Skip to main content

Sufentanil sublingual tablet system in the treatment of acute postoperative pain in adults: a profile of its use


The novel sufentanil sublingual tablet system (sufentanil STS; Zalviso®) provides an alternative option to opioid-based intravenous patient-controlled analgesia (IV PCA) for the management of acute moderate to severe postoperative pain in adults in the hospital setting. It overcomes some of the drawbacks associated with opioid-based IV PCA, as the preprogrammed, noninvasive design of the sufentanil STS avoids the risk of pump programming errors and other complications that can occur with IV PCA technology. With each device activation, the patient-controlled sufentanil STS device delivers a sublingual sufentanil 15 μg nanotablet, with patients self-administering to analgesia by varying the interval between doses (minimum between-dose interval 20 min; maximum recommended treatment duration 72 h). Relative to morphine IV PCA, sufentanil delivered by the STS is as effective in relieving post-operative pain with a more rapid onset of analgesia and, according to patient and healthcare professional assessments, provides higher rates of success and overall satisfaction, and is easier to use. Sublingual sufentanil is generally well tolerated, with an adverse event profile typical of that of other opioids and a relatively low risk of respiratory depression.

This is a preview of subscription content, access via your institution.

Fig. 1


  1. Argoff CE. Recent management advances in acute postoperative pain. Pain Pract. 2014;14(5):477–87.

    PubMed  Google Scholar 

  2. Misiolek H, Cettler M, Woron J, et al. The 2014 guidelines for post-operative pain management. Anaesthesiol Intensive Ther. 2014;46(4):221–44.

    Article  PubMed  Google Scholar 

  3. Palmer PP, Royal MA, Miller RD. Novel delivery systems for postoperative analgesia. Best Pract Res Clin Anaesthesiol. 2014;28(1):81–90.

    Article  PubMed  Google Scholar 

  4. Minkowitz HS. A review of sufentanil and the sufentanil sublingual tablet system for acute moderate to severe pain. Pain Manag. 2015;5(4):237–50.

    Article  PubMed  Google Scholar 

  5. Minkowitz HS, Candiotti K. The role of sublingual sufentanil nanotabs for pain relief. Expert Opin Drug Deliv. 2015;12(5):845–51.

    CAS  Article  PubMed  Google Scholar 

  6. Ballantyne JC, Carr DB, Chalmers TC, et al. Postoperative patient-controlled analgesia: meta-analyses of initial randomized controlled trials. J Clin Anesth. 1993;5:182–93.

    CAS  Article  PubMed  Google Scholar 

  7. Hudcova J, McNichol E, Quah C, et al. Patient-controlled opioid analgesia versus conventional opioid analgesia for postoperative pain. Cochrane Database Syst Rev. 2006;4:CD003348.

    Google Scholar 

  8. Panchal SJ, Damaraju CV, Nelson WW, et al. System-related events and analgesic gaps during postoperative pain management with the fentanyl iontophoretic transdermal system and morphine intravenous patient-controlled analgesia. Anesth Analg. 2007;105:1437–41.

    CAS  Article  PubMed  Google Scholar 

  9. Viscusi ER. Patient-controlled drug delivery for acute postoperative pain management: a review of current and emerging technologies. Reg Anesth Pain Med. 2008;33(2):146–58.

    PubMed  Google Scholar 

  10. Smith HS. The metabolism of opioid agents and the clinical impact of their active metabolites. Clin J Pain. 2011;27:824–38.

    Article  PubMed  Google Scholar 

  11. Zalviso 15 micrograms sublingual tablets. EU summary of product characteristics. London: European Medicines Agency; 2017.

  12. Mather LE. Opioids: a pharmacologist’s delight! Clin Exp Pharmacol Physiol. 1995;22:833–6.

    CAS  Article  PubMed  Google Scholar 

  13. Roscow CE. Sufentanil citrate: a new opioid analgesic for use in anaesthesia. Pharmacotherapy. 1984;4(1):11–9.

    Article  Google Scholar 

  14. Lotsch J. Pharmacokinetic-pharmacodynamic modeling of opioids. J Symptom Pain Manage. 2005;29(Suppl. 5):S90–103.

    Article  Google Scholar 

  15. Shafer SL, Flood PD. The pharmacology of opioids in geriatric patients. In: Silverstein JH, Rooke GE, Reves JG, et al., editors. Geriatric anaesthesiology. New York: Springer Science; 2007. p. 209.

    Google Scholar 

  16. Scott JC, Cooke JE, Stanski DR. Electroencephalographic quantitation of opioid effect: comparative pharmacodynamics of fentanyl and sufentanil. Anaesthesiology. 1991;74(1):34–42.

    CAS  Article  Google Scholar 

  17. Minkowitz HS, Singla NK, Evashenk MA, et al. Pharmacokinetics of sublingual sufentanil tablets and efficacy and safety in the management of postoperative pain. Reg Anesth Pain Med. 2013;38(2):131–9.

    CAS  Article  PubMed  Google Scholar 

  18. Bailey PL, Streisand JB, East KA, et al. Differences in magnitude and duration of opioid-induced respiratory depression and analgesia with fentanyl and sufentanil. Anesth Analg. 1990;70(1):8–15.

    CAS  Article  PubMed  Google Scholar 

  19. Ved SA, Dubois M, Carron H, et al. Sufentanil and alfentanil pattern of consumption during patient-controlled analgesia: a comparison with morphine. Clin J Pain. 1989;5(Suppl 1):S63–70.

