Brand: COMBINEX ™ Oral Suspension
DELIVERY FORM: «drench» for oral administration.
- Levamisole hydrochloride 37.5 mg/mL (equivalent to 3.75%)
- Triclabendazole: 50 mg/mL (equivalent to 5.0%)
CHEMICAL CLASS of the active ingredient(s):
- Levamisol: imidazothiazole
- Triclabendazole: benzimidazole
PARASITES CONTROLLED* (spectrum of activity)
* Country-specific differences may apply: read the product label.
- Roundworms: mature and developing immature stages Ostertagia, Haemonchus, Trichostrongylus, Cooperia, Nematodirus, Bunostomum, Chabertia, Oesophagostomum) and lung worms (Dictyocaulus).
- Liver flukes: Fasciola hepatica from two week old early immature to adult fluke, thus indicated against both acute and chronic fascioliasis.
* Country-specific differences may apply: read the product label.
- 7.5 mg levamisole hydrochloride and 10 mg triclabendazole per kg bodyweight; This represents 1 ml product per 5 kg bodyweight.
Read the product label for further details on dosing
- LD50 (acute oral) in rats:
- Levamisole: 180 mg/kg (for the a.i.)
- Triclabendazole: >5000 mg/kg (for the a.i.).
- LD50 (acute dermal) in rats: n.a.
Suspected poisoning? Read the articles on levamisole safety and on triclabendazole safety in this site.
Withholding periods (=withdrawal times) for meat & milk (country-specific differences may apply: read the product label)
- Meat: UK 56 days
- Milk for human consumption: UK: Not authorised for use in ewes producing milk for human consumption including during the dry period. Do not use within 1 year prior to the first lambing in ewes intended to produce milk for human consumption.
WARNING !!!: Never use on humans, dogs or cats
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
Risk of resistance? YES
Resistance of gastrointestinal roundworms to levamisole in ruminants is a serious and increasing problem, particularly in sheep and goats, but also in cattle. Levamisole resistance is usually less strong and widespread than resistance to benzimidazoles, but nevertheless a serious problem. The most affected worm species in sheep are: Haemonchus spp, Ostertagia spp /Teladorsagia spp, Trichostrongylus spp, Nematodirus spp, Chabertia ovina.
Resistance of liver flukes to triclabendazole (and albendazole) in sheep was already discovered in the mid 1990's in Australia. Since then it has been reported in several other countries (e.g. New Zealand, UK, Ireland, Spain, Argentina), also in cattle (e.g. Australia, The Netherlands, Argentina). However, the incidence so far is not that serious as for roundworm resistance to benzimidazoles and other nematicides. Nevertheless, in certain regions products with triclabendazole may not protect livestock adequately against liver flukes.
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.
Alternative chemical classes/active ingredients to prevent resistance of gastrointestinal roundworms through product rotation:
- Benzimidazoles, e.g. albendazole, febantel, fenbendazole, oxfendazole, etc. Even worse resistance problems than levamisole.
- Derquantel: available so far only for sheep in combination with abamectin.
- 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.
- 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.
- Nitroxinil: effective only against certain gastrointestinal roundworms (e.g. Bunostomum spp, Haemonchus spp, Oesophagostomum spp). Not available in some countries.
Alternative chemical classes/active ingredients to prevent resistance of liver flukes through product rotation:
- Closantel (salicylanilide): In sheep effective only against ≥8 weeks old liver flukes.
- Clorsulon: In sheep effective only against ≥8 weeks old liver flukes.
- Nitroxinil: In sheep effective only against ≥8 weeks old liver flukes.
- Oxyclozanide (salicylanilide): In sheep effective only against ≥12 weeks old liver flukes.
- Rafoxanide (salicylanilide): In sheep effective only against ≥6 weeks old liver flukes.
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.
Are the active ingredients of this product ORIGINAL* or GENERICS**?
- Levamisole: GENERIC (introduced in the 1960s by JANSSEN)
- Triclabendazole: GENERIC (introduced in the 1970s by CIBA-GEIGY)
*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: UK
GENERIC BRANDS available? Rather few, if at all, with this particular composition.
Click here to learn more about GENERIC vs. ORIGINAL drugs.
For an overview on the most used drench brands for livestock click here.
COMBINEX (in some countries ENDEX or FASINEX SUPER) is the original brand of triclabendazole + levamisole drenches from ELANCO, introduced in the late 1970s (by CIBA-GEIGY).
Triclabendazole is a narrow-spectrum benzimidazole introduced in the 1970s (by CIBA-GEIGY). It has no efficacy against roundworms or tapeworms. However it was and remains the only flukicide effective against adults as well as all immature stages of liver flukes, which are the most damaging stages due to their destructive migration through the liver tissues. For this reason it has been for decades and still remains the most widely used livestock flukicide worldwide. It is ineffectivy against any external parasites (ticks, flies, lice, mites, etc) of livestock. It is abundantly used in ruminants, but not in other livestock, horses or pets. It is also used in human medicines. It not used in agriculture.
Because it is effective against all stages of immature flukes, triclabendazole is appropriate to treat acute fascioliasis, caused my massive infections with larvae migrating through the liver.
Levamisole is a veteran anthelmintic. It was introduced by JANSSEN already in the 1960s (NILVERM, RIPERCOL). It has a broad-spectrum of activity 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 scarcely used in horses and pets. It is not used in agriculture.
As many other anthelmintics (e.g. benzimidazoles, monepantel, tetrahydropyrimidines) both triclabendazole 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.
Thanks to its higher solubility in water levamisole is also available as a pour-on and as an injectable for livestock, but only in some countries.
Unfortunately, resistance of several gastrointestinal roundworms to levamisole is already very high and very frequent worldwide in sheep and goats, slightly lower in cattle, which has significantly reduced its usage in livestock. Nowadays more convenient pour-ons and injectables containing macrocyclic lactones (e.g. abamectin, doramectin, eprinomectin, ivermectin, moxidectin) are often preferred over drenches with levamisole or benzimidazoles. Macrocyclic lactones (ML) also ensure several weeks protection against re-infestation by several worm species, in contrast with levamisole or benzimidazole drenches that lack any residual effect. However, resistance of gastrontestinal worms to ML is alredy quite frequent in sheep and goats, less common in cattle but increaising.
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. In cattle, a fiber-rich diet also increases the bioavailability of fenbendazole.
Triclabendazole 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.
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.
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