EPSOLAY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EPSOLAY (EPSOLAY).
EPSOLAY (ivermectin) is an antiparasitic agent derived from avermectins. It acts by binding selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate nerve and muscle cells, leading to increased permeability to chloride ions and hyperpolarization of the cell, resulting in paralysis and death of the parasite. It also interacts with other ligand-gated chloride channels, such as those gated by gamma-aminobutyric acid (GABA). Ivermectin does not readily cross the blood-brain barrier in humans and has minimal affinity for mammalian ligand-gated chloride channels.
| Metabolism | Ivermectin is extensively metabolized in the liver, primarily by the CYP450 enzyme system, specifically CYP3A4. Metabolism involves hydroxylation and demethylation. It is also a substrate for P-glycoprotein transport. The drug and its metabolites are excreted almost exclusively in feces over approximately 12 days, with less than 1% excreted in urine. |
| Excretion | Primarily renal excretion of unchanged drug (approximately 60-70% of the absorbed dose) with hepatic metabolism accounting for the remainder; fecal excretion is minimal. |
| Half-life | Terminal elimination half-life is approximately 2 to 4 minutes following intravenous administration; clinically, this rapid clearance limits systemic exposure and allows for localized effect. |
| Protein binding | 61% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 2.7 L/kg, indicating extensive distribution into tissues beyond the vascular space. |
| Bioavailability | Bioavailability following topical application via the transurethral delivery system is approximately 7-10% of the administered dose; systemic absorption is limited. |
| Onset of Action | Onset of action following topical application to the prostate via a transurethral delivery system is within minutes; clinical effect (symptom relief) observed shortly after procedure. |
| Duration of Action | Duration of action following topical application with the transurethral delivery system is sustained for up to 6 months; clinical improvement in urinary symptoms persists over this period. |
Topical: Apply a pea-sized amount to the entire face once daily in the morning. Deliver 1-2 pumps to palm and apply to clean, dry face.
| Dosage form | CREAM |
| Renal impairment | No dosage adjustment required for renal impairment. Not studied in severe renal impairment. |
| Liver impairment | No dosage adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Approved for age 9 years and older. Same dosing as adults: apply a pea-sized amount once daily. Safety and efficacy in children under 9 not established. |
| Geriatric use | No specific dose adjustment recommended. Clinical studies did not include sufficient patients aged 65 and over to determine if they respond differently. Use with caution due to possible increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EPSOLAY (EPSOLAY).
| Breastfeeding | Unknown excretion into human milk. Caution advised. M/P ratio not established. Consider developmental benefits of breastfeeding vs maternal need for drug and potential adverse effects on nursing infant. |
| Teratogenic Risk | FDA Pregnancy Category C. No adequate and well-controlled studies in pregnant women. Animal studies have shown fetal abnormalities at doses higher than human plasma concentrations. Risk cannot be ruled out. Avoid use during first trimester. In second and third trimester, use only if potential benefit justifies potential risk to fetus. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to ivermectin or any component of the formulation","Concurrent treatment with diethylcarbamazine (DEC) in onchocerciasis due to risk of severe Mazzotti reaction"]
| Precautions | ["Risk of severe allergic reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis","Potential for neurotoxicity (e.g., dizziness, somnolence, tremor) especially in patients with compromised blood-brain barrier (e.g., meningeal inflammation, Loa loa co-infection)","In patients with onchocerciasis, destruction of microfilariae can cause Mazzotti reaction (fever, pruritus, urticaria, arthralgia, myalgia, lymphadenitis, ophthalmic lesions)","Use with caution in patients with liver disease, as metabolism is hepatic","Use with caution in patients with HIV/AIDS due to risk of disseminated strongyloidiasis and need for adjunctive therapy","Potential for drug interactions with CYP3A4 and P-glycoprotein substrates/inhibitors (e.g., statins, warfarin, ketoconazole)","May cause corneal edema or visual disturbances if optic nerve involvement is present in onchocerciasis - monitor ophthalmologically"] |
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| Fetal Monitoring |
| Monitor for signs of preterm labor and fetal growth restriction. Ultrasound monitoring for fetal weight and amniotic fluid index recommended. Maternal monitoring for blood pressure, renal function, and signs of pulmonary edema. |
| Fertility Effects | No significant reproductive toxicity in animal studies. In males, no impairment of fertility at clinically relevant doses. Effect on female fertility not specifically studied. Use in women of childbearing potential requires effective contraception. |