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JADA 142(4) http://jada.ada.org April 2011 407

C A S E R E P O R TC L I N I C A L P R A C T I C E

utes. Rapid pain relief is obtained from the por-tion of OTFC absorbed through the highly vas-cularized mucosa (25 percent). The remaining75 percent is swallowed into the gastroin-testinal tract, where two-thirds of this amountis either metabolized by the liver or eliminatedthrough the intestines.1,2,5-7 A prolonged anal-gesic effect is obtained from the remaining,more slowly absorbed intestinal portion ofOTFC.

OTFC is prescribed in multiple formulations,from 200 to 1,600 micrograms, allowing fortitration of the dosage to meet individualpatient needs. It can be abused and becomeaddictive.5 Adverse effects and adverse reactionsother than addiction include respiratory depres-sion, central nervous system depression, drymouth, constipation, hypotension, bradycardiaand dental caries.8,9 Consequently, its recom-mended use is limited to four lozenges per day,although some reports indicate that one to 10lozenges (mean, 3.7) of 200 to 1,600 µg perlozenge are being used.2

CASE REPORTIn October 2009, a 19-year-old man was referredby his dentist to the Columbia University Col-lege of Dental Medicine’s Salivary Gland Centerbecause of total dental coronal destruction.

We conducted an oral examination and foundthat the patient’s teeth had no crowns (Figure1). We did see the retained roots of 31 teeth andthat the maxillary left lateral incisor wasmissing. The patient’s oral hygiene was good,and the mucosa appeared to be normally moist.All salivary duct orifices were patent, with

normal salivary flows evident when we mas-saged the respective salivary gland aggressively.A panoramic radiograph showed the roots of 31teeth, some of which had periapical pathology(Figure 2).

The patient had been diagnosed seven yearspreviously with trigeminal neuralgia thatinvolved the left side of his face and extendedfrom the upper eyelid to the cheek. When weasked the patient about the status of his teethin previous years, he said that until he was 16years old his teeth were “decent” and that hehad been receiving dental care occasionally. Torelieve the pain from the trigeminal neuralgia,he took standard analgesic medications and car-bamazepine; however, their use did not result ineffective pain relief, and he said his facial painhad become “unbearable.” Consequently, hisphysician prescribed OTFC (800 µg) lollipopsfour times a day. After one month, the pain wasnot totally relieved, and the patient illegallyobtained OTFC “off the street” and institutedhis own regimen of eight to 10 lozenges (1,200µg per lozenge) per day. He maintained eachlozenge in his mouth for about 30 minutes. Thepatient was adamant in his claim that thedental problems developed five to six monthsafter he started using the OTFC lozenges.Before coming to the Salivary Gland Center inOctober 2009, he had already been weaned off ofOTFC, and his psychiatrist had prescribed psy-chotherapeutic medications.

We contacted the referring dentist, and heforwarded dental radiographs that wereobtained in January 2006. When we reviewedthese radiographs, we saw an intact dentitionwith coronal caries involving a few teeth (Figure3). These radiographs substantiated thepatient’s claim that the gross carious destruc-

Figure 2. Panoramic radiograph obtained in 2009 showing complete coronal carious destruction with retention of roots of31 teeth; the maxillary left lateral incisor was missing.

Figure 1. Intraoral view from 2009 of multiple retained roots.

ABBREVIATION KEY. BTP: Breakthrough pain.OTFC: Oral transmucosal fentanyl citrate.

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Oral transmucosal fentanyl citrate(OTFC) is a Schedule II controlled nar-cotic substance that has an analgesicpotency substantially greater than that

of morphine.1 The U.S. Food and Drug Adminis-tration approved OTFC for use in managingbreakthrough pain (BTP) in patients withcancer. BTP is characterized by transient painflare-ups that are rapid in onset, short in dura-tion and moderate to severe in intensity.1,2 BTPoccurs if standardized pain treatment offers norelief from an existing persistent painfulstate.1,2 Although OTFC has been approved bythe U.S. Food and Drug Administration for BTPonly in patients with cancer, it is being used off-label for back pain, bone injuries, migraine andother chronic moderate to severe pain fromnonmalignant sources.2-4

