Bulletin

Hydrocortisone Sodium Succinate

26 October 2009

Products Affected - Description

Hydrocortisone sodium succinate, A-Hydrocort, Hospira (formerly Abbott)
250 mg vials (NDC 00074-5672-02) - discontinued
500 mg vials (NDC 00074-5673-04) - discontinued
1000 mg vials (NDC 00074-5674-08) - discontinued

Reason for the Shortage

Hospira (formerly Abbott) has hydrocortisone sodium succinate available. Previously, the company had indefinitely suspended production of their hydrocortisone sodium succinate products in order to ensure adequate production of other medications.^1,2
Pfizer has all hydrocortisone presentations available.³

Estimated Resupply Dates

Hospira (formerly Abbott) has indefinitely suspended production of 250, 500, and 1000 mg presentations of hydrocortisone sodium succinate.¹ Hospira has the 100 mg presentation now available.¹
Pfizer purchased Pharmacia April 16, 2003, and is now responsible for all Pharmacia products, including Solu-Cortef.³
Pfizer has all presentations available.³

Implications for Patient Care

Methylprednisolone and hydrocortisone are 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.⁶ Both medications may also be used to prevent adverse reactions in patients receiving monoclonal antibodies, blood products, or other agents.^7-9

Hydrocortisone possesses both mineralocorticoid and glucocorticoid activity and is generally considered the first-line agent for treating adrenocrotical insufficiency. Because other corticosteroids primarily have glucocorticoid activity (Table 1), concomitant mineralocorticoid supplementation with fludrocortisone may be required in these patients.^9,10,11 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.^12-15

Oral methylprednisolone and hydrocortisone are as effective as the injectable products.¹⁶ 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.

Hydrocortisone

Institutions should consider conserving supplies of hydrocortisone injection for critical indications, such as use in neonates.
Institutions may prepare intravenous hydrocortisone doses from larger vials to avoid wastage. Hydrocortisone solutions of 10 mg/mL in 0.9% sodium chloride injection, stored in polypropylene syringes, are stable for 21 days under refrigeration or for 7 days at room temperature.¹⁹ Clinicians should consult specialized references for additional stability and compatibility information.
In situations where oral drug administration is possible, oral hydrocortisone is the preferred alternative agent. Divide large oral doses into smaller ones to increase the patient's 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 of benzyl alcohol as a preservative. Methylprednisolone and hydrocortisone injections contain approximately 9 mg/mL of benzyl alcohol when the product is diluated with the accompanying diluent.^6,9,14
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.^20,21
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 of benzyl alcohol).²⁰ Some clinicians have used dexamethasone in doses of up to 6 mg/kg as a single intravenous injection in patients with life-threatening shock.¹¹ For a 70 kg patient, the dose is equivalent to 420-1005 mg of benzyl alcohol, depending on the preparation of dexamethasone used.

Table 1. Glucocorticoid comparison^6,16

Agent	Equivalent Dose (approx- imate mg)	Route of Adminis- tration	Relative Anti- inflammatory Potency	Relative Mineralo- corticoid Potency	Biologic Half-Life (hours)
Betamethasone^a	0.6-0.75	IM, PO	20-30	0	36-54
Dexamethasone	0.75	IM, IV, PO	25-30	0	36-54
Hydrocortisone^a,b	20	IM, IV, PO	1	2	8-12
Methylprednisolone^a	4	IM, IV, PO	5	0	18-36
Prednisolone	5	PO	4	1	18-36
Prednisone	5	PO	4	1	18-36

^a Betamethasone suspension for injection was in short supply.²²
^b 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 injections in specific clinical situations