    Article  PubMed  Google Scholar 

  20. Becker LD, Paulson BA, Miller RD, et al. Biphasic respiratory depression after fentanyldroperidol or fentanyl alone used to supplement nitrous oxide anesthesia. Anesthesiology. 1976;44(4):291–6.

    CAS  Article  PubMed  Google Scholar 

  21. Stoeckel H, Schüttler J, Magnussen H, et al. Plasma fentanyl concentrations and the occurrence of respiratory depression in volunteers. Br J Anaesth. 1982;54(10):1087–95.

    CAS  Article  PubMed  Google Scholar 

  22. US National Institutes of Health. 2017. Accessed 29 Jun 2017.

  23. Committee for Medicinal Products for Human Use (CHMO). Zalviso: EU public assessment report (EPAR). London: European Medicines Agency; 2015.

  24. Ringold FG, Minkowitz HS, Gan TJ, et al. Sufentanil sublingual tablet system for the management of postoperative pain following open abdominal surgery: a randomized, placebo-controlled study. Reg Anesth Pain Med. 2015;40(1):22–30.

    Article  PubMed  Google Scholar 

  25. Jove M, Griffin DW, Minkowitz HS, et al. Sufentanil sublingual tablet system for the management of postoperative pain after knee or hip arthroplasty: a randomized, placebo-controlled study. Anesthesiology. 2015;123(2):434–43.

    CAS  Article  PubMed  Google Scholar 

  26. Melson TI, Boyer DL, Minkowitz HS, et al. Sufentanil sublingual tablet system vs. intravenous patient-controlled analgesia with morphine for postoperative pain control: a randomized, active-comparator trial. Pain Pract. 2014;14(8):679–88.

    Article  PubMed  PubMed Central  Google Scholar 

  27. DiDonato KP. Phase 3 dosing observations by surgery type for the sufentanil sublingual tablet system (15 mcg): implications for clinical practice [slide presentation]. In: European Society of Regional Anesthesia Congress; 2016.

  28. Melson T, Turan A, Minkowitz H, et al. Sufentanil sublingual tablet 15mcg vs IV PCA morphine: a comparative analysis of patient satisfaction and drug utilization by surgery type [abstract no. ORA05]. Reg Anesth Pain Med. 2016;41(5 Suppl. 1):e85.

  29. Minkowitz H, Ringold F, Jove M, et al. Efficacy and safety of the sufentanil sublingual tablet system (SSTS) in Class 1 and 2 obese patients: the effect of BMI on analgesic response [abstract no. T-P-3144 plus poster]. In: The Obesity Society and American Society for Metabolic & Bariatric Surgery Annual Meeting. 2015.

  30. Katz P, Takyar S, Di Donato K, et al. Indirect treatment comparison of the tolerability of two non-invasive patient controlled analgesia treatments for acute post-operative pain management. Reg Anesth Pain Med. 2016;41(5 Suppl 1):e89–90.

    Google Scholar 

  31. Katz P, Takyar S, Palmer P, et al. Sublingual, transdermal and intravenous patient-controlled analgesia for acute post-operative pain: systematic literature review and mixed treatment comparison. Curr Med Res Opin. 2017;33(5):899–910.

    CAS  Article  PubMed  Google Scholar 

  32. Itri L. Re: Voluntary discontinuation and withdrawal from market of IONSYS® (fentanyl iontophoretic transdermal system), CII. Parsippany: The Medicines Company; 2017.

    Google Scholar 

  33. Leykin Y, Busetto N, Laudani A. Sufentanil sublingual tablet system (SSTS): a new opportunity for postoperative pain relief after bariatric surgery [abstract no EP-34 plus poster]. In: 1st IFSO European Chapter Symposium; 2017. .

  34. Leykin Y, Busetto N, Laudani A. Safety and efficacy of sufentanil sublingual tablet system for postoperative pain relief after laparotomic hysterectomy [abstract no. 08AP01-3 plus poster]. In: European Society of Anaesthesiology Congress; 2017.

  35. Sufentanil sublingual nanotablets. drug safety database [data on file]. Aachen: Grünenthal GmbH; 2017.

    Google Scholar 

  36. Frampton JE. Sublingual sufentanil: a review in acute postoperative pain. Drugs. 2016;76(6):719–29.

    CAS  Article  PubMed  Google Scholar 

Download references


The manuscript was updated from Drugs, 2016;76(6):719-29 [36], and was reviewed by: C.T. Hartrick, Beaumont Health System, Troy (MI), USA; A.L. Kovac, Department of Anesthesiology, University of Kansas Medical Center, Kansas City (KS), USA; A. Laudani, Anesthesia and Intensive Care Unit, Azienda per l’Assistenza Sanitaria, Pordenone, Italy; A. Valente, Anesthesiologist Department, University Hospital of Parma, Parma, Italy; D.W. Wheeler, University Department of Anaesthesia, University of Cambridge, Cambridge, UK. During the peer review process, the marketing authorization holder (Grünenthal GmbH) of the sufentanil STS was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Katherine A. Lyseng-Williamson.

Ethics declarations


The preparation of this review was not supported by any external funding.

Conflict of interest

K.A. Lyseng-Williamson and J.E. Frampton are employees of Adis/Springer, are responsible for the article content and declare no conflicts of interest. Additional information about this Adis Review Q&A can be found at

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lyseng-Williamson, K.A., Frampton, J.E. Sufentanil sublingual tablet system in the treatment of acute postoperative pain in adults: a profile of its use. Drugs Ther Perspect 33, 409–417 (2017).

Download citation

  • Published:

  • Issue Date:

  • DOI: