Fluoxetine
Fluoxetine hydrochloride
Also known as: Prozac · Reconcile · Sarafem · fluoxetini hydrochloridum · LY110140 · Fluoxetine hydrochloride
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Treatment of canine separation anxiety in conjunction with a behavior modification plan | 1-2 mg/kg PO once daily | PO | q24h | — | 🌎 NA |
| Separation anxiety and noise aversions | 1-2 mg/kg PO once daily | PO | q24h | Continue until 2 months after satisfactory response, then discontinue gradually | 🌎 NA |
| Adjunctive pharmacological intervention for conflict-related aggression | 1-2 mg/kg PO once a day | PO | q24h | — | 🌎 NA |
| Compulsive disorders | 1-2 mg/kg PO once daily | PO | q24h | — | 🌎 NA |
| Adjunctive treatment of behavior disorders | 1-1.5 mg/kg PO once daily | PO | q24h | — | 🌎 NA |
| Adjunctive treatment of behavior disorders | 1 mg/kg PO once daily (up to 3 mg/kg PO once daily) | PO | q24h | — | 🌎 NA |
| Separation anxiety, compulsive disorders, and aggression | 1-2 mg/kg | PO | q24h | Long-term as directed | 🌍 EU |
- Separation anxiety and noise aversions: Use with behavioral therapy. May use long-term. Some dogs require life-long treatment. May add a benzodiazepine during seasonal noise fears.
- Adjunctive pharmacological intervention for conflict-related aggression: May take up to 4 weeks for efficacy.
- Separation anxiety, compulsive disorders, and aggression: Use in association with a behaviour modification plan. Caution with aggression.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Adjunctive treatment of aggression | 0.5-1.5 mg/kg PO once daily | PO | q24h | — | 🌎 NA |
| To help control urine marking or separation anxiety | 0.5-1 mg/kg (2.55 mg per cat) PO once daily | PO | q24h | — | 🌎 NA |
| To control pruritus when other therapies have failed | 1-5 mg/cat PO once daily | PO | q24h | Assess therapy after 1-4 weeks. Taper off dose over 6-8 weeks. | 🌎 NA |
| Generalized anxiety disorder | 0.5-1.5 mg/kg PO once daily | PO | q24h | — | 🌎 NA |
| Urine spraying, psychogenic alopecia, and aggression | 0.5-1.0 mg/kg | PO | q24h | Long-term as directed | 🌍 EU |
- To control pruritus when other therapies have failed: Advise obtaining baseline lab work.
- Urine spraying, psychogenic alopecia, and aggression: Similar precautions for aggression apply as in dogs.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Fluoxetine is a widely used Selective Serotonin-Reuptake Inhibitor (SSRI) antidepressant utilized in veterinary medicine to manage a variety of behavioral disorders in dogs and cats.
In dogs, it is FDA-approved (as Reconcile®) for the treatment of separation anxiety when used in conjunction with a behavior modification plan. It is also used off-label for aggression, stereotypic behaviors (obsessive-compulsive disorders), and generalized anxiety. In cats, it is frequently prescribed for inappropriate elimination (urine marking), aggression, anxiety, and psychogenic alopecia/pruritus.
Clinical Pearl: Fluoxetine requires a significant lag time (typically 4 to 8 weeks) before full clinical efficacy is observed. This is due to the time required for postsynaptic receptor downregulation. Owners must be counseled to remain patient and compliant during this initial period.
Mechanism of action
Fluoxetine acts by selectively binding to and inhibiting the presynaptic serotonin transporter (SERT) in the central nervous system.
- Inhibition of Reuptake: Blockade of SERT prevents the reuptake of serotonin (5-HT) into the presynaptic neuron.
- Increased Synaptic Serotonin: This leads to an accumulation of serotonin in the synaptic cleft → prolonged activation of postsynaptic 5-HT receptors.
