1 C: formic acid, methanoic acid 2 C’s: acetic acid, ethanoic acid
Tolfedine CS - Vetoquinol · 2016-10-19 · Tolfenamic acid is extensively bound to plasma albumin...
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03/2016 TOLF CS W.P. 12 HOURS IN THE MILK Fast & Continuous Tolfedine ® CS & Fast Continuous • LENGTH OF ACTION • EFFICACY • SPEED OF ACTION Sterile aqueous solution containing 4.0% w/v tolfenamic acid as active ingredient and 1.04% w/v benzyl alcohol as preservative. Pharmacological properties and pharmacokinetic particulars: Tolfenamic acid (N-(2- methyl-3-chlorophenyl) anthranilic acid) is a non-steroidal anti-inflammatory drug (NSAID) belonging to the fenamate group. Tolfenamic acid exerts anti-inflammatory, analgesic and antipyretic activities. The anti-inflammatory activity of tolfenamic acid is mainly due to an inhibition of cyclo-oxygenase and thus to a reduction of the synthesis of prostaglandins and thromboxanes, which are important inflammatory mediators. In cattle a mean maximum plasma concentration of about 1.2mg/mL was obtained at about 1 hour and in pigs a mean maximum plasma concentration of about 2.3mg/mL was obtained at about 1 hour. The volume of distribution is about 1.3L/kg in cattle and pigs. Tolfenamic acid is extensively bound to plasma albumin (>97%). Tolfenamic acid is distributed in all the organs with a higher concentration in the plasma, digestive tract, liver, lungs and kidneys, on the other hand the concentration in the brain is low. Tolfenamic acid and its metabolites cross the placenta poorly. Tolfenamic acid distribution involves extracellular fluids where concentrations similar to plasma are achieved both in healthy and inflamed peripheral tissues. It also appears in milk in the active form, mainly associated with the curds. Tolfenamic acid undergoes extensive enterohepatic recirculation which results in prolonged concentrations being found in plasma. In cattle and pigs, tolfenamic acid is eliminated mainly unchanged in faeces (–30%) and urine (–70%). INDICATIONS For use by or under the direction of a registered veterinarian as an aid in the treatment of pneumonia and acute mastitis in cattle and metritis-mastitis-agalactia in pigs. DIRECTIONS FOR USE Restraints: DO NOT inject cattle other than into muscle tissue high on the side of the neck (see leaflet for diagram). Injection of product into muscles other than as described is likely to result in residues in meat above the MRL or ESI. Precautions: Repeat treatments or higher doses could result in residues above the MRL unless the label withholding period is extended. The prescribing Veterinarian would need to advise on an extended withholding period. Safe use of TOLFEDINE CS Injection during pregnancy has not been established. Dosage and Administration: Use the contents within 3 months of first broaching of the vial. Discard the unused portion. RE-TREATMENT INTERVAL: A single treatment regime consists of either 1 x IV injection (cattle) or 2 x IM injections at 48h (cattle) or 1 x IM injection (pigs). DO NOT repeat treatment less than 21 days after treatment of pigs, or 28 days after last treatment of cattle. CATTLE – Pneumonia: 2mg/kg (1mL per 20kg bw) by intramuscular injection high on the neck. Treatment may be repeated once only after 48 hours. Mastitis: 4mg/kg (1mL per 10kg bw) as a single intravenous injection. PIGS – Metritis-mastitis-agalactia: 2mg/kg (1mL per 20kg bw) as a single intramuscular injection into the rump. WITHHOLDING PERIODS MEAT – Cattle by intramuscular administration: DO NOT USE less than 10 days before slaughter for human consumption. Cattle by intravenous administration: DO NOT USE less than 4 days before slaughter for human consumption. Pigs by intramuscular administration: DO NOT USE less than 6 days before slaughter for human consumption. MILK – Cattle by Intramuscular or Intravenous Administration: Milk collected from cows within 12 hours (1 milking) following treatment MUST NOT BE USED for human consumption or processing, or fed to bobby calves. TRADE ADVICE EXPORT SLAUGHTER INTERVAL (ESI): DO NOT USE less than 21 days (pigs) or 28 days (cattle) before slaughter for export. The ESI on this label was correct at the time of label approval. Before using this product, confirm the current ESI from the registrant on 1800 032 355 or the APVMA website (www.apvma.gov.au/residues/ESI.shtml). FIRST AID: If poisoning occurs, contact a doctor or Poisons Information Centre. Phone Australia 131 126. Store below 30°C (Room temperature) away from direct sunlight. Dispose of empty containers by wrapping with paper and putting in garbage. Presentation: Tolfedine CS is available in vials containing 50 mL, 100 mL or 250 mL. Tolfedine® CS Injection - Tolfenamic acid 40 mg/mL Phone: 1800 032 355 Fax: 1800 648 460 Unit 302.2, 6-12 Boronia Road, Da Vinci Business Park, Brisbane Airport, Qld, 4008 PO Box 112 Pinkenba QLD 4008 | ABN: 6400 6949 480 www.vetoquinol.com www.vetoquinol.com.au Tolfedine ® CS
Transcript of Tolfedine CS - Vetoquinol · 2016-10-19 · Tolfenamic acid is extensively bound to plasma albumin...
