Closamectin Pour-On (Ivermectin, Closantle)

Click here to Download Data Sheet Summary of Product Characteristics 1 NAME OF THE VETERINARY MEDICINAL PRODUCT Closamectin Pour-On Solution for Cattle. 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Active ingredient(s) Ivermectin 5 mg/mL Closantel (as closantel sodium) 200 mg/mL Excipients Brilliant Blue FCF (E133) 0.1 mg/mL For a full list of excipients see section 6.1. 3 PHARMACEUTICAL FORM Pour-On solution. A clear blue/green solution. 4 CLINICAL PARTICULARS 4.1 Target Species Cattle. Active ingredient(s) Ivermectin 5 mg/mL Closantel (as closantel sodium) 200 mg/mL Excipients Brilliant Blue FCF (E133) 0.1 mg/mL For a full list of excipients see section 6.1. 4.2 Indications for use, specifying the target species For the treatment of mixed trematode (fluke) and nematode or arthropod infestations due to roundworms, lungworms, eyeworms, warbles, mites and lice of cattle. Gastrointestinal roundworms (adults and fourth stage larvae) Ostertagia ostertagi (including inhibited O. ostertagi), Haemonchus placei, Trichostrongylus axei, Trichostrongylus colubriformis, Cooperia spp, Oesophagostomum radiatum, Nematodirus helvetianus (adult), Strongyloides papillosus (adult). Lungworms (adult and fourth stage larvae) Dictyocaulus viviparus Trematodes (adult and late immatures) Fasciola gigantica Fasciola hepatica Treatment of fluke at 12 weeks (mature) >95% efficacy. Treatment of fluke at 7 weeks (late immature) >95% efficacy. Eyeworms (adult) Thelazia spp Cattle grubs (parasitic stages) Hypoderma bovis, Hypoderma lineatum Lice Linognathus vituli, Haematopinus eurysternus, Damalinia bovis Mange Mites Chorioptes bovis, Sarcoptes scabiei var bovis 4.3 Contraindications Do not use in cases of known hypersensitivity to the active substances. Do not apply to areas of skin which have mange, scabs or other lesions or to areas contaminated with mud or manure. Avermectins may not be well tolerated in non-target species (cases of intolerance with fatal outcome are reported in dogs – especially Collies, Old English Sheepdogs and related breeds or crosses, and also in turtles/tortoises). 4.4 Special warnings for each target species Care should be taken to avoid the following practices because they increase the risk of development of resistance and could ultimately result in ineffective therapy. - Too frequent and repeated use of anthelmintics from the same class, over an extended period of time. - Underdosing which may be due to underestimation of bodyweight, misadministration of the product, or lack of calibration of the dosing device. The effect of rain on the pour-on formulation at the time of and after application has not been investigated. For maximum effect animals should be kept indoors or undercover following treatment, when there is rain or an imminent risk of rain. Suspected clinical cases of resistance to anthelmintics should be further investigated using appropriate tests (e.g., Faecal Egg Count Reduction Test). Where the results of the tests strongly suggest resistance to a particular anthelmintic, an anthelmintic belonging to another pharmacological class and having a different mode of action should be used. Resistance to ivermectin has been reported in Cooperia spp in cattle. Therefore the use of this product should be based on local epidemiological information about the susceptibility of the Cooperia spp and recommendations on how to limit further selection for resistance to anthelmintics. 4.5 Special precautions for use (i)Special precautions for use in animals: None (ii)Special precautions to be taken by the person administering the veterinary medicinal product to animals: The veterinary medicinal product may be irritating to human skin and eyes and the user should be careful not to apply it to himself or other persons. Operators should wear nitrile rubber gloves and boots with a waterproof coat when applying the product. Protective clothing should be washed after use. If accidental skin contact occurs, wash the affected area immediately with soap and water. If accidental eye exposure occurs, flush the eyes immediately with water and get medical attention. Do not smoke or eat whilst handling the product. Wash hands after use. Use only in well ventilated areas or outdoors. (iii)Other Precautions Regarding the Environment. Treated cattle should not have direct access to ponds, streams or ditches for 14 days after treatment. 4.6 Adverse reactions (frequency and seriousness) Undesirable effects are not expected when the product is used at the recommended dose rate 4.7 Use during pregnancy, lactation or lay The product is safe for use during pregnancy and lactation. However, the product is not permitted for use in animals producing milk for human consumption, including pregnant animals intended to produce milk for human consumption. 4.8 Interaction with other medicinal products and other forms of interaction None known. 