Hailed as the wonder drug for tropical diseases, ivermectin has many uses for humans, pets, and livestock. This drug has alleviated the burden of river blindness and elephantiasis for millions of people. Novel uses are still being discovered – it is a promising agent for combating viral infections and cancer. Read on to learn more about the uses, safety, and side effects of ivermectin.

What is Ivermectin?

Ivermectin (Stromectol, Mectizan, Sklice, Heartgard) is a semisynthetic deworming and anti-inflammatory drug derived from avermectin – a bacterial macrocyclic lactone, produced by the Streptomyces avermitilis bacterium [1].

Together with penicillin and aspirin, ivermectin is one of the drugs that has had the greatest impact on the health and wellbeing of humankind [2].

Most of us have never heard of it. Yet, people in rural parts of Africa and Latin America know this drug well, and millions are taking it to combat parasite infections [3].

It started out as a multi-purpose veterinary drug in 1981. Six years later it was registered for human use [3].

It is used in the treatment of many parasitic infections in humans, pets, and livestock alike.

It has been used in two globally coordinated mass campaigns to eliminate river blindness (onchocerciasis) and elephantiasis (lymphatic filariasis) [4, 5].

This broad-spectrum antiparasitic agent is on the WHO’s list of essential medicines [6].

In addition to its antiparasitic effects, new uses for this drug are continually being found [3].

The scientists who discovered this drug received a Nobel prize in 2015.

Mechanism of Action

Antiparasitic

Ivermectin has a high affinity for invertebrate (roundworm and arthropod) glutamate-gated channels. It causes the influx of chloride ions into muscle and nerve cells, which results in subsequent paralysis and death of the parasite [4].

Ivermectin has a lower affinity for glutamate- and GABA-gated channels in mammals. These means it is less likely to mess with them. Also, these are only found in the brain, and ivermectin is unable to cross the blood-brain barrier [4].

Ivermectin also suppresses the ability of the parasite to release proteins that help it to evade our natural immune defenses (parasites most likely increase IL-10). Therefore, with the help of this drug, our immune response can overcome parasites and eliminate them [2, 7].

Anti-inflammatory

Ivermectin suppresses inflammatory responses by blocking the inflammatory cytokine cascade (it decreases TNF-alpha, IL-1, IL-6, IL-8 levels, and NF-kB activity) [4, 8, 9].

Antiviral

Importin alpha/beta is a transporter whose function is critical to the life cycle of many viruses. Ivermectin disrupts importin alpha/beta function inside of the cells [10, 11].

Anticancer

Ivermectin may slow down cancer growth by blocking WNT-TCF pathways (these are involved in cell growth and migration) and DDX23 [11].

Uses

1) River Blindness

River blindness (onchocerciasis) is a tropical disease caused by the worm Onchocerca volvulus.

Larvae of this worm create nodules under the skin where they mature into adults. After mating, female worms can release up to 1,000 larvae a day for some 10 to 14 years. These move through the body causing skin rashes, lesions, intense itching, swelling, and depigmentation. They also invade the eye, causing visual impairment and loss [2].

Clinical trials spanning over three decades, including thousands of people, have shown the drug is effective in controlling the infection [12, 13, 14, 15, 16, 17, 18].

A single dose (150 mcg ivermectin/kg body weight) of ivermectin is effective against larvae, but not against the adult form. That is why the treatment needs to be periodically repeated (once or twice a year, every few years). Repeated doses have partial-to-permanent sterilizing effects on adult worms after 4 or more consecutive treatments [19].

2) Elephantiasis

Elephantiasis (lymphatic filariasis) is caused by worm invasion into the lymphatic system. This disease threatens over 1 billion people in more than 80 countries. Causative agents include Wuchereria bancrofti, Brugia malayi, and B. timori [2].

The parasites are transmitted to humans through the bite of an infected mosquito and develop into adult worms in the lymphatic vessels, causing severe damage and swelling (lymphoedema). Common symptoms include painful, disfiguring swelling of the legs and genital organs [2].

A single dose of Ivermectin is successful in clearing larval stages associated with both Wuchereria bancrofti and Brugia malayi infections. It works even better in combination with other drugs like diethylcarbamazine or albendazole – clearing 99% of larvae after one year and 96% after two years [2].

Multiple clinical trials testify to the effectiveness of ivermectin against elephantiasis [20, 21, 22, 23, 24].

