MIBOLERONE
Chemistry - A non-progestational, androgenic, anabolic, antigonadotropic, 19-nor-steroid, mibolerone occurs as a white, crystalline solid. Mibolerone may also be known as dimethylnortestosterone.
Cheque® Drops is stable under ordinary conditions and temperatures.
Although not approved, mibolerone at dosages of 50 micrograms per day will prevent estrus in thecat, but its use is generally not recommended because of the very narrow therapeutic index of thedrug in this species (see the Adverse effects and Overdosage sections for more information).
Contraindications/Precautions - Mibolerone is contraindicated in female dogs with perianaladenoma, perianal adenocarcinoma or other androgen-dependent neoplasias. It is also contraindicated in patients with ongoing or a history of, liver or kidney disease. The manufacturer also recommends not using the drug in Bedlington Terriers.
Mibolerone should not be used in pregnant bitches. Masculinization of the female fetuses willoccur. Alterations seen may include, changes in vagina patency, multiple urethral openings in thevagina, a phallus-like structure instead of a clitoris, formation of testes-like structures, and fluidaccumulation in the vagina and uterus. Because it may inhibit lactation, it should not be used innursing bitches.
The manufacturer recommends discontinuing the product after 24 months of use. It should not beused to try to attempt to abbreviate an estrous period or in bitches prior to their first estrous period.
In the cat, dosages of 60 micrograms/day have caused hepatic dysfunction and 120 micrograms/day have caused death. Other adverse effects that have been noted in cats, include clitoralhypertrophy, thyroid dysfunction, os clitorides formation, cervical dermis thickening, and pancreaticdysfunction.
Overdosage/Toxicology Studies - Many toxicology studies have been performed in dogs. Thedrug did not cause death in doses up to 30, 000 micrograms/kg/day when administered to beaglesfor 28 days. For a more detailed discussion of the toxicology of the drug, the reader is referred tothe package insert for Cheque® Drops .
In the cat, dosages of as low as 120 micrograms/day have resulted in fatalities.
Drug/Laboratory Interactions - Mibolerone has been reported to cause thyroid dysfunction incats.
Storage, Stability, Compatibility
The manufacturer (Upjohn) states that the compound inCheque® Drops is stable under ordinary conditions and temperatures.
Pharmacology - MIBOLERONE
Mibolerone acts by blocking the release of lutenizing hormone (LH) from theanterior pituitary via a negative feedback mechanism. Because of the lack of LH, follicles willdevelop to a certain point, but will not mature and hence no ovulation or corpus luteum developmentoccurs. The net result is a suppression of the estrous cycle if the drug is given prior to (as much as30 days) the onset of proestrus. After discontinuation of the drug, the next estrus may occur within7-200 days (avg. 70 days).Uses, Indications - Cheque® Drops are labeled as indicated "for estrous (heat) prevention in adultfemale dogs not intended primarily for breeding purposes." In clinical trials it was 90% effective insuppressing estrus.Although not approved, mibolerone at dosages of 50 micrograms per day will prevent estrus in thecat, but its use is generally not recommended because of the very narrow therapeutic index of thedrug in this species (see the Adverse effects and Overdosage sections for more information).
Pharmacokinetics - MIBOLERONE
Mibolerone is reported to be well absorbed from the intestine after oraladministration and is rapidly metabolized in the liver to over 10 separate metabolites. Excretion isapparently equally divided between the urine and feces.Contraindications/Precautions - Mibolerone is contraindicated in female dogs with perianaladenoma, perianal adenocarcinoma or other androgen-dependent neoplasias. It is also contraindicated in patients with ongoing or a history of, liver or kidney disease. The manufacturer also recommends not using the drug in Bedlington Terriers.
Mibolerone should not be used in pregnant bitches. Masculinization of the female fetuses willoccur. Alterations seen may include, changes in vagina patency, multiple urethral openings in thevagina, a phallus-like structure instead of a clitoris, formation of testes-like structures, and fluidaccumulation in the vagina and uterus. Because it may inhibit lactation, it should not be used innursing bitches.
The manufacturer recommends discontinuing the product after 24 months of use. It should not beused to try to attempt to abbreviate an estrous period or in bitches prior to their first estrous period.
Adverse Effects, Warnings
Immature females may be more prone to develop adverse reactionsthan more mature females. In prepuberal females, mibolerone can induce premature epiphysealclosure, clitoral enlargement, and vaginitis. Adverse effects that may be seen in the adult bitch, include mild clitoral hypertrophy (may be partially reversible), vulvovaginitis, increased body odor, abnormal behavior, urinary incontinence, voice deepening, riding behavior, enhanced symptoms ofseborrhea oleosa, epiphora (tearing), hepatic changes (intranuclear hyaline bodies) and increasedkidney weight (without pathology). Although reported, overt hepatic dysfunction would beconsidered to occur rarely in dogs. With the exception of residual mild clitoral hypertrophy, adverseeffects will generally resolve after discontinuation of therapy.In the cat, dosages of 60 micrograms/day have caused hepatic dysfunction and 120 micrograms/day have caused death. Other adverse effects that have been noted in cats, include clitoralhypertrophy, thyroid dysfunction, os clitorides formation, cervical dermis thickening, and pancreaticdysfunction.
Overdosage/Toxicology Studies - Many toxicology studies have been performed in dogs. Thedrug did not cause death in doses up to 30, 000 micrograms/kg/day when administered to beaglesfor 28 days. For a more detailed discussion of the toxicology of the drug, the reader is referred tothe package insert for Cheque® Drops .
In the cat, dosages of as low as 120 micrograms/day have resulted in fatalities.
Drug Interactions
Increased seizure activity has been reported in a dog after receiving mibolerone who was previously controlled on phenytoin. Mibolerone should generally not be usedconcurrently with progestins or estrogen agents.Drug/Laboratory Interactions - Mibolerone has been reported to cause thyroid dysfunction incats.