Oral Ivermectin Therapeutic Cheat Sheet

Ivermectin is a semi-synthetic derivative of avermectins, a class of macrocyclic lactones with broad-spectrum anti-parasitic effects. Its unique mechanism of action, favorable safety profile, and anti-inflammatory properties make ivermectin invaluable in the treatment of a wide range of cutaneous parasitic infestations, including scabies. We continue our series, Therapeutic Cheat Sheet, with a closer look at oral ivermectin.

                                      Oral Ivermectin Therapeutic Cheat Sheet

Compiled by: Olive Osuoji, MD, Reviewed by: Adam Friedman, MD

TRADE NAME^1-2

• • Stromectol

MECHANISM OF ACTION ^1-6

• • Ivermectin selectively binds to glutamate-gated ion channels in invertebrates, increasing chloride ion permeability, leading to paralysis and death of parasites.⁴

• • Ivermectin functions as a gamma-aminobutyric acid (GABA) agonist but does not readily cross the blood-brain barrier in humans, ensuring a good safety profile.^3-4

• • Ivermectin suppresses inflammatory response by inhibiting liposaccharide (LPS)-induced cytokine production, reducing levels of tumor necrosis factor alpha (TNF-a), interleukin (IL)-1β, and IL-6. ^4-5

FDA APPROVED FOR ^1-3

• • Gastrointestinal Strongyloidiasis
  • Onchocerciasis

OFF-LABEL DERMATOLOGIC USES

• • Scabies
  • Cutaneous demodicosis
  • Refractory body/head lice
  • Pediculosis palpebrarum
  • Ocular and cutaneous rosacea
  • Blepharitis
  • Cutaneous larva migrans
  • Cutaneous larva currens
  • Myiasis
  • Cutaneous gnathostomiasis
  • Filariasis 

DOSING⁸

• • Oral ivermectin dosing is variable depending on the condition being treated and the patient’s response. Generally, 150-250 mcg/kg as a single dose is recommended, with a repeat dose on day 7 or 14 for scabies and strongyloidiasis.

SIDE EFFECTS^1-3,8     

Ivermectin is well tolerated, with side effects reported in <4% of patients

• • CNS/Psychiatric Effects
    • Headache, dizziness, somnolence, vertigo, tremor, stupor, coma, seizures

• • Skin Effects
    • Pruritus, urticaria, delayed hypersensitivity reaction ranging from morbilliform rash to severe cutaneous adverse reaction:

• • Severe Cutaneous Reactions 

• • • Stevens-Johnson Syndrome (SJS)
    • Toxic Epidermal Necrolysis (TEN)
    • Drug Hypersensitivity Syndrome (DHS)

• • Hematological Effects
    • Decreased white blood cell counts, eosinophilia, increased hemoglobin

• • Cardiovascular/respiratory Effects
    • Orthostatic hypotension, tachycardia, peripheral edema, ECG changes, worsening asthma

• • Gastrointestinal Effects
    • Abdominal pain, diarrhea, nausea, vomiting, constipation

• • Hepatic Effects
    • Elevated ALT/AST, hepatitis, elevated bilirubin

• • Other Effects
    • Fatigue, anorexia, asthenia

WARNINGS AND PRECAUTIONS

• • Patients treated with ivermectin may experience a Mazzoti reaction, an immunologic response in approximately ~10% of patients treated for onchocerciasis. Symptoms include headache, fevers, myalgia, arthralgia, lymphadenitis, cardiovascular effects, and ocular or skin manifestations including pruritus and various primary and secondary lesions. ^2,8 Triggered by antigen release from dying microfilariae,⁹ the reaction generally resolves with supportive care and discontinuation of ivermectin.²

• • A single oral dose of ivermectin may be ineffective in some scabies patients due to its lack of ovocidal action, requiring a second dose to kill newly hatched mites.^6,7

 CONTRAINDICATIONS

• • Contraindicated in patients with a history of hypersensitivity to ivermectin or any of its components
  • Contraindicated in patients with nervous system disorders.
  • Ivermectin is not recommended in children younger than 5 years or less than 15kg in weight due to a theoretical risk of CNS adverse events.^6,8 However, studies have documented its use in this population without major side effects.^4,10

DRUG INTERACTIONS

• • Ivermectin may enhance the anticoagulant effects of Vitamin K antagonists (e.g. warfarin).⁸

PREGNANCY AND BREASTFEEDING

• • Ivermectin is classified as FDA Pregnancy Category C, and its use during pregnancy is not recommended. Pregnancy status should be confirmed before administering ivermectin to patients who may become pregnant.⁸

