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Morphine Sulfate: Oral Concentrated Solution

Last Updated: September 7, 2010
Status: Resolved

Products Affected - Description

Morphine sulfate concentrated oral solution, 20 mg/mL, Lannett
30 mL bottle (NDC 00527-1425-36) - discontinued
120 mL bottle (NDC 00527-1425-62) - discontinued
240 mL bottle (NDC 00527-1425-63) - discontinued

 
Morphine sulfate concentrated oral solution, 20 mg/mL, Ethex
30 mL bottle (NDC 58177-0886-01) - discontinued
120 mL bottle (NDC 58177-0886-03) - discontinued
240 mL bottle (NDC 58177-0886-05) - discontinued
0.25 mL unit dose, package of 30 (NDC 58177-0888-80) - discontinued
0.50 mL unit dose, package of 30 (NDC 58177-0889-81) - discontinued
1 mL unit dose Inveamp, package of 30 (NDC 58177-0886-56) - discontinued
15 mL bottle with dropper (NDC 58177-08886-57) - discontinued

Morphine sulfate concentrated oral solution, 20 mg/mL, Glenmark
30 mL bottle (NDC 68462-0349-37) - discontinued
120 mL bottle (NDC 68462-0349-21) - discontinued
240 mL bottle (NDC 68462-0349-24) - discontinued

Morphine sulfate concentrated oral solution, 20 mg/mL, Mallinckrodt
15 mL bottle, package of 6 (NDC 00406-0830-15) - discontinued
30 mL bottle, package of 6 (NDC 00406-0830-30) - discontinued
120 mL bottle, package of 6 (NDC 00406-0830-12) - discontinued
240 mL bottle, package of 6 (NDC 00406-0830-24) - discontinued
15 mL bottle (NDC 00406-8003-15) - discontinued
30 mL bottle (NDC 00406-8003-30) - discontinued
120 mL bottle (NDC 00406-8003-12) - discontinued
240 mL bottle (NDC 00406-8003-12) - discontinued

Roxanol, 20 mg/mL, Xanodyne
30 mL bottle (NDC 66479-0560-03) - discontinued
120 mL bottle (NDC 66479-0560-12) - discontinued
240 mL bottle (NDC 66479-0560-24) - discontinued

Reason for the Shortage

  • FDA sent warning letters in late-March, 2009 to several suppliers of unapproved narcotics. These companies had until May 29, 2009 to stop manufacturing new product and distributors had until June 28, 2009 to stop shipping product.1 Detailed information on the unapproved products can be found on the FDA web site.
  • On April 9, 2009, FDA modified their decision for morphine sulfate oral solution 20 mg/mL and extended the deadline to stop manufacturing for 180 days after any pharmaceutical company receives FDA approval for a morphine sulfate solution 20 mg/mL product.2
  • Roxane received approval for morphine sulfate oral solution 20 mg/mL on January 25, 2010. In March 2010, the FDA warned manufacturers of unapproved morphine sulfate oral solution 20 mg/mL that they may not manufacture or distribute these products after July 24, 2010.3
  • In December 2008, KV Pharmaceuticals, which markets prescription medications through Ethex, voluntarily suspended shipment of all prescription tablet products.4 In early 2009, FDA filed an injunction against KV Pharmaceuticals preventing the company from manufacturing any products until all issues are resolved.5 In late February, 2010, KV Pharmaceuticals announced that Ethex Corporation will cease operation.6
  • Lannett states the shortage was due to increased demand for product. The company is awaiting FDA approval.7
  • Mallinckrodt states they were working with the FDA to resolve the shortage situation. The company discontinued all unapproved morphine sulfate presentations in May, 2010 and is currently awaiting FDA approval.8
  • Glenmark has discontinued all presentations of morphine sulfate 20 mg/mL solution.9
  • Xanodyne has discontinued all presentations of Roxanol 20 mg/mL solution.10

Estimated Resupply Dates

FDA Approve Products:

  • Morphine sulfate oral solution, 10 mg / 5 mL and 20 mg / 5 mL
    • Roxane has available morphine sulfate oral solution 10 mg / 5 mL in 5 mL (NDC 00054-0237-55), 100 mL (NDC 00054-0237-49) and 500 mL (NDC 00054-0237-63) sizes. Roxane also has available 20 mg / 5 mL  in 100 mL (NDC 00054-0238-49) and 500 mL (NDC 00054-0238-63) sizes.11 
  • Morphine sulfate concentrated oral solution, 20 mg/mL
    • Roxane has morphine sulfate concentrated solution available in 30 mL (NDC 00054-0352-44) and 120 mL (NDC 00054-0352-50) bottles.11