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TOLF
CS
W.P. 12 HOURS IN THE MILK
Fast & Continuous
Tolfedine® CS & Fast Continuous • LENGTH OF ACTION
• EFFICACY• SPEED OF ACTION
Sterile aqueous solution containing 4.0% w/v tolfenamic acid as active ingredient and 1.04% w/v benzyl alcohol as preservative. Pharmacological properties and pharmacokinetic particulars: Tolfenamic acid (N-(2-methyl-3-chlorophenyl) anthranilic acid) is a non-steroidal anti-inflammatory drug (NSAID) belonging to the fenamate group. Tolfenamic acid exerts anti-inflammatory, analgesic and antipyretic activities. The anti-inflammatory activity of tolfenamic acid is mainly due to an inhibition of cyclo-oxygenase and thus to a reduction of the synthesis of prostaglandins and thromboxanes, which are important inflammatory mediators. In cattle a mean maximum plasma concentration of about 1.2mg/mL was obtained at about 1 hour and in pigs a mean maximum plasma concentration of about 2.3mg/mL was obtained at about 1 hour. The volume of distribution is about 1.3L/kg in cattle and pigs. Tolfenamic acid is extensively bound to plasma albumin (>97%). Tolfenamic acid is distributed in all the organs with a higher concentration in the plasma, digestive tract, liver, lungs and kidneys, on the other hand the concentration in the brain is low. Tolfenamic acid and its metabolites cross the placenta poorly. Tolfenamic acid distribution involves extracellular fluids where concentrations similar to plasma are achieved both in healthy and inflamed peripheral tissues. It also appears in milk in the active form, mainly associated with the curds. Tolfenamic acid undergoes extensive enterohepatic recirculation which results in prolonged concentrations being found in plasma. In cattle and pigs, tolfenamic acid is eliminated mainly unchanged in faeces (–30%) and urine (–70%).INDICATIONSFor use by or under the direction of a registered veterinarian as an aid in the treatment of pneumonia and acute mastitis in cattle and metritis-mastitis-agalactia in pigs.DIRECTIONS FOR USERestraints: DO NOT inject cattle other than into muscle tissue high on the side of the neck (see leaflet for diagram). Injection of product into muscles other than as described is likely to result in residues in meat above the MRL or ESI.Precautions: Repeat treatments or higher doses could result in residues above the MRL unless the label withholding period is extended. The prescribing Veterinarian would need to advise on an extended withholding period. Safe use of TOLFEDINE CS Injection during pregnancy has not been established.Dosage and Administration: Use the contents within 3 months of first broaching of the vial. Discard the unused portion.
RE-TREATMENT INTERVAL: A single treatment regime consists of either 1 x IV injection (cattle) or 2 x IM injections at 48h (cattle) or 1 x IM injection (pigs). DO NOT repeat treatment less than 21 days after treatment of pigs, or 28 days after last treatment of cattle. CATTLE – Pneumonia: 2mg/kg (1mL per 20kg bw) by intramuscular injection high on the neck. Treatment may be repeated once only after 48 hours.Mastitis: 4mg/kg (1mL per 10kg bw) as a single intravenous injection.
