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Hailed as the wonder drug of 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.
Note: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific literature. Please discuss your medications with your doctor.
What is Ivermectin?
Ivermectin (trade names: Mectizan, Stromectol, Sklice, Heartgard) is a semisynthetic deworming and anti-inflammatory drug derived from avermectin – a bacterial macrocyclic lactone, produced by the Streptomyces avermitilis bacterium [R].
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 [R].
It started out as a multi-purpose veterinary drug in 1981. Six years later it was registered for human use [R].
It is used in the treatment of many parasitic infections in humans, pets, and livestock alike.
This broad-spectrum antiparasitic agent is on the WHO’s list of essential medicines [R].
In addition to its antiparasitic effects, new uses for this drug are continually being found [R].
The scientists who discovered this drug received a Nobel prize in 2015.
Mechanism of Action
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 [R].
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 [R].
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 [R, R].
1) Ivermectin Treats 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 [R].
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 [R].
2) Ivermectin Is Effective Against 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 [R].
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 [R].
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 [R].
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% [R].
Higher dosages killed parasites better [R].
3) Ivermectin Treats 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% [R, R].
Apart from strongyloidiasis, ivermectin is also effective in treating other worm infections.
In a randomized double-blind 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 [R].
4) Ivermectin Is Effective Against Head Lice
In a DB-RCT of 765 patients, a single 10-minute application of 0.5% ivermectin on dry hair freed 78% of subjects of lice after two weeks [R].
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 [R].
5) Ivermectin Can Help Against Scabies (Mites)
While topical permethrin is the most effective treatment for scabies, oral ivermectin does reduce the persistence of mites [R].
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 [R].
6) Ivermectin 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 [R].
In a randomized study of 962 subjects with rosacea, ivermectin cream efficiently decreased inflammatory lesions and achieved high patient satisfaction [R].
In two DB-RCTs, 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% [R].
7) Ivermectin May Combat Viruses
This drug inhibits viral replication, and as a result, the virus can’t spread inside the body [R].
8) Ivermectin May Combat Cancer
9) Ivermectin 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 [R].
Similarly, this drug was found to reduce survival and blood feeding of the mosquito (Anopheles gambiae) that transmits malaria [R].
However, ivermectin was less effective against the mosquito (Aedes aegypti) that transmits yellow fever, dengue, and Zika [R].
Veterinary Uses of Ivermectin
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 [R]:
- Heartworm (Dirofilaria immitis)
- Intestinal roundworms
- Mange mites
- Ticks – specifically Boophilus sp.
- Biting flies
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 [R]:
- 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 [R].
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 [R].
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 [R].
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 [R].
Ivermectin is well tolerated in humans and other mammals [R].
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 [R].
The FDA categorizes Ivermectin as a category C drug, which means its use should be avoided during pregnancy. Animal studies indicate that toxic doses of ivermectin cause fetal malformations [R].
However, in studies where ivermectin was inadvertently given to pregnant women, there were no evident increases in birth defects, stillbirth, or congenital malformations [R].
Safety of ivermectin-use in children weighing less than 15 kg and under 5 years of age has been avoided due to a fear of neurotoxicity, with the drug possibly being able to cross the not yet fully developed blood-brain barrier [R].
However, no significant adverse effects were recorded in a study of 18 children aged from 14 months to 17 years [R].
Side effects as the result of Ivermectin treatment are usually minor and temporary [R].
- Burning sensation of the skin
- Itching, dry skin, and skin irritation
- Rash, urticaria
- Stomach pain
- Constipation or diarrhea
- Nausea and vomiting
In rare cases, the drug may cause encephalopathy (brain inflammation) [R].
Overdose can also result in [R]:
- 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.
- Muscle pain
In river blindness, in the first couple of days patients can experience [R]:
- Muscle and joint pain
- Tender/swollen lymph nodes
- Low blood pressure
- Elevated resting heart rate (tachycardia)
- Acute respiratory distress
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 [R, R, R].
Loa loa can be contracted in Western and Central Africa.
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 [R].
In dogs, the insecticide spinosad can increase the potency of ivermectin, by increasing its transport across the blood-brain barrier [R].
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 [R].
The MDR1 gene produces the P-glycoprotein, a membrane transport protein active in the liver and blood-brain barrier.
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) [R].
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 [R].
This is because people with CYP3A5*1 have large amounts of the enzyme [R].
These people break down drugs such as ivermectin more rapidly than do people without this enzyme [R].
Because this is the original gene variant, it doesn’t have an SNP designation.
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