Non-FDA Approved Products:
  • Morphine sulfate concentrated oral solution, 20 mg/mL
    • Lannett has discontinued all unapproved presentations of morphine sulfate concentrated solution.7
    • Mallinckrodt has discontinued all unapproved morphine sulfate presentations.8  

Implications for Patient Care

Morphine is an opioid analgesic used to treat chronic and acute pain.12

Safety

If switching between products, ensure patients receive an appropriate dose and are monitored for adverse effects and efficacy. Deaths have resulted when oral morphine concentrate 20 mg/mL was confused with conventional morphine solution 20 mg/5 mL.13

Alternative Agents & Management

  • Other opiate agonists are available and may be acceptable alternatives for pain.
  • Morphine concentrated oral solution 20 mg/mL and oxycodone concentrated solution 20 mg/mL are in short supply.6-10 Table 1 summarizes the availability and approval status of selected oral liquid narcotic products.
  • Table 2 gives equianalgesic doses of selected opiate agonists.12, 14-16 Table 3 compares the pharmacodynamic and pharmacokinetic properties of these agonists.14,15,17,18 Because analgesic equivalency varies among individual patients and specific clinical situations, dosage adjustments will be required.

 

Table 1. Availability of selected oral liquid narcotic medications

Product

Approval Statusa

Availability

Morphine sulfate 20 mg/mL

Approved

Available

Morphine sulfate 10 mg/5 mL or 20 mg/5 mL

Approved

Available

Oxycodone 20 mg/mL

Unapproved

Backordered

Oxycodone 5 mg/5 mL

Unapproved

Intermittent back order

Oxycodone 5 mg/5mL plus acetaminophen 325 mg/5 mL (Roxicet)

Approved

Available

Hydromorphone (Dilaudid) 1 mg/mL

Approved

Available

Methadone 10 mg/mL

Approved

Available

Hydrocodone 7.5 mg/15 mL plus acetaminophen solution 500 mg/15mL

Approved

Available

aAn approved drug product will be listed by drug name or active ingredient



Table 2. Equianalgesic doses of selected opiate agonists by route of administration
a,b 12, 14-16

Opioid Agonist

Intramuscular (IM) Administration

Oral (PO) Administration

Hydrocodone

IM route not available

30 mg

Hydromorphone

1.5 mg

7.5 mg

Methadone

Acute pain: 10 mg
Chronic pain: 2-4 mg

Acute pain: 20 mg
Chronic pain: 2-4 mg

Morphine

10 mg

Acute pain: 60 mgc
Chronic pain: 30 mg

Oxycodone

IM route not available

20 to 30 mg

aDoses listed are considered to produce analgesia equivalent to morphine 10 mg IM.
bIM equivalence is based on single-dose studies comparing the listed drugs with morphine to establish relative analgesic potency. Oral equivalence is based on dosage recommendations for converting from injection to PO administration. Although clinical trials are not available and pharmacokinetic profiles may vary, most clinicians consider the opioid doses equivalent for all injectable routes of administration, including IM, subcutaneous, and intravenous.
cThe 3:1 oral:injectable morphine conversion ratio is based on clinical experience in chronic pain patients. The 6:1 oral:injectable morphine conversion ratio is based on an acute pain potency study.


Table 3. Pharmacodynamics and Pharmacokinetics of selected opiate agonists
14,15,17,18

Opioid Agonist

Activity at Specific Opiate Receptors

Onset of Action (minutes)

Time to Peak Effect (minutes)

Duration of Action (hours)

Half-Life (hours)

Hydrocodone

mu: not quantified

10-20

No information

4-8

4

Hydromorphone

mu: not quantified

15-30

30-60

4-6

2-4

Methadone

mu: high

PO: < 30-60
IM, IV: < 10-20

30-60

Short term: 4-6
Long term: > 8

15-40

Morphine

mu: high
kappa-1: low
kappa-3: low

PO: 15-60
IV: = 5
PR: 20-60

PO, IM, SQ: 30-60
IV: 20

3-7

1.5-4.5

Oxycodone

mu: not quantified

10-15

30-60

3-6

3

Abbreviations: IM = intramuscular administration; IV = intravenous administration; PO = oral administration; PR = rectal administration; SQ = subcutaneous administration.