A placebo-controlled study of 15 villages in India (population approximately 26,800) showed that 4 cycles of single-dose ivermectin given to 54-77% of the population decreased the prevalence of the infection by 60 to 80% [25].

Higher dosages killed parasites better [26].

3) Intestinal Worm Infections

Strongyloidiasis is a tropical disease affecting millions of people worldwide. It is caused by the parasitic roundworm Strongyloides stercoralis.

Ivermectin is the drug of choice for strongyloidiasis, killing the worms in the intestine. It works better than other available drugs and has fewer side effects. Two doses given 1 to 14 days apart have a cure rate of 94 to 100% [27, 28].

In randomized trials of 60, 198, and 90 patients, a single dose cured 83%, 56.6%, and 96.8% of patients, respectively [29, 30, 31].

Apart from strongyloidiasis, ivermectin is also effective in treating other worm infections.

In a double-blind randomized controlled trial of 816 people with gut worm infections, ivermectin had a cure rate of 100% for Ascaris (large roundworm), 66.7% for Trichuris (whipworms), 33.3% for hookworm and 52.9% for Enterobius (pinworms) infection [32].

4) Head Lice

In a double-blind randomized controlled trial of 765 patients, a single 10-minute application of 0.5% ivermectin on dry hair freed 78% of subjects of lice after two weeks [33].

Oral ivermectin was also effective as a treatment of head lice with a 77% effectiveness. However, the study suggests that lice can become resistant to the drug in about 7% of cases [34].

5) Scabies (Mites)

While topical permethrin is the most effective treatment for scabies, oral ivermectin does reduce the persistence of mites [35].

In a study of 200 patients, 82.6% of the patients that received oral ivermectin showed marked improvement, compared to a 44.4% improvement with a more traditional lindane lotion [36].

6) Can Help Soothe Rosacea

A 1% ivermectin cream has been developed as a treatment for rosacea, a chronic inflammatory skin disorder. It is effective in reducing inflammatory lesions associated with this disease after only 2 weeks of treatment [37].

In a randomized study of 962 subjects with rosacea, ivermectin cream efficiently decreased inflammatory lesions and achieved high patient satisfaction [38].

In two double-blind randomized controlled trials, 38 to 40% of those receiving ivermectin cream achieved treatment success compared to 12 to 19% of people receiving placebo. Ivermectin decreased inflammatory lesion counts by about 75% [39].

7) May Combat Viruses

In cell studies, ivermectin was active against mosquito-borne viruses such as the chikungunya virus, semliki forest virus, sindbis virus, dengue, West Nile virus, and yellow fever [40, 11].

This drug inhibits viral replication, and as a result, the virus can’t spread inside the body [11].

8) May Combat Cancer

Ivermectin delayed tumor growth in 3 different mouse models of leukemia. This drug can kill leukemia cells by increasing the production of reactive oxygen species (ROS) [41].

Ivermectin also decreased the growth of lung and colon cancer (when these cancers were WNT-TCF-dependent) and glioma (brain cancer) in mice, without side effects [42, 43].

9) May Help Prevent Mosquito-Transmitted Diseases

Many diseases are transmitted by insects. Ivermectin is also effective against them.

For example, ivermectin given to local cattle reduced the survival of the tsetse fly that transmits animal and human sleeping sickness (trypanosomiasis) in sub-Saharan Africa [44].

Similarly, this drug was found to reduce survival and blood feeding of the mosquito (Anopheles gambiae) that transmits malaria [45].

However, ivermectin was less effective against the mosquito (Aedes aegypti) that transmits yellow fever, dengue, and Zika [46].

Veterinary Uses

Ivermectin is approved for use in cattle, sheep, horses, pigs, dogs, and cats. It acts as an anti-parasitic agent in the treatment of worms and arthropods, including [47]:

  • Heartworm (Dirofilaria immitis)
  • Intestinal roundworms
  • Mange mites
  • Ticks – specifically Boophilus sp.
  • Biting flies
  • Screw-worm
  • Lice

Animal Warnings

A mutation in the MDR1 (multidrug resistant) gene, responsible for encoding an important blood-brain barrier protein, results in hypersensitivity (dilation of the pupils, salivation, somnolence/sleepiness, depression, disorientation, loss of muscle coordination, tremors, coma and possible death) to ivermectin in some dog breeds, specifically [48]:

  • Smooth collies
  • Rough collies
  • Australian shepherds
  • Miniature Australian shepherds
  • Shetland sheepdogs
  • Silken windhounds
  • Longhaired whippets
  • White Swiss shepherds

Kittens are particularly susceptible to ivermectin toxicity. They can experience diarrhea, loss of muscle coordination, and coma [49].

