Ivermectin for chickens

So on some chicken forums I've heard that people are using Ivermectin "off-label" to treat their poultry for parasites (such as mites and lice) and they recommend an egg witholding period of 7 days. It's off-label as there have been very few studies looking at the metabolism of this drug through avians. In December last year, there has been one scientific study done on Ivermectin and poultry. So is there a clear answer to it's safety in poultry and more importantly, how long before you can eat the eggs?

Ivermectin is lipid soluble drug that has been around for quite a few decades and was first used in humans for parasite control. It's use has now spread to commercial livestock and is used in cattle, sheep and pigs. So there is known information about Ivermectin use in these animals, just not poultry. One of the reasons for this was the rather short lifespan of commercial poultry. Meat birds are generally slaughtered a few months after hatching, so not long enough for major parasite outbreaks to occur. The intensive egg producing chickens live for about a year or two and under shed conditions are less likely to be exposed to parasites. Not sure what parasite problems the free range egg producers have.  Searching online, I have found a few articles that use Ivermectin on poultry, but they originate in generally middle eastern countries. Those articles focused more on the efficacy of the drug than the pharmacokinetics of the drug.

So how does it work?

Look at all those lice eggs!

Nerve cells have glutamate ion channels, ion channels are important in cellular signaling and these channels open and close to start off a signaling pathway within the cell. Ivermectin binds to receptors of these channels and keep them open all the time, allowing ions to enter, creating an ion imbalance. The cell then signals wrongly and generally leads to paralysis. Doesn't this all sound dangerous? Well, mammals have a blood brain barrier, which stops majority of large chemicals from passing through the membrane and into the brain tissues. This membrane prevents Ivermectin from passing and effecting the nerve cells in the brain. However, I think at large doses, it could effect cell signaling in other tissues.

Anyway, to get back on track, there are three ways to administer Ivermectin, intravenously, orally or topically. The one I have come across most for poultry are the topical versions.

So in commercial animals, Ivermectin is generally not metabolised, it is just excreted in pretty much the same structure, and is excreted in their faeces. Because Ivermectin is lipid soluble, it tends to accumulate in fatty tissue, such as the liver but because of it's large structure, it does not cross the blood brain barrier in mammals. Hence why it is toxic to parasites but not to humans.  What is interesting is that different animals all demonstrate different pharmacokinetics of the drug. Some animals distribute the drug throughout the body faster when taken in an oral form, some others in a topical application. It all indicates that the drug activity cannot be easily translated from different animal species. In general though, most animals had better drug distribution/retention when it was administered topically. Most likely because it gets absorbed in the fatty layers of the skin.

So in birds, to show it's effectiveness, one study counted parasite eggs in the chickens poo (what a great job that must have been!). A 0.5% pour on dose was used (they didn't say how much  of the pour on they used though) and they counted eggs in the poo for up to 28 days after it was administered. This was for a gastrointestinal parasite and they saw a 59% reduction in parasite eggs just after one day of treatment. So it's effective in internal parasites. Other papers have reported their chickens gaining weight after treatment with Ivermectin (used at a rate of 500ug/kg: 0.00005% topical application) because it killed the parasites that were sucking the life out of them.

This year, someone finally published a paper on the residual effects of Ivermectin in poultry (probably because so many people use it on their chickens). Rather annoyingly, they administered it in drinking water and by injection, so not topically. However there was some interesting information that would assist in determining an egg withdrawal period.

Ivermectin (IVM) residues after oral administration

Firstly the above graph shows detected Ivermectin residues in the yolk only and none was detected in the whites. This is because there is no fat in the whites and Ivermectin is fat soluble. Secondly, it shows a peak residue limit at approximately 8 days and levels do not return to baseline until about two and half weeks later. What does this tell us?

When injected (400ug/kg: 0.00004%), the half life of the drug was about 2 days (it took 2 days for the concentration of the drug to be halved within the body). This same dose was presented in drinking water as well over a period of 5 days. At approximately after a week, the level of Ivermectin is about 50ng/gm of egg yolk.

Yolks are approximately 20gm in weight, meaning each yolk you eat will give you 1000ng or 1ug. A dose of Ivermectin to humans is 200ug/kg to treat headlice, so say if you weigh 50kg you would be administered 10,000ug of Ivermectin, or 10mg, equal to 10,000 eggs!

Does this mean you are ok to eat the eggs?

Well, there are Ivermectin residue limits set for animal products. For dairy milk, the limit set in Australia is 50ug/kg and 40ug/kg in the fat of meat. In the egg yolk, at day 8, there is approximately 50ug/kg of Ivermectin in each yolk. So just at the limits accepted in Australia.

Confused? So am I, it seems that each animal distributes this drug rather differently and there doesn't seem to be a consistent dosing rate. There needs to be more research done, especially on the topical application, especially since this is being sold for use in show birds to treat mites.

This is what I understand so far:

1. If applied to the skin, it tends to accumulate within the skin.
2. If given orally, it tends to accumulate within the liver
3. Ivermectin is not metabolised and is generally excreted in the same form. So say if you do eat eggs with it, you will be getting Ivermectin in its intact form and not a by product
4. It kills parasites when topically applied at a rate of 5mg/ml (0.5%) - this is the concentration of the product, not the dose applied. The dose (for say a 2kg bird) would then be 0.25% if they applied 1ml
5. It will end up in the egg yolk, but clears after 8 days when applied in water. Would this apply to a topical application, probably but the bioavailability of the drug would not be as great when applied topically. This means that when ingested, the drug tends to circulate throughout the tissues more than when applied topically. Meaning that it would be present in tissues producing the egg more easily when Ivermectin is given in food, rather than water.
6. When given orally, at approximately 1 week after dosing, the level of Ivermectin is roughly at the maximum residual limit allowed in animal products for Australia

So what do I do?

With this information, I only administer Ivermectin to my animals when I know they are not laying, such as during the winter months. Other times of the year, they will be treated for parasites with poultry dusts such as Pestene, which are allowed to be used with laying hens.

So what should you do?

It's up to you to decide if you would like to eat the eggs or not. I give the info, so you are armed with scientific knowledge and not just hearsay.

Reference

Ivermectin pharmacokinetics, metabolism, and tissue/egg residue profiles in laying hens (2015) Journal of Agricultural and Food Chemistry, 63:10327-10332

Tags: Ivermectin, egg residue, poultry, Ivomec, hens, chickens, egg