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dwerten · 05-25-2010, 08:10 PM

CCNU (Lomustine) is a very effective addition to or replacement for prednisone immune suppression in prednisone resistant cases, for cases that relapse off of prednisone or when prednisone adverse effects are too severe. Lomustine is a nitrosourea compound used in the treatment of certain neoplasic diseases and is a potent immune suppressor primarily due to its toxic effect on lymphocytes. It alkylates DNA and RNA but is not cross resistant with other alkylating agents such as Cytoxan. Since the drug has high lipid solubility and it is not ionized at physiological pH, it crosses the blood-brain barrier very well reaching 50 percent or greater than plasma levels. Lomustine is most commonly used to treat brain tumors and lymphosarcoma.

The primary toxicity of the drug is bone marrow suppression causing leukopenia and delayed thrombocytopenia. The toxic effects on the bone marrow are cumulative. The delayed thrombocytopenia is only a problem if the drug is dosed once every three weeks rather than every four weeks. Using every 4-week dosing thrombocytopenia does not occur. Some dogs, toward the end of one year of therapy, start to become too leukopenic on a dose that previously did not cause this. For this reason hemograms should be watched closely toward the end of therapy.
The only other major toxicity is gastrointestinal causing vomiting and diarrhea especially if the dose is high enough to cause excess myelosuppression. If the dog has severe neutropenia and gastrointestinal bleeding from a lomustine overdose, shock, sepsis and death can occur quickly. Lomustine is reported to be hepatoxic in dogs at times when used at high doses of 90/.meter squared every 3 to 4 weeks at the same time other hepatotoxic drugs like trimethoprim-sulfadiazine or drugs that interfere with its hepatic metabolism such as cimetidine are given.14 It is very unlikely this hepatotoxicity will occur at the immunosuppressive doses used for autoimmune disease as long as therapy does not exceed one year. Serum chemistry monitoring for hepatotoxicity can be done after the first treatment then every three months thereafter.

05-25-2010, 08:10 PM	#75
dwerten BANNED! Join Date: May 2007 Location: USA Posts: 11,073	CCNU (Lomustine) is a very effective addition to or replacement for prednisone immune suppression in prednisone resistant cases, for cases that relapse off of prednisone or when prednisone adverse effects are too severe. Lomustine is a nitrosourea compound used in the treatment of certain neoplasic diseases and is a potent immune suppressor primarily due to its toxic effect on lymphocytes. It alkylates DNA and RNA but is not cross resistant with other alkylating agents such as Cytoxan. Since the drug has high lipid solubility and it is not ionized at physiological pH, it crosses the blood-brain barrier very well reaching 50 percent or greater than plasma levels. Lomustine is most commonly used to treat brain tumors and lymphosarcoma. The primary toxicity of the drug is bone marrow suppression causing leukopenia and delayed thrombocytopenia. The toxic effects on the bone marrow are cumulative. The delayed thrombocytopenia is only a problem if the drug is dosed once every three weeks rather than every four weeks. Using every 4-week dosing thrombocytopenia does not occur. Some dogs, toward the end of one year of therapy, start to become too leukopenic on a dose that previously did not cause this. For this reason hemograms should be watched closely toward the end of therapy. The only other major toxicity is gastrointestinal causing vomiting and diarrhea especially if the dose is high enough to cause excess myelosuppression. If the dog has severe neutropenia and gastrointestinal bleeding from a lomustine overdose, shock, sepsis and death can occur quickly. Lomustine is reported to be hepatoxic in dogs at times when used at high doses of 90/.meter squared every 3 to 4 weeks at the same time other hepatotoxic drugs like trimethoprim-sulfadiazine or drugs that interfere with its hepatic metabolism such as cimetidine are given.14 It is very unlikely this hepatotoxicity will occur at the immunosuppressive doses used for autoimmune disease as long as therapy does not exceed one year. Serum chemistry monitoring for hepatotoxicity can be done after the first treatment then every three months thereafter.