BROMOTRIMIDINE POWDER

Transcription

1 PRODUCT NUMBER: DATE: 20 DRAFT ZIP-SEAL BASE LABEL (Page 1 of 1) th March 2012 (Image) PRESCRIPTION ANIMAL REMEDY KEEP OUT OF REACH OF CHILDREN FOR ANIMAL TREATMENT ONLY BROMOTRIMIDINE POWDER ACTIVE CONSTITUENTS: SULFADIMIDINE 430 mg/g TRIMETHOPRIM 86 mg/g BROMHEXINE HYDROCHLORIDE 8.6 mg/g For the treatment of respiratory infections in horses, due to organisms susceptible to the combination of sulfadimidine and trimethoprim. 250g NET [500g NET] [1.5kg NET] READ THE ATTACHED LEAFLET BEFORE USING THIS PRODUCT. BROMOTRIMIDINE POWDER READ THE ATTACHED LEAFLET BEFORE USING THIS PRODUCT. DIRECTIONS FOR USE: For oral use only. Administer on dampened food or mixed with honey or molasses. One level large scoop contains Sulfadimidine 5g, Trimethoprim 1g and Bromhexine Hydrochloride 100mg. Horses: One level large scoop per 200kg bodyweight twice daily. MEAT WITHHOLDING PERIOD (HORSES): DO NOT USE less than 28 days before slaughter for human consumption. FIRST AID: If poisoning occurs, contact a doctor or Poisons Information Centre. Phone Australia ; New Zealand DISPOSAL [To be stated on 250[500]g Pack Size Only]: Dispose of empty container by wrapping with paper and putting in garbage. DISPOSAL [To be stated on 1.5kg Pack Size Only]: Triple or (preferably) pressure rinse with water and dispose of rinsate in a disposal pit specifically marked and set up for this purpose clear of waterways, vegetation and roots. Do not dispose of undiluted chemicals on-site. Return clean container for recycling where this is an option or for disposal at a landfill authorised to accept that waste. If neither of these options are available, break, crush or puncture and bury the container below 500 mm in a disposal pit specifically marked and set up for this purpose clear of waterways, vegetation and roots. Empty containers and product should not be burned. STORAGE: Store below 30 C (Room Temperature). Protect from light. APVMA Approval Number: 37740/55238 Marketed by: IAH Sales Pty Ltd. A.B.N Healey Circuit, Huntingwood, NSW 2148 Australia. Telephone (61) (2) Fax (61) (2) Website: info@iahp.com.au The Australia/World Symbol is a registered trademark of International Animal Health Products P/L. Bromotrimidine is a trademark of International Animal Health Products P/L. Copyright All Rights Reserved. CONDITION OF SALE: This product is sold on the express condition that it must be used strictly in accordance with the manufacturer s instruction for use. No warranty whether expressed or implied, is given for any and all damages, which may arise for goods not used in accordance with the manufacturer s instructions. [B] Exp. BROMOTRIMIDINE POWDER (Draft Text Zip-Seal Base Label Clean) (37740_55238_250[500]g,[1.5kg]_IMMEDIATE_TXL_V03.pdf)

