Case Report Collision Tumour Affecting the Paranasal Sinuses of a Geriatric Donkey S

EQUINE VETERINARY EDUCATION / AE / APRIL 2012 163

Case Report Collision tumour affecting the paranasal sinuses of a geriatric donkey S. Witte*, P. O. E. Mueller†, C. Kosarek‡, J. L. Webb§ and E. W. Howerth§ Qatar Equestrian Federation, Doha, State of Qatar; Departments of Large Animal Medicine† and Pathology§, College of Veterinary Medicine, University of Georgia, Athens, Georgia; and ‡Animal Cancer Care Clinic, Fort Lauderdale, Florida, USA.

Keywords: horse; donkey; sinonasal adenocarcinoma; spindle cell carcinoma; frontal sinus; maxillary sinus

Summary The incidence of equine sinonasal tumours is difficult to quantify but they remain relatively uncommon (Head and Tumours of the paranasal sinuses are relatively uncommon Dixon 1999; Tremaine and Dixon 2001a). This makes the in the horse. A collision tumour occurs when 2 separate phenomenon of 2 separate neoplasms growing tumour types arise in close proximity to each other and concurrently even more unusual. Two separate neoplasms encroach on one another. This report describes the arising in close proximity to each other and invading each presence of neoplasia comprising glandular tissue and other are collectively known as a collision tumour. Collision spindle cells growing concurrently in the frontal and tumours have rarely been reported in the veterinary caudal maxillary sinus of a geriatric donkey. As far as the literature (Barnes et al. 1990; Inoue and Wada 2000). They authors are aware, this is the first description of a possible are uncommon in man and few case reports describe their collision tumour in an equid. location in the sinuses or nasal cavity (Cantor et al. 1981; Kumar et al. 2004; Satake et al. 2005). This report describes Introduction the clinical and histopathological findings in a 28-year-old donkey diagnosed with a collision tumour of the paranasal sinuses involving both the chonchofrontal and caudal Tumours of the equine paranasal sinuses and nasal cavity maxillary sinuses. can be divided into those that originate from the soft tissues and those that arise from cartilage and/or bone. Case history The most common neoplasm of the head is the squamous cell carcinoma (Acland et al. 1984; Hance and Bertone A 28-year-old male miniature donkey presented to the 1993; Dixon and Head 1999; Head and Dixon 1999). Other University of Georgia Veterinary Teaching Hospital soft tissue masses include adenomas, adenocarcinomas, (UGA-VTH) with a 3 week history of unilateral, right-sided undifferentiated sarcomas, fibrosarcomas, myxomas, epistaxis. The owner had noted small volumes of frank melanomas, haemangiosarcomas, angiomas, blood emanating periodically from the right nostril. angiosarcomas and lymphosarcomas (Hance and Attempts by the referring veterinarian to treat the Bertone 1993; Dixon and Head 1999; Head and Dixon 1999; condition with oral antimicrobials (trimethoprim/ Barakzai and Dixon 2003), Calcified tumours of the sulphonamides for 3 weeks) had been unsuccessful. The paranasal sinuses include ossifying fibromas, osteomas, donkey was otherwise healthy although there was a osteosarcomas, ameloblastic odontomas and compound previous history of laminitis 5 years prior to this or complex odontomas (Cannon et al. 1976; Roberts et al. presentation. 1978; Gibbs and Lane 1987; Lane et al. 1987; Schumacher et al. 1988; Hance and Bertone 1993; DeBowes and Case progression Gaughan 1998; Dixon and Head 1999; Head and Dixon 1999; Brounts et al. 2004; Orsini et al. 2004; Puff et al. 2006). During physical examination, the donkey was in good Recently, cementomas have been reported in 2 horses physical condition (weighing 380 kg), bright, alert and (Schaaf et al. 2007). responsive, and all vital parameters were within normal limits. A moderate volume of mucopurulent nasal *Corresponding author email: [email protected] discharge was emanating from the right nostril. During

Fig 2: Preoperative lateral skull radiograph demonstrating a circumscribed opacity within the frontal and caudal maxillary sinuses (a). A fluid line is evident wihin the caudal maxillary sinus (b).

