Microsoft word - day 210_spc_karidox

SUMMARY OF PRODUCT CHARACTERISTICS
NAME OF THE VETERINARY MEDICINAL PRODUCT
KARIDOX 100 mg/ml oral solution for use in drinking water for chickens and pigs QUALITATIVE AND QUANTITATIVE COMPOSITION
Doxycycline (as doxycycline hyclate) . 100 mg Excipients to . 1 ml For a full list of excipients, see section 6.1 PHARMACEUTICAL FORM
Oral solution for use in drinking water.
4. CLINICAL PARTICULARS

4.1. Target species

Indications for use, specifying the target species
CHICKENS (BROILERS) Prevention and treatment of chronic respiratory disease (CRD) and mycoplasmosis caused by microorganisms sensitive to doxycycline. PIGS Prevention of clinical respiratory disease due to Pasteurella multocida and Mycoplasma hyopneumoniae sensitive to doxycycline. The presence of the disease in the herd should be established before treatment.
4.3. Contraindications

Do not use in case of hypersensitivity to tetracyclines. Do not use in animals with hepatic dysfunction. Do not use in young/growing animals.
4.4. Special
warnings
for each target species
Special precautions for use
Special precautions for use in animals Avoid administration in oxidised drinking equipment. Resistance against doxycycline may vary; therefore use of the product should be based on culture and sensitivity of micro-organisms from diseased cases on the farm or from recent experience on the farm. Inappropriate use of the product may increase the prevalence of bacteria resistant to doxycycline and may decrease the effectiveness of treatment with tetracyclines, due to the potential for cross-resistance. Special precautions to be taken by the person administering the veterinary medicinal product to animals Do not handle the product if you are hypersensitive to tetracyclines. Wear gloves, work overall and approved safety glasses. This product is acid and likely to be irritant. Avoid contact with skin and eyes. In case of contact with skin, rinse immediately with plenty of water. In case of contact with eyes, rinse immediately with copious amounts of water and seek medical advice. Do not smoke, eat or drink while handling this product. Administer the product with caution. The product can be harmful by skin contact and inhalation and may cause eye irritation. In case of accidental ingestion seek medical advise and show the label to the doctor. If any symptom should appear, such as a cutaneous eruption, seek prompt medical advice. Swelling of the face, lips or eyes or respiratory difficulties are the most serious signs which require urgent medical attention. Adverse reactions (frequency and seriousness)
Allergic and photosensitivity reactions can occur. Intestinal flora may be affected if treatment is very prolonged, and this may result in digestive disturbance. Use during pregnancy, lactation or lay
Do not administer to laying birds four weeks before the start of lay and during lay The product should not be used during pregnancy or lactation Interaction with other medicinal products and other forms of
interaction
Doxycycline absorption may be reduced by the presence of high quantities of calcium, iron, magnesium or aluminium in the diet. Do not administer together with antacids, kaolin and iron preparations. Do not administer together with bactericidal antibiotics. The solubility of the product is pH dependent and will precipitate if mixed in alkaline solution Do not administer with milk replacers Amounts to be administered and administration route
ORAL ROUTE, IN DRINKING WATER - CHICKEN (broilers): 10 - 20 mg of doxycycline / kg bw / day for 3-5 days (i.e. 0.5-1.0 ml of product / litre of drinking water / day). - PIGS: 10 mg of doxycycline / kg b.w. / day for 5 days (i.e. 1 ml of To ensure a correct dosage bodyweight should be determined as accurately as possible to avoid underdosing. The uptake of medicated water depends on the clinical condition of the animals. In order to obtain the correct dosage the concentration of doxycycline has to be adjusted accordingly. Use appropriate and properly calibrated dosing equipment. Medicated water should be the only drinking source. The medicated water is only usable for 24 hours and should be made freshly every day. The remaining medicated water should be disposed of in accordance with local requirements. If no improvement in clinical signs is seen within the treatment duration, the diagnosis should be reviewed and treatment changed.
4.10. Overdose (symptoms, emergency procedures, antidotes)


