Levamisole Hydrochloride. What is Levamisole Hydrochloride?

What is Levamisole Hydrochloride?

Levamisole Hydrochloride (Levamisole HCL), is an anthelmintic (anti-worm) agent commonly used in large livestock such as cattle, pigs, and sheep. In 1971 it was found to have immunostimulatory properties and investigation into its use in humans began to expand. Currently, Levamisole HCL is used in humans for diseases related to imbalances in the regulation of immune responses or deficiencies of the immune system, including autoimmune diseases, chronic and recurrent diseases, chronic infections, and cancer. It has beneficial effects on host defense mechanisms and restores depressed immune responses in animals and humans.  Another interesting use of levamisole in humans is as a treatment for common warts (verruca Vulgaris).

News of its anthelmintic efficacy and immune system benefits has been known among aquatic hobbyists for years. The problem, however, is that there is not much in the way of definitive information on its use and application in the hobby. Anecdotal accounts of how it has worked for those ‘outside the box’ aquarists who first braved its use with fish, and accounts of personal experience with Levamisole in individual aquariums are helpful, but the ‘your mileage may vary’ factor is immense. A word about its usefulness in treating internal parasites in the ornamental fish trade has spread, but information regarding its use is limited and sometimes conflicting. From the information I have found thus far, Levamisole HCL is safe to use in aquaria and effective against many internal parasites, especially nematodes, when used in appropriate dosages. It does not harm the bio-filter, plants, invertebrates, or uninfected fish. As an added benefit, it boosts the immune competence of fish, humans, large animals, birds, and some reptiles.

This article hopes to pull together what scientific information is available, a bunch of individual accounts, apply some common sense and put together in one place a helpful guide to the use of Levamisole for treating aquarium fish.

Why would anyone use a cattle/pig/sheep de-wormer in a fish tank?

Do you want to know why?

Internal parasites that can be treated effectively by levamisole are endemic. They are everywhere. Fish are also susceptible to these parasites. Since the parasites are what we are attempting to eliminate from our fish, we need a medication that is designed to affect those parasites.

Does the medication need to be labeled for ‘fish only’ use? Not if you know what the medication is composed of, whether it contains any chemicals or additives that would be harmful to fish, if it will work in water, how it works, and what the possible side effects may be. Many medicines that are used in ‘fish only’ preparations are also used in humans and animals.

Medications like:

• Neomycin
• Kanamycin
• Erythromycin

• Magnesium Sulfate

In fact, manufacturers of fish-specific medications are beginning to package their products in loose powdered or liquid form.

The single most important factor once you’ve decided that a non-fish-specific medication is safe to use in aquaria is determining the correct dosage. We’ll look into that factor later. For now, let’s look at its chemical composition and how it works.

Levamisole Hydrochloride is the LEVO-rotatory form (left-handed) of tetramisole. The DEXTRO isomer (right-handed) contributes to the toxicity, but not the therapeutic effect so it has been removed in marketed preparations.

Levamisole HCL is light-sensitive. Store product in tightly closed light-resistant containers. Leave off tank lights when treating.

There is also a phosphate form of Levamisole.

 

How does Levamisole HCL work?

How does Levamisole HCL work as an antiparasitic agent?

Levamisole HCL is absorbed through the gut, can also be absorbed through the skin, and is distributed throughout the body. Levamisole affects the neurotransmitters and paralyzes the worm (spastic paralysis). The fish then passes the inactive worms. Good gravel vacuuming is advised after treatment to remove the paralyzed (but still live) worms.  It is not ovicidal, which means it will not affect eggs already present, but it will affect the larval stage of the worm. To ensure complete eradication of the parasite treat again after remaining eggs have hatched.

How does Levamisole HCL work as an immunomodulator?

The mechanism of action for its immunostimulating effects is not well understood. It is believed that it restores cell-mediated immune function in peripheral T-lymphocytes and stimulates phagocytosis by monocytes. The drug appears to restore depressed immune function rather than to stimulate response to above-normal levels. There are multitudes of medical studies being done with its use in humans and animals, the goal being to attain an understanding of its immunomodulating mechanism. The mechanism will be defined, with time. However, at the time of the writing of this article, there is no complete answer to this question. For us, it is enough to know that it does stimulate immune function in fish that are suffering due to parasites or disease.