Skull radiographs demonstrated a region of increased opacity that was linearly demarcated from a region of decreased opacity within the caudal maxillary sinus. This was consistent with intrasinus fluid. In addition, a circumscribed opacity was noted within the frontal sinus which also projected into the caudal maxillary sinus (Fig 2). Complete blood cell count and fibrinogen were normal. Due to an inability to biopsy the mass via the nasal passage and the high index of suspicion for neoplasia, a surgical approach was made to the affected area via a nasofrontal osteoplastic flap (Freeman et al. 1990). Preoperatively, the donkey was administered potassium penicillin (22,000 iu/kg bwt i.v. q. 6 h) and gentamicin Fig 1: a) Preoperative endoscopic findings at the caudal right nasal (6.6 mg/kg bwt i.v. q. 24 h). Analgesic therapy consisted passage. The deformed and collapsed dorsal conchus (a) of phenylbutazone (2.2 mg/kg bwt i.v. q. 12 h). A well occludes the ethmoid region (b). b) View of the normal left ethmoid region. The normal dorsal conchus (a) and ethmoid circumscribed mass, measuring approximately 5 cm in turbinates (b) are visible. diameter was removed with relative ease. The tumour appeared to originate from the caudal maxillary sinus and ethmoid region and was carefully removed through a combination of digital and blunt dissection. Although the endoscopy of the upper portion of the respiratory tract amount of subsequent haemorrhage was not significant there was narrowing and partial occlusion of the caudal the sinus was packed with sterile gauze packing, which portion of the right nasal passage which restricted exited via a sinonasal fistula created at surgery and was evaluation of both the nasomaxillary aperture and the attached at the right nostril. The gauze packing was ethmoid region (Fig 1a). Endoscopy of the left ethmoid removed 48 h after surgery. Preoperative antimicrobials region demonstrated no abnormalities (Fig 1b). and nonsteroidal anti-inflammatory medication were

populations (Fig 4). In some areas, the 2 neoplasms were separated by connective tissue while in other areas the 2 populations invaded one another. The first population was glandular in appearance and composed of small acini formed by small cuboidal cells and larger coalescing a follicles lined by cuboidal to columnar cells. Lumens of the acinar and follicular structures contained eosinophilic homogeneous to stringy secretion. The cells had lightly eosinophilic cytoplasm and a round nucleus with stippled c chromatin and one or 2 small nucleoli. Anisokaryosis was mild. Three mitotic figures were seen in 10 40x fields. The second population of cells was a densely cellular d proliferation of spindle-shaped cells arranged in thick b bundles separated by a moderate amount of fibrous stroma. These cells had a moderate amount of elongated eosinophilic cytoplasm and an oval to elongate nucleus with dense chromatin. Nuclei in adjacent cells sometimes lined up along the same end of the cells, producing a palisading appearance. Anisocytosis and anisokaryosis were minimal. Twenty-nine mitiotic figures were observed in 10 40x fields. Large areas of necrosis and haemorrhage were present but no vascular or lymphatic invasion by Fig 3: Endoscopic view of the right ethmoid region 3 months after either cell population was observed. The tissue sample surgery. Note the gross remodelling of the caudal aspect of the obtained at 3 month re-evaluation demonstrated dorsal concha (a) and the associated cicatrix and adhesion histological characteristics of the glandular portion of the formation (b) resulting from tumour resection. Also visible are small neoplasm alone. Moderate anisocytosis and anisokaryosis buds of tissue growing throughout the region (c) as well as mucus aggregates (d). was observed in this tissue and the mitotic figures had increased to 7 per 10 40x fields. Routine immunohistochemistry was performed on 4 mm continued for 3 days. On the third post operative day, the paraffin embedded sections of the mass removed at patient was discharged from the hospital. Financial surgery. The antibodies used and results of staining are constraints precluded further adjunct therapy. summarised in Table 1. Three months after surgery, the donkey presented to the hospital for re-evaluation. The donkey reportedly had right-sided serosanguinous nasal discharge for 2–3 weeks Discussion post surgery but had otherwise been doing well. Physical examination was normal. The site of the sinus flap was A portion of this sinonasal tumour was glandular (epithelial) completely healed and there was no evidence of nasal in origin while a separate portion was composed of discharge. With the exception of a small amount of fluid spindloid cells that were also epithelial in origin, based present within the caudal maxillary sinus, radiographs of on immunohistochemistry. Whether these cell groups the skull revealed no abnormalities. The right ethmoid differentiated along 2 different lines from a tumour of stem region was visible on endoscopy and was covered in a cell origin or 2 separate tumours had arisen and collided in web of mucous and fibrous material (Fig 3). Small buds of this patient (a collision tumour) is not clear. Based on the tissue were biopsied for histopathology. Approximately 13 histopathological appearance a diagnosis of a collision months after the surgery the owner reported that the tumour seems most likely. donkey had been subjected to euthanasia after As is evidenced by their sparse documentation, becoming recumbent and exhibiting seizure activity in the collision tumours are rarities even in man. A collision pasture. No necrospy was performed. tumour affecting a human sinus was first reported in 1981 and appeared to have developed secondary to Histopathological findings intrasinus contrast instillation many years previously (Cantor et al. 1981). More recently, the rare occurrence The mass removed from the frontonasal sinus was fixed in of an esthesioneuroblastoma in combination with a 10% neutral buffered formalin, processed, embedded in squamous cell carcinoma was described affecting the paraffin (FFEP), sectioned at 5 mm and stained with nasal passage of an aged human patient (Kumar et al. haematoxylin and eosin (HE). 2004). The subepithelial connective tissue was expanded by The glandular component of the tumour of this report the presence of 2 separate but adjacent, neoplastic cell was classified as an adenocarcinoma based on the

