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Contra-indications
Do not use by the intravenous or intramuscular route.
Do not use in cattle producing milk for human consumption.
Not for use in species other than cattle and swine as severe adverse reactions including fatalities in dogs may occur.
Special warnings for each target species
None
Special precautions for use
As this product does not contain any antimicrobial preservative, swab septum before removing each dose.
Use sterile needle and syringe.
When using the 200 ml, 500 ml and 1000 ml pack sizes, use only automatic-syringe equipment.
Adverse reactions
At therapeutic doses, ivermectin has no adverse effect on cattle or swine since it does not readily penetrate their central nervous systems.
Transitory discomfort has been observed in some cattle and pigs following subcutaneous administration.
A low incidence of soft tissue swelling at the injection site has been observed in both species. These reactions have disappeared without treatment.
Use during pregnancy, lactation or lay
Studies have shown a wide safety margin and, at the recommended dosage, no adverse effect on breeding performance were observed.
Do not use in non-lactating dairy cows including pregnant heifers within 60 days of calving.
Interactions
None known
Pharmacological particulars
Pharmacodynamic properties
Ivermectin is a highly-active, broad-spectrum, internal and external antiparasitic of the avermectin family.
Ivermectins are isolated after fermentation of the soil organism Streptomyces avermitilis.
Ivermectin acts by inhibiting nerve impulses.
Its mode of action includes γ-aminobutyric acid or GABA, neurotransmitter inhibitor at the level of presynaptic nerve terminations or at the level of neuromuscular junctions.
Ivermectin stimulates GABA liberation at presynaptic nerve terminations (in nematodes) or the neuromuscular junctions (in arthropodes, acarids, flies and fleas), which leads to the paralysis and death of the relevant parasites.
Acetylcholine, the main peripheric neurotransmitter, is not affected by ivermectin. Furthermore, ivermectin does not enter the central nervous system in the mammals, where GABA acts as neurotransmitter.
Pharmacokinetic properties
The biological half-life afforded by an injectable formulation is significantly longer than the intrinsic half-life of the drug (intravenous bolus). Slower absorption associated with the parenteral route (subcutaneous injection), compared to the oral administration, has been attributed to precipitation of the drug at the injection site.
The low solubility of ivermectin in water, its formulation in non-aqueous preparation and its deposition in the subcutaneous tissue favour a slow absorption from the site of injection, which may account for its prolonged residence in the bloodstream.
In cattle
Following a subcutaneous administration of the recommended dosage (1 ml for 50 kg bodyweight), the elimination half-life is obtained after 15 hours with a plasma peak achieved after 50 hours. The concentrations progressively decrease with an elimination half-life of 128 hours. Studies have shown that the liver is the target tissue with the highest residue levels recovered. All other tissues showed lower residues: fat> kidney>muscle. The injection site had residues shortly after treatment but by day 28 the average residues were negligible. After administration of tritium-labelled ivermectin, faeces collected during the first 7 days after dosing contained almost all the dosed radioactivity. Only about 1 %-2 % of the dosed radioactivity was excreted in the urine. About 40 %-50 % of the excreted radioactivity was present as unaltered drug.
In swine
Following a subcutaneous administration of the recommended dosage (1 ml per 33 kg bodyweight), the ivermectin plasma peak is observed after 1.5 days with 13.71 ng/ml. The concentration then remains stable for 4 days (concentrations over Cmax /2) before decreasing with an elimination half-life of 1 day. Studies have shown that liver is the target tissue. Following an injection of 0.4 mg/kg, no liver residues (< 2ppb) were found at 28 days post dose. After administration of tritium-labelled ivermectin, faeces collected during the first 7 days after dosing contained only about 36 % of the dosed radioactivity. Less than 1 % of the dosed radioactivity was found in the urine. About 40 % of the excreted radioactivity was unaltered drug.
Pharmaceutical particulars
Major incompatibilities
None known
Shelf life
3 years.
In use shelf life: 3 months.
Special precautions for storage
Do not store above 30°C.
Following withdrawal of the first dose, use the product within 3 months.
Dispose of unused material.
Avoid introduction of contamination.
Protect from light.
Immediate packaging
Sizes: 50 ml, 200 ml, 500 ml and 1000 ml colourless multidose LDPE vials with plastic overcap covering rubber stopper and aluminium overseal.
Not all pack sizes may be marketed.
Disposal
Any unused product or waste material should be disposed of in accordance with national requirements.
EXTREMELY DANGEROUS TO FISH AND AQUATIC LIFE. Do not contaminate ponds, waterways or ditches with the product or used container.
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