2 DRAFT ZIP-SEAL ATTACHED LEAFLET (Page 1 of 4) PRESCRIPTION ANIMAL REMEDY KEEP OUT OF REACH OF CHILDREN FOR ANIMAL TREATMENT ONLY BROMOTRIMIDINE POWDER ACTIVE CONSTITUENTS: SULFADIMIDINE 430 mg/g TRIMETHOPRIM 86 mg/g BROMHEXINE HYDROCHLORIDE 8.6 mg/g For the treatment of respiratory infections in horses due to organisms susceptible to the combination of sulfadimidine and trimethoprim. 250g NET [500g NET] [1.5kg NET] PHARMACOLOGY Sulfadimidine is a pyrimidine sulfonamide antimicrobial agent. Sulfonamides, being structural analogues of para-aminobenzoic acid (PABA), competitively inhibit the incorporation of PABA into dihydropteric acid, the precursor of folic acid. Subsequent reduction in the level of folic acid reduces the production of nucleic acids in sensitive bacteria. Mammalian cells require preformed folic acid and thus are unaffected by sulfonamides. The antibacterial actions of sulfonamides are reduced in the presence of blood, pus and tissue breakdown products, which contain purines and thymidine, as the bacterial requirement for folic acid is decreased in such media. Sulfadimidine is readily absorbed following oral administration and therapeutic plasma levels are rapidly attained. Sulfadimidine is widely distributed to all body tissues and fluids. Concentrations are above plasma levels in kidney; similar to plasma levels in pleural, peritoneal, synovial and ocular fluids; slightly lower in CSF, muscle and milk. Sulfadimidine undergoes extensive metabolism via acetylation, hydroxylation, oxidation and conjugation. The parent compound and its metabolites are excreted predominantly in the urine by glomerular filtration. Sulfadimidine undergoes passive tubular resorption thus prolonging the time course of drug action. Plasma half-life in the horse has been variously estimated at between 6.4 and 9.8 hours. Trimethoprim is a diaminopyrimidine antimicrobial agent. It acts by preventing the reduction of dihydrofolate to tetrahydrofolate which is required by bacteria for biosynthesis of purines, pyrimidines and some amino acids. Trimethoprim is readily absorbed from the gastrointestinal tract and, like sulfadimidine, rapidly reaches therapeutic levels in plasma. It is widely distributed in body tissues/fluids including bone, prostate, CSF, pleural, peritoneal, synovial and ocular fluids. Studies in humans and several animal species have demonstrated that trimethoprim reaches higher concentrations in all tissues, except brain, than those achieved in plasma. The drug is extensively metabolised in the horse and is excreted in the urine by glomerular filtration and active tubular secretion. Plasma half-life in the horse has been variously estimated at between 4.1 hours and 4.6 hours. Sulfadimidine and trimethoprim have similar antibacterial spectra, trimethoprim being approximately 20 times more potent than sulfadimidine. The combination blocks two sequential obligate enzymatic reactions in the microbial folate synthetic pathway. A synergistic action is demonstrated by the enhanced antimicrobial activity (potentiation) of the combination compared with the antimicrobial activity of either agent singly. The minimum inhibitory concentrations (MICs) of the combination for susceptible bacteria are substantially lower than those of either of the individual agents. The combination of sulfonamide/trimethoprim is bactericidal while either drug alone is bacteriostatic.

3 DRAFT ZIP-SEAL ATTACHED LEAFLET (Page 2 of 4) Folate-synthesising bacteria which are resistant or moderately resistant to either drug alone are frequently susceptible to the combination. The correlation of antibacterial sensitivity in vitro cf. in vivo is among the highest of all antimicrobial agents. The spectrum of bacteria sensitive to the combination includes: Staphylococci, Streptococci, Fusobacterium, Enterobacter, Corynebacterium (excluding Corynebacterium [Rhodococcus] equi), Salmonella, Shigella, Klebsiella, Pasteurella, Haemophilus, Proteus spp. and most E. coli; some Brucella and Nocardia spp. Most Pseudomonas spp. are insensitive. Resistance to the combination by gram-negative bacteria is associated with the presence of R Factors. Resistance by Staphylococcus aureus and Haemophilus spp. is chromosomal, and is rarely encountered except in patients previously exposed to the combination. Bromhexine Hydrochloride is a synthetic derivative of the alkaloid, vasicine. Bromhexine acts selectively on mucopolysaccharide-producing goblet cells in the respiratory tract to a far greater extent than in other organs. Its action is threefold: (i) (ii) (iii) Bromhexine causes de-polymerization of mucopolysaccharide, reducing viscosity and tenacity of respiratory mucus. This facilitates expectoration and suppresses tussive irritation. Increased production of highly viscous bronchial and alveolar secretion is not only a clinical sign of, but also an exacerbating factor in, respiratory disease. Disordered ciliary function and difficult expectoration set up a vicious cycle in which mucus tenacity may lead to chronic bronchitis. Bromhexine is a specific agent to prevent this complication. It has minimal secretolytic effect where mucus viscosity is initially low. Bromhexine increases the permeability of the alveolar/capillary barrier. This increases the concentration of antibacterial agents in respiratory secretions, obtaining a greater luminal dose effect at the site of the disease. There are specific protein changes in bronchial secretion following bromhexine administration. After 2-3 days there is a significant increase in gamma globulin and a decline in albumin and alpha globulin. The gamma globulins which increase are IgA and IgG. IgM is unchanged. Bromhexine is rapidly absorbed following oral administration, peak plasma levels being reached within approximately one hour. It is lipophilic and is rapidly redistributed from plasma into respiratory, liver and adipose tissue. Bromhexine undergoes extensive hepatic metabolism and is excreted via the urine and bile. Antimicrobial Action A study in association with the University of Sydney, has established MICs of the 5:1 combination of sulfadimidine and trimethoprim for the major bacterial respiratory pathogens (primary and secondary) considered of clinical significance in the horse under Australian conditions. Microorganisms used in MIC determination were isolated from clinical cases of respiratory disease, and are therefore of particular relevance to equine practice in Australia. A microorganism is considered susceptible if the mean drug concentration is twice the MIC for that microorganism. The following bacteria were demonstrated sensitive to the combination at the recommended dose rate: Actinobacillus equuli Actinobacillus suis-like Escherichia coli Pasteurella caballi Proteus vulgaris Staphylococcus aureus Staphylococcus intermedius Streptococcus equi subspecies equi Streptococcus equi ss zooepidemicus The degree of potentiation attained by combining the two antimicrobial agents was demonstrated in that study which revealed in all susceptible pathogens substantially lower MICs for the combination than for either agent alone. Antimicrobial activity of the combination was found to be up to 1024 times that of sulfadimidine alone, and up to 128 times that of trimethoprim alone.

