FLUOXETINE HCL
Chemistry - A member of the phenylpropylamine-derivative antidepressant group, fluoxetinediffers both structurally and pharmacologically from either the tricyclic or monoamine oxidaseinhibitor antidepressants. Fluoxetine HCl occurs as a white to off-white crystalline solid.
Approximately 50 mg is soluble in 1 ml of water.
Uses, Indications - While there has been considerable interest and lay press coverage of the use offluoxetine in dogs, there is a general lack of scientific information available on its usefulness. Thedrug purportedly may have efficacy in treating stereotypic and obsessive-compulsive behaviors aswell as phobic disorders, however much more experience and study is necessary before it or theother serotonin inhibitors can be routinely recommended..
Fluoxetine and its principal metabolite, norfluoxetine (active) are apparently distributed throughoutthe body with highest levels found in the lungs and the liver. CNS concentrations are detectedwithin one hour of dosing. In humans, fluoxetine is approximately 95% bound to plasma proteins.
Fluoxetine crosses the placenta in rats, but it is unknown if it does so in other species. Fluoxetineenters maternal milk in concentrations about 20-30% of those found in the plasma.
Fluoxetine is primarily metabolized in the liver to a variety of metabolites, including norfluoxetine, which is active. Both fluoxetine and norfluoxetine are eliminated slowly. In humans, the eliminationhalf of fluoxetine is about 2-3 days and norfluoxetine, about 7-9 days. Wide interpatient variationdoes occur however. Renal impairment does not apparently affect elimination rates substantially, butliver impairment will decrease clearance rates.
Dosages may need to be reduced in patients with severe hepatic impairment.
Fluoxetine's safety during pregnancy has not been established. Preliminary studies done in ratsdemonstrated no overt teratogenic effects. The drug is excreted into milk (20-30% of plasma levels)so caution is advised in nursing patients.
Treatment of fluoxetine overdoses consist of symptomatic and supportive therapy. Gut emptyingtechniques should be employed when warranted and otherwise not contraindicated. Diazepamshould be used to treat seizures.
Fluoxetine may enhance the effects of the following psychometric agents: diazepam (increased half life), haloperidol (increased extrapyramidal effects), lithium (increased lithium levels), L-tryptophan (CNS stimulation, GI distress), tricyclic antidepressants (increased tricyclic side effects), and buspirone (increased anxiety).
Preliminary studies indicate that the use of fluoxetine and monoamine oxidase inhibitors may cause significant morbidity. It is recommended in human medicine to discontinue the use of fluoxetine at least 5 weeks before beginning monoamine oxidase inhibitors and discontinuing monoamine oxidase inhibitors at least two weeks before beginning fluoxetine.
Approximately 50 mg is soluble in 1 ml of water.
Storage, Stability, Compatibility
Capsules should be stored in wel -closed containers. The oralliquid should be stored in tight, light-resistant containers. Both products should be stored at roomtemperature.Pharmacology - FLUOXETINE HCL
Fluoxetine is a highly selective inhibitor of the reuptake of serotonin in the CNSthereby potentiating the pharmacologic activity of serotonin. Fluoxetine apparently has little effecton other neurotransmitters (e.g., dopamine or norepinephrine).Uses, Indications - While there has been considerable interest and lay press coverage of the use offluoxetine in dogs, there is a general lack of scientific information available on its usefulness. Thedrug purportedly may have efficacy in treating stereotypic and obsessive-compulsive behaviors aswell as phobic disorders, however much more experience and study is necessary before it or theother serotonin inhibitors can be routinely recommended..
Pharmacokinetics - FLUOXETINE HCL
Fluoxetine is apparently well absorbed after oral administration. In a studydone in beagles, approximately 70% of an oral dose reached the systemic circulation. The presenceof food altered the rate, but not the extent of absorption. The oral capsules and oral liquidapparently are bioequivalent.Fluoxetine and its principal metabolite, norfluoxetine (active) are apparently distributed throughoutthe body with highest levels found in the lungs and the liver. CNS concentrations are detectedwithin one hour of dosing. In humans, fluoxetine is approximately 95% bound to plasma proteins.
Fluoxetine crosses the placenta in rats, but it is unknown if it does so in other species. Fluoxetineenters maternal milk in concentrations about 20-30% of those found in the plasma.
Fluoxetine is primarily metabolized in the liver to a variety of metabolites, including norfluoxetine, which is active. Both fluoxetine and norfluoxetine are eliminated slowly. In humans, the eliminationhalf of fluoxetine is about 2-3 days and norfluoxetine, about 7-9 days. Wide interpatient variationdoes occur however. Renal impairment does not apparently affect elimination rates substantially, butliver impairment will decrease clearance rates.
Contraindications, Precautions, Reproductive Safety
Fluoxetine is considered to be contraindicated in patients with known hypersensitivity to it, as well as those receiving monoamineoxidase inhibitors (see Drug Interactions below). It should be used with caution in patients withdiabetes mellitus as it may alter blood glucose. Its effect on patients with seizure disorders is notknown (some overdose patients have developed seizures), so use with caution in these patients.Dosages may need to be reduced in patients with severe hepatic impairment.
Fluoxetine's safety during pregnancy has not been established. Preliminary studies done in ratsdemonstrated no overt teratogenic effects. The drug is excreted into milk (20-30% of plasma levels)so caution is advised in nursing patients.
Adverse Effects, Warnings
The adverse effect profile in dogs has not been well established. Inhumans, potential adverse effects are extensive and diverse, but most those most commonly notedinclude anxiety, nervousness, insomnia, drowsiness, fatigue, dizziness, anorexia, nausea, diarrheaand sweating. About 15% of human patients discontinue treatment due to adverse effects.Overdosage, Acute Toxicity
The LD50 for rats is 452 mg/kg. Five of six dogs given an oral"toxic" dose developed seizures that immediately stopped after giving IV diazepam. The doghaving the lowest plasma level of fluoxetine that developed seizures, had a level twice that expectedof a human taking 80 mg day (highest recommended dose).Treatment of fluoxetine overdoses consist of symptomatic and supportive therapy. Gut emptyingtechniques should be employed when warranted and otherwise not contraindicated. Diazepamshould be used to treat seizures.
Drug Interactions
Fluoxetine is highly bound to plasma proteins and could potentially displaceother highly bound drugs (e.g., warfarin, phenylbutazone, digitoxin, etc). Clinical significance isnot clear.Fluoxetine may enhance the effects of the following psychometric agents: diazepam (increased half life), haloperidol (increased extrapyramidal effects), lithium (increased lithium levels), L-tryptophan (CNS stimulation, GI distress), tricyclic antidepressants (increased tricyclic side effects), and buspirone (increased anxiety).
Preliminary studies indicate that the use of fluoxetine and monoamine oxidase inhibitors may cause significant morbidity. It is recommended in human medicine to discontinue the use of fluoxetine at least 5 weeks before beginning monoamine oxidase inhibitors and discontinuing monoamine oxidase inhibitors at least two weeks before beginning fluoxetine.