- Receptor Downregulation: Chronic elevation of synaptic serotonin eventually leads to the downregulation and desensitization of autoreceptors (e.g., 5-HT1A), which correlates with the onset of anxiolytic, anticompulsive, and anti-aggressive clinical effects.
Fluoxetine has minimal affinity for other neurotransmitter receptors (such as dopamine, norepinephrine, histamine, or acetylcholine), which accounts for its relatively favorable side effect profile compared to tricyclic antidepressants (TCAs).
Safety & warnings
Contraindications
- Known hypersensitivity to fluoxetine
- Concurrent use of Monoamine Oxidase Inhibitors (MAOIs), including selegiline and amitraz (found in some tick collars)
- Patients with epilepsy or a history of seizures
- Concurrent use with drugs that lower the seizure threshold (e.g., acepromazine, chlorpromazine)
- Known sensitivity to fluoxetine or other SSRIs
- History of seizures or epilepsy
Adverse effects
- Anorexia or decreased appetite (common, often transient)
- Lethargy or depression
- Gastrointestinal upset (vomiting, diarrhea)
- Anxiety, irritability, or restlessness
- Insomnia or hyperactivity
- Panting (dogs)
- Changes in elimination patterns (cats)
- Paradoxical aggressive behavior (in previously unaggressive animals)
- Seizures (rare but possible)
- Weight loss
- Trembling
- Gastrointestinal disturbances
- Paradoxical increase in anxiety
- Increased aggression
Precautions
- Seizure Disorders: Use is contraindicated in patients with a history of seizures.
- Diabetes Mellitus: Use with caution as fluoxetine may alter blood glucose levels, necessitating insulin adjustments.
- Hepatic Impairment: Dosages may need to be reduced in patients with severe liver disease due to decreased clearance.
- Tapering: Because of the long half-life of the active metabolite (norfluoxetine), tapering off the drug is generally only necessary when a patient has been on the drug long-term (>8 weeks).
- Pregnancy/Nursing: Safety is not fully established (FDA Category C in humans). Excreted in milk at 20-30% of plasma levels; use caution in nursing animals.
Drug interactions
Increased risk for serotonin syndrome
May decrease or reverse the effects of SSRIs (acts as a serotonin antagonist)
Fluoxetine may increase diazepam and alprazolam plasma levels
Increased risk for hyponatremia
May alter insulin requirements (can alter blood glucose)
Increased risk for serotonin syndrome
High risk for serotonin syndrome; use contraindicated. A 5-week washout is required after stopping fluoxetine before starting an MAOI, and a 2-week washout if switching from an MAOI to fluoxetine.
Serotonin syndrome-like adverse effects possible
Increased plasma levels of phenytoin possible
Fluoxetine may increase these beta-blocker's plasma levels; atenolol may be safer to use
SSRIs can inhibit the metabolism of tramadol to active metabolites, decreasing efficacy and increasing toxicity risk (serotonin syndrome, seizures)
Fluoxetine may increase TCA blood levels and increase the risk for serotonin syndrome
Increased plasma levels of trazodone possible
Fluoxetine may increase the risk for bleeding
Risk of fatal serotonin syndrome. Fluoxetine should not be used within 2 weeks of MAOI treatment, and MAOIs should not be used within 6 weeks of fluoxetine treatment.
Fluoxetine antagonizes the effects of anticonvulsants and lowers the seizure threshold.
Lowers seizure threshold, increasing the risk of seizures.
Increased risk of bleeding in the case of tissue trauma.
Increased risk of serotonin syndrome. Use alongside trazodone may be considered in exceptional cases only with careful monitoring.
Increased risk of serotonin syndrome.
Monitoring
- Efficacy of the behavior modification plan and reduction of clinical signs
- Appetite and body weight (due to risk of anorexia)
- Signs of adverse effects (GI upset, lethargy, paradoxical aggression, seizures)
- Behavioral response and changes in aggression
- Signs of serotonin syndrome (tremors, agitation, hyperthermia)
- Gastrointestinal tolerance
Pharmacokinetics
Half-life
Absorption
Well absorbed after oral administration. In dogs, ~70% of an oral dose reaches systemic circulation. Food alters the rate, but not the extent, of absorption. Transdermal bioavailability in cats is poor (~10% of oral route).