Side Effects

Ivermectin is well tolerated in humans and other mammals [37].

In a double-blind dose escalation study of 68 healthy people, ivermectin was generally well tolerated, with no associated brain toxicity for doses up to 10 times the highest FDA-approved dose of 200 microgram/kg. Adverse experiences were similar between ivermectin and placebo and did not increase with dose [50].

Side effects as the result of Ivermectin treatment are usually minor and temporary [1].

Common side effects occur at a low incidence and include [51, 52]:

  • Burning sensation of the skin
  • Itching, dry skin, and skin irritation
  • Rash, urticaria
  • Fatigue
  • Stomach pain
  • Anorexia
  • Constipation or diarrhea
  • Nausea and vomiting
  • Dizziness
  • Drowsiness
  • Vertigo
  • Tremor

In rare cases, the drug may cause encephalopathy (brain inflammation) [53].

Overdose can also result in [52]:

  • Swelling
  • Weakness
  • Headaches
  • Seizures
  • Ataxia (lack of voluntary muscle coordination)
  • Shortness of breath
  • Contact dermatitis

Finally, some side effects are specific to the disease and are caused by dying parasites.

In elephantiasis, in the first 24 hours following therapy, patients can experience [54, 23]:

  • Headaches
  • Muscle pain
  • Fever

In river blindness, in the first couple of days patients can experience [55]:

  • Itching
  • Rash
  • Headaches
  • Muscle and joint pain
  • Tender/swollen lymph nodes
  • Low blood pressure
  • Dizziness
  • Elevated resting heart rate (tachycardia)
  • Fever
  • Weakness
  • Fainting
  • Acute respiratory distress

Contraindications

Ivermectin shouldn’t be administered to people with high Loa loa (roundworm species) parasite counts. These parasites, when dying, can cause functional impairment, coma, and serious (possibly fatal) effects on the brain (such as encephalopathy). The more parasites in the patient – the higher the risk [56, 57, 58].

Loa loa can be contracted in Western and Central Africa.

During Pregnancy and Breastfeeding

The FDA categorized Ivermectin as a category C drug under the old risk classifications system. Animal studies indicate that toxic doses of ivermectin cause fetal malformations. However, in studies where ivermectin was inadvertently given to pregnant women, there were no evident increases in birth defects, stillbirth, or congenital malformations [59].

Levels of ivermectin are low in breastmilk. Caution is advised, but ivermectin is not contraindicated in breastfeeding mothers [60].

Drug Interactions

Ivermectin is broken down by liver CYP3A4 enzymes [61].

Drugs that inhibit the CYP3A4 can increase ivermectin levels in the body and may increase the risk of side effects.

Many drugs inhibit CYP3A4, including statins, HIV protease inhibitors, dexamethasone, lidocaine, barbiturates (such as phenobarbital, butalbital), benzodiazepines (such as clonazepam, lorazepam), and valproic acid.

Also, drugs that inhibit P-glycoprotein (MDR1) may allow the transport of ivermectin across the blood-brain barrier [62].

Drugs that inhibit P-glycoprotein include verapamil, trifluoperazine, cyclosporine, tamoxifen, vincristine, clarithromycin, erythromycin, and omeprazole.

In dogs, the insecticide spinosad can increase the potency of ivermectin, by increasing its transport across the blood-brain barrier [63].

Finally, taking ivermectin after a high-fat meal resulted in increased absorption of ivermectin into the bloodstream. High-fat meals may increase the risk of liver dysfunction due to the increase in ivermectin absorption [64].

Dosage

River blindness/onchocerciasis – A single annual oral dose of 150 mcg ivermectin/kg body weight, taken on an empty stomach with water. The dose can be repeated every 12 months, or at intervals as short as 3 months [52].

Elephantiasis/lymphatic filariasis – Clinical studies apply a single dose of ivermectin, over the range of 20-400 micrograms/kg. The treatment may need to be repeated for a couple of years [26].

Strongyloidiasis – A single oral dose of 200 mcg ivermectin/kg body weight, on an empty stomach with water. In general, additional doses are not necessary. However, follow-up stool examinations should be performed to verify eradication of infection [52].