a) c)

b) d)

Fig 4: Sinonasal tumour composed of 2 separate neoplastic populations. a) The submucosa is expanded by 2 tumours separated by connective tissue (white C). One neoplasm is composed of spindle cells (white S) and one of small glandular acini whose small lumens contain eosinophilic secretion (white G). Arrows point to surface epithelium. Bar = 1 mm. HE staining. b) Area where the spindle cell tumour (S) is invading into the glandular tumour (G). In this area, the glandular tumour has larger coalescing follicular structures filled with eosinophilic homogeneous to stringy secretion and cellular debris. Bar = 200 mm. HE staining. c) Higher magnification of glandular area in (a) showing small acini formed by relatively uniform cuboidal cells and lumens filled with homogeneous eosinophilic secretion. Bar = 100 mm. HE staining. d) Higher magnification of spindle cell neoplasm. Arrow points to palisading nuclei reminiscent of peripheral nerve sheath tumour or schwannoma. Bar = 100 mm. HE staining. follicular or acinar arrangement of the cuboidal to metastasise to the local lymph nodes (Arencibia et al. columnar cells that comprised this tissue and the presence 2000). No lymph node biopsies were obtained in the of secretory material. The immunohistochemical staining donkey of this report; however, no overt enlargement of pattern (Table 1) (pancytokeratin positive, e-cadherin the lymph nodes was noted on physical examination. The positive and vimentin negative) further supported this biopsy sample obtained at the 3 month re-evaluation was diagnosis. Positive S-100 staining is, however, unusual for an reported to be an adenocarcinoma. It seems plausible adenocarcinoma and the significance of this finding is that the progressive growth of this tumour and potential unknown. Although not as common as squamous extension through the cribiform plate might explain the cell carcinoma (Head and Dixon 1999), sinonasal clinical signs of seizure-like activity observed in this donkey adenocarcinoma has been reported frequently in the one year following surgery and immediately prior to literature (Head and Dixon 1999), is characteristically euthanasia. aggressive in its growth at the primary site and carries a Differential diagnoses for the spindle cell portion of poor long-term prognosis (Mugera 1970; Reynolds et al. the tumour prior to immunohistochemistry 1979; Hill et al. 1989; Zaruby et al. 1993; Puff et al. 2006). This include leiomyosarcoma, melanoma, meningioma, a tumour is locally invasive and has a tendency to neuroectodermal neoplasm (e.g. esthesioneuroblastoma)

TABLE 1: Immunohistochemical staining

Staining of Staining of Staining of pre-existing Antibody Cellular origin of antibody spindle cells glandular cells surface epithelium

S-100 Protein Neural crest cells (e.g. Negative Positive Negative melanocytes, Schwann cells) Synaptophysin Neuroendocrine cells Negative Negative Negative Neuron specific enolase (NSE) Neural differentiation Negative Negative Negative Glial fibrillary acidic protein (GFAP) Glial differentiation Negative Negative Negative Thyroglobulin Thyroid follicular cells Negative Negative Negative Pancytokeratin Epithelial cells Positive Positive Positive Cytokeratin (A1/A3) Eptihelial cells Negative Positive (patchy) Positive Vimentin Mesenchymal cells Negative Negative Negative Neurofilament Neurons Negative Negative Negative E-cadherin Intraepithelial adhesion molecule Negative Positive Positive

Uptake of stain through either of the 2 abnormal cell types (spindloid or glandular cells) or through the normal adjacent surface epithelium is shown.