What if I overdose my fish?

The LD-50 (the lethal dose of a compound for 50% of animals exposed) of levamisole is 250 mg/l per 24 hours.  This level of dosage is much higher than that which is prescribed for use in a freshwater bath (the method used in our fish tanks). Only extreme overdosing with this medication will result in death to your fish. Few accounts of adverse side effects in aquaria have been noted even with much higher than currently accepted appropriate dosing.

How long will it stay in my fish and how do I get it out of my tank?

Levamisole HCL is rapidly absorbed into the digestive system. Less than 6% of the medication is excreted unchanged in the urine and feces. Half-lives for several species have been recorded:

Cattle: 4 – 6 hours
Swine: 3.5 – 6.8 hours
Dogs:   1.8 – 4 hours
I have not been able to locate any studies that determine the half-life of Levamisole HCL in fish. If you know of any, please post a comment to this article.

Absorption is systemic within 3 – 4 hours. Within three days 70% of the medication will be gone from the fish via its excretory system. The vast majority of the compound will have been metabolized by your fish. The remainder can be removed by water changes and/or adding activated charcoal to your filtration system.

De-bunking a common misunderstanding about Levamisole HCL.

Does Levamisole HCL require a pH of below 7.0 to be effective?

In a word, NO.

This common misconception regarding the uselessness of Levamisole HCL  in higher pH water needed a definitive answer.

Let’s apply some common sense.  When we look around at the other uses of Levamisole HCL we find that one common formulation of Levamisole HCL is administered by adding it to livestock drinking water.  Are all water supplies the same? It seemed unlikely to me that among all the farms using this medication, every water supply would have a pH below 7.0.

After some digging around all over the Internet and phone calls to various Veterinarians and chemical companies, the answer I was given by Dr. Hal Sinclair of IVX Animal Health was both clear and simple. Levamisole base (C₁₁H₁₂N₂S) is unstable in water and will degrade rapidly as pH levels increase. Levamisole HCL will not. It’s the addition of the hydrochloride molecule that makes the difference.

Levamisole HCL is stable in water for up to 90 days and will do its job in aquaria with both low and high pH values.

Taking the space to go through all this chemistry may be more than you want to know.  However, chemistry plays a large role in fishkeeping. It helps to be somewhat comfortable with the basics to comprehend the Nitrogen cycle, and to balance the aquatic environments in which our fish live. Planted tank gurus especially, spend time understanding the chemistry of their tanks for both fish and plant benefit.

Chemistry has already helped us to answer the pH question which has been plaguing the community for years. We will need it again in order to determine the effective dosing of Levamisole HCL to cure our fish. Knowing the chemical formula, the molecular weight, and the specific gravity of the molecule will give us the information we need to make some calculations that will help us to do just that.

Which parasites will respond to treatment with Levamisole?

Levamisole has been found highly effective in the treatment of mature and developing immature stages of major stomach and bowel worm species in cattle and sheep including gastrointestinal worms such as Stomach worms—Haemonchus spp; Ostertagia spp; Trichostrongylus spp; Roundworms— Nematodirus spp (which include threadworms);  Cooperia spp; Nodular worms—Oesophagostomum; Chabertia spp; Hookworms—Bunostomum spp; Necator spp; and Ancylostoma spp; and Lungworms— Dictyocaulus spp. Nematodes (roundworms) in particular are a common problem. Nematodes such as Capillaria, Eustronggylides, Camallanus, and Contracaecum are common among many fish species. Levamisole is highly effective as a treatment against nematode species.

It is INEFFECTIVE as a treatment for:

• Cestodes (tapeworms)
  For Cestodes the recommended treatment is Praziquantel.
• Trematodes (flatworms or flukes)
  For Monogenean Trematodes with a direct life cycle, the suggested treatment is Formalin, administered as a short-term or prolonged bath.
  For  Digenean Trematodes which have a complex life cycle, using differing hosts, the best control is to break the life cycle of the parasite. Elimination of the first intermediate host, the freshwater snail is often recommended.

How can I tell which parasite is affecting my fish?