Genetics

MDR1

The MDR1 gene produces the P-glycoprotein, a membrane transport protein active in the liver and blood-brain barrier.

rs1045642

Those with the rs1045642 T variant have an increased risk of a suboptimal response to the drug (higher parasite load despite many years of treatment) [65].

CYP3A5

CYP3A5 is an enzyme found in the liver and the digestive system that breaks down pretty much the same drugs as CYP3A4.

Patients with two CYP3A5*1 variants are more likely to be suboptimal responders [65].

This is because people with CYP3A5*1 have large amounts of the enzyme [66].

These people break down drugs such as ivermectin more rapidly than do people without this enzyme [67].

Because this is the original gene variant, it doesn’t have an SNP designation.

It is found in 45 to 94% of Africans, 8 to 15% of whites, and 23 to 40% of Asians [68, 69].

Natural Alternatives

A number of compounds found naturally in plants have parasite-killing potential. These natural options may boost the immune system and possibly aid in fighting off infections.

However, it’s important to note that most of these natural alternatives have not been studied in humans.

If you suspect you have a parasitic infection, it’s vital that you consult your doctor. Infections that do not receive proper medical treatment can become worse and result in serious complications.

1) Papaya

Besides being a popular fruit, papaya may have significant anti-parasitic effects as well.

Several animal studies have revealed that papaya seeds are effective against multiple species of parasites [70, 71, 72].

These results led a group of researchers in Kenya to examine the benefits of a papaya seed porridge in children. The study, which includes 326 children, found a 63.9% reduction of roundworm eggs. Papaya seeds also reduced the number of children with ringworms by 20% [73].

This parasite killing power likely comes from enzymes inside the plant called cysteine protease. These enzymes disrupt the parasites ability to move, leading to their death [74].

2) Garlic

The various compounds found inside garlic have a number of health benefits, including anti-parasitic activity [75].

Based on animal studies, garlic may be effective against several kinds of parasites, including intestinal worms [76, 77, 78].

Clinical trials have mainly focused on garlic’s effect on leishmaniasis, a common kind of infection spread through sandflies [79].

For example, one study of 70 people found that a topical garlic gel was effective in 81% of patients [75].

In a different trial using a garlic extract, 91.6% of leishmaniasis patients were cured within 22 days [75].

3) Berberine

Berberine is a chemical compound found in many different plants, including barberry, Oregon grape, and goldenseal [80].

Research is currently exploring its use in a variety of conditions, like diabetes, high cholesterol and heart disease [80].

Animal and cell studies show that berberine is effective against a number of parasite species, such as roundworm in dogs [81, 82, 83, 84].

Berberine and pyrimethamine (a malaria medication) are more effective against resistant malaria infections compared to other drug combinations, according to a study of 215 people [85].

Cell studies have found that berberine increases IL-12 and decreases IL-10, which may explain how the compound helps eliminate parasites [86].

4) Clove

Cloves are a flower bud from the tree Syzygium aromaticum. Most known for being an aromatic spice, cloves may have anti-parasite effects as well.

A compound inside clove oil called eugenol is able to kill several types of parasites. It is also effective against certain species of ticks and mites [87, 88, 89].

For instance, a cell study found that clove oil kills up to 99% of mites. However, the effectiveness diminishes after 3 months [87].

5) Curcumin

Curcumin is one of the active compounds found inside turmeric. According to animal and cell studies, it may help in various parasite infections including roundworms and intestinal parasites [90, 91, 92, 93].

One mouse study found that turmeric powder is effective against water-borne parasites. It also enhances the effect of praziquantel, an anti-parasite medication [90].

6) Pumpkin

Research in animals shows that pumpkin seed extracts may be effective against parasites, especially intestinal tapeworms [94, 95].

However, you might have to eat a lot of seeds to see any benefit. A dosing study in rats found that a minimum of 23 grams of seeds was needed to see a parasite-killing effect. This is equivalent to about 73 pumpkin seeds [96].

Want More Targeted Ways to Combat Inflammation?

If you’re interested in natural and more targeted ways of lowering your inflammation, we at SelfHacked recommend checking out this inflammation DNA wellness report. It gives genetic-based diet, lifestyle and supplement tips that can help reduce inflammation levels. The recommendations are personalized based on your genes.

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About the Author

Mathew Eng, PharmD

PharmD

Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.

Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

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