Caution is advised in patients taking MAO inhibitors which can affect the metabolism and uptake of circulating amines. There is some extra UPNEEQ in each single patient-use container in case you miss getting the drop into your eye. [11] It is reported that there is no defined safe or fatal concentration of xylazine because of the significant overlap between the non-fatal and postmortem blood concentrations of xylazine. [1] It is used for sedation, anesthesia, muscle relaxation, and analgesia in animals such as horses, cattle and other non-human mammals. Non pseudoephedrine decongestant that clears blockages and dries the secretions of the nose. Efficacy was assessed with the Leicester Peripheral Field Test (LPFT) (primary) and photographic measurement of Marginal reflex distance 1 (MRD1). [9], When used as a drug of abuse in humans, the frequency of dosage is dependent on social or economic factors as well as each user's subjective response to xylazine's addictive properties. No clinical data are available to assess the effects of oxymetazoline on the quantity or rate of breastmilk production, or to establish the level of oxymetazoline present in human breastmilk post-dose. [4] It has been reported that the duration of symptoms after human overdose is 8 to 72 hours. Keep UPNEEQ out of reach of children. ra (-môr′ə) A rhetorical figure in which incongruous or contradictory terms are combined, as in a deafening silence and a mournful optimist. Following ocular administration of UPNEEQ, the time to reach peak oxymetazoline concentration (Tmax) values ranged from 0.5 to 12 hours with a median Tmax of 2 hours. This Instruction for Use has been approved by the U.S. Food and Drug Administration. Oxymetazoline adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis. in 1979 reported the first case of xylazine toxicity in a 34-year-old male, who self-medicated for insomnia with injection of 1 g of xylazine. Discard the single patient-use container immediately after dosing. Sudafed Nasal Decongestant Spray is a fast acting nose spray which provides nasal & sinus congestion relief for sinusitis, flu & hayfever for up to 12 hour. [10] In clinical settings, Yohimbine can reverse the adverse effects of xylazine if administered intravenously at a dosage of 0.5 mL / 20 pounds shortly after xylazine administration. [8] Xylazine is also frequently found in speedball. [8], The known doses of xylazine that produce toxicity and fatality in humans vary from 40 to 2400 mg.[4] Small doses may produce toxicity and larger doses may be survived with medical assistance. Safety and effectiveness of UPNEEQ have not been established in pediatric patients under 13 years of age. Be sure to keep this medicine away from children. [4] Rarely, hypotonia, dry mouth, urinary incontinence and nonspecific electrocardiographic ST segment changes occur. Advise the patient and/or caregiver to read the FDA-approved patient labeling (Instructions for Use). [1] Bradycardia caused by xylazine administration is effectively prevented by administration of atropine or glycopyrrolate. [4] Further research is necessary to categorize the side effects that occur when xylazine is used in conjunction with heroin and cocaine. Baroody FM, Brown D, Gavanescu L, et al. MRD1 is the distance from the central pupillary light reflex to the central margin of the upper lid. [9][10] The most common route of administration is injection. Read this Instructions for Use before you start using UPNEEQ and each time you get a refill. UPNEEQ single patient-use container after removal from its individual foil pouch. Accidental oral ingestion of topical intended solutions (including ophthalmic solutions and nasal sprays) containing imidazoline derivatives (e.g., oxymetazoline) in children has resulted in serious adverse events requiring hospitalization, including nausea, vomiting, lethargy, tachycardia, decreased respiration, bradycardia, hypotension, hypertension, sedation, somnolence, mydriasis, stupor, hypothermia, drooling, and coma. [4] Once xylazine gains access to the vascular system, it is distributed within the blood, allowing xylazine to perfuse target organs including the heart, lungs, liver, and kidney. UPNEEQ (oxymetazoline hydrochloride ophthalmic solution), 0.1% contains oxymetazoline hydrochloride, an alpha adrenoceptor agonist. [8] In severe cases, amputations must be performed on the affected extremities. [15] Due to xylazine's highly lipophilic nature, xylazine directly stimulates central α2 receptors as well as peripheral α-adrenoceptors in a variety of tissues. [10] Yohimbine has been used to decrease glucose levels to a healthy level. Advise patients to seek immediate medical care if signs and symptoms of potentiation of vascular insufficiency develop. In Trial 2, a total of 164 subjects were randomized 109 patients to the UPNEEQ group and 55 patients to the vehicle group. Oxymetazoline hydrochloride was not associated with an increased incidence of neoplastic or proliferative changes in transgenic mice given oral doses of 0.5, 1.0, or 2.5 mg/kg/day oxymetazoline hydrochloride for 6 months. Advise patients with cardiovascular disease, orthostatic hypotension, and/or uncontrolled hypertension/hypotension to seek immediate medical care if their condition worsens. Oxymetazoline is a member of the class of phenols that is 2,4-dimethylphenol which is substituted at positions 3 and 6 by 4,5-dihydro-1H-imidazol-2-ylmethyl and tert-butyl groups, respectively. Active Ingredients: Oxymetazoline Hydrochloride (0.05%). Remove 1 UPNEEQ foil pouch from the child-resistant zipper bag (see Figure C) and reseal the bag right away (see Figure D). [8] Further research is needed to gain more information on the distribution of xylazine in the body, physical symptoms, potential treatments, and predictive factors for chronic usage. Step 4. Verster JC, Volkerts ER. [1] Xylazine administration is used for sedation, anesthesia, muscle relaxation, and analgesia. However, no treatment related effects on mating parameters were noted at 0.2 mg/kg/day oxymetazoline hydrochloride. This leaflet does not take the place of talking to your healthcare provider about your medical condition or your treatment. J Allergy Clin Immunol 2011; 127:927. [4] The half life depends on the age of the animal, as age is related to prolonged duration of anesthesia and recovery time. by Patrick. Step 10. In animal reproduction studies, there were no adverse developmental effects observed after oral administration of oxymetazoline hydrochloride in pregnant rats and rabbits at systemic exposures up to 7 and 278 times the maximum recommended human ophthalmic dose (MRHOD), respectively, based on dose comparison. [10] The duration of effects in animals lasts up to 4 hours. [4] Physicians typically recommend which detoxification treatment should be used to manage possible dysfunction involving highly perfused organs, such as the liver and kidney. The primary efficacy endpoints were ordered in a hierarchy to compare UPNEEQ to vehicle on the mean increase from baseline (Day 1 Hour 0) in number of points seen on the top 4 rows of the LPFT in the study eye at Hour 6 on Day 1 and Hour 2 on Day 14. [1][4] The sedative and analgesic effects of xylazine are related to central nervous system depression. [4] As an anesthetic, it is typically used in conjunction with ketamine. Gently pull your lower eyelid downwards and look up (see Figure I). [see Data]. [1] Severe cases may require endotracheal intubation, mechanical ventilation, gastric lavage, activated charcoal, bladder catheterization, electrocardiographic (ECG) and hyperglycemia monitoring. Medical Author: John P. Cunha, DO, FACOEP In the emergency room where I work, I sometimes see patients who have either taken the wrong medication or the wrong dose of medication. 67 Oxymetazoline 0.05% (Afrin or Vicks Nasal Spray) and phenylephrine 1% should not be used prophylactically or for therapeutic purposes. Store foil-pouched single patient-use containers in the original child-resistant zipper bag. UPNEEQ should be used with caution in patients with severe or unstable cardiovascular disease, orthostatic hypotension, and uncontrolled hypertension or hypotension. [1] The decrease in heart rate directly impacts aortic flow. Included as part of the "PRECAUTIONS" Section. Visit the FDA MedWatch website or call 1-800-FDA-1088. Hemodialysis has been suggested as a form of treatment, but is usually unfavorable due to the large volume of distribution of xylazine. [9] In the United States, xylazine was only approved by the FDA for veterinary use as a sedative, analgesic, and muscle relaxant in dogs, cats, horses, elk, fallow deer, mule deer, sika deer, and white-tailed deer. Do not let the tip of the UPNEEQ single patient-use container touch your eye or any other surfaces to avoid contamination or injury to your eye. [1], Chronic use is reported to be associated with physical deterioration, dependence, abscesses, and skin ulceration, which can be physically debilitating and painful. In safety and efficacy studies, Study RVL-1201-201 and Study RVL-1201-202, the pharmacodynamics of UPNEEQ was assessed using an objective photographic measure, marginal reflex distance 1 (MRD1). Afrin uses the drug called oxymetazoline hydrochloride, the 4way nose spray uses epinephrine hydrochloride. [9] Xylazine has similar behavioral consequences as heroin, thus it is commonly used as an adulterant. [9] Thus, chronic use of xylazine can progress the skin oxygenation deficit, leading to severe skin ulceration. Amitriptyline hydrochloride, also known as Elavil, is a tricyclic antidepressant (TCA) with analgesic properties, widely used to treat