ivermectin (Rx)

Frequency Not Defined

Abdominal pain

Asthenia

Hypotension

Mild EKG changes

Peripheral & facial edema

Transient tachycardia

Dizziness

Headache

Hyperthermia

Insomnia

Somnolence

Vertigo

Pruritus

Rash

Urticaria

Diarrhea

Nausea

Vomiting

Eosinophilia

Leukopenia

ALT/AST increased

Limbitis

Myalgia

Tremor

Blurred vision

Mild conjunctivitis

Punctate opacity

Mazzotti reaction (with onchocerciasis)

Edema

Fever

Lymphadenopathy

Ocular damage

Pruritus rash

Conjunctival hemorrhage (with onchocerciasis)

Hepatitis

Contraindications

Hypersensitivity to ivermectin

Cautions

Strongyloidiasis: The patient should be reminded of the need for repeated stool examinations to document clearance of infection with Strongyloides stercoralis; not active against disseminated Strongyloides, only intestinal

Onchocerciasis: The patient should be reminded that treatment does not kill the adult Onchocerca volvulus parasite, and therefore repeated follow-up and retreatment is usually required

Long-term studies in animals have not been performed to evaluate carcinogenic potential of ivermectin

Therapy had no adverse effects on fertility in rats in studies at repeated doses of up to 3 times maximum recommended human dose of 200 mcg/kg (on a mg/m²/day basis)

Immunocompromised patients may require repeated treatment; control of extraintestinal strongyloidiasis may require suppressive therapy (eg, once monthly)

Mazzotti reactions

• Microfilaricidal drugs, such as diethylcarbamazine citrate (DEC-C), might cause cutaneous and/or systemic reactions of varying severity (the Mazzotti reaction) and ophthalmological reactions in patients with onchocerciasis
• These reactions are probably due to allergic and inflammatory responses to the death of microfilariae; onchocerciasis treated patients may experience these reactions in addition to clinical adverse reactions possibly related to the drug itself
• The treatment of severe Mazzotti reactions has not been subjected to controlled clinical trials; oral hydration, recumbency, intravenous normal saline, and/or parenteral corticosteroids have been used to treat postural hypotension; antihistamines and/or aspirin have been used for most mild to moderate cases

Loiasis

• Rarely, patients with onchocerciasis who are also heavily infected with Loa loa may develop a serious or even fatal encephalopathy either spontaneously or following treatment with an effective microfilaricide
• The following adverse experiences have been reported in these patients, pain (including neck and back pain), red eye, conjunctival hemorrhage, dyspnea, urinary and/or fecal incontinence, difficulty in standing/walking, mental status changes, confusion, lethargy, stupor, seizures, or coma
• This syndrome has been seen very rarely following the use of ivermectin; in individuals who warrant treatment with ivermectin for any reason and have had significant exposure to Loa loa-endemic areas of West or Central Africa, implement pretreatment assessment for loiasis and careful post-treatment follow-up

Drug interactions overview

• Post-marketing reports of increased INR (International Normalized Ratio) have been rarely reported when ivermectin was co-administered with warfarin

Pregnancy category: C

Pregnancy

There are no studies in pregnant women; epidemiologic studies during pregnancy are insufficient to inform a drug-associated risk of adverse developmental outcomes, because either the timing of administration during gestation was not accurately ascertained or the administration occurred only during the second trimester; however, systemic exposure from topical use of ivermectin is much lower than that from oral use

In animal reproduction studies, ivermectin induced adverse developmental outcomes when orally administered to pregnant mice, rats and rabbits during the period of organogenesis only at or near doses that were maternally toxic to the pregnant females

Lactation

There is information available on the presence of ivermectin in human milk in 4 lactating women after a single 150 mcg/kg oral dose of ivermectin; however, there is insufficient information from this study to determine effects of ivermectin on breastfed infant or on milk production

Topical ivermectin systemic exposure is much lower than that for oral ivermectin; furthermore, amount of ivermectin present in human milk after topical application to lactating women has not been studied

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed infant or from underlying maternal condition

Lactation: Enters breast milk (AAP Committee states compatible with nursing)

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

Binds glutamate-gated Cl ion channels in invertebrate nerve and muscle cells; produces paralysis, death of parasite

Absorption

Well absorbed

Peak serum time: 4 hr

Peak effect: 3-6 months (treatment of orchocerciasis); 3 months (treatment of strongyloides)

Distribution

Protein bound: 93%

Vd: 3-3.5 L/kg

Does not cross blood-brain barrier

Metabolism

Hepatic (CYP3A4, CYP2D6, CYP2E1)

Elimination

Half-life: 18 hr

Excretion: Feces; urine (<1%)