(Loupal and Mikula 1985; Dopke et al. 2005), schwannoma Authors’ declaration of interests (Puff et al. 2006), peripheral nerve sheath tumour and myoepithelioma. Immunohistochemistry helped in the No conflicts of interest have been declared. further characterisation of this tumour (Table 1). Pancytokeratin positive and vimentin negative staining References meant that this spindle cell population is most likely Acland, H.M., Orsini, J.A., Elkins, S., Lee, J.W., Jr, Lein, D.H. and Morris, epithelial and not mesenchymal in origin. D.D. (1984) Congenital ethmoid carcinoma in a foal. J. Am. vet. Immunohistochemical staining specifically ruled out med. Ass. 184, 979-981. leiomyosarcoma (negative staining for smooth muscle Arencibia, A., Vazquez, J.M., Jaber, R., Gil, F., Ramirez, J.A., Rivero, M., actin), melanoma (negative staining for S-100) and Gonzalez, N. and Wisner, E.R. (2000) Magnetic resonance imaging meningioma (negative staining for e-cadherin). Based and cross sectional anatomy of the normal equine sinuses and nasal passages. Vet. Radiol. Ultrasound 41, 313-319. on the morphological appearance of palisading Barakzai, S.Z. and Dixon, P.M. (2003) Sinonasal myxoma in a nuclei, a peripheral neuroectodermal tumour such four-year-old thoroughbred gelding. Vet. Rec. 152, 210-211. as schwannoma, peripheral nerve sheath tumour or Barnes, M., Duray, P., DeLuca, A., Anderson, W., Sindelar, W. and esthesioneuroblastoma were considered highly likely, Kinsella, T. (1990) Tumor induction following intraoperative particularly in conjunction with the specific tumour radiotherapy: late results of the National Cancer Institute canine trials. Int. J. Radiat. Oncol. Biol. Phys. 19, 651-660. location. However, neural origin could not be confirmed as S-100 and other markers specific for this type of Brounts, S.H., Hawkins, J.F., Lescun, T.B., Fessler, J.F., Stiles, P. and Blevins, W.E. (2004) Surgical management of compound odontoma in two differentiation were negative. Myoepithelioma was ruled horses. J. Am. vet. med. Ass. 225, 1423-1427, 1393. out due to the negative staining for smooth muscle actin. Cannon, J.H., Grant, B.D. and Sande, R.D. (1976) Diagnosis and surgical As a result of our inability to further define this tumour, treatment of cystlike lesions of the equine paranasal sinuses. J. Am. spindle cell carcinoma of unknown origin remains the best vet. med. Ass. 169, 610-613. diagnosis for this portion of the mass. Cantor, J.O., Adelglass, J., Cerreta, J.M., Kancherla, P.L. and Samara, M. (1981) Collision tumor of the frontal sinus: evidence In general, tumours affecting the paranasal sinus of the of prior intrasinus instillation of thorotrast. Laryngoscope 91, horse have been reported with a high rate of recurrence 798-803. after surgical excision and carry a poor long-term DeBowes, R.M. and Gaughan, E.M. (1998) Congenital dental disease of prognosis with surgery alone (Hance and Bertone 1993; horses. Vet. Clin. N. Am.: Equine Pract. 14, 273-289. Dixon and Head 1999; Head and Dixon 1999; Arencibia Dixon, P.M. and Head, K.W. (1999) Equine nasal and paranasal sinus et al. 2000; Tremaine and Dixon 2001b). Adjunct treatment tumours: part 2: a contribution of 28 case reports. Vet. J. 157, 279-294. options include radiation and/or chemotherapy (Theon Dopke, C., Grone, A., von Borstel, M., von Oppen, T., Boeve, M.H. and 1998). Radiation therapy can best be administered to the Baumgartner, W. (2005) Metastatic esthesioneuroblastoma in a sinuses via teletherapy delivered from a linear accelerator. horse. J. comp. Pathol. 132, 218-222. Effective chemotherapy is impractical in the sinuses due to Freeman, D.E., Orsini, P.G., Ross, M.W. and Madison, J.B. (1990) A large an inability to assure prolonged contact time and frontonasal bone flap for sinus surgery in the horse. Vet. Surg. 19, adequate concentrations. Financial constraints precluded 122-130. adjunct post operative treatment in this patient. However, Gibbs, C. and Lane, J.G. (1987) Radiographic examination of the facial, nasal and paranasal sinus regions of the horse. II. Radiological even with adjunct therapy, the long-term prognosis for this findings. Equine vet. J. 19, 474-482. aged donkey diagnosed with 2 tumour types within its sinus Hance, S.R. and Bertone, A.L. (1993) Neoplasia. Vet. Clin. N. Am.: Equine remained poor. Pract. 9, 213-234.