Related Shortages

References

  1. FDA Center for Drug Evaluation and Research. FDA News. FDA acts to halt marketing of certain unapproved prescription narcotic drugs. Food and Drug Administration, Department of Health and Human Services. Accessed August 24, 2010.
  2. FDA Center for Drug Evaluation and Research. FDA Announces Extension of Enforcement Discretion Related to Morphine Sulfate Oral Solution 20 mg/mL. Food and Drug Administration, Department of Health and Human Services. Accessed August 24, 2010.
  3. FDA Center for Drug Evaluation and Research. Unapproved Narcotics Containing Morphine Sulfate, Hydromorphone, or Oxycodone. Accessed August 24, 2010
  4. FDA Center for Drug Evaluation and Research. Recall Press Release: Ethex Corporation Issues Nationwide Voluntary Recall of Products. Food and Drug Administration, Department of Health and Human Services. Accessed August 24, 2010.
  5. KV Pharmaceuticals. KV Pharmaceutical Reaches Agreement with U.S. Department of Justice. Accessed August 24, 2010
  6. American Society of Health-System Pharmacists. Federal Injunction Halts Production at KV Pharmaceutical. Accessed August 24, 2010.
  7. Lannett (personal communications). February 19, March 3, March 26, April 1, 7, 29, June 2, 11, and 30, July 22, August 19, September 8, October 20, and November 24, 2009; and January 4, February 5, March 24, May 11, June 30, August 23, and September 7, 2010.
  8. Mallinckrodt (personal communications). February 19, March 3, March 26, April 1, 7, 29, June 2, 11, and 30, July 22, August 17, October 20, November 24, and December 15, 2009; and January 4, February 5, March 24, May 11, July 5, and August 23, 2010.
  9. Glenmark (personal communication). April 29, 2009, June 2, August 19, October 20, November 24, and December 14 and 15, 2009; and January 4, February 5, March 25, May 12, and July 1, 2010.
  10. Xanodyne (personal communications). February 19, March 3, March 26, April 1, 7, 13, 29, June 2, 11, and 30, July 2 and 22, August 19, September 8, October 1, October 20, November 24, and December 15, 2009.
  11. Roxane (personal communications). February 19, March 3, March 26, April 1, April 7, June 2, 11, and 30, July 22, August 19, September 8, October 1, October 20, November 24, and December 15, 2009; and January 4, February 5, March 24, May 11, June 30, and August 24, 2010. 
  12. Lipman, A, ed. Pain Management for Primary Care Clinicians. Bethesda, MD: American Society of Health-System Pharmacists; 2004:59-90.
  13. Institute for Safe Medication Practices. ISMP Medication Safety Alert. Morphine oral concentrate no longer available. April 9, 2009: 14(7). Institute for Safe Medication Practices. Accessed August 24, 2009.
  14. Opiate agonists. In: McEvoy GK, ed. AHFS 2001 Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2009:2185-2228.
  15. Lacy CF, Armstrong LL, Goldman MP, Lance LL, eds. Drug Information Handbook. 17th ed. Hudson, OH: Lexi-Comp; 2008-2009.
  16. Narcotic agonist analgesics. In: Wickersham RM, Novak KK, managing eds., eds. Drug Facts and Comparisons. St. Louis, MO: Wolters Kluwer Health, Inc.; 2008: 784-802.
  17. Gutstein HB, Akil H. Opioid analgesics. In: Hardman JG, Limbird LE, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill Health Professions Division; 2001:569-620.
  18. Way WY, Fields, HL, Way, EL. Opioid analgesics and antagonists. In: Katzung BG, ed. Basic and Clinical Pharmacology. Stamford, Ct: Appleton & Lange,1998: 496-515.

Updated

Updated September 7, 2010 by Michelle Wheeler, Pharm.D., Drug Information Specialist. Created April 13, 2009 by Jane Chandramouli, Pharm.D., Drug Information Specialist and Erin Fox, Pharm.D., Manager, Drug Information Service. University of Utah, Drug Information Service. Copyright 2010, Drug Information Service, University of Utah, Salt Lake City, UT.

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