agents & Management

  • Table 1 compares the available glucocorticoid products, and Table 2 addresses alternatives in specific situations.

    Methylprednisolone
  • Institutions should consider conserving supplies of methylprednisolone injection for critical indications, such as spinal cord injuries, exacerbations of multiple sclerosis, or optic neuritis.
  • Institutions may prepare intravenous methylprednisolone doses from larger vials to avoid wastage. Methylprednisolone solutions of 10 mg/mL in 0.9% sodium chloride injection, stored in polypropylene syringes, are stable for 21 days under refrigeration.15 Methylprednisolone solutions of 0.25, 2.5, or 5 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for 7 days at room temperature; methylprednisolone combined with a variety of agents is stable in syringes for 2-72 hours at room temperature.16 Clinicians should consult specialized references for additional stability and compatibility information.
  • In situations where oral drug administration is possible, prednisone or oral methylprednisolone are the preferred alternative agents. Divide large oral doses into smaller ones to increase the patients’ ability to tolerate the medication.
  • Consider IV injections of dexamethasone for patients who are unable to take oral medications.

    Benzyl Alcohol Content
    Dexamethasone injection contains 10 mg/mL benzyl alcohol as a preservative.12,13 Hydrocortisone and methylprednisolone sodium succinate contain benzyl alcohol in varying amounts depending on the quantity of methylprednisolone or diluent used.5,7
  • Adverse reactions to benzyl alcohol are most common following intrathecal administration of products containing benzyl alcohol or administration of such products to low birth weight infants.17,18
  • There are limited data regarding the safe maximum dose of benzyl alcohol for adults. Adults may safely receive a rapid intravenous infusion of a product containing up to 270 mg of benzyl alcohol (27 mL of a product containing 10 mg/mL benzyl alcohol).17

    Table 1. Glucocorticoid comparison6,8 

    Agent

    Equivalent Dose (approximate mg)

    Route of Administration

    Relative Anti-inflammatory Potency

    Relative Mineralocorticoid Potency

    Biologic Half-Life (hours)

    Betamethasone

    0.6–0.75

    IM, PO

    20–30

    0

    36–54

    Dexamethasone

    0.75

    IM, IV, PO

    25–30

    0

    36–54

    Hydrocortisonea

    20

    IM, IV, PO

    1

    2

    8–12

    Methylprednisolone

    4

    IM, IV, PO

    5

    0

    18–36

    Prednisolone

    5

    PO

    4

    1

    18–36

    Prednisone

    5

    PO

    4

    1

    18–36

    a
    Some patients may not be able to tolerate the higher mineralocorticoid activity of hydrocortisone.
Table 2. Alternatives to methylprednisolone sodium succinate and hydrocortisone sodium succinate injection in specific clinical situations

Situation

Alternatives

Dose

Comments

Spinal cord injury patients19-24

Dexamethasone

This use is controversial.

Dexamethasone 100 mg IV as a single dose has been used to treat spinal cord compression21 and gunshot wounds to the spine.22

Doses ranging from 24 – 40 mg IV as a daily dose have been used to treat acute spinal cord injury.23

An equivalent dose of the usual methylprednisolone dose is 5.6 mg/kg IV over 1 hour, followed by IV infusion at 1 mg/kg /hour although clinicians should note this dose has not been evaluated in clinical trials.

The use of high-dose methylprednisolone in acute spinal cord injury is controversial as there is little evidence that neurologic outcomes are improved.24

 

Continuous infusion may not need to be administered as long as with methylprednisolone due to dexamethasone’s longer biologic half-life. Studies in the literature used dexamethasone for 12-24 hours.

 

Exacerbation of multiple sclerosis25-28

Dexamethasone

Dexamethasone 2 mg IV q 6 hours for 7 days, followed by gradually decreasing oral dosage to zero over the next 7 days.25

Methylprednisolone 1 g is approximately equivalent to 187.5 mg of dexamethasone although clinicians should note this dose has not been evaluated in clinical trials for the treatment of exacerbations of multiple sclerosis.

Small studies comparing IV methylprednisolone to oral agents demonstrated no difference in efficacy.27 However, the study groups were not large enough to detect slight differences in efficacy and the results indicated only that there is not a large difference in efficacy between IV and oral regimens.

Solid organ transplant patients5,6

Substitute with oral methylprednisolone, if possible

See Table 1

It may be necessary to split large doses to improve the tolerability of oral corticosteroids.

