Safety, contraindications and genetic risk

Labrador Retriever — Copper storage disease in certain Labrador lines

Some Labrador Retriever lines carry an inherited predisposition to hepatic copper accumulation. In these dogs, injectable GHK-Cu introduces a copper load the liver handles poorly. Baseline and follow-up liver values are essential, and the topical route — which produces minimal systemic absorption — is strongly preferred.

Border Collie — MDR1 (ABCB1) mutation risk — genetic testing required before ivermectin

This breed carries a meaningful frequency of the MDR1 gene mutation, which prevents the drug-efflux protein at the blood-brain barrier from clearing ivermectin out of the central nervous system. Affected dogs develop neurotoxicity at doses other dogs tolerate without difficulty, and at the investigational oncology doses discussed on this site that reaction can be fatal. A cheek-swab test through Washington State University or a commercial laboratory settles the question and must be done before the first dose.

Australian Shepherd — MDR1 (ABCB1) mutation risk — genetic testing required before ivermectin

This breed carries a meaningful frequency of the MDR1 gene mutation, which prevents the drug-efflux protein at the blood-brain barrier from clearing ivermectin out of the central nervous system. Affected dogs develop neurotoxicity at doses other dogs tolerate without difficulty, and at the investigational oncology doses discussed on this site that reaction can be fatal. A cheek-swab test through Washington State University or a commercial laboratory settles the question and must be done before the first dose.

Rough Collie — MDR1 (ABCB1) mutation risk — genetic testing required before ivermectin

This breed carries a meaningful frequency of the MDR1 gene mutation, which prevents the drug-efflux protein at the blood-brain barrier from clearing ivermectin out of the central nervous system. Affected dogs develop neurotoxicity at doses other dogs tolerate without difficulty, and at the investigational oncology doses discussed on this site that reaction can be fatal. A cheek-swab test through Washington State University or a commercial laboratory settles the question and must be done before the first dose.

Shetland Sheepdog — MDR1 (ABCB1) mutation risk — genetic testing required before ivermectin

This breed carries a meaningful frequency of the MDR1 gene mutation, which prevents the drug-efflux protein at the blood-brain barrier from clearing ivermectin out of the central nervous system. Affected dogs develop neurotoxicity at doses other dogs tolerate without difficulty, and at the investigational oncology doses discussed on this site that reaction can be fatal. A cheek-swab test through Washington State University or a commercial laboratory settles the question and must be done before the first dose.

Old English Sheepdog — MDR1 (ABCB1) mutation risk — genetic testing required before ivermectin

This breed carries a meaningful frequency of the MDR1 gene mutation, which prevents the drug-efflux protein at the blood-brain barrier from clearing ivermectin out of the central nervous system. Affected dogs develop neurotoxicity at doses other dogs tolerate without difficulty, and at the investigational oncology doses discussed on this site that reaction can be fatal. A cheek-swab test through Washington State University or a commercial laboratory settles the question and must be done before the first dose.

Bedlington Terrier — Inherited copper storage disease — GHK-Cu contraindicated by the injectable route

Bedlington Terriers carry an autosomal recessive copper storage disorder caused by a COMMD1 gene deletion, which prevents normal biliary copper excretion and leads to progressive hepatic accumulation and cirrhosis. Injectable GHK-Cu introduces additional copper into a system already unable to clear it and should not be used. Topical application produces minimal systemic absorption and is the only route worth considering, with hepatic monitoring.

⚠ TB-500: Contraindicated with active cancer

TB-500 is associated with promoting angiogenesis and cell migration in preclinical models — the same two processes tumours depend on to grow and spread. Any dog with a known or suspected malignancy should be screened and cleared before this compound is considered.

⚠ GHK-Cu: Copper storage disease in predisposed breeds

Bedlington Terriers and certain Labrador Retriever lines carry an inherited copper storage disorder. In these dogs the injectable route risks hepatic copper accumulation. Hepatic function must be monitored, and the topical route is strongly preferred.

⚠ IGF-1 LR3: Contraindicated with active cancer

IGF-1 signalling directly drives cell proliferation. In a dog with an existing malignancy that is precisely the wrong signal. Screening before use is mandatory, not advisory.

⚠ IGF-1 LR3: Hypoglycaemia risk

IGF-1 LR3 has insulin-like activity and can lower blood glucose. Tremors, disorientation, weakness, or collapse are emergencies. Blood glucose must be monitored, and diabetic dogs require direct veterinary management.

⚠ MGF: Contraindicated with active cancer

As an IGF-1 family growth factor, MGF promotes cell proliferation. It should not be used in a dog with known or suspected malignancy.

⚠ PNC-27: No companion animal data exists

Every published finding on PNC-27 comes from cell culture or rodent models. There are no canine trials, no canine pharmacokinetics, and no canine safety data. This compound is included for completeness of the research landscape, not as a recommendation. It should only ever be considered under direct veterinary oncology supervision.

⚠ Fenbendazole: Bone marrow suppression with extended dosing

Pancytopenia has been documented in dogs receiving fenbendazole at extended daily doses beyond the labelled three-day deworming course. This is the specific reason protocols use three-on / four-off cycling and require regular CBC monitoring. Pale gums, lethargy, or appetite loss warrant immediate veterinary attention.

⚠ Fenbendazole: Do not combine with vincristine or paclitaxel

These chemotherapy agents share fenbendazole's microtubule-destabilising mechanism. Concurrent use risks additive toxicity. Any dog on conventional chemotherapy needs its oncologist involved before fenbendazole is added.

⚠ Ivermectin: MDR1 gene mutation — testing is mandatory

Dogs carrying the MDR1 (ABCB1) mutation cannot clear ivermectin from the brain and suffer neurotoxicity at doses other dogs tolerate. At the investigational oncology doses discussed here, that reaction can be fatal. Affected breeds include Collies, Australian Shepherds, Shetland Sheepdogs, Old English Sheepdogs, Border Collies, Long-haired Whippets, and any mixed breed with herding ancestry. The test is a simple cheek swab available through Washington State University and commercial laboratories. It must be done before the first dose.