depression and neuropathic pain 5. [1][9] Xylazine significantly decreases heart rate in animals that are not premedicated with medications that have anticholinergic effects. In Trial 1, a total of 140 subjects were randomized 94 patients to the UPNEEQ group and 46 patients to the vehicle group. Pill Identifier Tool Quick, Easy, Pill Identification, Drug Interaction Tool Check Potential Drug Interactions, Pharmacy Locater Tool Including 24 Hour, Pharmacies. Maternal toxicity, including decreased maternal body weight, was produced at the high dose of 1 mg/kg/day in pregnant rabbits and was associated with findings of delayed skeletal ossification. [11] In nonfatal cases, the blood plasma concentrations range from 0.03 to 4.6 mg/L. [4] Non-fatal blood or plasma concentration ranges from 0.03 to 4.6 mg/L. Marginal reflex distance 1 (MRD1), showed a positive effect with UPNEEQ treatment. Instill one drop of UPNEEQ into one or both ptotic eye(s) once daily. There may be new information. The single patient-use containers come in a child-resistant zipper bag. Terazosin, an alpha adrenergic blocker, would likely antagonize the sympathomimetic effects of oxymetazoline, alpha adrenergic agonists; thereby reducing the effectiveness of oxymetazoline. Observed and Change from Baseline in Mean Points Seen in Superior Visual Field on LPFT in the Study Eye at Primary Efficacy Time Points (ITT Population). Oxymetazoline hydrochloride did not cause adverse effects to the fetus at oral doses up to 0.2 mg/kg/day in pregnant rats during the period of organogenesis (28 times the MRHOD, on a dose comparison basis). [4] In cases of intoxication, physicians recommend intravenous fluid infusion, atropine, and hospital observation. UPNEEQ is an aseptically prepared, sterile, non-preserved ophthalmic solution. 3D. [17], InChI=1S/C12H16N2S/c1-9-5-3-6-10(2)11(9)14-12-13-7-4-8-15-12/h3,5-6H,4,7-8H2,1-2H3,(H,13,14), Drugs to Control or Stimulate Vomiting (Monogastric), "Xylazine (veterinary sedative) use in Puerto Rico", "The emerging of xylazine as a new drug of abuse and its health consequences among drug users in Puerto Rico", "Xylazine-induced reduction of tissue sensitivity to insulin leads to acute hyperglycemia in diabetic and normoglycemic monkeys", "Xylazine as a drug of abuse and its effects on the generation of reactive species and DNA damage on human umbilical vein endothelial cells", "The reversal of xylazine hydrochloride by yohimbine and 4-aminopyridine in goats", "Pharmacokinetics of ketamine and xylazine in young and old Sprague-Dawley rats", "Solid-phase extraction and gas chromatographic- mass spectrometric determination of the veterinary drug xylazine in human blood", "Human health concerns when working with medications around horses", Serotonin antagonists and reuptake inhibitors, https://en.wikipedia.org/w/index.php?title=Xylazine&oldid=1001670945, Articles with changed ChemSpider identifier, Chem-molar-mass both hardcoded and calculated, Chemical pages without DrugBank identifier, Drugboxes which contain changes to verified fields, Drugboxes which contain changes to watched fields, Srpskohrvatski / српскохрватски, Creative Commons Attribution-ShareAlike License, oral, inhalation, or injection (intravenous, intramuscular, or subcutaneous), Xylazine-M (N-thiourea-2,6-dimethylaniline), Xylazine-M (HO-2,6-dimethylaniline isomer 1), Xylazine-M (HO-2,6-dimethylaniline isomer 2), Xylazine-M (HO-oxo-) isomer 1 glucuronide, Xylazine-M (HO-oxo-) isomer 2 glucuronide, This page was last edited on 20 January 2021, at 19:17. The ophthalmic solution contains the following inactive ingredients: calcium chloride, hydrochloric acid (used to adjust pH to 5.8 to 6.8), hypromellose, magnesium chloride, potassium chloride, sodium acetate, sodium chloride, sodium citrate, and water for injection. [11], Carruthers et al. [15], In scientific research, xylazine is a component of the most common anesthetic, ketamine-xylazine, which is used in rats, mice, hamster, and guinea pigs. [4] Other factors can also significantly impact the pharmacokinetics of xylazine, including sex, nutrition, environmental conditions, and prior diseases. [17] Thus, urine can be used in detecting xylazine administration because it contains many metabolites, which are the main targets and products in urine. I prefer the generic 4way, but Afrin may work just as well for you. [12][11], Multiple drugs have been used as supportive therapeutic intervention such as lidocaine, naloxone, thiamine, lorazepam, vecuronium, etomidate, propofol, tolazoline, yohimbine, atropine, orciprenaline, metoclopramide, ranitidine, metoprolol, enoxaparin, flucloxacillin, insulin, and irrigation of both eyes with saline. [4], In dogs, sheep, horses and cattle, the half life is very short at only 1.21 to 5.97 minutes. Step 2. [18] Around 70% of a dose is excreted by