Brand: COMBIZOLE Oral Suspension
Company: OSMONDS
DELIVERY FORM: «drench» for oral administration.
- Fenbendazole 25.0 g/L (equivalent to 2.5%)
- Levamisole hydrochloride 37.5 mg/mL (equivalent to 3.75%)
CHEMICAL CLASS of the active ingredient(s):
- Fenbendazole: benzimidazole
- Levamisol: imidazothiazole
INDICATIONS: SHEEP
PARASITES CONTROLLED (spectrum of activity)
- Gastrointestinal roundworms: Bunostomum, Chabertia, Cooperia, Haemonchus, Nematodirus, Oesophagostomum, Ostertagia, Trichostrongylus
Lungworms: Dictyocaulus
Tapeworm: Moniezia spp
RECOMMENDED DOSE*
- 1ml product per 5 kg bw, equivalent to 5 mg/kg fenbendazole and 7.5 mg/kg levamisole hydrocloride
Read the product label for specific details on dosage.
* Country-specific differences may apply: read the product label.
SAFETY
- LD50 (acute oral) in rats:
- Fenbendazole: >10000 mg/kg (for the a.i.)
- Levamisole: 180 mg/kg (for the a.i.)
- Fenbendazole: >10000 mg/kg (for the a.i.)
Suspected poisoning? Read the articles on fenbendazole safety and levamisole safety in this site.
Withholding periods (=withdrawal times) for meat & milk (country-specific differences may apply: read the product label)
- Meat: Ireland 21 days
- Milk for human consumption: Ireland Not permitted for use in sheep producing milk for human consumption.
You may be interested in the following articles in this site dealing with the general safety of veterinary products:
- Safety for humans
- Safety for domestic animals
- Safety for the environment
- Hazard classifications of pesticides
RESISTANCE PREVENTION
Risk of resistance? YES
Unfortunately, resistance of several gastrointestinal roundworms to fenbendazole (and other benzimidazoles) and levamisole is already very high and very frequent worldwide in sheep and goats. Double (i.e. simultaneous) resistance to both chemical classes is also possible. The most affected worm species are:
- Sheep & goats: Haemonchus spp, Ostertagia spp /Teladorsagia spp, Trichostrongylus spp, Nematodirus spp, Chabertia ovina.
This means that if this product does not achieve the expected efficacy against the mentioned parasites, it can be due to resistance and not to incorrect use, which is usually the most frequent cause of product failure.
It is generally accepted that the use of mixtures of active ingredients with different modes of action can delay the appearance of resistance. But only if the concerned parasites are susceptible to all the actives in the mixture. If not, the mixture is likely to promote multi-resistant parasites, because the selection pressure against all actives remains in place. Mixtures such as this one may provide peace-of mind to those users that do not know the resistance status of worms in their property: probably one of the actives will work... This may be the case for a while. But the risk that some worm species become resistant to all components after a few years using the same or comparable mixtures is considerable. If it is not too late, a better alternative is to determine the resistance status in the property and to rotate among products (not mixtures) against which the worms have not yet developed resistance, stopping the use of those chemical classes that have already shown resistance problems.
Alternative chemical classes/active ingredients to prevent resistance of gastrointestinal roundworms through product rotation:
- Derquantel: available so far only in combination with abamectin in some countries.
- Macrocyclic lactones (e.g. abamectin, doramectin, eprinomectin, ivermectin, moxidectin, etc.). Resistance to macrocyclic lactones is also increasing and strengthening quickly in many countries.
- Monepantel: available only for sheep & goats in some countries (e.g. Australia, UK & EU, New Zealand). First cases of resistance reported in New Zealand in 2013.
- Nitroxinil: effective only against certain gastrointestinal roundworms (e.g. Bunostomum spp, Haemonchus spp, Oesophagostomum spp). Not available in some countries.
- Salicylanilides (e.g. closantel): effective only against certain gastrointestinal roundworms. Not available in some countries. Resistance to closantel has been reported in some countries.
- Tetrahydropyrimidines (e.g. morantel, pyrantel): effective only against certain gastrointestinal roundworms. Not available in some countries. Resistance to morantel has been reported in some countries.
These alternative products may not be available in all countries, or may not be available as drenches, or may not be effective against all the concerned parasites.