Head, K.W. and Dixon, P.M. (1999) Equine nasal and paranasal sinus Reynolds, B.L., Stedham, M.A., Lawrence, J.M., 3rd and Heltsley, J.R. tumours. Part 1: review of the literature and tumour classification. (1979) Adenocarcinoma of the frontal sinus with extension to the Vet. J. 157, 261-278. brain in a horse. J. Am. vet. med. Ass. 174, 734-736. Hill, F.W., Moulton, J.E. and Schiff, P.H. (1989) Exophthalmos in a horse Roberts, M.C., Groenendyk, S. and Kelly, W.R. (1978) Ameloblastic resulting from an adenocarcinoma of the frontal sinus. J. S. Afr. vet. ondontoma in a foal. Equine vet. J. 10, 91-93. Ass. 60, 104-105. Satake, N., Yoshida, S., Jinnouchi, O. and Sekita, T. (2005) Adenoid cystic Inoue, M. and Wada, N. (2000) Immunohistochemical detection of p53 carcinoma of maxillary sinus with metastatic hepatocellular and p21 proteins in canine testicular tumours. Vet. Rec. 146, 370-372. carcinoma. Case report. APMIS 113, 450-455. Kumar, S., Nampoothiri, P., Venugopal, M. and Padmanabhan, P. (2004) Schaaf, K.L., Kannegieter, N.J. and Lovell, D.K. (2007) Calcified Esthesioneuroblastmoma as a collision tumor. Indian J. Otolaryngol. tumours of the paranasal sinuses in three horses. Aust. vet. J. 85, Head Neck Surg. 56, 295-296. 454-458. Lane, J.G., Gibbs, C., Meynink, S.E. and Steele, F.C. (1987) Radiographic Schumacher, J., Smith, B.L. and Morgan, S.J. (1988) Osteoma of examination of the facial, nasal and paranasal sinus regions of the paranasal sinuses of a horse. J. Am. vet. med. Ass. 192, 1449-1450. horse: I. Indications and procedures in 235 cases. Equine vet. J. 19, Theon, A.P. (1998) Radiation therapy in the horse. Vet. Clin. N. Am.: 466-473. Equine Pract. 14, 673-688, viii. Loupal, G. and Mikula, M. (1985) Olfaktorius-Neuroblastom bei einem Tremaine, W.H. and Dixon, P.M. (2001a) A long-term study of 277 cases Pferd. Pferdeheilkunde 1, 65-69. of equine sinonasal disease. Part 1: details of horses, historical, Mugera, G.M. (1970) Adenocarcinoma of frontal sinus in a horse. Bull. clinical and ancillary diagnostic findings. Equine vet. J. 33, 274- Epizoot. Dis. Afr. 18, 171-173. 282. Orsini, J.A., Baird, D.K. and Ruggles, A.J. (2004) Radiotherapy of a Tremaine, W.H. and Dixon, P.M. (2001b) A long-term study of 277 cases recurrent ossifying fibroma in the paranasal sinuses of a horse. J. Am. of equine sinonasal disease. Part 2: treatments and results of vet. med. Ass. 224, 1483-1486, 1454. treatments. Equine vet. J. 33, 283-289. Puff, C., Ohnesorge, B., Wagels, R. and Baumgartner, W. (2006) An Zaruby, J.F., Livesey, M.A. and Percy, D.H. (1993) Ethmoid unusual mucinous osteoma with features of an ossifying fibroma in adenocarcinoma perforating the cribriform plate in the horse. the nasal cavity of a horse. J. comp. Pathol. 135, 52-55. Cornell Vet. 83, 283-289.