OTFC, which is intended for use by opiate-tolerant people, is formulated as a berry-flavored lozenge, containing 2 grams of sucrose,placed at the end of a plastic stick. The patientapplies the lollipop to the buccal mucosa androtates it while sucking and swallowing. Thelozenge usually dissolves within 20 to 30 min-

Dr. Mandel is the director, Salivary Gland Center, and the associate dean and a clinical professor, Division of Oral and Maxillofacial Surgery, Columbia University College of Dental Medicine, 630 West 168th St., New York, N.Y. Address reprint requests to Dr. Mandel.Ms. Carunchio is a research assistant, Salivary Gland Center, and a fourth-year student, Columbia University College of Dental Medicine, New York City.

Rampant caries from oral transmucosalfentanyl citrate lozenge abuseLouis Mandel, DDS; Michele J. Carunchio, BS

AB ST RACTBackground. Oral transmucosal fentanyl citratelozenges (lollipops) are indicated for the oral manage-ment of breakthrough cancer pain. When abused,these sucrose-containing lozenges can cause rampantdental caries.Case Description. The authors examined a 19-year-old man whose dentist referred him because oftotal dental coronal destruction. After the authorsquestioned the patient, they concluded that his fre-quent oral use of sucrose-containing opioid fentanyl citrate lozenges across a three-year period caused thedental condition.Clinical Implications. Dentists should be awarethat oral transmucosal fentanyl citrate lozenges arebeing prescribed off-label for the control of pain fromnonmalignant sources. Fentanyl citrate’s effectiveanalgesic potency can lead to misuse and potentialabuse. Early recognition of its misuse could preventsevere dental caries and the need for extensive dentalrestoration.Key Words. Fentanyl citrate; caries; sucrose; opioid.JADA 2011;142(4):406-409.


To Add On page 12 add: © 2011 American Dental Association. Republished by Medical Online Publication SAL with permission of American Dental Association. All rights reserved. JADA 2011, Volume 142, No 5, Page 478-479 On page 17 add: © 2011 American Dental Association. Republished by Medical Online Publication SAL with permission of American Dental Association. All rights reserved. JADA 2011, Volume 142, No 5, Page 493-504 On page 31 add: © 2011American Dental Association. Republished by Medical Online Publication SAL with permission of American Dental Association. All rights reserved. JADA 2011, Volume 142, No 5, Page 531-539 On page 40 add: © 2011 American Dental Association. Republished by Medical Online Publication SAL with permission of American Dental Association. All rights reserved. JADA 2011, Volume 142, No 5, Page 506-513 On page 49 add: © 2011 American Dental Association. Republished by Medical Online Publication SAL with permission of American Dental Association. All rights reserved. JADA 2011, Volume 142, No 4, Page 411-414 On page 54 add: © 2011 American Dental Association. Republished by Medical Online Publication SAL with permission of American Dental Association. All rights reserved. JADA 2011, Volume 142, No 4, Page 406-409 On page 59 add: © 2011 American Dental Association. Republished by Medical Online Publication SAL with permission of American Dental Association. All rights reserved. JADA 2011, Volume 142, No 4, Page 441-444 On page 63 add: © 2011 American Dental Association. Republished by Medical Online Publication SAL with permission of American Dental Association. All rights reserved. JADA 2011, Volume 142, No 5, Page 553-555 On page 66 add: © 2011 American Dental Association. Republished by Medical Online Publication SAL with permission of American Dental Association. All rights reserved. JADA 2011, Volume 142, No 5, Page 574 10 JADA Middle East vol 2 No 4 July-August 2011

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utes. Rapid pain relief is obtained from the por-tion of OTFC absorbed through the highly vas-cularized mucosa (25 percent). The remaining75 percent is swallowed into the gastroin-testinal tract, where two-thirds of this amountis either metabolized by the liver or eliminatedthrough the intestines.1,2,5-7 A prolonged anal-gesic effect is obtained from the remaining,more slowly absorbed intestinal portion ofOTFC.