Graft-versus-host disease in bone marrow transplant patients5,6

Substitute with oral therapy when possible

See Table 1

It may be necessary to split large doses to improve the tolerability of oral corticosteroids.

Physiologic replacement in neonates and pediatric patients9,10,29,30

Dexamethasone

Hydrocortisone

Neonates:*

Dexamethasone 0.022–0.045 mg/kg/day IV divided every 6-12 hours

Hydrocortisone 6-8 mg/m2/day IV given in 2-3 divided doses. Alternative regimens are 0.25-0.75 mg/kg/day (or 6-8 mg/m2/day) PO divided every 8 hours, OR 0.25-0.35 mg/kg/dose IM once daily

Pediatric patients: Dexamethasone 0.03 – 0.15 mg/kg/day IV divided every 6-12

Hydrocortisone 0.5-0.75 mg/kg/day PO divided every 8 hours, OR 0.25-0.35 mg/kg/dose IM once daily

Taper doses for patients receiving therapy > 7-10 days to avoid acute pituitary-adrenal insufficiency.

In neonates, hydrocortisone may be the preferred agent for adrenal replacement because of concerns about possible detrimental effects of dexamethasone on neurologic development and because dexamethasone injection contains significant amounts of benzyl alcohol.9-13

Traumatic optic neuropathy31-33

Dexamethasone

Dexamethasone 20 mg (or 0.25 mg/kg) IV q 6 hours for 48 hours

One small study comparing dexamethasone (0.25 mg/kg, or 20 mg, IV q 6 hours for 48 hours) and methylprednisolone (30 mg/kg IV load followed by 15 mg/kg IV q 6 hours for 48 hours) found no difference in final visual results.31

Optic neuritis34-36

No alternative

This use is controversial.

Methylprednisolone 1 g IV daily for 3 days followed by an oral steroid taper.34,35

Critical indication: consider reserving methylprednisolone for these patients.

Methylprednisolone therapy speeds visual recovery compared to placebo, but does not change the long-term visual prognosis.34,35