It is highly recommended to periodically check the resistance status of each property performing appropriate tests (e.g. fecal egg counts) under supervision of a veterinary doctor. Such tests are now routinely available for most producers in developed countries.
Learn more about resistance and how it develops.
MARKETING
Are the active ingredients of this product ORIGINAL* or GENERICS**?
- Fenbendazole: GENERIC (introduced in the 1970s)
- Levamisole: GENERIC (introduced in the 1960s)
*Meaning that they are still patent protected and generics are not yet available
**Meaning that they have lost patent protection and may be acquired from manufacturers of generic active ingredients other than the holder of the original patent.
COUNTRIES where this brand/product is marketed: Ireland
GENERIC BRANDS available? YES. This product tself is a combination o generic active ingredients.
Click here to learn more about GENERIC vs. ORIGINAL drugs.
For an overview on the most used drench brands for livestock click here.
COMMENTS
COMBIZOLE Oral Suspension is a drench brand from OSMONDS combining 2 generic active ingredients with different modes of action against gastrointestinal worms of sheep: fenbendazole and levamisole hydrochloride.
Fenbendazole is a veteran anthelmintic introduced in the 1970s (by HOECHST). It shows broad-spectrum efficacy against roundworms (gastrointestinal and pulmonary) & tapeworms, but is ineffective against flukes. Fenbendazole also kills eggs of roundworms (ovicidal activity). As all benzimidazoles, fenbendazole has no efficacy whatsoever against external parasites (ticks, flies, lice, mites, etc). Among the benzimidazoles fenbendazole is quite comparable with oxfendazole in terms of efficacy and safety. Fenbendazole is massively used in livestock and horses worldwide, much less in pets. It is not used in agriculture.
Levamisole is another veteran anthelmintic introduced by JANSSEN already in the 1960s (NILVERM, RIPERCOL). It shows broad-spectrum efficacy against roundworms (gastrointestinal and pulmonary) but no efficacy whatsoever against tapeworms and flukes. It is also completely ineffective against external parasites of livestock (ticks, flies, lice, mites, etc). Levamisole has been used massively worldwide in countless generic formulations. It still remains one of the most preferred low-cost anthelmintics for livestock worldwide. It is less used in pets. It is not used in agriculture.
Fenbendazole and levamisole administered as a drench have no residual effect, i.e. they kill the parasites shortly after administration, but do not significantly protect the animals against re-infestation by infective stages in their environment.
In ruminants, reducing the amount of feed slows down the exit flow of the rumen and prolongs the time during which the active ingredient remains there and is absorbed. Consequently it is advisable to reduce the access of animals to feed (especially to fresh pasture, not to water) 24 hours before administration. For the same reason, it is better to keep the animals away from food for about 6 hours after drenching. However sick or weak animals should not be kept away from food and fasting animals should have access to water.
Fenbendazole active ingredient is a solid compound poorly soluble in water and in drenches it is formulated as a suspension (not as a solution or as an emulsion). A key unfavorable feature of all suspensions is that the suspended solid particles tend to fall down to the bottom of the container and sediment, very much like sand in water. This means that suspensions must be thoroughly shaken before use. How fast the suspension sediments and how easily shaking the container redistributes the suspension depends on the formulation quality. A good formulation sediments slowly and shaking will re-suspend it quickly. Bad formulations sediment quickly and shaking re-suspends them slowly.
Thoroughly shaking suspensions before use is crucial for efficacy. If the active ingredient remains in the sediment, a few animals may get most of the active ingredient and will be overdosed, and the large majority will get almost only solvents and will be underdosed.
Click here for general information on good practices for the prevention and control of gastrointestinal worms in livestock.
DISCLAIMER
This article IS NOT A PRODUCT LABEL. It offers complementary information that may be useful to veterinary professionals and users that are not familiar with veterinary antiparasitics.
Information offered in this article has been extracted from publications issued by manufacturers, government agencies (e.g. EMEA, FDA, USDA, etc.) or in the scientific literature. No guarantee is given on its accuracy, integrity, sufficiency, actuality and opportunity, and any liability is denied. Read the site's DISCLAIMER.
In case of doubt contact the manufacturer or a veterinary professional.