General Information

Moxidectin is a macrocyclic lactone anthelmintic medicine.

Moxidectin is specifically indicated for the treatment of onchocerciasis due to Onchocerca volvulus in patients aged 12 years and older.

Moxidectin is supplied as a tablet for oral administration. The recommended dosage is a single dose of 8 mg (four 2 mg tablets) taken orally with or without food.

Mechanism of Action

Moxidectin is a macrocyclic lactone anthelmintic medicine. The mechanism by which moxidectin exhibits its effect against Onchocerca volvulus (O. volvulus) is not known. Studies with other nematodes suggest that moxidectin binds to glutamate-gated chloride channels (GluCl), gamma-aminobutyric acid (GABA) receptors and/or ATP-binding cassette (ABC) transporters. This leads to increased permeability, influx of chloride ions, hyperpolarization and muscle paralysis. Additionally, there is a reduction in motility of all stages of the parasite, excretion of immunomodulatory proteins, and the fertility of both male and female adult worms. Antimicrobial activity Moxidectin is active against the microfilariae of O. volvulus. Studies suggest that moxidectin is not effective in killing the adult worms, however, it inhibits intra-uterine embryogenesis and release of microfilariae from the adult worms.

Side Effects

Adverse effects associated with the use of Moxidectin may include, but are not limited to, the following:

• eosinophilia
• pruritus
• musculoskeletal pain
• headache
• lymphopenia
• tachycardia
• rash
• abdominal pain
• hypotension
• pyrexia
• leukocytosis
• influenza-like illness
• neutropenia
• cough
• lymph node pain
• dizziness
• diarrhea
• hyponatremia
• peripheral swelling

Clinical Trial Results

The FDA approval of Moxidectin Tablets 8 mg in the treatment of onchocerciasis was based on data from two randomized, double-blind, active-controlled trials in patients with O. volvulus infection, Trial 1 in 1,472 patients and Trial 2, a dose-ranging trial. Patients in the trials received a single oral dose of moxidectin or ivermectin, the active control medication. Efficacy was assessed by skin microfilarial density (microfilariae/mg skin) from the mean of 4 skin snips per person per time point up to 18 months post-treatment.

Trial 1 recruited adult and adolescent patients ≥ 12 years with a body weight ≥ 30 kg and ≥ 10 microfilariae/mg skin. Mean (± SD) pretreatment skin microfilarial density was 39.5 (± 30.7), 69.6% had ≥ 20 microfilariae/mg skin and 39.7% had at least one ocular microfilaria. Patients who were not previously exposed to ivermectin community directed treatment programs were recruited from the sub-Saharan African region (Democratic Republic of Congo, Liberia, and Ghana). Moxidectin was statistically superior to ivermectin in mean skin microfilarial density and the proportion of patients with undetectable skin microfilariae at 1 month, 6 months and 12 months.

Safety and efficacy was assessed in the smaller single ascending dose trial 2, comparing 2 mg (n = 44), 4 mg (n = 45) (2 mg and 4 mg are not approved doses) and 8 mg (n = 38) single doses of moxidectin to ivermectin. Trial 2 was conducted in Ghana in adults aged ≥ 18 to ≤ 60 years with O. volvulus infection. Analysis of the baseline-to-12-month change in skin microfilarial density for the proposed moxidectin 8 mg dose showed statistically significant superiority to ivermectin.