OTFC is prescribed in multiple formulations,from 200 to 1,600 micrograms, allowing fortitration of the dosage to meet individualpatient needs. It can be abused and becomeaddictive.5 Adverse effects and adverse reactionsother than addiction include respiratory depres-sion, central nervous system depression, drymouth, constipation, hypotension, bradycardiaand dental caries.8,9 Consequently, its recom-mended use is limited to four lozenges per day,although some reports indicate that one to 10lozenges (mean, 3.7) of 200 to 1,600 µg perlozenge are being used.2

CASE REPORTIn October 2009, a 19-year-old man was referredby his dentist to the Columbia University Col-lege of Dental Medicine’s Salivary Gland Centerbecause of total dental coronal destruction.

We conducted an oral examination and foundthat the patient’s teeth had no crowns (Figure1). We did see the retained roots of 31 teeth andthat the maxillary left lateral incisor wasmissing. The patient’s oral hygiene was good,and the mucosa appeared to be normally moist.All salivary duct orifices were patent, with

normal salivary flows evident when we mas-saged the respective salivary gland aggressively.A panoramic radiograph showed the roots of 31teeth, some of which had periapical pathology(Figure 2).

The patient had been diagnosed seven yearspreviously with trigeminal neuralgia thatinvolved the left side of his face and extendedfrom the upper eyelid to the cheek. When weasked the patient about the status of his teethin previous years, he said that until he was 16years old his teeth were “decent” and that hehad been receiving dental care occasionally. Torelieve the pain from the trigeminal neuralgia,he took standard analgesic medications and car-bamazepine; however, their use did not result ineffective pain relief, and he said his facial painhad become “unbearable.” Consequently, hisphysician prescribed OTFC (800 µg) lollipopsfour times a day. After one month, the pain wasnot totally relieved, and the patient illegallyobtained OTFC “off the street” and institutedhis own regimen of eight to 10 lozenges (1,200µg per lozenge) per day. He maintained eachlozenge in his mouth for about 30 minutes. Thepatient was adamant in his claim that thedental problems developed five to six monthsafter he started using the OTFC lozenges.Before coming to the Salivary Gland Center inOctober 2009, he had already been weaned off ofOTFC, and his psychiatrist had prescribed psy-chotherapeutic medications.

We contacted the referring dentist, and heforwarded dental radiographs that wereobtained in January 2006. When we reviewedthese radiographs, we saw an intact dentitionwith coronal caries involving a few teeth (Figure3). These radiographs substantiated thepatient’s claim that the gross carious destruc-

Figure 2. Panoramic radiograph obtained in 2009 showing complete coronal carious destruction with retention of roots of31 teeth; the maxillary left lateral incisor was missing.

Figure 1. Intraoral view from 2009 of multiple retained roots.

ABBREVIATION KEY. BTP: Breakthrough pain.OTFC: Oral transmucosal fentanyl citrate.


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tion of the teeth had developed in the precedingthree years. This finding pointed to the use andabuse of the topically applied sucrose-containingOTFC as the key factor in the patient’s dentaldeterioration.

In view of the condition of the patient’s teeth,we deemed that a restorative approach to treat-ment was feasible. We performed full-mouthextractions and referred the patient to aprosthodontist for denture construction.

DISCUSSIONSome patients who use addictive drugs may besusceptible to rampant caries. An interplay offactors that include drug-induced hyposaliva-tion, poor oral hygiene and craving for sweetsplays a role in the development of dental caries.Although OTFC use is associated with such con-ditions, its high sucrose content and method ofapplication are unique causes of extensivecaries when compared with other addictiveagents, particularly when it is abused.

Sucrose is added to OTFC for flavoring, but italso serves as the sole substrate for the syn-thesis of extracellular glucans. This process ismediated by normally occurring oral Strepto-coccus mutans and facilitated by the bacteria’ssurface enzyme glucosyltransferase.10,11 The glu-cans promote adhesion of S. mutans to toothsurfaces on which the bacteria take part in fer-menting the carbohydrate sucrose.12,13 Theresulting acid overwhelms the protective effectof the thin salivary pellicle on the tooth surfaceand contributes to enamel demineralization.