NADA #141-306, Approved by FDA Do not use DORMOSEDAN GEL in horses with pre-existing atrioventricular (AV) or sino-atrial As with all alpha2-adrenoceptor agonists, the potential for isolated cases of hypersensitivity, (SA) blocks, respiratory disease, or chronic renal failure. including paradoxical response (excitation), exists. WARNINGS: DORMOSEDAN GEL has not been evaluated in ponies, miniature horses, or horses younger For sublingual use in horses only. Do not use in horses intended for human consumption. than one year of age. (detomidine hydrochloride) HUMAN WARNINGS: Not for human use. Keep out of the reach of children. Use imperme- DORMOSEDAN GEL has not been evaluated for use in breeding, pregnant, or lactating horses. Alpha -agonist oromucosal gel 2 able gloves during drug administration and during procedures that require contact ADVERSE REACTIONS: Rx only with the horse’s mouth. Following sublingual administration of detomidine oromucosal gel, Clinical field study: For Sedation and Restraint in Horses Only drug concentrations up to 0.072 mg/mL were measured at 30 minutes post dose in equine In a US field study of 270 horses sedated to facilitate completion of various veterinary and CAUTION: saliva, equivalent to less than one percent of the original detomidine concentration in the gel. husbandry procedures, the following adverse reactions were reported in 202 horses treated Federal law restricts this drug to use by or on the order of a licensed veterinarian. Mean drug concentrations fall to less than 0.010 mg/mL by 2 hours after drug administration, with DORMOSEDAN GEL and 68 horses treated with placebo: after which a slow decline occurs for several additional hours. INDICATIONS: Table 2: Adverse reactions (number of horses) during the clinical field study DORMOSEDAN GEL is indicated for sedation and restraint in horses. DORMOSEDAN GEL can be absorbed following direct exposure to skin, eyes, or mouth, and may cause irritation. Skin and mucosal contact with the product should be avoided. Use DOSAGE AND ADMINISTRATION: DORMOSEDAN GEL Placebo impermeable gloves at all times. DORMOSEDAN GEL produces sedation when administered sublingually at 0.018 mg/lb Clinical Sign N = 202 N = 68 (0.040 mg/kg). DORMOSEDAN GEL must be placed beneath the tongue of the horse and is In case of accidental eye exposure, rinse abundantly with fresh water. In case of accidental Sweating 20 0 not meant to be swallowed. The dosing syringe delivers the product in 0.25 mL increments. skin exposure, wash with soap and water. Remove contaminated clothing. Penile relaxation 12 0 The following dosing table may be used to determine the correct dose of DORMOSEDAN Appropriate precautions should be taken while handling and using gel syringes. Accidental Bradycardia (≤ 20 bpm) 11 0 GEL (Table 1). exposure could cause adverse reactions, including sedation, hypotension, and bradycardia. Second degree AV block 9 0 Table 1: Sublingual dosing of DORMOSEDAN GEL Seek medical attention immediately but do not drive because sedation or changes in blood Frequent urination 9 0 pressure may occur. Piloerection 4 0 Approx. body Range of Approx. body Range of Dose volume Individuals with cardiovascular disease (for example, hypertension or ischemic heart disease) Marked ataxia 3 0 weight (lb) doses (mg/lb) weight (kg) doses (mg/kg) (mL) should take special precautions to avoid exposure to this product. 330–439 0.023–0.017 150–199 0.051–0.038 1.00 Facial/oral edema 3 0 Caution should be exercised when handling sedated horses. Handling or any other sudden Hypersalivation 2 0 440–549 0.022–0.017 200–249 0.047–0-038 1.25 stimuli, including noise, may cause a defense reaction in an animal that appears to be Nasal discharge 2 0 550–659 0.021–0.017 250–299 0.046–0.038 1.50 heavily sedated. Flatulence 1 0 660–769 0.020–0.017 300–349 0.044–0.038 1.75 Rare cases of human abuse of detomidine products have been reported. DORMOSEDAN GEL Muscle tremors 1 1 770–879 0.019–0.017 350–399 0.043–0.038 2.00 should be managed to prevent the risk of diversion, through such measures as restriction 880–989 0.019–0.017 400–449 0.043–0.038 2.25 of access and the use of drug accountability