4.11. Withdrawal period

Pigs: 7 days. Eggs: Not permitted for use in laying birds producing eggs for human consumption
5. PHARMACOLOGICAL PROPERTIES
5.1. Pharmacodynamic
properties
Doxycycline is a bacteriostatic agent that acts by interfering with the bacterial protein syntesis of sensitive species. Doxycycline is a semi-synthetic tetracycline derived from oxytetracicline. It acts on the subunit 30S of the bacterial ribosome, to which is linked reversibly, blocking the union between aminoacyl-tRNA (transfer RNA) to the mRNA-ribosome complex, preventing the addition of new aminoacids into the growing peptide chain and thus interfering with protein synthesis. Doxycycline is active against Gram-positive and Gram-negative bacteria. Spectrum of activity: In vitro sensitivity of doxycycline against Pasteurella multocida and Bordetella bronchiseptica strains isolated from pigs has been determined by means of a plate diffusion method, and against Mycoplasma hyopneumoniae by a dilution method, with MIC90 values of 0.517 µg/ml, 0.053 µg/ml and 0.200 µg/ml, respectively. According to the NCCLS standard, strains sensitive to doxycycline have MIC values below or equal to 4 µg/ml and those resistant have MIC values above or equal to 16 µg/ml. There are at least two mechanisms of resistance to tetracyclines. The most important mechanism is due to decreased cellular accumulation of the drug. This is due to the establishment of either a pump elimination path or an alteration in the transport system that limits the uptake of tetracycline. The alteration in the transport system is produced by inducible proteins codified in plasmids and transposons. The other mechanism is evidenced by decreased ribosome affinitiy for the Tetracycline-Mg2+ complex owing to chromosomal mutations. Resistance to tetracyclines may not only be the result of therapy with tetracyclines, but may also be caused by therapy with other antibiotics leading to selection of multi-resistant strains including tetracyclines. Although minimal inhibitory concentrations (MIC) tend to be lower for doxycycline than for older generation tetracyclines, pathogens resistant to one tetracycline are generally also resistant to doxycycline (cross resistance). Both long term treatment and treating for an insufficient length of time and/or sub-therapeutic dosages can select for antimicrobial resistance and should be avoided. 5.2. Pharmacokinetic
particulars
Doxycycline is bioavailable after oral administration. When orally administered, it reaches values greater than 70% in most species. Feeding can modify the oral bioavailability of doxycycline. In fasting conditions bioavailability is around 10-15% when the animal is fed. Doxycycline is well distributed through the body as it is highly lipid soluble. It accumulated in liver, kidney, bones and intestine; enterohepatic recycling occurs. In lungs, it always reaches higher concentrations than in plasma. Therapeutic concentrations have been detected in aqueous humour, myocardium, reproductive tissues, brain and mammary gland. Plasma protein binding is 90-92%. 40% of the drug is metabolized and largely excreted through faeces (biliary and intestinal route), mainly as microbiologically inactive conjugates. CHICKENS (broilers) After oral administration, doxycycline is rapidly absorbed reaching maximum concentrations (Cmax) around 1.5 h. Bioavailability was about 75%. The presence of food in the gastrointestinal tract reduces its absorption, reaching a bioavailability around 60% and extending considerably the time at which it reaches the maximum peak concentration, (tmax) 3.3 h. PIGS After an oral dose of 10 mg/kg/day, the concentration at steady state (Css) was around 1.30 µg/mL and plasma elimination half-life (t1/2) was 7.01 h. 6. PHARMACEUTICAL PARTICULARS

6.1. List of excipients


6.2. Incompatibilities
Do not mix with other veterinary medicinal products. 6.3. Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 15 months Shelf life after dilution according to directions: 24 hours Shelf-life after first opening the immediate packaging: 1 month
6.4. Special precautions for storage


6.5. Nature and composition of immediate packaging

The product is packaged in white high-density polyethylene containers of 1 L and 5 L. Containers are closed with a screw cap of the same material with induction sealing. 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. MARKETING AUTHORISATION HOLDER
LABORATORIOS KARIZOO, S.A. Polígono Industrial La Borda Mas Pujades, 11-12 08140 – CALDES DE MONTBUI (Barcelona) Spain MARKETING AUTHORISATION NUMBER
DATE OF FIRST AUTHORISATION / RENEWAL OF THE
AUTHORISATION
DATE OF REVISION OF THE TEXT

Source: http://www.karizoo.com/arxius/productes/eb2783e7f3b2b4325b44b88382c0ab27.pdf