Are fluoxetine (selective serotonin reuptake inhibitor) pulvule capsules the same formulation as they have always been?

Fluoxetine Pulvule Capsules: Formulation and Composition

Fluoxetine pulvule capsules are the same formulation they have always been, containing fluoxetine hydrochloride in a gelatin capsule with various inactive ingredients including starch, silicone, titanium dioxide, iron oxide, and specific colorants depending on the dosage strength. 1

Composition and Physical Characteristics

• Prozac® (fluoxetine) pulvule capsules contain fluoxetine hydrochloride equivalent to 10 mg, 20 mg, or 40 mg of fluoxetine 1
• The capsules have specific color coding based on dosage strength:
  • 10 mg and 20 mg pulvules contain FD&C Blue No. 1 1
  • 40 mg pulvules contain both FD&C Blue No. 1 and FD&C Yellow No. 6 1
• The pulvule is a specific type of gelatin capsule that has maintained the same formulation since its introduction 1

Pharmacological Properties

• Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that blocks the presynaptic reuptake of serotonin, increasing its availability at the synaptic cleft 2
• This blockade leads to downregulation of inhibitory serotonin autoreceptors, which eventually heightens serotonergic neuronal firing rate and increases serotonin release 2
• The multistep process explains the delayed onset of therapeutic effects seen with fluoxetine treatment 2, 3

Pharmacokinetic Considerations

• Fluoxetine has a long elimination half-life of 1-3 days for the parent compound and 7-15 days for its active metabolite norfluoxetine 4, 1
• After oral administration of a 40 mg dose, peak plasma concentrations of 15-55 ng/mL are observed after 6-8 hours 1
• The pulvule capsule, oral solution, and weekly capsule dosage forms of fluoxetine are bioequivalent 1
• Food does not significantly affect the systemic bioavailability of fluoxetine, although it may delay absorption by 1-2 hours 1

Clinical Implications

• The standard dosing for most indications is 20 mg taken once daily in the morning 4
• Fluoxetine is FDA-approved for major depressive disorder, OCD, bulimia nervosa, premenstrual dysphoric disorder, panic disorder, and bipolar disorder (in combination with olanzapine) 2
• It is the only SSRI FDA-approved for major depression in children/adolescents aged 8 years or older 2
• The long half-life essentially precludes a withdrawal phenomenon, which is a clinical advantage over other SSRIs 5

Important Distinctions from Other Formulations

• Standard pulvule capsules differ from Prozac Weekly™ capsules, which are a delayed-release formulation containing enteric-coated pellets equivalent to 90 mg of fluoxetine 1
• The enteric coating in the weekly formulation delays absorption by 1-2 hours relative to the immediate-release pulvule capsules 1
• The oral solution contains fluoxetine hydrochloride equivalent to 20 mg/5 mL along with alcohol 0.23%, benzoic acid, flavoring agent, glycerin, purified water, and sucrose 1

Metabolism Considerations

• Fluoxetine is extensively metabolized in the liver to norfluoxetine (its active metabolite) and other unidentified metabolites 1
• About 7% of the population has reduced activity of CYP2D6 enzyme, leading to slower metabolism and higher concentrations of fluoxetine 1
• Long-term fluoxetine use at 20 mg/day can convert approximately 43% of extensive metabolizers to poor metabolizers through enzyme inhibition 3

In summary, fluoxetine pulvule capsules have maintained the same formulation since their introduction, with consistent composition and pharmacological properties that have made them a standard treatment option for various psychiatric conditions.