ivermectin

Brand: Stromectol

Prototype Drug
Drug Class: macrocyclic lactone antiparasitic
Drug Family: antiparasitic
Subclass: avermectin antiparasitic agent
Organ Systems: infectious-disease

Mechanism of Action

Binds glutamate-gated chloride channels exclusive to invertebrate nervous systems; potentiates GABA at invertebrate neuromuscular junctions; causes hyperpolarization and paralysis of parasites; mammalian safety due to absence of GluCl channels and P-gp exclusion from CNS.

glutamate-gated chloride channels (GluCl) in invertebrate neurons and muscle cells

Indications

  • onchocerciasis (river blindness) — microfilaricidal
  • strongyloidiasis
  • lymphatic filariasis (mass drug administration)
  • scabies (including crusted/Norwegian scabies)
  • pediculosis (lice) — for treatment-resistant cases

Contraindications

  • ivermectin hypersensitivity
  • Loa loa microfilaremia (>2500 mf/mL — encephalopathy risk)
  • concurrent P-gp inhibitors in meningitis (theoretical BBB penetration)

Adverse Effects

Common

  • Mazzotti reaction (fever, urticaria, edema, arthralgia from dying microfilariae)
  • GI upset
  • dizziness

Serious

  • encephalopathy/neurotoxicity (in Loa loa coinfection or P-gp mutations that allow CNS entry)
  • Mazzotti reaction with hypotension (in heavy infestations)

Pharmacokinetics (ADME)

Absorption high-fat meal increases absorption 2.5-fold; administration with food recommended
Distribution large Vd; high lipophilicity; excluded from CNS in normal hosts by P-glycoprotein
Metabolism hepatic CYP3A4
Excretion fecal (almost entirely); renal <1%
Half-life 18 hours
Onset 4 hours
Peak 4 hours
Duration variable; single dose for most indications
Protein Binding 93%
Vd large

Drug Interactions

Drug / Agent Mechanism Severity
warfarin ivermectin may increase INR; monitor during and after therapy moderate
P-gp inhibitors may allow CNS penetration; theoretical neurotoxicity risk moderate

Nursing Considerations

  1. Administer with food or water; high-fat meal improves absorption for strongyloidiasis treatment.
  2. For scabies: after treatment, bedding, clothing, and towels must be washed in hot water; household contacts should be evaluated.
  3. Advise patients about Mazzotti reaction (flu-like symptoms after treatment of onchocerciasis) — this represents immune response to dying parasites and can be managed with antihistamines and antipyretics.
  4. Screen for Loa loa exposure in patients from endemic areas (Central Africa) before mass drug administration campaigns.

Clinical Pearls

  • Ivermectin is one of the most transformative drugs in global health — its deployment for onchocerciasis and lymphatic filariasis elimination programs has dramatically reduced the burden of these tropical diseases; its discoverers received the 2015 Nobel Prize in Medicine.
  • P-glycoprotein at the blood-brain barrier is essential for preventing ivermectin CNS entry in mammals; certain collies (MDR1/ABCB1 mutation) and humans with P-gp mutations lack this protection, resulting in ivermectin neurotoxicity at standard doses.

Safety Profile

Pregnancy avoid
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required