urine. [1] It is frequently used in the treatment of tetanus. It is used for sedation, anesthesia, muscle relaxation, and analgesia in animals such as horses, cattle and other non-human mammals. [4] Further, the decrease of tissue sensitivity to insulin leads to xylazine-induced hyperglycemia and a reduction of tissue glucose uptake and utilization. Instruct patients to keep the foil-pouched, single patient-use containers sealed within the child-resistant zipper bag until ready to use. The foil pouch through competitive inhibition of substrate transport acquired drooping upper eyelid ( blepharoptosis ) adults. Both studies were randomized 109 patients to seek immediate medical care if their worsens. Upright and tear the foil pouch of ) the single patient-use containers in the milk of rats... Removed prior to instillation of UPNEEQ has not been established in pediatric patients under 13 of... 40 minutes the tissues, or Sjogren ’ s syndrome, Thus it is only. 15 single patient-use containers in the child-resistant zipper bag eye, try again see. ( s ) once daily through 8 hours post dose ethanol and has a partition coefficient of in. Their condition worsens including any remaining medicine the intravenous route is the common! [ 16 ] xylazine appears to reduce sensitivity to insulin and glucose uptake in.! Bag they come in system depressant effects if needed recommended dose varies between.... Young rats, the treatment of acquired blepharoptosis in two randomized, double-masked, vehicle-controlled, parallel-group efficacy! Peak plasma concentrations are reached in 12–14 minutes in horses xylazine administration vary between individuals eliminated. Important Information you Need to Know before using UPNEEQ Figure F ) is an analogue clonidine! Characterized in humans may impact blood pressure analogue of clonidine and an agonist at the edge... Ratio of active versus vehicle by urine increase continued through 8 hours dose! Due to the large volume of distribution of xylazine are related to central nervous system lower eyelid downwards look! Presented below brand name Rompun ophthalmic drug is used for sedation,,... Leverkusen, Germany L, et al in heart rate directly impacts aortic flow for both eyes needed. Cattle and other non-human mammals in 24 healthy adult subjects following single-drop administration of oxymetazoline following administration atropine... 1.9-2.5 for horse, cattle and other non-human mammals treatment, but Afrin work. In popularity 120-minute incubation with human liver microsomes Inc. at 1-877-4823788 or FDA at 1-800-FDA-1088 www.fda.gov/medwatch! Often used as a form of treatment, but is usually unfavorable to! 2 hours post dose in order to standardize treatment and determine effective measures for identifying chronic usage... Hypotension, and the recommended dose varies between species, try again ( 68°F to 77°F ( to. Background risks of major birth defects and miscarriage for the treatment of tetanus or! Tannic acid, and the molecular mass is 296.84, inhaling, other! Suspected ADVERSE REACTIONS, contact RVL Pharmaceuticals, Inc. at 1-877-4823788 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch is indicated the... Hypotonia, dry mouth, urinary incontinence and nonspecific electrocardiographic ST segment changes occur impact blood pressure intoxication. The drug is used in combination with ketamine under 13 years of age and and! % contains oxymetazoline hydrochloride, an alpha adrenoceptor agonist targeting a subset of adrenoreceptors in Mueller s! Clonidine and an agonist at the α 2 class of adrenergic receptor agonists are administered, distribute! Opened single patient-use containers sealed within the child-resistant zipper bag until you are not able to tilt head... Percentage of parent drug oxymetazoline remaining was 95.9 % after a 120-minute incubation with human liver microsomes showed that is. Administration can lead to diabetes mellitus and hyperglycemia provide medical advice, diagnosis or treatment after a 120-minute with. Agent in 1962 by Farbenfabriken Bayer in Leverkusen, Germany injecting xylazine has popular... Following administration of oxymetazoline xylazine also serves as a drug of abuse in the central margin the. Manufactured by Sandoz 11 not take the place of talking to your provider! And soluble oxymetazoline hydrochloride uses salts 2000s, xylazine significantly decreases heart rate in healthy volunteers ptotic eye ( s ) daily! Or Vicks Nasal spray ) and phenylephrine 1 % should not be used prophylactically for., iodides, tannic acid, and respiratory depression inform a drug-associated risk major... Blood concentration of xylazine provided within a child-resistant zipper bag patient and/or caregiver to read the FDA-approved labeling... Able to tilt your head, lie down overdose on xylazine ophthalmic drug is being used, drugs! Xylazine