Anipryl (selegiline), also known as L-Deprenyl, is a monoamine oxidase inhibitor (MAOI) that treats Cushing's Disease and Canine Cognitive Dysfunction Syndrome (senility). Anipryl requires a prescription from your veterinarian. Anipryl increases the concentration of a nervous system messenger chemical called dopamine. Higher levels of dopamine improve many cognitive processes. Treating Cushing's Disease has traditionally been centered on suppressing the adrenal gland's production and release of cortisone. However, this approach has a high potential for side effects. Selegiline has allowed for a new approach by suppressing the pituitary gland directly.
Tablets are white, convex tablets containing 2, 5, 10, 15, and 30 mg of selegiline HCl.
Selegiline is an irreversible inhibitor of monoamine oxidase (MAO). MAOs are widely distributed throughout the body and are subclassified into 2 types, A and B, which differ in their substrate specificity and tissue distribution. Selegiline is believed to be a selective inhibitor of MAO-B at recommended dosages in the dog due to its greater affinity for type B enzyme active sites compared to type A sites. In CNS neurons, MAO plays a role in the catabolism of catecholamines, (dopamine, and, to a lesser extent, norepinephrine and epinephrine) and serotonin. Selegiline may have pharmacologic effects unrelated to MAO-B inhibition. There is some evidence that it may increase dopaminergic activity by other mechanisms, including increasing synthesis and release of dopamine into the synapse as well as interfering with dopamine re-uptake from the synapse. Effects resulting from selegiline administration may also be mediated through its metabolites. Two of its 3 principal metabolites, L-amphetamine and L-methamphetamine, have pharmacological actions of their own. However, the extent to which these metabolites contribute to the effects of selegiline is unknown.
Therapeutic effects of selegiline are thought to result in part from enhanced catecholaminergic nerve function and increased dopamine levels in the CNS. The pathogenesis of the development of clinical signs associated with cognitive decline is considered to be partly a result of a decrease in the level of catecholamines in the CNS and deficiencies in neurotransmission.7 There is evidence which points to hypothalamic dopamine deficiency playing a role in the pathogenesis of pituitary dependent hyperadrenocorticism in the dog.
USES AND INDICATIONS:
Anipryl tablets are indicated for the control of clinical signs associated with canine cognitive dysfunction syndrome (CDS) and control of clinical signs associated with uncomplicated canine pituitary dependent hyperadrenocorticism (PDH).
CONTRAINDICATIONS AND PRECAUTION:
Anipryl is contraindicated in patients with known hypersensitivity to this drug. In humans, selegiline is contraindicated for use with meperidine and this contraindication is often extended to other opioids.
Federal law restricts this drug to use by or on the order of a licensed veterinarian.
ADVERSE EFFECTS AND WARNINGS:
Anipryl should not be administered at doses exceeding those recommended (0.5-2.0 mg/kg once daily).
In humans, concurrent use of MAO inhibitors with alpha-2 agonists has resulted in extreme fluctuations of blood pressure; therefore, blood pressure monitoring is recommended with concurrent use in dogs. Also, in humans, severe CNS toxicity including death has been reported with the combination of selegiline and tricyclic antidepressants, and selegiline and selective serotonin reuptake inhibitors. Although no such adverse drug interactions were reported in the clinical trials in dogs, it seems prudent to avoid the combination of Anipryl and selective serotonin reuptake inhibitors (e.g., fluoxetine) as well as Anipryl and tricyclic (e.g., clomipramine, amitriptyline, imipramine) or other antidepressants.
At least 14 days should elapse between discontinuation of Anipryl and initiation of treatment with a tricyclic antidepressant or selective serotonin reuptake inhibitor. Because of the long half-life of fluoxetine and its active metabolites, at least 5 weeks should elapse between discontinuation of fluoxetine and initiation of treatment with Anipryl.
Concurrent use of Anipryl with ephedrine or potential MAO inhibitors, such as amitraz, is not recommended.
For animal use only. Keep out of the reach of children and other animals.
