LILLY-FLUOXETINE 20 MG CAPSULE

Indications

• Major depressive disorder
• Bulimia nervosa
• Obsessive-compulsive disorder
• Panic disorder
• Menopausal symptoms (unlicensed use)

Dosage

Adults: Initially, 20 mg once daily. The dose may be

Mechanism of action

Fluoxetine operates through the monoaminergic hypothesis of depression, which links low serotonin levels to depressive symptoms. By selectively inhibiting the presynaptic reuptake of serotonin, fluoxetine increases the concentration of 5-hydroxytryptamine (5-HT) in the synaptic cleft. It exhibits a high affinity for serotonin transporters, a weak affinity for noradrenaline transporters, and no affinity for dopamine transporters. This selectivity allows for enhanced serotonin activity while minimizing interactions that could lead to adverse effects.

Pharmacodynamics

The pharmacodynamic profile of fluoxetine is characterized by its ability to sustain elevated levels of serotonin in the brain, particularly in areas associated with mood regulation. It demonstrates a relatively poor binding affinity to various receptor types, which contributes to a favorable side effect profile when compared to older antidepressants, such as tricyclics. Fluoxetine's interaction with the 5-HT2C receptor may also enhance noradrenaline and dopamine levels in specific brain regions, contributing to its overall antidepressant effects.

Pharmacokinetics

Fluoxetine has a long half-life, ranging from 4 to 6 days, which allows for once-daily dosing and requires careful consideration when adjusting doses or managing potential overdose. It is metabolized primarily in the liver via CYP2D6 and CYP2C19 pathways, leading to the formation of its active metabolite norfluoxetine, which also contributes to its therapeutic effects. The drug is excreted mainly via urine, with a small percentage eliminated unchanged. Caution is advised in patients with renal impairment, and dose adjustments may be necessary in hepatic impairment.

Contra-indications

• Hypersensitivity to fluoxetine or any of its components
• Concomitant use with monoamine oxidase inhibitors (MAOIs)
• History of QT-interval prolongation
• Use in children under 12 years (unlicensed use)

Adverse effects

• Chills
• Feeling abnormal
• Mood alterations
• Muscle twitching
• Self-injurious behavior
• Temperature sensation alterations
• Bone fractures
• Neutropenia
• Speech disorders

Interactions

• Fluoxetine + selumetinib: Moderate (increases exposure)
• Fluoxetine + terbinafine: Moderate (increases exposure)
• Fluoxetine + fedratinib: Unknown (increases exposure)
• Fluoxetine + haloperidol: Unknown (increases concentration)
• Fluoxetine + lomitapide: Unknown (increases exposure)

Precautions

• Use with caution in patients with renal impairment (creatinine clearance less than 30 mL/minute)
• Monitor for withdrawal symptoms when discontinuing treatment
• Counsel patients regarding effects on driving and skilled tasks

Pregnancy

Use only if the potential benefit justifies the potential risk to the fetus. Caution is advised due to possible risks.

Breast-feeding

Present in breast milk; avoid use if possible during breastfeeding.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Tablets: 10 mg, 20 mg
• Oral solution: 4 mg per 1 ml
• Dispersible tablets: 20 mg

Mechanism of action

The monoaminergic hypothesis of depression emerged in 1965 and linked depression with dysfunction of neurotransmitters such as noradrenaline and serotonin. Indeed, low levels of serotonin have been observed in the cerebrospinal fluid of patients diagnosed with depression. As a result of this hypothesis, drugs that modulate levels of serotonin such as fluoxetine were developed. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) and as the name suggests, it exerts it's therapeutic effect by inhibiting the presynaptic reuptake of the neurotransmitter serotonin. As a result, levels of 5-hydroxytryptamine (5-HT) are increased in various parts of the brain. Further, fluoxetine has high affinity for 5-HT transporters, weak affinity for noradrenaline transporters and no affinity for dopamine transporters indicating that it is 5-HT selective. Fluoxetine interacts to a degree with the 5-HT_2C receptor and it has been suggested that through this mechanism, it is able to increase noradrenaline and dopamine levels in the prefrontal cortex.

Pharmacodynamics

Fluoxetine blocks the serotonin reuptake transporter in the presynaptic terminal, which ultimately results in sustained levels of 5-hydroxytryptamine (5-HT) in certain brain areas. However, fluoxetine binds with relatively poor affinity to 5-HT, dopaminergic, adrenergic, cholinergic, muscarinic, and histamine receptors which explains why it has a far more desirable adverse effect profile compared to earlier developed classes of antidepressants such as tricyclic antidepressants.