Besides promoting adhesion of S. mutans totooth surfaces, glucans increase the porosity ofdental plaque.10,11 The increased porosity per-

mits deeper penetration of sucrose into theplaque and results in greater acid productionimmediately adjacent to the tooth surface.11,12

Plaque is a biofilm that adheres to tooth sur-faces. It consists of bacterial aggregates (mainlyS. mutans), bacterial extracellular products(mainly glucans) and salivary polymers. Thebiofilm is held together by matrix of extracel-lular products and protects the contained organ-ized community of bacterial colonies. Becausethe biofilm has a low concentration of calciumand phosphate ions, it enhances enamel mineralloss and susceptibility to caries.11

Stephan14,15 first showed that oral bacteriareadily metabolize sugars to form the acid thatlowers the pH of plaque. However, the Vipeholmdental caries study16 first demonstrated thelinkage of sugar with caries. The study’s resultsestablished that the more frequently sugar isconsumed, the greater the caries risk. The fre-quency of sugar ingestion is just as important asthe amount, because it causes prolonged acidexposure of the enamel below its critical pH and favors selection of the acid-loving S.mutans.11,12,17,18 Furthermore, sugar consumedbetween meals is more cariogenic than that con-sumed during a meal because masticatoryactivity promotes sugar clearance.12,16

The initial attachment of plaque to a dentalsurface begins with pellicle formation. S. mu-tans attaches to the pellicle, and, with the pro-duction of glucans, the stickiness increases andfacilitates the close apposition of acid-producingS. mutans to the tooth surface.10 The presence ofacid in the deeper confines of plaque protectsthe acid from the surface-buffering and lavagingaction of saliva.

Figure 3. Intraoral radiographs obtained in 2006. Radiograph courtesy of Dr. Luciano Ghisalberti.


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The inhibitory action all opioid agents—inthis case fentanyl—has on salivary productionis another factor in the cariogenicity of OTFC.19

Through several mechanisms, saliva inhibitsbut does not prevent acid erosion of teeth.18,20-22

Saliva physically dilutes acid and lavages itaway when the patient swallows. Saliva isinstrumental in the formation of the protectivedental pellicle and neutralizes acids. In addi-tion, saliva is supersaturated with calcium andphosphate ions, thus reducing the rate ofenamel dissolution while simultaneouslyhelping with remineralization.

Other than a poster presentation at the 2007meeting of the American Academy of PhysicalMedicine and Rehabilitation,23 we were not ableto find any reports in the literature regardingOTFC-associated extensive dental breakdown.The manufacturer’s package insert warns ofdental decay and advises dental consultations.24

When we investigated the patient’s medicalhistory, we found that his caregivers had recog-nized the presence of an addiction. In our dis-cussions with the patient, it was apparent thathe had abused OTFC. The abuse originatedfrom the drug’s off-label use, which is as high as90 percent.4 OTFC’s effectiveness can lead to itsmisuse. The fact that the patient used thesucrose-containing OTFC more frequently thanindicated for three years was instrumental inthe destruction of his tooth crowns.

CONCLUSIONThe topical use and the frequency of applicationof sucrose-containing OTFC lozenges, combinedwith the opioid agent’s ability to decrease sali-vation, are the major causes of carious coronaldestruction. Secondary factors usually includepoor oral hygiene and a sugar craving. �

Disclosure. Dr. Mandel and Ms. Carunchio did not report any disclosures.

The authors thank Dr. Sidney Eisig, chairman, Division of Oraland Maxillofacial Surgery, Columbia University College of DentalMedicine, New York City, for making this case available for study.

1. Mystakidou K, Tsilika E, Tsiatas M, Vlahos L. Oral transmu-cosal fentanyl citrate in cancer pain management: a practical appli-cation of nanotechnology. Int J Nanomedicine 2007;2(1):49-54.

2. Taylor DR, Webster LR, Chun SY, et al. Impact of breakthrough

pain on quality of life in patients with chronic, noncancer pain:patient perceptions and effect of treatment with oral transmucosalfentanyl citrate (OTFC, Actiq). Pain Med 2007;8(3):281-288.

3. Landy SH. Oral transmucosal fentanyl citrate for the treatmentof migraine headache pain in outpatients: a case review. Headache2004;44(8):762-766.