The best way to determine if your fish is suffering from parasites, and which kind they are is to have the fish examined by a fish health specialist (veterinarian). Accurate diagnosis of an internal parasite infestation in aquatic animals is often outside of the ability of the average hobbyist. Stool samples, slides, microscopes, and sometimes necroscopy, or in the worst-case scenario, autopsy, is the most effective way to determine exactly what parasite is inside your fish. Many of us are just not equipped or knowledgeable enough to perform the necessary diagnostic procedures.  What we can do is observe our fish, become aware of what symptoms may indicate parasitic infection, and learn what methods are best used to treat them.

Levamisole HCL is not a cure-all but it is a good first line of defense against many parasites common to wild-caught fish.

Nematode infections in fish will present with one or more of the following externally observable symptoms:

1. 1. Hemorrhaging (bloody streaks in fins or body)
   2. White/translucent stringy feces
   3. Inflammation
   4. External lumps or nodules
   5. Necrosis (dead or dying tissue)
   6. Cysts
   7. Granulomas – which are a reaction by immune cells trying to wall off some foreign body (like a worm). They can look like little brown rocks in the shape of the worm but will have a distinct clear edge.
   8. Wasting
   9. Bloated abdomen with fish exhibiting otherwise normal behavior
   10. Worms protruding from the anus (specifically Camallanus)

   A little bit about parasites in general and nematodes in particular.
   

   Healthy fish can carry a low load of parasites without ever showing outwardly visible signs. Fish that are stressed or sick are immune-compromised and will find it difficult to keep down parasitic infections. Fish carrying a heavy parasite load also become more susceptible to secondary bacterial infections. Because parasites are everywhere, wild-caught fish can be assumed to be harboring parasites whether they appear healthy or not. Quarantine tank treatment with Levamisole HCL prior to placing new wild-caught fish into an established community tank is advised. This will both eliminate parasites (those affected by Levamisole HCL) and boost the immune system of your fish, helping them keep at bay any secondary infections as a result of parasitic damage.

   The severity of damage caused by parasitic infection depends on a number of factors. The number of worms present in the fish, age and species of the fish, and the sites of infection all affect the level of damage caused by the parasite. Most adult nematodes are found in the digestive tract. However, adult and other life stages of worms can be found in muscle tissue, organs, and tissues surrounding the organs. Levamisole HCLworks primarily in the digestive tract so parasites located in organs or tissues may be unaffected by treatment.

   Nematodes have two major categories of life stages, direct and indirect. As indirect hosts, fish can be either the final host, excreting eggs that begin the life cycle all over again or the intermediate host as shown below:

In this case, the fish is infected with the parasite, then eaten by another fish, bird, or mammal where the parasites will develop into reproductive adults.

The nematode eggs/larvae enter an intermediate host before being eaten by fish which are the final host. The eggs develop into reproductive adults within the fish. Some intermediate hosts are snails, Tubifex worms, or insect larvae.

Nematodes with a direct life cycle do not need an intermediate host. One fish can spread the infection directly to another by eating either eggs or larvae.

Because Levamisole HCL is not harmful to the bio-filter, fish, plants, or invertebrates you can safely treat them within the community tank. In fact, it is best to do so to eliminate possible parasites in any intermediate hosts that may be in the tank. Fish that are suffering from secondary bacterial infections due to parasitic worm damage should be removed from a quarantine tank for appropriate antibiotic treatment.

How do I use Levamisole Hydrochloride?

Some resistance to Levamisole HCL action has been noted in farm animals. Be sure to complete the full course of treatment to avoid the development of resistant strains in fish. Because it is light sensitive, store any unused medication in opaque containers. Remove any carbon used in your filtration as it will absorb the chemical. Turn off UV lighting.

Levamisole HCL is available in several formulations. Below are some manufacturer packaging examples. There are many. You can buy different types of Levamisole HERE and if you are in the EU, so you can buy HERE.

Examples of the bolus variety and the injectable are on the right.

The bolus form is messy. It requires crushing the pill, determining the amount of powder needed, dissolving in tank water, filtering through a coffee filter then adding the liquid to the tank.

There are other forms out there, such as Levamisole HCL drench, oral solutions, oral feed mixes, topical solutions, and gel formulas. Check the formulation composition for additional medicines, additives, or agents before using them in your fish tank. Some forms are unsuitable for use with fish due to other ingredients.