FAVERIN 100 MG

Indications

• Major depressive disorder
• Obsessive-compulsive disorder
• Generalized anxiety disorder
• Social anxiety disorder
• Body dysmorphic disorder

Dosage

Children: Refer to the BNF for Children for paediatric dosing guidelines.

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Fluvoxamine's exact mechanism of action is not fully elucidated, but it is known to inhibit the reuptake of serotonin at the neuronal membrane's serotonin reuptake pump. This inhibition enhances the activity of serotonin on 5-HT1A autoreceptors. Unlike many other psychotropic agents, fluvoxamine exhibits minimal affinity for adrenergic, cholinergic, dopaminergic, and histaminergic receptors, suggesting a targeted action primarily on serotonin pathways.

Pharmacodynamics

As a potent and selective inhibitor of neuronal serotonin reuptake, fluvoxamine's antidepressant, anti-obsessive-compulsive, and antibulimic effects are linked to its ability to increase serotonin levels in the synaptic cleft. This results in enhanced serotonergic neurotransmission, which is crucial for mood regulation and anxiety reduction. The drug has minimal effects on norepinephrine and dopamine reuptake, further specifying its action among SSRIs.

Pharmacokinetics

Fluvoxamine is absorbed well from the gastrointestinal tract, with peak plasma concentrations typically reached within 3 to 8 hours post-administration. It undergoes extensive hepatic metabolism primarily via cytochrome P450 enzymes, particularly CYP1A2, with an elimination half-life of about 15 to 26 hours. The drug is primarily excreted as metabolites in the urine, and its pharmacokinetics can be significantly affected by drug interactions, particularly with substances that inhibit or induce hepatic enzymes.

Interactions

• fluvoxamine + agomelatine: Severe (increases exposure)
• fluvoxamine + fedratinib: Severe (increases exposure)
• fluvoxamine + melatonin: Severe (increases exposure)
• fluvoxamine + tizanidine: Severe (increases exposure)
• fluvoxamine + antiarrhythmics: Moderate (increases exposure)
• fluvoxamine + propafenone: Moderate (increases exposure)
• fluvoxamine + antipsychotics, second generation: Moderate (increases concentration)
• fluvoxamine + clozapine: Moderate (increases concentration)
• fluvoxamine + olanzapine: Moderate (increases exposure)
• fluvoxamine + benzodiazepines: Moderate (increases exposure)

Pregnancy

Consult relevant guidelines as fluvoxamine should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Fluvoxamine is excreted in breast milk; caution is advised when administered to nursing mothers.

Storage

Store at room temperature, away from moisture and heat.

Indications

• Major depressive disorder
• Obsessive-compulsive disorder
• Panic disorder
• Menopausal symptoms, particularly hot flushes, in women with breast cancer (unlicensed use)

Dosage

Children: Refer to BNF for Children for appropriate dosing.

Adults: Initially 50–100 mg daily, taken in the evening, increased gradually up to a maximum of 300 mg daily if necessary; doses over 150 mg should be given in divided doses. For obsessive-compulsive disorder, start at 10 mg daily, increasing gradually to a maximum of 40 mg daily.

Mechanism of action

Fluvoxamine maleate works by selectively inhibiting the reuptake of serotonin (5-HT) in the brain, increasing the availability of serotonin in the synaptic cleft. This action is believed to contribute to its antidepressant and anxiolytic effects. Additionally, fluvoxamine may have effects on other neurotransmitter systems, including sigma-1 receptors, which can modulate various neurobiological pathways.

Pharmacodynamics

The pharmacodynamic effects of fluvoxamine maleate include increased serotonin levels in the brain, which can lead to improvements in mood, anxiety, and compulsive behaviors. Fluvoxamine has a relatively rapid onset of action, with therapeutic effects often observed within 1-4 weeks of starting treatment. However, it may take longer for some patients to achieve optimal benefits.

Pharmacokinetics

Fluvoxamine is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 4-6 hours after oral administration. It is extensively metabolized in the liver, primarily by cytochrome P450 enzymes, and has a half-life of about 15-20 hours. The drug is excreted mainly in urine as metabolites. The presence of hepatic impairment can alter the pharmacokinetics of fluvoxamine, necessitating dose adjustments.

Contra-indications

• Hypersensitivity to fluvoxamine or any of its components
• Severe hepatic impairment
• Concurrent use with monoamine oxidase inhibitors (MAOIs)
• Severe renal impairment

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Somnolence
• Insomnia
• Dry mouth
• Sweating
• Tremor
• Dizziness
• Fatigue
• Sexual dysfunction
• Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults

Interactions

• Increased risk of serotonin syndrome when combined with other serotonergic agents
• Potential interaction with anticoagulants, increasing the risk of bleeding
• May increase plasma levels of other drugs metabolized by cytochrome P450 enzymes

Precautions

• Use with caution in patients with a history of seizure disorders
• Monitor for signs of serotonin syndrome
• Gradual dose reduction is recommended upon discontinuation to avoid withdrawal symptoms
• Caution in patients with a history of bipolar disorder
• Patients with a history of glaucoma should be monitored

Pregnancy

Increased risk of congenital malformations, particularly if used in the first trimester. Use only if potential benefits outweigh risks.

Breast-feeding

Fluvoxamine is present in breast milk, but the amount is generally considered too small to be harmful. Caution is advised.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Formulations

• Fluvoxamine maleate 50 mg tablets
• Fluvoxamine maleate 100 mg tablets
• Fluvoxamine maleate oral suspension

Mechanism of action

The exact mechanism of action of fluvoxamine has not been fully determined, but appears to be linked to its inhibition of CNS neuronal uptake of serotonin. Fluvoxamine blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT_1A autoreceptors. Studies have also demonstrated that fluvoxamine has virtually no affinity for α₁- or α₂-adrenergic, β-adrenergic, muscarinic, dopamine D₂, histamine H₁, GABA-benzodiazepine, opiate, 5-HT₁, or 5-HT₂ receptors, despite having an affinity for binding to σ1 receptors.

Pharmacodynamics

Fluvoxamine, an aralkylketone-derivative agent, is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) that differs structurally from other SSRIs. It is used to treat the depression associated with mood disorders. It is also used on occassion in the treatment of body dysmorphic disorder and anxiety. The antidepressant, antiobsessive-compulsive, and antibulimic actions of Fluvoxamine are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. <i>In vitro</i> studies show that Fluvoxamine is a potent and selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. Moreover, apart from binding to σ1 receptors, fluvoxamine has no significant affinity for adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT_1A, 5HT_1B, 5HT₂), or benzodiazepine receptors; antagonism of such receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs. Furthermore, some studies have demonstrated that the chronic administration of Fluvoxamine was found to downregulate brain norepinephrine receptors (as has been observed with other drugs effective in the treatment of major depressive disorder), while others suggest the opposite.