In clinical trials, 404 dogs treated with Anipryl for as long as 18 months were monitored for the occurrence of adverse events. Many of the observations listed in the following table may be associated with the underlying disease (PDH or CDS), the advanced age of the patients or the development of unrelated concurrent disease. One index of relative importance, however is whether or not a reaction caused treatment discontinuation. Eighteen dogs (4%) experienced one or more of the following adverse events that led either to discontinuation of therapy with Anipryl, dismissal from the study, or a reduction in dose: restlessness/agitation, vomiting, disorientation, diarrhea, diminished hearing, possible drug interaction (weakness, confusion, incoordination and ï¿½seizure-likeï¿½ activity while being treated concurrently with metronidazole, prednisone, and trimethoprim sulfa), increase in destructive behavior in a dog with separation anxiety, anorexia, anemia, stiffness and polydipsia.
DOSAGE AND ADMINISTRATION:
CDS: The recommended dosage for oral administration for the control of clinical signs associated with CDS is 0.5-1.0 mg/kg once daily, preferably administered in the morning. Initially, dogs should be dosed to the nearest whole tablet. Adjustments should then be made based on response and tolerance to the drug.
PDH: The recommended dosage for the control of clinical signs associated with canine PDH is 1.0 mg/kg once daily, preferably administered in the morning. If no improvement is observed after 2 months of therapy, dosage may be increased to a maximum of 2.0 mg/kg once daily. If no improvement is seen after 1 month at the higher dose or if at any time clinical signs progress, the dog should be re-evaluated. In dogs whose clinical signs of PDH progress despite Anipryl therapy in the absence of concurrent disease, alternative therapy should be considered.
Dogs should be monitored closely for possible adverse events associated with any increase in dose.
Clinical Use of Anipryl in CDS: CDS is an age-related deterioration of cognitive abilities characterized by behavioral changes not wholly attributable to a general medical condition such as neoplasia, infection, or organ failure. CDS is typified by multiple cognitive impairments which affect the dog's function. In clinical trials, the observed behavioral changes associated with CDS in older dogs included: disorientation, decreased activity level, abnormal sleep/wake cycles, loss of housetraining, decreased or altered responsiveness to family members, and decreased or altered greeting behavior. In clinical trials, Anipryl was shown to be effective in controlling clinical signs associated with CDS. After 4 weeks of treatment, dogs treated with Anipryl showed significant improvement when compared to placebo-treated controls in sleeping patterns, housetraining, and activity level. Some dogs showed increased improvement up to 3 months, however, onset, duration and magnitude of response varied with individual dogs.
The diagnosis of CDS in dogs is a diagnosis of exclusion, based on thorough behavioral and medical histories, in conjunction with appropriate diagnostic work-up and testing.11 Periodic patient monitoring to evaluate the response and tolerance to the drug and for the presence of concurrent or new disease is recommended.
Clinical Use of Anipryl in PDH: Clinical signs of PDH seen in clinical trials included panting, reduced activity, polydipsia, polyuria, changes in sleep patterns, altered appetite, obesity, alopecia, abdominal distention, reduced skin elasticity, thin skin, poor hair growth, pyoderma, decreased responsiveness to attention, and decreased enthusiasm of greeting. In clinical studies involving 125 evaluable cases of naturally occurring PDH, Anipryl was shown to be effective in controlling clinical signs associated with the disease. On physical examination, abdominal distention was the parameter which most consistently improved following treatment with Anipryl. Based on owner assessments, activity level was the parameter most consistently evaluated as ï¿½improvedï¿½. Approximately 60% of the dogs were evaluated by the veterinarians and owners to be ï¿½slightly improvedï¿½ to ï¿½improvedï¿½ after 1 month of Anipryl therapy. By month 2, veterinarians reported that approximately 77% were ï¿½slightly improvedï¿½ to ï¿½improvedï¿½. Approximately 20% of dogs did not respond to Anipryl and were deemed treatment failures.
Those dogs that responded to Anipryl tended to do so within 1-2 months after treatment was initiated. Response to therapy varied between patients with some dogs showing improvement in all presenting clinical signs and others showing improvement in only 1-2 parameters. Duration of response was also variable, with some dogs continuing on Anipryl for over 1 year with good control of clinical signs and others showing an initial response to therapy only to be followed within several months by recurrence of clinical signs of PDH. There was no correlation demonstrated between an individual dog's clinical response to Anipryl and that dog's low dose dexamethasone suppression test results, therefore, monitoring should be based on history and physical examination findings.
Store at controlled room temperature 20ï¿½-25ï¿½C (68ï¿½-77ï¿½F).