Enurace 10mg tablets (pack of 60)

1. NAME OF THE VETERINARY MEDICINAL PRODUCT UK, NL, IT, BE, DE, ES: ENURACE 10, 10 mg tablets for dogs FR: ENURACE petit chien, comprimé

2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains: Active substance: 8.1 mg Ephedrine equivalent to 10 mg Ephedrine Hydrochloride. Excipients: Ponceau 4R (E124) 0.08 mg For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM Tablets. Round, pink tablet with break line on one side and inscription ENURACE 10 on the other side.

4. CLINICAL PARTICULARS

4.1 Target species Ovariohysterectomised female dogs.

4.2 Indications for use, specifying the target species Treatment of urinary incontinence caused by urethral sphincter mechanism incompetence in ovariohysterectomised female dogs.

4.3 Contraindications Do not use in dogs with glaucoma. Do not use in case of hypersensitivity to Ephedrine or to any of the excipients.

4.4 Special warnings for each target species This product is not suitable for treatment of inappropriate urination resulting of behaviour problems.

4.5 Special precautions for use i. Special precautions for use in animals The safety and the efficacy of the product has not been assessed in dogs under 5kg. Do not use the product in dogs under 5 kilogram of bodyweight. Revised: June 2019 AN: 01805/2018 Page 2 of 5 As ephedrine is an alpha and beta adrenergic receptor agonist, the product should be used with caution in dogs with cardiovascular disease and only after a comprehensive risk/benefit analysis by the attending veterinarian. The dog’s cardiovascular functionality should be carefully assessed before the start of the treatment with the product and it should be periodically monitored during the treatment. In addition, a similar approach should be adopted in animals suffering from partial urethral obstruction, hypertension, diabetes mellitus, hyperadrenocorticism, hyperthyroidism or other metabolic disorders. It should be mentioned that the Polyuria/Polydipsia (PU/PD) frequently accompanying the aforementioned conditions may be falsely diagnosed as urinary incontinence. ii. Special precautions to be taken by the person administering the veterinary medicinal product to animals Ephedrine hydrochloride could be toxic if ingested. Adverse effects may include insomnia and nervousness, dizziness, headache, increased blood pressure, increased sweating and nausea. Ingestion may be fatal, especially in children. To avoid accidental ingestion, the product must be used and kept out of the reach of children. Always replace the cap securely after use. In the event of accidental ingestion, most importantly by children, seek immediate medical attention showing the physician the package insert. It is strongly recommended that pregnant women should wear gloves for administration. Wash hands after administration.

4.6 Adverse reactions (frequency and seriousness) Cardiovascular effects like tachycardia, atrial fibrillation, stimulation of the heart activity; and vasoconstriction. Stimulation of the central nervous system leading to sleeplessness, excitation, anxiety and muscle tremors. Panting. Mydriasis. Cystitis. Bronchodilatation and decrease of mucus release in the respiratory mucosal membranes. Reduction of the motility and tone of the intestinal wall. Due to the nature of Ephedrine the mentioned effects can occur at the recommended therapeutic dose, with anxiety and cardiovascular effects being the most prevalent. In 10% of the treatments, side effects have been observed in efficacy studies. Revised: June 2019 AN: 01805/2018 Page 3 of 5

4.7 Use during pregnancy, lactation or lay Not applicable.

4.8 Interaction with other medicinal products and other forms of interaction Ephedrine may interact with other sympathicomimetics. Ephedrine may enhance glucocorticoid metabolism. Concomitant use with MAO-inhibitors may cause hypertension. Ephedrine can enhance the activity of products of the same class as theophylline. Volatile anaesthetics may enhance the sensitivity of the myocardium to the cardiovascular effects of Ephedrine. Concomitant use with cardiac glycosides, quinine and tricyclic antidepressants can cause arrhythmias. Vascular constrictions can occur after concomitant treatment with ergot alkaloids and oxytocin. Substances leading to an increase in pH of the urine are able to prolong the excretion of ephedrine, whereas substances leading to a decrease in pH of the urine are able to accelerate the excretion of ephedrine.

4.9 Amounts to be administered and administration route For oral administration only. A starting dose of 2 mg Ephedrine HCl per kg of bodyweight per day, divided in two oral doses is recommended. Dogs can be dosed according to the following table: Weight Dose (Number of tablets) (kg) Dose (mg/day) per day 1 st gift 2 nd gift 5 10 1 ½ ½ 7,5 15 1 ½ ½ 1 10 20 2 1 1 12,5 25 2 ½ 1 1 ½ 15 30 3 1 ½ 1 ½ 17,5 35 3 ½ 1 ½ 2 For weights superior or equal to 20 kg, use a higher strength of the product. Desired therapeutic effect and occurrence of adverse effects have to be monitored approximately at 14 days, 1 month, 3 months and 6 months after the start. Based on the observed effect in comparison with the expected effect and taking into account the occurrence of adverse effects, the individual dose should be adjusted. The dose should be adjusted to find the lowest effective dose. Once the effective dose has been established, dogs should still be monitored at regular intervals, e.g. every six months. The product should be administered before meals in a piece of food. A maximum dose of 5 mg/ kg of bodyweight per day has to be respected. Revised: June 2019 AN: 01805/2018 Page 4 of 5

4.10 Overdose (symptoms, emergency procedures, antidotes) The signs of overdose resemble those of the adverse reactions as described in section 4.6. In case of overdose, it is useful to accelerate excretion of ephedrine by acidification of the urine and enhanced diuresis.

4.11 Withdrawal period(s) Not applicable.

5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic group: symphaticomimetic ATCvet code: QG04BX90

5.1 Pharmacodynamic properties Ephedrine directly stimulates alpha- and beta-adrenergic receptors, present in all organ systems. It also stimulates the release of catecholamines from sympathic neurons. Since Ephedrine passes the blood-brain barrier, it also induces effects that are mediated through the central nervous system. Ephedrine specifically causes a contraction of the internal urethral sphincter muscles and a relaxation of the bladder muscles through a sympathicomimetic action on the adrenergic receptors.

5.2 Pharmacokinetic particulars Ephedrine is rapidly absorbed and the bioavailability is high. Ephedrine is widely distributed over the body. Degradation by demethylation to Norephedrine is the major metabolic pathway. Within 48 hours, urinary excretion accounts for elimination of 80 to 90 % of the administered dose, at high urinary acidity.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients Ponceau 4R (E124) Colloidal Silica Lactose Monohydrate Maize starch Magnesium Stearate

6.2 Major incompatibilities None known.

6.3 Shelf life Shelf-life of the veterinary medicinal product as packaged for sale: 5 years. Revised: June 2019 AN: 01805/2018 Page 5 of 5

6.4 Special precautions for storage Do not store above 25°C. Store in the original container. Divided tablets should be returned in the original package and used in the subsequent dose. Close the cap to the click.

6.5 Nature and composition of immediate packaging White polypropylene container containing 60 tablets, with child-resistant closure system, in a cardboard carton. The packaging might also contain a polyurethane cover-up.

6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER Ecuphar NV Legeweg 157-i 8020, Oostkamp Belgium

8. MARKETING AUTHORISATION NUMBER Vm 32742/4001

9. DATE OF FIRST AUTHORISATION 30 March 2010

10. DATE OF REVISION OF THE TEXT June 2019 PROHIBITION OF SALE, SUPPLY AND/OR USE To be supplied only on veterinary prescription. Approved 28 June 2019