Pet Safety / Compounds / Selamectin (Revolution)

Is Selamectin (Revolution) safe for dogs and cats?

Low risk for pets

Selamectin presents low risk to dogs in most breeds at FDA-approved topical doses. The topical route provides substantially lower peak systemic blood levels than oral macrolide administration, giving selamectin a more favorable safety margin in MDR1-deficient breeds compared to oral ivermectin. However, MDR1/ABCB1 genetic sensitivity still applies — Collies, Australian Shepherds, Shetland Sheepdogs, and related herding breeds with the 4-bp MDR1 deletion may experience mild neurotoxicity (ataxia, sedation) at topical selamectin doses. MDR1 genetic testing is advisable for susceptible breeds before initiating therapy. At recommended monthly spot-on doses, selamectin is well-tolerated in the vast majority of dogs, with local application site reactions (temporary hair loss, pruritus) the most common reported adverse events. Avoid concurrent use of P-gp inhibitors (ketoconazole, cyclosporine).

What is selamectin (revolution)?

The IUPAC name is (1R,4S,5'S,6R,6'S,8R,10E,12S,13S,14E,16E,20R,21Z,24S)-6'-cyclohexyl-24-hydroxy-21-hydroxyimino-12-[(2R,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-5',11,13,22-tetramethylspiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2'-oxane]-2-one.

Also known as: (1R,4S,5'S,6R,6'S,8R,10E,12S,13S,14E,16E,20R,21Z,24S)-6'-cyclohexyl-24-hydroxy-21-hydroxyimino-12-[(2R,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-5',11,13,22-tetramethylspiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2'-oxane]-2-one, selamectin, Revolution, UK-124,114.

IUPAC name
(1R,4S,5'S,6R,6'S,8R,10E,12S,13S,14E,16E,20R,21Z,24S)-6'-cyclohexyl-24-hydroxy-21-hydroxyimino-12-[(2R,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-5',11,13,22-tetramethylspiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2'-oxane]-2-one
CAS number
220119-17-5
Molecular formula
C43H63NO11
Molecular weight
770.0 g/mol
SMILES
CC1CCC2(CC3CC(O2)CC=C(C(C(C=CC=C4COC5C4(C(C=C(C5=NO)C)C(=O)O3)O)C)OC6CC(C(C(O6)C)O)OC)C)OC1C7CCCCC7
PubChem CID
9578507

Risk for dogs

Low risk

Selamectin presents low risk to dogs in most breeds at FDA-approved topical doses. The topical route provides substantially lower peak systemic blood levels than oral macrolide administration, giving selamectin a more favorable safety margin in MDR1-deficient breeds compared to oral ivermectin. However, MDR1/ABCB1 genetic sensitivity still applies — Collies, Australian Shepherds, Shetland Sheepdogs, and related herding breeds with the 4-bp MDR1 deletion may experience mild neurotoxicity (ataxia, sedation) at topical selamectin doses. MDR1 genetic testing is advisable for susceptible breeds before initiating therapy. At recommended monthly spot-on doses, selamectin is well-tolerated in the vast majority of dogs, with local application site reactions (temporary hair loss, pruritus) the most common reported adverse events. Avoid concurrent use of P-gp inhibitors (ketoconazole, cyclosporine).

Regulatory consensus

1 regulatory bodyhas classified Selamectin (Revolution).

AgencyYearClassificationNotes
IARC2023Not evaluated by IARC — selamectin is an FDA/CVM-approved topical spot-on veterinary macrolide antiparasitic for dogs and cats; chemically a semisynthetic avermectin derivative; treats and prevents fleas, heartworm, ear mites, sarcoptic mange, and ticks; MDR1/ABCB1 breed sensitivity applies; no carcinogenicity classification

Regulators apply different standards of evidence — animal-data weighting, exposure-pattern assumptions, epidemiological power thresholds — which is why two scientific bodies can review the same data and reach different conclusions. The disagreement is the data.

Where pets encounter selamectin (revolution)

  • Industrial FacilitiesManufacturing plants, Chemical storage areas, Waste treatment sites
  • Occupational EnvironmentsFactories, Warehouses, Transportation vehicles

Safer alternatives

Lower-risk approaches that achieve a similar outcome to Selamectin (Revolution):

  • Alternative drug class; Non-pharmacological therapy; Lowest effective dose
    Trade-offs: Direct chemical substitution requires verification that the replacement does not introduce new hazards (regrettable substitution). Conduct full hazard assessment of proposed alternative before adoption.
    Relative cost: 1.2-2×

Frequently asked questions

Is selamectin (revolution) safe for pets?

Selamectin presents low risk to dogs in most breeds at FDA-approved topical doses. The topical route provides substantially lower peak systemic blood levels than oral macrolide administration, giving selamectin a more favorable safety margin in MDR1-deficient breeds compared to oral ivermectin. However, MDR1/ABCB1 genetic sensitivity still applies — Collies, Australian Shepherds, Shetland Sheepdogs, and related herding breeds with the 4-bp MDR1 deletion may experience mild neurotoxicity (ataxia, sedation) at topical selamectin doses. MDR1 genetic testing is advisable for susceptible breeds before initiating therapy. At recommended monthly spot-on doses, selamectin is well-tolerated in the vast majority of dogs, with local application site reactions (temporary hair loss, pruritus) the most common reported adverse events. Avoid concurrent use of P-gp inhibitors (ketoconazole, cyclosporine).

What products contain selamectin (revolution)?

Selamectin (Revolution) appears in: Manufacturing plants (Industrial facilities); Chemical storage areas (Industrial facilities); Factories (Occupational environments); Warehouses (Occupational environments).

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Sources (1)

  1. Selamectin Revolution Zoetis FDA CVM Topical Spot-On; Monosaccharide Avermectin GluCl Chloride Channel; Flea Heartworm Ear Mite Sarcoptic Mange Tick Dogs Cats; Sebaceous Gland Depot Transdermal 4.4% Bioavailability; MDR1 ABCB1 Lower Risk Topical vs Oral; Human Skin Contact Wash Hands Post-Application; Log Kow 7.7 Aquatic Daphnia Ecotoxicity; Bathing Swimming Caution Post-Application (2023) — regulatory

Reference data, not professional advice. Aggregates publicly available regulatory and scientific data; not a substitute for veterinary, medical, legal, or regulatory advice. Why we built ALETHEIA →