Is Milbemycin oxime safe for dogs and cats?
Moderate risk for petsMilbemycin oxime presents a low to moderate risk to dogs depending on breed and MDR1/ABCB1 genetic status. In MDR1 wild-type dogs (the majority of dog breeds), milbemycin oxime at FDA-approved doses (0.5–1 mg/kg monthly) has an excellent safety margin for heartworm prevention and parasite control. The primary safety concern is neurotoxicity in MDR1-deficient dogs (Rough/Smooth Collies: ~70% carrier rate; Australian Shepherds, Shetland Sheepdogs, Border Collies, and related herding breeds: variable carrier rates of 10–50%). MDR1 −/− homozygous dogs are at high risk of severe neurological toxicity (ataxia, tremors, coma) even at approved doses. MDR1 +/− heterozygotes have intermediate susceptibility. Veterinary prescribers should: (1) perform MDR1 genetic testing for susceptible breeds before prescribing macrolide antiparasitics; (2) use alternative antiparasitic classes if MDR1 −/− status is confirmed. Concurrent use with drugs that inhibit P-glycoprotein (e.g., ketoconazole, cyclosporine) can increase CNS milbemycin levels even in MDR1 wild-type dogs.
What is milbemycin oxime?
The IUPAC name is (1R,4S,5'S,6R,6'R,8R,10E,13R,14E,16E,20R,21Z,24S)-6'-ethyl-24-hydroxy-21-hydroxyimino-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;(1R,4S,5'S,6R,6'R,8R,10E,13R,14E,16E,20R,21Z,24S)-24-hydroxy-21-hydroxyimino-5',6',11,13,22-pentamethylspiro[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'R,8R,10E,13R,14E,16E,20R,21Z,24S)-6'-ethyl-24-hydroxy-21-hydroxyimino-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;(1R,4S,5'S,6R,6'R,8R,10E,13R,14E,16E,20R,21Z,24S)-24-hydroxy-21-hydroxyimino-5',6',11,13,22-pentamethylspiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2'-oxane]-2-one, Interceptor flavor tabs, Milbemite, CGA-179246.
- IUPAC name
- (1R,4S,5'S,6R,6'R,8R,10E,13R,14E,16E,20R,21Z,24S)-6'-ethyl-24-hydroxy-21-hydroxyimino-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;(1R,4S,5'S,6R,6'R,8R,10E,13R,14E,16E,20R,21Z,24S)-24-hydroxy-21-hydroxyimino-5',6',11,13,22-pentamethylspiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2'-oxane]-2-one
- CAS number
- 129496-10-2
- Molecular formula
- C63H88N2O14
- Molecular weight
- 1097.4 g/mol
- SMILES
- CCC1C(CCC2(O1)CC3CC(O2)CC=C(CC(C=CC=C4COC5C4(C(C=C(C5=NO)C)C(=O)O3)O)C)C)C.CC1CCC2(CC3CC(O2)CC=C(CC(C=CC=C4COC5C4(C(C=C(C5=NO)C)C(=O)O3)O)C)C)OC1C
- PubChem CID
- 20056431
Risk for dogs
Moderate riskMilbemycin oxime presents a low to moderate risk to dogs depending on breed and MDR1/ABCB1 genetic status. In MDR1 wild-type dogs (the majority of dog breeds), milbemycin oxime at FDA-approved doses (0.5–1 mg/kg monthly) has an excellent safety margin for heartworm prevention and parasite control. The primary safety concern is neurotoxicity in MDR1-deficient dogs (Rough/Smooth Collies: ~70% carrier rate; Australian Shepherds, Shetland Sheepdogs, Border Collies, and related herding breeds: variable carrier rates of 10–50%). MDR1 −/− homozygous dogs are at high risk of severe neurological toxicity (ataxia, tremors, coma) even at approved doses. MDR1 +/− heterozygotes have intermediate susceptibility. Veterinary prescribers should: (1) perform MDR1 genetic testing for susceptible breeds before prescribing macrolide antiparasitics; (2) use alternative antiparasitic classes if MDR1 −/− status is confirmed. Concurrent use with drugs that inhibit P-glycoprotein (e.g., ketoconazole, cyclosporine) can increase CNS milbemycin levels even in MDR1 wild-type dogs.
Regulatory consensus
1 regulatory bodyhas classified Milbemycin oxime.
| Agency | Year | Classification | Notes |
|---|---|---|---|
| IARC | 2023 | Not evaluated by IARC — milbemycin oxime is an FDA/CVM-approved veterinary macrolide antiparasitic (dogs, cats) for heartworm prevention, mite treatment, and intestinal parasite control; no carcinogenicity classification; primary safety concern is neurotoxicity in MDR1 (ABCB1)-deficient dog breeds (Collies, Shetland Sheepdogs, Australian Shepherds and related breeds with P-glycoprotein deficiency) |
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 milbemycin oxime
- Industrial Facilities — Manufacturing plants, Chemical storage areas, Waste treatment sites
- Occupational Environments — Factories, Warehouses, Transportation vehicles
Safer alternatives
Lower-risk approaches that achieve a similar outcome to Milbemycin oxime:
-
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 milbemycin oxime safe for pets?
Milbemycin oxime presents a low to moderate risk to dogs depending on breed and MDR1/ABCB1 genetic status. In MDR1 wild-type dogs (the majority of dog breeds), milbemycin oxime at FDA-approved doses (0.5–1 mg/kg monthly) has an excellent safety margin for heartworm prevention and parasite control. The primary safety concern is neurotoxicity in MDR1-deficient dogs (Rough/Smooth Collies: ~70% carrier rate; Australian Shepherds, Shetland Sheepdogs, Border Collies, and related herding breeds: variable carrier rates of 10–50%). MDR1 −/− homozygous dogs are at high risk of severe neurological toxicity (ataxia, tremors, coma) even at approved doses. MDR1 +/− heterozygotes have intermediate susceptibility. Veterinary prescribers should: (1) perform MDR1 genetic testing for susceptible breeds before prescribing macrolide antiparasitics; (2) use alternative antiparasitic classes if MDR1 −/− status is confirmed. Concurrent use with drugs that inhibit P-glycoprotein (e.g., ketoconazole, cyclosporine) can increase CNS milbemycin levels even in MDR1 wild-type dogs.
What products contain milbemycin oxime?
Milbemycin oxime appears in: Manufacturing plants (Industrial facilities); Chemical storage areas (Industrial facilities); Factories (Occupational environments); Warehouses (Occupational environments).
See Milbemycin oxime in the pets app
Look up products containing milbemycin oxime, compare to alternatives, and explore the full data record.
Open in pets View raw API dataSources (1)
- Milbemycin Oxime FDA CVM Interceptor Sentinel Trifexis; Streptomyces hygroscopicus Macrolide Milbemycin A3 A4 Oxime; GluCl GABA-Gated Chloride Channel Invertebrate; MDR1 ABCB1 P-Glycoprotein Collie Herding Breed Neurotoxicity; Dirofilaria Heartworm Prevention; Demodex Sarcoptes Mange; WSU MDR1 Genetic Testing; Log Kow Aquatic Invertebrate Ecotoxicity; IARC Not Evaluated (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 →