• • Prior studies indicate that unintentional ivermectin exposure in mass treatment programs has not been associated with adverse pregnancy outcomes, including abortion or congenital malformations, nor any harmful effects on mothers or their children.⁴

• • Ivermectin is excreted in human breastmilk in low concentrations;¹¹ however its clinical significance remains unclear. Treatment should only be considered if the risk of delaying treatment outweighs the potential risk to the newborn.²

  LAB MONITORING

• • No routine laboratory monitoring is required

FURTHER READING

If you would like to learn more about oral ivermectin, check out the following articles in the Journal of Drugs in Dermatology:

Ivermectin in Dermatology

Del Giudice P, Chosidow O, Caumes E

Abstract

Ivermectin, a broad-spectrum anti-parasitic agent first used in veterinary medicine, is active against numerous species of helminths and arthropods. For the past few years, world-wide reports on the use of ivermectin in various parasitic diseases with cutaneous tropism have led to its use in the field of skin parasitology. In this paper we review parasitoses which have been treated with ivermectin; mainly, filariasis, strongyloidiasis, cutaneous larva migrans, and scabies and head lice.

J Drugs Dermatol. 2003 Jan;2(1):13-21.

Over 25 years of Clinical Experience With Ivermectin: An Overview of Safety for an Increasing Number of Indications

Kircik LH, Del-Rosso JQ, Leyton AM et al

Abstract

Although the broad-spectrum anti-parasitic effects of the avermectin derivative ivermectin are well documented, its anti-inflammatory activity has only recently been demonstrated. For over 25 years, ivermectin has been used to treat parasitic infections in mammals, with a good safety profile that may be attributed to its high affinity to invertebrate neuronal ion channels and its inability to cross the blood–brain barrier in humans and other mammals. Numerous studies report low rates of adverse events, as an oral treatment for parasitic infections, scabies and head lice. Ivermectin has been used off-label to treat diseases associated with Demodex mites, such as blepharitis and demodicidosis. New evidence has linked Demodex mites to rosacea, a chronic inflammatory disease. Ivermectin has recently received FDA and EU approval for the treatment of adult patients with inflammatory lesions of rosacea, a disease in which this agent has been shown to be well tolerated. After more than 25 years of use, ivermectin continues to provide a high margin of safety for a growing number of indications based on its anti-parasitic and anti-inflammatory activities.

J Drugs Dermatol. 2016 Mar;15(3):325-32.

REFERENCES

1. 1. Merck Sharp & Dohme LLC. Drug label information. Stromectol (Ivermectin) 3 mg Tablets. Revised Nov, 2024. https://www.merck.com/product/usa/pi_circulars/s/stromectol/stromectol_pi.pdf

1. 2. Stromectol (Ivermectin) Package Insert. Revised March, 2022.

https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/050742s030lbl.pdf

1. 3. Edenbridge Pharmaceuticals LLC. Drug label information. Ivermectin Tablets USP, 3mg https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=847a1dd7-d65b-4a0e-a67d-d90392059dac&type=display
   4. Kircik LH, Del Rosso JQ, Layton AM, Schauber J. Over 25 Years of Clinical Experience With Ivermectin: An Overview of Safety for an Increasing Number of Indications. J Drugs Dermatol. 2016 Mar;15(3):325-32.

1. 1. Zhang X, Song Y, Ci X, et al. Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice. Inflamm Res. 2008;57(11):524-529.

1. 6. Dourmishev AL, Dourmishev LA, Schwartz RA. Ivermectin: pharmacology and application in dermatology. Int J Dermatology. 2005;44(12):981-988.
   7. Currie BJ, McCarthy JS. Permethrin and Ivermectin for Scabies. N Engl J Med. 2010 Feb 25;362(8):717-25.
   8. Ivermectin: Drug information. In: UpToDate, Connor RF (Ed), Wolters Kluwer.
   9. Ito T. Mazzotti reaction with eosinophilia after undergoing oral ivermectin for scabies. J Dermatol. 2013 Sep;40(9):776-7.
   10. Levy M, Martin L, Bursztejn A ‐, et al. Ivermectin safety in infants and children under 15 kg treated for scabies: a multicentric observational study. Br J Dermatol. 2020;182(4):1003-1006.
   11. Johnson-Arbor K. Ivermectin: a mini-review. Clinical Toxicology. 2022;60(5):571-575.

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