Related Shortages

References

  1. Hospira (personal communications). January 15, 2013.
  2. Bedford Laboratories, Customer Service (personal communication). June 2, 2011.
  3. Pfizer (personal communications). February 7, March 14 and 27, April 11, May 9, 19, and 29, July 14, and August 1 and 15, 2014.
  4. Fresenius Kabi (personal communications). February 11, March 14, April 2 and 11, May 6, 19, and 28, July 14, 16, and 30, and August 18, 2014.
  5. Solu-Medrol [product information]. New York, NY: Pfizer; May 2012.
  6. Lacy CF, Armstrong LL, Goldman MP, Lance LL. Drug Information Handbook. 20th ed. Hudson, OH: Lexi-Comp;2011-2012:1056-1059.
  7. Solu-Cortef [product information]. New York, NY: Pfizer; July 2012.
  8. Corticosteroids general statement. In: McEvoy GK, Snow EK, Kester L, Litvak K, Miller J, Welsh OH, eds. AHFS DI (Lexi-Comp Online). Bethesda, MD: American Society of Health-System Pharmacists; 2013.
  9. Siberry GK, Iannone R, eds. The Harriet Lane Handbook. 15th Edition. St. Louis, MO: Mosby, Inc.;2000.
  10. Young TE, Mangum B, eds. Neofax 2010. Raleigh, NC: Acorn Publishing; 2010.
  11. Pagliaro AM. Administering drugs to infants, children, and adolescents. In: Pagliaro LA, Pagliaro AM, eds. Problems in Pediatric Drug Therapy. 4th ed. Washington, DC: American Pharmaceutical Association; 2002:1-86.
  12. Dexamethasone sodium phosphate injection [product information]. Shirley, NY: American Regent; December 2009.
  13. Dexamethasone sodium phosphate injection [product information]. Schaumburg, IL: APP; January 2008.
  14. Hutchison TA, Shahan DR, Anderson ML, eds. Micromedex 2.0 [internet database]. Greenwood Village, CO: Truven Health Analytics; 2013.
  15. Gupta VD. Chemical stability of methylprednisolone sodium succinate after reconstitution in 0.9% sodium chloride injection and storage in polypropylene syringes. Int J Pharm Compd. 2001;5(2):148-150.
  16. Pharmacia & Upjohn, Medical Information (written communication). April 7, 2000.
  17. Benzyl alcohol toxicity (Drug Consult). In: Hutchison TA, Shahan DR eds. Drugdex System. Greenwood Village, CO: Micromedex. (Last modified October 2010) Accessed January 16, 2013.
  18. Storey RA. Benzyl alcohol. In: Rowe RC ed. Handbook of Pharmaceutical Excipients, 6th ed. Washington, DC: American Pharmaceutical Association;2009:64-66.
  19. Bjerre JS. Effect of glucocorticoids on ICP in patients with a cerebral tumour. Acta Neurol Scand. 1997;96:167-170.
  20. Ducker TB and Zeidman SM. Spinal cord injury: role of steroid therapy. Spine. 1994;19(20):2281-2287.
  21. Zaidat OO, Ruff RL. Treatment of spinal epidural metastasis improves patient survival and functional state. Neurology. 2002;58:1360-1366.
  22. Heary RF, Vaccaro AR, Mesa JJ. Steroids and gunshot wounds to the spine. Neurosurgery. 1997;41(3):576-584.
  23. Kiwerski JE. Application of dexamethasone in the treatment of acute spinal cord injury. Injury. 1993;24(7): 457-460.
  24. Short DJ, Masry WS, Jones PW. High dose methylprednisolone in the management of acute spinal cord injury – a systematic review from a clinical perspective.
  25. Anderson P, Goodkin DE. Glucocorticosteroid therapy for multiple sclerosis: a critical review. J Neurological Sci. 1998;160(1):16-25.
  26. Tselis AC and Lisak RP. Multiple sclerosis: therapeutic update. Arch Neurol. 1999;56:277-280.
  27. Heun R, Sliwka U, Ruttinger H, Schimrigk K. Intrathecal versus systemic corticosteroids in the treatment of multiple sclerosis: results of pilot study. J Neurol. 1992;239(1):31-35.
  28. Barnes D, Hughes RAC, Morris RW et al. Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis. Lancet. 1997;349(9056):902-06.
  29. Zenk KE, Sills JH, Koeppel RM, eds. Neonatal Medications and Nutrition A Comprehensive Guide. Santa Rosa, CA: NICU Ink Book Publishers; 1999; 145-150.
  30. Takemoto CK, Hodding JH, Kraus DM, eds. Pediatric Dosage Handbook. 16th Edition. Hudson, OH: Lexi-Comp, Inc.;2009-2010.
  31. Spoor TC, Hartel CS, Lensink DB, Wilkinson MJ. Treatment of traumatic optic neuropathy with corticosteroids. Am J Ophthalmol. 1990;110:665-669.
  32. Seiff SR. High dose corticosteroids for treatment of vision loss due to indirect injury to the optic nerve. Ophthalmic Surg. 1990;21:389-395.
  33. Baker SM, Hurwitz JJ. Sports and industrial ophthalmology. Ophthalmol Clin North Am. 1999;12:435-455.
  34. Eggenberger ER. Inflammatory optic neuropathies. Ophthalmol Clin North Am. 2001;14(1):73-82.
  35. Frohman EM. Multiple sclerosis. Med Clin North Am. 2003;87(4):867-897.
  36. Hickman SJ, Kapoor R, Jones SJ, et al. Corticosteroids do not prevent optic nerve atrophy following optic neuritis. J Neurol Neurosurg Psychiatry. 2003;74:1139-1141.

Updated

Updated August 18, 2014 by Michelle Wheeler, PharmD Drug Information Specialist. Created April 12, 2001, by Cyndie Taylor, PharmD, Drug Information Specialist, and M. Christina Beckwith, PharmD, Drug Information Specialist. Copyright 2014, Drug Information Service, University of Utah, Salt Lake City, UT.

Disclaimer

This information is provided through the support of Novation to ASHP solely as a service to its members, which shall not use this information for their further commercial use. The content was prepared by the Drug Information Center of University of Utah. Novation, ASHP, and the University of Utah make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, which respect to such information, and specifically disclaim all such warranties. Users of this information are advised that decisions regarding the use of drugs and drug therapies are complex medical decisions and that in using this information, each user must exercise his or her own independent professional judgment. Neither Novation, ASHP nor the University of Utah assumes any liability for persons administering or receiving drugs or other medical care in reliance upon this information, or otherwise in connection with this bulletin. Neither Novation, ASHP nor University of Utah endorses or recommends the use of any drug.

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