Morphine Sulfate: Oral Concentrated Solution

20 October 2009

Products Affected - Description

Reason for the Shortage

• FDA sent warning letters in late-March, 2009 to several suppliers of unapproved narcotics. These companies have until May 29, 2009 to stop manufacturing new product and distributors have 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
• In December 2008, KV Pharmaceuticals, which markets prescription medications through Ethex, voluntarily suspended shipment of all prescription tablet products.³ In early 2009, FDA filed an injunction against KV Pharmaceuticals preventing the company from manufacturing any products until all issues are resolved.⁴
• Lannett states the shortage is due to increased demand for product.⁵
• Mallinckrodt states they are working with the FDA to resolve the shortage situation.⁶
• Glenmark states the shortage is due to increased demand for the product.⁷

Estimated Resupply Dates

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.⁸ These products are FDA approved.

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.⁸
• Lannett has all presentations of morphine sulfate concentrated solution on back order and is releasing product as it becomes available.⁵
• Mallinckrodt has all single-count presentations of morphine sulfate concentration solution on back order. The company is releasing product as it becomes available. All 6 count presentations were discontinued in early-June, 2009.⁶
• Xanodyne has all presentations of Roxanol 20 mg/mL solution on long-term back order and the company cannot estimate a release date.⁹
• Glenmark has available morphine sulfate 20 mg/mL in 120 mL bottles (NDC 68462-0349-21). The other morphine sulfate 20 mg/mL products are on back order and the company could not estimate a release date.⁷

Implications for Patient Care

Morphine is an opioid analgesic used to treat chronic and acute pain.¹⁰

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.¹¹

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 suppy.^5-9 Table 1 summarizes the availability and approval status of selected oral liquid narcotic products.
• Table 2 gives equianalgesic doses of selected opiate agonists.^{10, 12-14} Table 3 compares the pharmacodynamic and pharmacokinetic properties of these agonists.^12,13,15,16 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	Unapproved	Backordered
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

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.

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

• Alfentanil Injection— Resolved
• Butorphanol Injection— Resolved
• Choline Magnesium Trisalicylate
• Codeine Phosphate Oral Solution— No Longer Available
• Diazepam Injection— Resolved
• Fentanyl Transdermal System Patch— Resolved
• Hydrocodone Tablets
• Hydromorphone Hydrochloride Injection
• Indomethacin Capsules— Resolved
• Meperidine— Resolved
• Meperidine / Promethazine— No Longer Available
• Methadone Hydrochloride Injection— Resolved
• Methadone Hydrochloride Tablets— Resolved
• Methadone Injection— Resolved
• Methadone Oral Tablets and Liquid— Resolved
• Morphine PCA Syringes— Resolved
• Morphine Sulfate— No Longer Available
• Morphine Sulfate: Extended-Release Products
• Oxycodone Combinations Capsules and Tablets
• Oxycodone Extended-Release Tablets— Resolved
• Oxycodone Tablets, Capsules, and Solutions
• Pentazocine / Naloxone Tablets
• Remifentanil Hydrochloride— Resolved
• Sufentanil Injection— Resolved

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 June 18, 2009.
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 June 18, 2009.
3. 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 June 18, 2009.
4. American Society of Health-System Pharmacists. Federal Injunction Halts Production at KV Pharmaceutical. Accessed June 18, 2009.
5. Lannett (personal communications). February 19, March 3, March 26, April 1, 7, 29, June 2, 11, and 30, July 22, August 19, September 8, and October 20, 2009.
6. Mallinckrodt (personal communications). February 19, March 3, March 26, April 1, 7, 29, June 2, 11, and 30, July 22, August 17, and October 20, 2009.
7. Glenmark (personal communication). April 29, 2009, June 2, August 19, and October 20, 2009.
8. 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, and October 20, 2009.
9. 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, and October 20, 2009.
10. Lipman, A, ed. Pain Management for Primary Care Clinicians. Bethesda, MD: American Society of Health-System Pharmacists; 2004:59-90.
11. 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 June 18, 2009.
12. Opiate agonists. In: McEvoy GK, ed. AHFS 2001 Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2009:2185-2228.
13. Lacy CF, Armstrong LL, Goldman MP, Lance LL, eds. Drug Information Handbook. 17th ed. Hudson, OH: Lexi-Comp; 2008-2009.
14. 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.
15. 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.
16. 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 October 20, 2009 by Leslie Jensen, 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 2009, Drug Information Service, University of Utah, Salt Lake City, UT.

Back to Drug Shortage Product Bulletins