# 053 Sublingual Morphine, 2nd ed


Author(s): Debra Gordon RN, MS, FAAN

Background The preferred route of administration of analgesics for most patients in pain is oral (PO). Soluble tablets of morphine are available for sublingual (SL) administration in patients who are unable to swallow oral analgesics. The advantage of using SL morphine over intermittent IV boluses is a longer duration of action. An IV bolus may last only 1-2 hours, whereas SL morphine may provide relief for up to 4 hours.

Pharmacology Sublingual administration of morphine is often used to treat breakthrough pain in an attempt to hasten analgesic onset and peak; however, available data do not support more rapid absorption of morphine through the sublingual mucosa when compared with the oral route (1-3). Indeed, a number of clinical studies have found no substantial advantage to the use of SL morphine over oral morphine (4-6).

  • Mean time to maximum concentration has been shown to be shorter following PO morphine (0.8 + 0.35hr) compared with SL (1.75 + 1.30 hr), indicating that SL morphine is likely swallowed and absorbed gastrointestinally rather than through the oral mucosa (3).
  • The bioavailability (amount of drug eventually made available to the systemic circulation) of SL morphine is only 9% compared with 23.8% after an oral solution (however, the PO and SL doses should be considered equianalgesic when calculating doses).
  • Agents are most readily absorbed through the oral mucosa when they are potent, non-ionized at physiological pH, and lipid soluble (see Fast Fact #103). Morphine has a relatively low potency for an opioid, is 90% ionized at the pH of the mouth, and is one of the least lipid soluble opioids with a partition coefficient of 0.00001, providing an explanation for its low bioavailability and poor choice as a SL or buccal medication.

Formulation and Dosing There are several forms of short acting PO morphine available on the market. However, only the soluble tablets or the concentrated oral solution are suitable for SL use. Nonsoluble morphine sulfate immediate release (MSIR) tablets will not work because they are not soluble and will not liquefy under the tongue.

A usual starting dose for an opioid naïve patient is 5-30mg PO or SL every 3-4 hours. PO and SL doses are considered equianalgesic. The equianalgesic ratio of IV to PO morphine is 1:3 (10mg of IV morphine is approximately equianalgesic to 30mg PO/SL morphine).

This Fast Fact was adapted with permission from the University of Wisconsin Hospital & Clinics, Madison, WI Pain Patient Care Team ‘Pain Management Fast Facts – 5 Minute Inservice’ series.


  1. Osborne R, Joel S, Trew D, Slevin M. Morphine and metabolite behavior after different routes of morphine administration: demonstration of the importance of the active metabolite morphine-6-glucourinide. Clinical Pharmacology Therapy. 1990; 47:12-19.
  2. David T, Miser AW, Loprinzi CL, Kaur JS, Burnham NL, Dose AM, Ames MM. Comparative morphine pharmacokinetics following sublingual, intramuscular, and oral administration in patients with cancer. The Hospice Journal. 1993; 9(1):85-90.
  3. Colluzzi PH. Sublingual morphine: efficacy reviewed. J Pain Sympt Manage. 1998; 16(3):184-192.
  4. Pannuti F, Rossi AP, Lafelice G, et al. Control of chronic pain in very advanced cancer patients with morphine hydrochloride administered by oral, rectal, and sublingual routes: clinical report and preliminary results on morphine pharmacokinetics. Pharmacological Research Communications. 1982; 14(4):369-380.
  5. McQuay HJ, Moore RA, Bullingham RE. Sublinqual morphine, heroin, methadone, and buprenorphine: kinetics and effects. In: Foley KM & Inturrisi CE, eds. Advances in Pain Research and Therapy, Vol 8. New York, NY: Raven; 1986: pp 407-412.
  6. Robinson JM, Wilkie DJ, et al. Sublingual and oral morphine administration. Review and new findings. Nursing Clin N America. 1995; 30(4):725-743.

Fast Facts and Concepts are edited by Drew A. Rosielle MD, Palliative Care Center, Medical College of Wisconsin. For more information write to: drosiell@mcw.edu. More information, as well as the complete set of Fast Facts, are available at EPERC: www.eperc.mcw.edu.

Version History: This Fast Fact was originally edited by David E Weissman MD. 2nd Edition published July 2006. Current version re-copy-edited April 2009.

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Gordon D. Sublingual Morphine, 2nd Edition. Fast Facts and Concepts. July 2006; 53. Available at: http://www.eperc.mcw.edu/EPERC/FastFactsIndex/ff_053.htm.

Disclaimer: Fast Facts and Concepts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Facts cite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

ACGME Competencies: Medical Knowledge, Patient Care

Keyword(s): Pain – Opioids