Doses - LOMUSTINE (CCNU)
Dogs:For the treatment of brain neoplasms:
a) Initially, 60 mg/m2 PO; if toxicity is minimal the dosage is increased slowly to 80mg/m2. Treatments given every 5-8 weeks. CBC done every week between treatments.(Fulton 1991)
For the treatment of canine mast cell sarcoma: See the protocol in the appendix.
Monitoring Parameters - 1) CBC with platelets at least every 1-2 weeks until stable; then every 3months; 2) Liver function tests; initially before starting treatment and then every 3-4 months
Dosage Forms/Preparations/FDA Approval Status/Withholding Times - Veterinary-Approved Products: None
Human-Approved Products:Lomustine Capsules 10 mg, 40 mg, 100 mg; Dose Pack (two 100 mg capsules, two 40 mgcapsules & two 10 mg capsules) CeeNu® (Bristol-Myers Oncology); (Rx)
Loperamide - see Opiate Antidiarrheals
Storage, Stability, CompatibilityA benzoylphenylurea derivative, lufenuron isclassified as an insect development inhibitor. The drug is considered to be lipophilic. The commercially available tablets and suspension should be stored at room temperature (15-30°C). Themanufacturer states that intermittent exposure or exposure less than 48 hours to temperaturesoutside of storage recommendations for the tablets or suspension should not affect potency.
Lufenuron tablets are assigned a 4 year expiration date after manufacture; the suspension, 3 yearsafter manufacture; and Sentinel® tablets 3 years after manufacture. Opened pouches of the suspension are not recommended to be stored until the following dosing cycle.
PharmacologyLufenuron acts by inhibiting chitin synthesis, polymerization and deposition infleas, thereby preventing eggs from developing into adults. The exact mechanism for this action wasnot noted. Lufenuron does not kill adult fleas.
Uses, Indications - Lufenuron is approved for use in dogs and cats 6 weeks of age and older forthe control of flea populations. The combination product of lufenuron and milbemycin (Sentinel®)is indicated for use in puppies and dogs 4 weeks and older for prevention and control of fleapopulations, prevention of heartworm disease, control of adult hookworms, and the removal andcontrol of adult roundworms and whipworms.
PharmacokineticsApproximately 40% of an oral dose is absorbed with the remainder eliminated in the feces. To maximize oral absorption, the manufacturer recommends to administer inconjunction with or immediately after (within 30 minutes) a full meal. The drug is absorbed in thesmall intestine and stored in lipose tissue which acts as depot reservoir to slowly redistribute thedrug back into the circulation. While the drug concentrates in the milk of lactating animals, itapparently does not cause ill effects in nursing animals.
After cats receive the injectable product, 2 -3 weeks are required before blood levels attain effectiveconcentrations. Cats require a substantially higher oral dosage per kg than do dogs for equivalentefficacy. The drug is apparently not metabolized, but excreted unchanged into the bile andeliminated in the feces.
Contraindications, Precautions, Reproductive SafetyNo listed contraindications are noted.
The oral lufenuron products are considered to be safe to use in pregnant, breeding or lactatinganimals; safety of the injectable product in reproducing cats has not been formally established atthis time.
Adverse Effects, WarningsAdverse effects reported in dogs and cats after oral lufenuron include: vomiting, lethargy/depression, pruritus/urticaria, diarrhea, dyspnea, anorexia and reddenedskin. The manufacturer reports that the adverse reaction rate is less than 5 animals in one milliondoses.
After receiving the injectable product, a small lump at the injection site has been noted in somecats. A few weeks may be required for this to dissipate.
Overdosage - Growing puppies were dosed at levels up to 30X for 10 months without overt effecton growth or viability noted. Cats receiving oral dosages of up to 17X apparently were unaffected.