Situation	Alternatives	Dose	Comments
Premedication to prevent adverse reactions (i.e., in patients receiving antithymocyte globulin, muromonab-CD3, blood products,⁸ radiographic contrast media,⁷ or other agents)	Hydrocortisone Prednisone Methylpred- nisolone	Blood products: Hydrocortisone 50-100 mg IV Radiographic contrast media: Prednisone 50 mg PO 13, 7, and 1 hours before procedure, in combination with diphenhydramine and ephedrine Or Methylprednisolone 32 mg PO 12 and 2 hours before procedure, in combination with diphenhydramine Other agents: At clinician's discretion	Hydrocortisone is often the preferred alternative because of its shorter duration of action.
Spinal cord injury patients^23-28	Dexamethasone	This use is controversial. Dexamethasone 100 mg IV as a single dose has been used to treat spinal cord compression²⁵ and gunshot wounds to the spine.²⁶ Doses of 24-40 mg IV as a daily dose have been used to treat acute spinal cord injury.²⁷ An equivalent dose of the usual methylprednisolone dose is dexamethasone phosphate 5.6 mg/kg IV over 1 hour, followed by IV infusion at 1 mg/kg/hour; clinicians should note that 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.²⁹ Continuous infusion may not need to be administered as long as with methylpred- nisolone due to dexamethasone is longer biologic half-life. Studies in the literature used dexamethasone for 12-24 hours.
Exacerbation of multiple sclerosis^29-32	Dexamethasone	Dexamethasone phosphate 2 mg IV q 6 hours for 7 days, followed by gradually decreasing oral dosage to zero over the next 7 days²⁹ Methylprednisolone 1 g is approximately equivalent to 187.5 mg of dexamethasone, although clinicians should note that this dose has not been evaluated in clinical trials for the treatment of multiple sclerosis.	Small studies comparing IV methylprednisolone to oral agents demonstrated no difference in efficacy.³¹ 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 patients^6,7	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 patients^6,7	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 patients^11,12,33,34	Dexamethasone Hydrocortisone	Neonates: Dexamethasone 0.022-0.045 mg/kg/day IV in divided doses q 6-12 hours Hydrocortisone 6-8 mg/m² IV given in 2-3 divided doses. Alternative regimens are 0.25-0.75 mg/kg/day (or 6-8 mg/m²) PO in divided doses q 8 hours Or 0.25-0.35 mg/kg/dose IM once daily Pediatric patients: Dexamethasone 0.03-0.15 mg/kg/day IV in divided doses q 6-12 hours Hydrocortisone 0.5-0.75 mg/kg/day PO in divided doses q 8 hours Or 0.25-0.35 mg/kg/dose IM once daily	Gradually decrease the dosage for patients receiving therapy for > 7-10 days to avoid acute pituitary-adrenal insufficiency. In neonates, hydrocortisone may be the preferred agent for adrenal replacement therapy because of concerns about possible detrimental effects of dexamethasone on neurologic development and because dexamethasone injection contains significant amounts of benzyl alcohol.^11-14
Traumatic optic neuropathy^35-37	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.³⁵
Optic neuritis^38-40	No alternative	This use is controversial. Methylprednisolone 1 g IV daily for 3 days followed by an oral steroid taper.^38,39	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.^38,39

Related Shortages

Betamethasone Acetate and Sodium Phosphate Injection— Resolved
Fluticasone Propionate HFA Inhaler— Resolved
Methylprednisolone Acetate Injection— Resolved
Methylprednisolone Sodium Succinate
Prednisolone Tablets— Resolved
Triamcinolone Injection— Resolved

References

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Hospira (formerly Abbott), Marketing Department (written communication). June 2, 2004; and January 8, 2007.
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APP (American Pharmaceutical Partners, formerly Abraxis), Customer Service (personal communications). September 3 and 8, October 22, and November 15, 2004; and February 3, 2005; April 11, June 5, August 8, and September 11, 2006; January 11, March 12 and 26, 2007, April 17, May 7, June 11, August 27, September 17, November 7 and 21, and December 19, 2007; and January 11, February 4, March 4, April 8, August 14, September 12 and 26, November 3, 2008; and January 12, February 18, March 2, April 21, May 20, June 23, July 13 and 29, August 26, September 21, and October 26, 2009.
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Updated

Updated October 26, 2009, by Michelle Wheeler, Pharm.D., Drug Information Specialist. Created April 12, 2001, by Cyndie Taylor, Pharm.D., Drug Information Specialist, and M. Christina Beckwith, Pharm.D., Drug Information Specialist. Copyright 2009, Drug Information Service, University of Utah, Salt Lake City, UT.

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