Ivermectin is a macrocyclic lactone compound derived from the fermentation products of the soil bacterium Streptomyces avermitilis. This broad-spectrum antiparasitic drug has been widely used in both human and veterinary medicine since its introduction in the 1980s. Its impact on tropical diseases was recognized with a Nobel Prize in 2015. Ivermectin is highly effective against a variety of internal and external parasites, offering a wide margin of safety at therapeutic doses.
Targeting Parasite Nervous Systems
The primary and established mechanism of action for ivermectin involves disrupting the nervous and muscular systems of invertebrates, such as parasitic nematodes and arthropods. It achieves this effect by binding with high affinity to glutamate-gated chloride channels (GluCls), which are unique to invertebrate nerve and muscle cells. When ivermectin binds to these channels, it causes the channel pore to open, increasing the cell membrane’s permeability to chloride ions.
This influx of negatively charged chloride ions into the nerve or muscle cell results in hyperpolarization, which makes the cell less responsive to excitatory stimuli. The sustained opening of these channels effectively inhibits neurotransmission, leading to the paralysis and eventual death of the parasite.
The selective toxicity of ivermectin is attributed to two main factors that protect the human host. First, mammals generally lack GluCls, and the drug has a much lower affinity for the mammalian equivalent channels, such as GABA-gated chloride channels. Second, ivermectin is actively excluded from the central nervous system (CNS) by the blood-brain barrier at normal therapeutic doses. This dual protection mechanism ensures that the drug primarily targets the parasite with minimal effect on the human body.
Established Therapeutic Applications
The antiparasitic mechanism of ivermectin has made it the treatment of choice for several neglected tropical diseases, leading to its widespread use in mass drug administration programs. One of its most significant applications is in the treatment of Onchocerciasis, commonly known as River Blindness. Ivermectin works by killing the microfilariae, the larval stage of the Onchocerca volvulus parasite, substantially reducing the debilitating itching, skin lesions, and risk of blindness associated with the disease.
The drug is also a component in efforts to eliminate Lymphatic Filariasis (Elephantiasis) by targeting the larvae of the parasitic worms responsible for the disease. For intestinal infections, ivermectin is highly effective against Strongyloidiasis, caused by the Strongyloides stercoralis roundworm. A single dose of ivermectin is often curative for this infection, though follow-up testing is necessary to confirm the complete eradication of the parasite.
Ivermectin is also used to combat ectoparasitic infestations, including Scabies and head lice. For Scabies, caused by the Sarcoptes scabiei mite, both oral and topical formulations are utilized to treat the infestation.
Investigational Antiviral Actions
Beyond its established role as an antiparasitic drug, ivermectin has been investigated for potential antiviral properties against a range of viruses, including dengue, Zika, HIV-1, and SARS-CoV-2. The proposed mechanism for this non-parasitic activity centers on the host cell’s nuclear transport system. Ivermectin is thought to act as an inhibitor of the importin-alpha/beta-1 (Impα/β1) heterodimer, a protein complex responsible for transporting viral proteins into the host cell nucleus.
Many viruses rely on this importin pathway to shuttle their proteins into the nucleus to facilitate replication or to suppress the host’s antiviral response. By interfering with the Impα/β1 complex, ivermectin can potentially disrupt the viral life cycle at the cellular level. Initial in vitro studies, using cultured cells in a laboratory setting, demonstrated that ivermectin could significantly reduce the replication of certain viruses.
However, the concentrations of ivermectin required to achieve potent antiviral effects in these in vitro studies were substantially higher than the concentrations safely attainable in human plasma at approved doses. The current consensus from major health organizations is that available clinical trial data do not support the use of ivermectin for viral infections like COVID-19 outside of controlled research settings due to insufficient evidence of efficacy at safe human doses.
Administration and Safety Profile
Ivermectin is typically administered orally as a tablet, often as a single dose or a short course, though topical forms are also used for skin and scalp infestations like rosacea and lice. For parasitic infections, the dosage is usually weight-based, such as 150 to 200 micrograms per kilogram of body weight, and is generally taken on an empty stomach to optimize absorption. The drug is metabolized in the liver and excreted almost entirely in the feces, with a plasma half-life of approximately 18 hours in humans.
Ivermectin has a well-established safety profile at therapeutic dosages, and serious adverse events are rare. Common side effects are generally mild and may include moderate gastrointestinal issues such as nausea, vomiting, or diarrhea, as well as dizziness or headache.
A specific reaction known as the Mazzotti reaction can occur during treatment for Onchocerciasis. This is not an adverse drug reaction but rather a systemic inflammatory response to the mass die-off of microfilariae. This reaction can involve fever, rash, joint pain, and swollen lymph nodes, often requiring management with anti-inflammatory medications. Contraindications for ivermectin use include known allergy to the drug, and caution is advised in patients with pre-existing liver or kidney conditions. Its safety during pregnancy is not fully established, necessitating a careful risk-benefit assessment by a healthcare provider.