4.9 Amounts to be administered and administration route The veterinary medicinal product should be administered topically at a dosage rate of 500μg ivermectin per kg bodyweight and 20 mg closantel per kg bodyweight (1 mL per 10 kg). The formulation should be applied along the midline of the back in a narrow strip between the withers and the tail head. Assess bodyweight carefully prior to administration. The timing for treatment should be based on epidemiological factors and should be customised for each individual farm. A dosing programme should be established by a veterinary professional. * Dose rate 1 ml per 10 kg bodyweight 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary At doses of three times the recommended dose, no significant clinical signs were recorded. Ivermectin No antidote has been identified. Symptomatic treatment may be beneficial. Closantel like other salicylanilides is a potent uncoupler of oxidative phosphorylation and the safety index is not as high as is the case of many other anthelmintics. However where used as directed there are unlikely to be any untoward effects. Signs of overdosage can include slight loss of appetite, loose faeces, decreased vision and increased frequency of defecation. High doses may cause blindness, hyperventilation, general weakness and inco-ordination, hyperthermia, convulsions, tachycardia and in extreme cases death. Treatment of overdosage is symptomatic as no antidote has been identified. 4.11 Withdrawal Period(s) Cattle must not be treated within 28 days of slaughter for human consumption. Not permitted for use in animals producing milk for human consumption, including pregnant animals intended to produce milk for human consumption. 5 PHARMACOLOGICAL or IMMUNOLOGICAL PROPERTIES ATC Vet Code: QP54AA51 Pharmacotherapeutic Group: Ivermectin, combinations.   Bodyweight Dose Volume 250 ml  500 ml  1 Litre 2.5 Litres 5 Litres 100 kg 10 ml 25 50 100 250 500 150 kg 15 ml 16 33 66 166 333 200 kg 20 ml 12 25 50 125 250 250 kg 25 ml 10 20 40     300 kg 30 ml 8 16 33 83 166 350 kg 35 ml 7 14 28 71 142 400 kg 40 ml 6 12 25 62 125 450 kg 45 ml 5 11 22 55 111 500 kg 50 ml 5 10 20 50 100 550 kg 55 ml 4 9 18 45 90 5.1 Pharmacodynamic properties Ivermectin is an endectocide with activity against a wide range of internal and external parasites. Ivermectin is a macrocylic lactone and acts by inhibiting nerve impulses. It binds selectively and with high affinity to glutamate-gated chloride ion channels which occur in invertebrate nerve and muscle cells. This leads to an increase in the permeability of the cell membrane to chloride ions with hyperpolarization of the nerve or muscle cell, resulting in paralysis and death of the relevant parasites. Compounds of this class may also interact with other ligand-gated chloride channels, such as those gated by the neurotransmitter gammaaminobutyric acid (GABA). The margin of safety for compounds of this class is attributable to the fact that mammals do not have glutamate-gated chloride channels. The macrocylic lactones have a low affinity for other mammalian ligand-gated chloride channels and they do not readily cross the blood-brain barrier. Closantel is a member of the salicylanilide class of anthelmintics. Salicylanilides are hydrogen (proton) ionophores (referred to as oxidative phosphorylase uncouplers.) The chemical structure of salicylanilides illustrate the possession of a detachable proton. This type of molecule is lipophilic and is known to shuttle protons across membranes, in particular the inner mitochondrial membrane. Closantel acts by uncoupling oxidative phosphorylation. Closantel is a parasiticide with flukicide activity and efficacy against certain other helminths and arthropods. 5.2 Pharmacokinetic properties After topical administration of Closamectin Pour-On to cattle at a dose rate of 500 microgram ivermectin per kg and 20 mg closantel per kg the following parameters were observed: Ivermectin – Cmax of 19.13 ng/mL and AUC of 2440 ng.hr/mL; Closantel – Cmax of 68.5 microgram/mL and AUC of 35207 microgram.hr/mL. Ivermectin is only partially metabolised. In cattle, only about 1 to 2% is excreted in the urine the remainder is excreted in the faeces, approximately 60% of which is excreted as unaltered drug. The remainder is excreted as metabolites or degradation products. Salicylanilides are poorly metabolised and are excreted mainly unchanged. About 90% of closantel is excreted unchanged in the faeces and urine in cattle. 6 PHARMACEUTICAL PARTICULARS 6.1 List of excipients Brilliant Blue FCF (E133) Dye Anhydrous Ethanol Macrogol, Cetearyl Ethylhexanoate Isopropyl Myristate Povidone Denatonium Benzoate Trolamine Isopropylalcohol 6.2 Incompatibilities None known. 6.3 Shelf-life Shelf-life of the veterinary medicinal product as packaged for sale: 1 year. 6.4 Special precautions for storage Do not store above 25°C. Store upright in original container. Protect from light. Discard unused material. Avoid introduction of contamination. If stored at temperatures below 0°C, Closamectin Pour-On Solution for Cattle may appear cloudy. Allowing to warm at room temperature will restore the normal appearance without affecting efficacy. Flammable – keep away from heat, sparks, open flame or other sources of ignition. 6.5 Nature and composition of immediate packaging Translucent 250 mL and 1L HDPE containers with white HDPE caps and white 1L, 2.5L and 5L HDPE backpacks with white polypropylene screw caps. Not all packs sizes may be marketed. 6.6 Special precautions for the disposal of unused veterinary medicinal products or waste materials EXTREMELY DANGEROUS TO FISH AND AQUATIC LIFE. Do not contaminate surface waters or ditches with the product or used container. Any unused product or waste material should be disposed of in accordance with national requirements. 7 MARKETING AUTHORISATION HOLDER Norbrook Laboratories Limited Station Works Camlough Road Newry Co Down, BT35 6JP Northern Ireland 8 MARKETING AUTHORISATION NUMBER(S) VPA 10999/124/001 9 DATE OF THE FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 7th August 2009 10 DATE OF REVISION OF THE TEXT 5th May 2010