Distribution
Widely distributed throughout the body with highest levels in the lungs and liver. CNS concentrations are detected within 1 hour. Highly protein-bound (~95% in humans). Crosses the placenta and enters maternal milk (20-30% of plasma levels).
Metabolism
Primarily metabolized in the liver to a variety of metabolites, including the active metabolite norfluoxetine.
Elimination
Both fluoxetine and norfluoxetine are eliminated slowly. Renal impairment does not substantially affect elimination, but liver impairment decreases clearance rates.
Overdose
The LD50 for rats is 452 mg/kg.
Clinical Signs of Toxicity:
- Dogs: Vomiting, mydriasis (dilated pupils), lethargy, hyperactivity, and seizures. Seizures have been reported at doses twice the highest recommended human dose.
- Cats: Hypersalivation, vomiting, mydriasis, and excessive vocalization.
Treatment:
- Treatment is symptomatic and supportive.
- Gut emptying techniques (emesis, activated charcoal) should be employed if recent and not contraindicated (e.g., patient is seizing or comatose).
- Diazepam is the treatment of choice for controlling seizures.
- Cyproheptadine can be administered as a serotonin antagonist if serotonin syndrome is suspected.
Available products
Formulations
- Chewable tablets
- Oral capsules
- Oral solution
- Transdermal gel (compounded - note: poor bioavailability in cats)
- Oral tablets: 8 mg, 16 mg, 20 mg, 32 mg, 64 mg
Veterinary
- Fluoxetine Chewable Tablets: 8 mg, 16 mg, 32 mg, & 64 mg; Reconcile® (Lilly)
- Reconcile (8 mg, 16 mg, 32 mg, 64 mg chewable tablets)
Human-labeled
- Fluoxetine HCl Oral Tablets: 10 mg, 15 mg & 20 mg
- Fluoxetine HCl Oral Capsules: 10 mg, 20 mg, 40 mg & 90 mg (delayed-release); Prozac®, Sarafem®
- Fluoxetine HCl Oral Solution: 20 mg/5 mL (may contain alcohol, sucrose); Prozac®
- Prozac (10 mg, 20 mg, 60 mg capsules/tablets)
Regulatory status
Veterinary formulation (Reconcile) is licensed within Europe.
POM-V, POM. Monograph notes veterinary formulation is not currently available in the UK, though human generics may be used under the cascade.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Capsules and tablets should be stored in well-closed containers at room temperature. The oral liquid should be stored in tight, light-resistant containers at room temperature.
Client information
- Patience is Key: This medication often takes 4 to 8 weeks to show its full effect. Do not stop giving it just because you don't see immediate results.
- Behavior Modification: Fluoxetine is most effective when used alongside a behavior modification and training program recommended by your veterinarian.
- Side Effects: The most common side effects include lethargy, decreased appetite, vomiting, shaking, restlessness, diarrhea, and excessive whining. If these are severe or persist, contact your veterinarian.
- Appetite Loss: If your pet loses their appetite, try hand-feeding or temporarily increasing the palatability of their food (e.g., adding a little wet food or low-sodium broth).
- Do Not Stop Abruptly: Do not discontinue this medication suddenly without your veterinarian's guidance, as it may cause withdrawal-like signs or a relapse in behavior.
- Seizure Warning: Rarely, dogs may develop seizures while on this medication. If a seizure occurs, contact your veterinarian immediately.
- Tick Collars: Inform your veterinarian if you use tick collars, as some contain amitraz, which can cause a dangerous drug interaction (serotonin syndrome) when combined with fluoxetine.
- Keep this medication safely out of reach of children and other pets.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.