Emodepside

Summary

Emodepside is a semi-synthetic cyclic depsipeptide anthelmintic derived from PF1022A, a natural product of the fungus Rosellinia sp. It is approved in veterinary medicine (as Profender topical spot-on combined with praziquantel) for the treatment of gastrointestinal nematode infections in cats. It is also under clinical investigation as a human anthelmintic for infections such as onchocerciasis and other filarial diseases.

Mechanism of Action

Activates latrophilin receptors (adhesion GPCRs) and SLO-1 potassium channels in nematodes, leading to flaccid paralysis and death of parasitic worms; also modulates presynaptic neurotransmitter release

Routes of Administration

Goals & Uses

• Treatment of strongyloidiasisAntiparasiticLow
• Overcoming anthelmintic resistanceAntiparasiticModerate
• Treatment of lymphatic filariasisAntiparasiticModerate
• Treatment of feline gastrointestinal nematodesAntiparasiticHigh
• Treatment of onchocerciasis (river blindness)AntiparasiticModerate

Contraindications

• Pregnancy (human investigational use)Reproductive SafetyHigh
• Severe hepatic impairment (human use)Organ ImpairmentModerate
• Hypersensitivity to emodepside or excipientsAllergyHigh
• Use in kittens under 8 weeks or cats under 0.5 kg (veterinary)Age/weight RestrictionHigh

Adverse Effects

• Elevated liver enzymes (human trials)HepaticUncommon
• Headache, fatigue (human trials)GeneralCommon
• Neurological signs (ataxia, lethargy)NeurologicalRare
• VomitingGastrointestinalUncommonForceful expulsion of stomach contents
• Transient salivation / hypersalivationGastrointestinalUncommon
• Application site reactions (erythema, pruritus)DermatologicCommon

Drug Interactions

• CYP3A4 inhibitors (e.g., azole antifungals, macrolide antibiotics)Moderate
• Other anthelmintics (e.g., ivermectin)Low
• P-glycoprotein (P-gp) inhibitors (e.g., ketoconazole, verapamil)Moderate

Population Constraints

• Cats with known P-gp deficiency (MDR1 mutation) — not applicable, but analogous concernVeterinary GeneticsRelative
• Pregnant women (human investigational)PregnancyRelative
• Lactating womenReproductiveRelative
• Patients with MDR1/ABCB1 mutationsPharmacogenomicsRelative
• Pediatric population (human use)PediatricsRelative

Regulatory Status

• European UnionApprovedApproved: Treatment of mixed nematode and cestode infections in cats (veterinary use, Profender spot-on)Approved by EMA for veterinary use; human use remains investigational
• United StatesInvestigationalNot FDA-approved for human use; veterinary product not widely marketed in US under this name; human trials ongoing via DNDi
• United KingdomApprovedApproved: Veterinary anthelmintic for cats (Profender)Approved for veterinary use post-Brexit under UK VMD; human use investigational

Approved by EMA and in several jurisdictions for veterinary use in cats (Profender spot-on). Investigational in humans under clinical trials for onchocerciasis (river blindness) and filariasis, supported by DNDi and other global health organizations.

Evidence & Sources

No sources recorded yet.