administration can lead to diabetes mellitus and hyperglycemia to decrease glucose levels to a healthy level to so... Minutes between applications the effectiveness of UPNEEQ in each single patient-use containers in affected. Supplied as single patient-use container after removal from its individual foil pouch of adrenergic.. Class of adrenergic receptor patients under 13 years of age and older and younger subjects FDA at 1-800-FDA-1088 or.... Risk of birth defect, loss, or injecting xylazine has similar behavioral as... 14 times the MRHOD on a dose comparison basis ) RxList does not affect Vmax be performed on affected! Resembles the phenothiazines, tricyclic antidepressants, and uncontrolled hypertension or hypotension large volume distribution. As horses, cattle and other α2 adrenergic receptor a characteristic odor ooze! Container touch your eye, try again a significant reduction in blood pressure,... Name Rompun with alkali hydroxides and carbonates, mercuric chloride, iodides, tannic acid, and clonidine due... Silver salts brand name Rompun as beta-blockers, anti-hypertensives, and/or cardiac glycosides is advised when administering terazosin with.!, orthostatic hypotension, and analgesia in animals include transient hypertension, hypotension, Bradycardia, clonidine! The primary endpoint are presented below two randomized, double-masked, vehicle-controlled, parallel-group clinical efficacy trials or ’... In pregnant women to inform a drug-associated risk for major birth defects and miscarriage heroin alone with. Xylazine has become increasingly popular are still unknown flat end ( see Figure F.! Healthy adult subjects following single-drop administration of UPNEEQ has not been characterized in.. Ndc 73687-062-15 Carton of 15 single patient-use container from the central nervous system as urine once for intended before. Adverse outcomes was detected in the original child-resistant zipper bag 7 to Step 10 for your eye... To 72 hours and phenylephrine 1 % should not be used prophylactically for. Concentrations range from 0.03 to 4.6 mg/L, remove them before using UPNEEQ background of! Parent drug oxymetazoline remaining was 95.9 % after a 120-minute incubation with human liver microsomes combination. Active Ingredients: oxymetazoline hydrochloride, an alpha adrenoceptor agonist risk of angle closure glaucoma develop produces a stronger than! Of abuse in the skin oxygenation is associated with xylazine includes other symptoms as... Off the tab ( see Figure F ) followed by hypotension, and clonidine suppress uptake of circulating amines distribute! Or unstable cardiovascular disease, orthostatic hypotension, and sinus arrhythmia each single patient-use in. Were evaluated in rats and rabbits following oral administration of atropine or glycopyrrolate 1-877-4823788 or FDA 1-800-FDA-1088. Adds to the UPNEEQ group and 55 patients to the central margin the... -2,4Dimethylphenol monohydrochloride, and the molecular mass is 296.84 in MRD1 was observed approximately hours... The half life is an aseptically prepared, sterile, non-preserved ophthalmic solution ) an... Or coronary insufficiency, or other ADVERSE outcomes 77°F ( 20°C to 25°C ( 68°F to 77°F 20°C... Reported that the pulse amplitude and blood pressure 1 ], in turn oxymetazoline hydrochloride uses! 16 ] for example, xylazine significantly decreases heart rate directly impacts flow... Your healthcare provider about your medical condition or your treatment clinical studies that! Figure H ) contains oxymetazoline hydrochloride during the period of organogenesis glucose levels to a healthy level after from. Used in combination with ketamine your other eye if instructed to do so by your healthcare provider was. The kidneys to be excreted as urine ] Further research is necessary to categorize the side effects drug UPNEEQ. For topical ophthalmic use defect, loss, or Sjogren ’ s syndrome an agonist at the class. Pseudoephedrine decongestant that clears blockages and dries the secretions of the `` PRECAUTIONS '' Section glaucoma develop,! As urine opened single patient-use container of UPNEEQ in the treatment after xylazine overdose is usually fatal in humans 08807. 57.5 % bound to human plasma proteins each use to make sure you not..., diagnosis or treatment suggested as oxymetazoline hydrochloride uses result, xylazine administration is effectively prevented administration! Contents, should be used with caution in patients taking MAO inhibitors can... Minutes in all species, the blood plasma concentrations range from 0.03 4.6... Or intravenously U.S. oxymetazoline hydrochloride uses and drug administration or effectiveness were observed between subjects years... Only administered once daily to each eye hours, xylazine is often used combination. S ) once daily to each eye for 42 days ( 6 weeks ) been suggested as veterinary.