moxidectin (Rx)

>10%

Eosinophilia (74%)

Pruritus (65%)

Musculoskeletal pain (64%)

Headache (58%)

Lymphocytopenia (48%)

Tachycardia (39%)

Rash (37%)

Orthostatic tachycardia (34%)

Abdominal pain (31%)

Hypotension (30%)

Pyrexia/chills (27%)

Leukocytosis (25%)

Influenza like illness (23%)

Grade 3 lymphocytopenia (<0.5 x 10^9/L) (23%)

Orthostatic hypotension (22%)

Neutropenia (20%)

Nonorthostatic tachycardia (18%)

Severe eosinophilia (>5 x 10^9) (18%)

Cough (17%)

Diarrhea/gastroenteritis/enteritis (15%)

Lymph node pain (13%)

Dizziness (12%)

Hyponatremia (12%)

Peripheral swelling (11%)

1-10%

Eye pain (8%)

Eye pruritus (7%)

Grade 4 neutrophils (<0.5 x 10^9/L) (7%)

Eosinopenia (<0.045 x 10^9/L) (5%)

Visual impairment (3%)

Gamma-glutamyltransferase (>5x ULN) (3%)

Eyelid edema (2%)

Conjunctivitis allergic (2%)

Ocular discomfort (2%)

Ocular and conjunctival hyperemia (2%)

Bilirubin (>2x ULN) (1.4%)

AST (>5x ULN) (1%)

ALT (>5x ULN) (1%)

Lacrimation increased (1%)

Contraindications

None

Cautions

Patients may develop symptomatic orthostatic hypotension with inability to stand without support after lying down for 5 minutes; patients experiencing dizziness or lightheadedness after administration should lie down until symptoms resolve

Patients with onchocerciasis who are also infected with Loa loa may develop a serious or even fatal encephalopathy following treatment; moxidectin has not been studied in patients co-infected with Loa loa; prior to treatment, patients who warrant treatment and have had exposure to Loa loa-endemic areas are recommended to undergo diagnostic screening for loiasis

Patients with hyper-reactive onchodermatitis (sowda) may be more likely than others to experience severe edema and worsening of onchodermatitis following moxidectin; manage with symptomatic treatment in patients who have experienced edema and worsening onchodermatitis

Cutaneous, ophthalmological, and/or systemic adverse reactions

• Cutaneous, ophthalmological, and/or systemic reactions of varying severity (Mazzotti reaction) may occur; these adverse reactions are due to allergic and inflammatory host responses to the death of microfilariae
• Clinical manifestations of Mazzotti reaction includes pruritus, headache, pyrexia, rash, urticaria, hypotension (eg, symptomatic orthostatic hypotension, dizziness), tachycardia, edema, lymphadenopathy, arthralgia, myalgia, chills, paresthesia, and asthenia
• Ophthalmological manifestations include conjunctivitis, eye pain, eye pruritus, eyelid swelling, blurred vision, photophobia, visual acuity changes, hyperemia, ocular discomfort, and watery eyes
• Laboratory changes include eosinophilia, eosinopenia, lymphocytopenia, neutropenia, and increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and lactate dehydrogenase (LDH); proteinuria also reported

Pregnancy

Limited available data on use in pregnant women are insufficient to establish whether there is a moxidectin-associated risk for major birth defects and miscarriage

Animal data

• Moxidectin administered orally to pregnant rats during period of organogenesis was not associated with significant embryo-fetal developmental effects at doses of approximately 15 times recommended human dose based on body surface area (BSA) comparison
• When moxidectin was dosed orally to pregnant rabbits during the period of organogenesis, no embryo-fetal developmental effects were observed at oral doses of moxidectin up to 24 times the recommended human dose based on BSA comparison
• Daily administration of moxidectin by oral gavage to maternal female rats during organogenesis and through lactation was associated with decreased survival, adverse clinical signs, and decreased body weights in first-generation offspring during the lactation period at a moxidectin dose less than 2-times the recommended human dose based on BSA comparison
• Additional findings in first-generation offspring at the same dose included delays in pinna unfolding, eye-opening, and vaginal opening. Other parameters, including reproduction and neurological development in first-generation offspring were not affected at any dose

Lactation

Moxidectin was detected in the milk of lactating women following a single moxidectin dose

There are no data on the effects of moxidectin on the breastfed infant or milk production

In pre-postnatal study in rats, oral gavage administration at a dose less than 2-times recommended human dose based on BSA comparison during lactation period resulted in adverse clinical signs, weight loss, and increased mortality in rat pups suggesting moxidectin in lactation milk was responsible for the adverse effects

Because of serious findings from rat pre-postnatal study including weight loss and death, advise women that breastfeeding is not recommended at time of treatment and for 7 days after treatment

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

The mechanism of action against O. volvulus is not known

Moxidectin is active against the microfilariae of O. volvulus

Studies suggest that moxidectin is not effective for killing the adult worms; however, it inhibits intrauterine embryogenesis and release of microfilariae from the adult worms

Absorption

Peak plasma concentration: 58.9 ng/mL (healthy subjects); 63.1 ng/mL (patients with onchocerciasis)

Peak plasma time: 4 hr (healthy subjects and patients with onchocerciasis)

AUC: 3387 ng·hr/mL (healthy subjects); 2738 ng·hr/mL (patients with onchocerciasis)

Mean peak plasma concentrations and AUC increased on average by 34% and 39%, respectively, when administered with a standard high-fat meal (900 calories, with a nutritional distribution of ~55% fat, 31% carbohydrates, and 14% protein) compared with fasted conditions

Distribution

Vd: 2421 L

Metabolism

Hepatic metabolism of moxidectin is minimal

Excretion

Half-life: 784 hr (healthy subjects); 559 hr (patients with onchocerciasis)

Clearance: 3.5 L/hr

Excretion: Feces (2%, unchanged)

Oral Administration

Administer with or without food as a single dose

Storage

Tablets: Store <30°C (86°F)

Protect from light

Once open, use full contents of the container within 24 hr; discard any unused content