procedures appropriate to the clinical setting. Epiphora 1 0 Pale mucous membranes 1 0 990–1099 0.019–0.017 450–499 0.042–0.038 2.50 The material safety data sheet (MSDS) contains more detailed occupational safety informa- 1100–1209 0.019–0.017 500–549 0.042–0.038 2.75 tion. To report adverse reactions in users or to obtain a copy of the MSDS for this product Swollen sheath 1 0 1210–1320 0.019–0.017 550–600 0.041–0.038 3.00 call 1-800-366-5288. In a laboratory study, transient erythema of the mucous membranes was seen in 2 (of 8) horses that received the recommended dose of detomidine gel. Use impermeable gloves when handling the product. Remove the syringe from the outer Note to physician: This product contains an alpha2-adrenoceptor agonist. carton. While holding the plunger, turn the ring-stop on the plunger until the ring is able to PRECAUTIONS: Mild ataxia (horse stable but swaying slightly) was observed in 54% of DORMOSEDAN GEL- slide freely up and down the plunger. Position the ring in such a way that the side nearest the DORMOSEDAN GEL must be placed beneath the tongue of the horse. Unlike most oral treated horses and in 4% of the placebotreated horses at 40 minutes post treatment admin- barrel is at the desired volume marking. Turn the ring to secure it in place. Make sure that the veterinary products, this product is not meant to be swallowed. Swallowing could result istration. Moderate ataxia was observed in 25% of DORMOSEDAN GEL-treated horses (0% horse’s mouth contains no feed. Remove the cap from the tip of the syringe and save for cap in ineffectiveness. placebo) at 40 minutes post treatment. Moderate to marked ataxia continued to 90 minutes for 5% and to 120 minutes for 4% of DORMOSEDAN GEL-treated horses. replacement. Insert the syringe tip into the horse’s mouth from the side of the mouth, placing DORMOSEDAN GEL does not provide analgesia. Do not use for painful procedures. the syringe tip beneath the tongue at the level of the commisure of the mouth. Depress the Do not use with other sedative drugs because the effects may be additive. STORAGE INFORMATION: plunger until the ring-stop contacts the barrel, depositing the product beneath the tongue. Store at controlled room temperature 20-25°C (68-77°F), with excursions permitted to 15- Repeat dosing has not been evaluated. Take the syringe out of the horse’s mouth, recap the syringe and return it to the outer carton 30°C (59-86°F), in the original package. The use of an alpha -agonist reversal agent with DORMOSEDAN GEL has not been evaluated. for disposal. Remove gloves for disposal. 2 HOW SUPPLIED: For the best results, allow adequate time (a minimum of 40 minutes) between administra- Before initiating any procedure, allow sedation to fully develop.Nervous or excited horses 3.0 mL graduated oral dosing syringe, 7.6 mg/mL detomidine hydrochloride. with high levels of endogenous catecholamines may exhibit a reduced pharmacological tion of DORMOSEDAN GEL and beginning the procedure. In general, horses show sedative DORMOSEDAN is a trademark of Orion Corporation. response to alpha -adrenoceptor agonists like detomidine. In agitated horses, the onset of effects lasting approximately 90-180 minutes. 2 sedative effects could be slowed, or the depth and duration of effects could be diminished Mfd by: Dist by: Withhold food and water until the sedative effects of the product wear off. or nonexistent. When the product is administered, the animal should be allowed to rest in a Orion Corporation Pfizer Animal Health CONTRAINDICATIONS: quiet place for a minimum of 40 minutes. Turku, Finland Div. of Pfi zer Inc DORMOSEDAN GEL is contraindicated in horses with known hypersensitivity to detomidine. Do not use DORMOSEDAN GEL in horses with cardiovascular disease, respiratory disorders, New York, NY 10017 Intravenous potentiated sulfonamides should not be used in anesthetized or sedated horses liver or kidney diseases, or in conditions of shock, severe debilitation, or stress due to ex- Made in Finland as potentially fatal dysrhythmias may occur. treme heat, cold, fatigue, or high altitude. Protect treated horses from temperature extremes. Date: December 2, 2009