4. Passik SD, Kirsh KL. Weighing in on the off-label use of Actiqfor noncancer-related pain: a recipe for success or a recipe for dis-aster? Pain Med 2007;8(2):130-133.

5. Fine PG, Streisand JB. A review of oral transmucosal fentanylcitrate: potent, rapid and noninvasive opioid analgesia. J Palliat Med1998;1(1):55-63.

6. Moore PA, Cuddy MA, Magera JA, Caputo AC, Chen AH,Wilkinson LA. Oral transmucosal fentanyl pretreatment for outpa-tient general anesthesia. Anesth Prog 2000;47(2):29-34.

7. Davies AN, Vriens J. Oral transmucosal fentanyl citrate andxerostomia. J Pain Symptom Manage 2005;30(6):496-497.

8. Liappas IA, Dimopoulos NP, Mellos E, Gitsa OE, Liappas AI,Rabavilas AD. Oral transmucosal abuse of transdermal fentanyl. J Psychopharmacol 2004;18(2):277-280.

9. Martin TL, Woodall KL, McClellan BA. Fentanyl-related deathsin Ontario, Canada: toxicological findings and circumstances ofdeath in 112 cases (2002-2004). J Anal Toxicol 2006;30(8):603-610.

10. Rölla G. Why is sucrose so cariogenic? The role of glucosyl-transferase and polysaccharides. Scand J Dent Res 1989;97(2):115-119.

11. Paes Leme AF, Koo H, Bellato CM, Bedi G, Cury JA. The role ofsucrose in cariogenic dental biofilm formation: new insight. J DentRes 2006;85(10):878-887.

12. Zero DT. Sugars: the arch criminal? Caries Res 2004;38(3):277-285.

13. Kreth J, Zhu L, Merritt J, Shi W, Qi F. Role of sucrose in the fit-ness of Streptococcus mutans. Oral Microbiol Immunol 2008;23(3):213-219.

14. Stephan RM. Change in hydrogen-ion concentration on toothsurfaces and in carious lesions. JADA 1940;27(5):718-723.

15. Stephan RM. Intra-oral hydrogen-ion concentrations associatedwith dental caries activity. J Dent Res 1944;23(4):251-266.

16. Gustafsson BE, Quensel CE, Lanke LS, et al. The Vipeholmdental caries study: the effect of different levels of carbohydrateintake on caries activity in 436 individuals observed for five years.Acta Odontol Scand 1954;11(3-4):232-364.

17. Aires CP, Tabchoury CP, Del Bel Cury AA, Koo H, Cury JA.Effect of sucrose concentration on dental biofilm formed in situ andon enamel demineralization. Caries Res 2006;40(1):28-32.

18. Marshall TA, Eichenberger-Gilmore JM, Larson MA, WarrenJJ, Levy SM. Comparison of the intakes of sugars by young childrenwith and without dental caries experience. JADA 2007;138(1):39-46.

19. Götrick B, Akerman S, Ericson D, Torstenson R, Tobin G. Oralpilocarpine for treatment of opioid-induced oral dryness in healthyadults. J Dent Res 2004;83(5):393-397.

20. Hara AT, Ando M, González-Cabezas C, Cury JA, Serra MS,Zero DT. Protective effect of the dental pellicle against erosive chal-lenges in situ. J Dent Res 2006;85(7):612-616.

21. Dawes C. Salivary flow patterns and the health of hard andsoft tissues. JADA 2008;139(5 suppl):18S-24S.

22. Wolff MS, Larson C. The cariogenic dental biofilm: good, bad orjust something to control? Braz Oral Res 2009;23(suppl 1):31-38.

23. Gee S, Cunningham J, Rome J, et al. Dental disease and theuse of oral transmucosal fentanyl: a case report. Poster presented at:68th Annual Assembly & Technical Exhibition of the AmericanAcademy of Physical Medicine and Rehabilitation; Sept. 27-30, 2007;Boston.

24. Actiq (package insert). Frazer, Pa.: Cephalon; 2009.“www.actiq.com/pdf/actiq_package_insert_4_5_07.pdf ”. AccessedMarch 9, 2011.

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