4 DRAFT ZIP-SEAL ATTACHED LEAFLET (Page 3 of 4) Bioavailability Pharmacokinetic trials in horses have established that both sulfadimidine and trimethoprim are readily and rapidly absorbed after oral administration and reach therapeutic plasma levels within approximately 30 minutes of administration. Trial results demonstrate that the formulation is efficiently absorbed even when administered with food. Dosage Frequency MICs of the sulfadimidine-trimethoprim combination vary widely for the range of respiratory pathogens which are of significance in equine respiratory disease. In order to ensure efficacy against the major equine respiratory pathogens, the dose rate of Bromotrimidine Powder has been calculated to produce drug levels which would be therapeutic against those pathogens for which the MIC is greatest. Once-daily dosing of Bromotrimidine Powder at recommended dose rates will produce average steady state levels of sulfadimidine/trimethoprim which are effective against many of the major bacterial respiratory pathogens of clinical significance in horses in Australia. Trial results explain the long-standing success of once-daily dosing of Bromotrimidine and Trimidine powders in treating clinical cases of respiratory infection. Twice-daily dosing of Bromotrimidine Powder is recommended in preference to once-daily dosing as the minimum (trough) concentrations of sulfadimidine and trimethoprim are potentially subtherapeutic in some individuals for some sensitive pathogens under a once-daily dose regimen. CLINICAL APPLICATION Bromotrimidine Powder provides the field-proven broad-spectrum antibacterial/mucolytic combination in a palatable, easily dispersible formulation. The powder is conveniently administered on dampened food or mixed with honey or molasses. Bromotrimidine Powder is indicated for the treatment of respiratory infections caused by organisms susceptible to the combination of sulfadimidine and trimethoprim, or where such organisms are implicated as secondary pathogens, eg. pneumonia in foals, strangles, equine viral respiratory disease. Bromhexine is an effective mucolytic, reducing clinical signs and complications of respiratory disease. The use of Bromotrimidine Powder avoids the adverse side effects (such as sweating, excitation, tachycardia) which may result from the administration of β-adrenergic bronchodilators. Bacterial culture and sensitivity testing should be carried out in cases of non-responsive or chronic infection. INDICATIONS For the treatment of respiratory infections in horses due to organisms susceptible to the combination of sulfadimidine and trimethoprim. DIRECTIONS FOR USE For oral use only. Administer on dampened food or mixed with honey or molasses. One level large scoop contains sulfadimidine 5g, trimethoprim 1g and bromhexine hydrochloride 100mg. Horses: One level large scoop per 200kg bodyweight twice daily. MEAT WITHHOLDING PERIOD (HORSES): DO NOT USE LESS than 28 days before slaughter for human consumption. FIRST AID: If poisoning occurs, contact a doctor or Poisons Information Centre. Phone Australia , New Zealand

5 DRAFT ZIP-SEAL ATTACHED LEAFLET (Page 4 of 4) DISPOSAL [To be stated on 250[500]g Pack Size Only] Dispose of empty container by wrapping with paper and putting in garbage. DISPOSAL [To be stated on 1.5kg Pack Size Only] Triple or (preferably) pressure rinse with water and dispose of rinsate in a disposal pit specifically marked and set up for this purpose clear of waterways, vegetation and roots. Do not dispose of undiluted chemicals on-site. Return clean container for recycling where this is an option or for disposal at a landfill authorised to accept that waste. If neither of these options are available, break, crush or puncture and bury the container below 500 mm in a disposal pit specifically marked and set up for this purpose clear of waterways, vegetation and roots. Empty containers and product should not be burned. STORAGE Store below 30 C (Room Temperature). Protect from Light. APVMA Approval Number 37740/55238 Marketed by: IAH Sales Pty Ltd. A.B.N Healey Circuit, Huntingwood, NSW 2148 Australia. Telephone (61) (2) Fax (61) (2) Website: info@iahp.com.au The Australia/World Symbol is a registered trademark of International Animal Health Products P/L. Bromotrimidine is a trademark of International Animal Health Products P/L. Copyright All Rights Reserved. CONDITION OF SALE: This product is sold on the express condition that it must be used strictly in accordance with the manufacturer s instruction for use. No warranty whether expressed or implied, is given for any and all damages, which may arise for goods not used in accordance with the manufacturer s instructions.