PIGS – Metritis-mastitis-agalactia: 2mg/kg (1mL per 20kg bw) as a single intramuscular injection into the rump.WITHHOLDING PERIODSMEAT – Cattle by intramuscular administration: DO NOT USE less than 10 days before slaughter for human consumption. Cattle by intravenous administration: DO NOT USE lessthan 4 days before slaughter for human consumption. Pigs by intramuscular administration: DO NOT USE less than 6 days before slaughter for human consumption.MILK – Cattle by Intramuscular or Intravenous Administration: Milk collected from cows within 12 hours (1 milking) following treatment MUST NOT BE USED for humanconsumption or processing, or fed to bobby calves.TRADE ADVICEEXPORT SLAUGHTER INTERVAL (ESI): DO NOT USE less than 21 days (pigs) or 28 days (cattle) before slaughter for export. The ESI on this label was correct at the time of label approval. Before using this product, confirm the current ESI from the registrant on 1800 032 355 or the APVMA website (www.apvma.gov.au/residues/ESI.shtml).FIRST AID: If poisoning occurs, contact a doctor or Poisons Information Centre. Phone Australia 131 126.Store below 30°C (Room temperature) away from direct sunlight.Dispose of empty containers by wrapping with paper and putting in garbage.Presentation: Tolfedine CS is available in vials containing 50 mL, 100 mL or 250 mL.
Tolfedine® CS Injection - Tolfenamic acid 40 mg/mL
Phone: 1800 032 355 Fax: 1800 648 460Unit 302.2, 6-12 Boronia Road, Da Vinci Business Park, Brisbane Airport, Qld, 4008 PO Box 112 Pinkenba QLD 4008 | ABN: 6400 6949 480www.vetoquinol.com www.vetoquinol.com.au
Tolfedine® CS
Concentration of PGE2 (ng/ml)
Placebo
Tolfenamic acid 2 mg/kg
Times (hours)
0
0 8 16 24 32 40 48 56 64 72
2
4
6
8
10
12
14
16
Conc
entr
atio
n of
TXB
2 (n
g/m
l)
Conc
entr
atio
n of
PGE
2 (n
g/m
l)
Times (hours) Times (hours)
Carageenan SC+ Tolfedine® for Placebo IV
0 0-3 -3-1 1 2 4 6 69 912 12
20
40
40
30
20
10
60
80
100
120
PlaceboTolfenamic acid
10min
87.8 %
85.2 %
81.5 %
93.8 %
80.8 % 81.5 %
7879
8081
82
83
8485
86
8788
%
7476
7880
82
84
8688
90
9294
%
Response rate at day 3
Tolfedine®
MeloxicamCarprofen
6.7 % 4.8 %
27.3 %
0
30
25
20
15
10
5
%
Relapse rate between day 8 and day 14Response rate at day 7
Response rate at day 3 after treatment onset Response rate at day 7 after treatment onset
80
70
60
50
40
30
20
10
0
%
Tolfedine®
FlunixinKetoprofen80
70
60
50
40
30
20
10
0
%
68.7 % 68 %68 %
58 %62.3 %
57.7 %
Response rate at day 3 after treatment onset Response rate at day 7 after treatment onset
80
70
60
50
40
30
20
10
0
%
Tolfine®
FlunixinKetoprofen80
70
60
50
40
30
20
10
0
%
68.7 % 68 %68 %
58 %27.3 %
57.7 %
Response rate at day 3 after treatment onset Response rate at day 7 after treatment onset
80
70
60
50
40
30
20
10
0
%
Tolfedine®
FlunixinKetoprofen80
70
60
50
40
30
20
10
0
%
68.7 % 68 %68 %
58 %62.3 %
57.7 %
INFLAMMATION NO MORE!
LENGTH OF ACTION: the expert vet treatment
EFFICACY: high inflammation control… for your breeders satisfaction
SPEED OF ACTION: fast action… for urgent matter
Prostaglandins are the basic mediators of the vascular phase.
• After IV injection, Tolfedine® is fastly distributed to the inflammation site.• T1/2α = 0.16h Half of the dose has passed in tissues in 10 minutes.(2)
Clinical trial involving 90 beef cattles presenting BRD symptoms (3)
Response rate = recovery (no clinical signs) + noticeable improvement (no general sign, few local signs)
Tolfedine® a single shot with a long action: in vivo, Tolfedine® 2 mg/kg IM inhibits prostaglandins in exudate for more than 72 hours.(1)
Respiratory diseases
Mastitis
Tolfedine® fast results Tolfedine® sustainable results
Acute clinical mastitis: antimicrobial treatment +
Tolfedine® 1 shotFlunixin 3 daysKetoprofen 3 days
Treated with marbofloxacin +
Carprofen 1.4 mg/kg SCMeloxicam 0.5 mg/kg SCTolfenamic acid 2 mg/kg IM
Tolfedine® decreases the plasma thromboxane concentration in less than 1 hour.
Tolfedine® maintains low PGE2 level in tissues after inflammation stimulus.
One injection of Tolfedine® is as powerful as 3 days of treatment with Flunixin or Ketoprofen.(4)
