Fluvoxamine Maleate, LUVOX®, LUVOX CR®

• LUVOX®,  LUVOX CR®

1. Anti-depressant ( Selective Serotonine Re-uptake Inhibitors)

2. ---

   Anti-obsessional

• Tablets, 50 mg and 100 mg.

1. Depression (In Adults)

2. Obsessive-Compulsive Disorder:

• Significantly reduce the symptoms of obsessive-compulsive disorder in adults

1. Mechanism of Action: selective inhibition of presynaptic serotonin reuptake in brain neurons. ( SSRIs)

2. Pharmacodynamics: Primary pharmacological effect serotonin-potentiating properties due to blockade of the membrane pump mechanism responsible for neuronal serotonin reuptake.

Pharmacokinetics:

1. Metabolism: Fluvoxamine is mainly metabolized by CYP2D6 >>> can inhibit the metabolism of drugs metabolized P450 isoenzymes.
2. Absorption: completely absorbed following oral administration >>> Maximum plasma concentrations within 3-8 hours of dosing, not influenced by concomitant food intake.
3. Distribution: binding to human plasma proteins is approximately 80%.half-life is 15 hours; Steady-state plasma levels within 10 to 14 days.
4. Excretion: 94% excreted in urine in 48 hour

1. Depression: (Adult) 

• Initial Dose: 50 mg/day >>> At bedtime
• Maintenance dose: between 100-200 mg/day
• Max Dose: 300 mg/day

2. Obsessive-Compulsive Disorder: (Adult)

• Initial Dose: 50 mg/day >>> At bedtime
• Maintenance dose: between 100-300 mg/day
• Max Dose: 300 mg/day

3. Use in Hepatic or Renal Insufficiency:

• Should begin treatment with a low dose + be carefully monitored.

4. Renal Insufficiency: Carefully monitor the patient

5. Missed Dose: next dose should be taken at the normal time.

6. Administration: should be swallowed whole with water, Do not chew!

1. Drugs metabolized by CYP1A2, CYP3A4 and CYP2C that have a narrow therapeutic index: Theophylline, Tacrine, Mexiletine, and Clozapine, Carbamazepine, Methadone, Cyclosporine and Sildenafil, Phenytoin.

2. Monoamine oxidase (MAO) inhibitors

3. Methylene blue (intravenous dye)

4. linezolid

5. Thioridazine

6. Mesoridazine

7. Pimozide

8. Terfenadine

9. Astemizole

10. Cisapride

11. Tizanidine

12. ASA, Warfarin, NSAIDs

13. Propronolol

14. Ropinirole (Anti-Parkinson Agent)

 > 10%:

• Nausea
• Headache
• Somnolence
• Weakness
• Insomnia
• Diarrhea
• Dizziness
• Anorexia
• Xerostomia ( Dry mouth)
• Sexual Dysfunction >>> Abnormal Ejaculation

 < 10%:

• Akathisia/Psychomotor Restlessness: Decrease the dose
• Bone Fracture Risk: in administration of SSRIs/ SNRIs >>> caution in elderly patients ( Fall Risk)
• Hyperglycemia, hypoglycaemia, diabetes mellitus and decreased glucose tolerance.
• Abnormal Bleeding: abnormal platelet aggregation.
• Seizures
• Glaucoma
• Dyspepsia
• Myalgia
• Decreased Libido
• Anxiety

1. Hypersensitive to drug

2. Co administration with monoamine oxidase (MAO) inhibitors >>> methylene blue (intravenous dye) + linezolid (An antibiotic,reversible non- selective MAO inhibitor), L-tryptophan, oxitriptan , Triptans, Lithium, Tramadol, most Tricyclic antidepressants, Neuroleptics/Antipsychotics or John’s Wort >>>> Serotonin Syndrom!

3. Co-Administration with Thioridazine, Mesoridazine, Pimozide, Terfenadine, Astemizole, or Cisapride >>> Long QT interval >>> serious ventricular arrhythmias >>> Torsade de point arrhythmia >>> Sudden Death.

4. Co administration with Tizanidine.

1. Pregnancy: Category C

2. Lactation: Should not be administered to nursing mothers

1. Geriatrics (> 65 years of age): caution is recommended

2. Paediatrics (< 18 years of age): Not Indicated, potential association with behavioural and emotional changes, including self-harm).

3. Suicide/Suicidal Thoughts/ Clinical Worsening:

• Close supervision of patients is required.

4. Co-Administration of Fluvoxamine (SSRIs) along with MAOIs, L-tryptophan, oxitriptan , Triptans ( 5HT1 Agonist), Lithium, Tramadol, most Tricyclic antidepressants, Neuroleptics/Antipsychotics or John’s Wort >>> Serotonin Syndrome! At least two weeks elapse after SSRIs discontinuation is mandatory!

5. Caution in concomitant use with Benzodiazepins >>> Synergistic effect on psychomotor impairment.

6. Co-Administration Thioridazine, Mesoridazine, Pimozide, Terfenadine, Astemizole, or Cisapride >>> Long QT interval >>> serious ventricular arrhythmias

7. Co-Administration with Thioridazine, Mesoridazine, Pimozide, Terfenadine, Astemizole, or Cisapride >>> Long QT interval >>> serious ventricular arrhythmias >>> Torsade de point arrhythmia >>> Sudden Death.

8. Symptoms when discontinuing treatment:

• Dizziness, abnormal dreams, paresthesias and electric shock sensations),
• Sleep disturbances insomnia and intense dreams
• Agitation, irritability, anxiety, fatigue, confusion, emotional instability, headache, tremor, nausea, vomiting, diarrhea, sweating, palpitations.
• If Flovoxamine is used until or shortly before birth, discontinuation effects in the newborn may occur.
• Discontinuation Symptoms: should NOT be discontinued abruptly >>> do a gradual reduction.

9. Disturbance of Glycemic Control: Especially during early treatment >>> hyperglycemia, hypoglycaemia, diabetes mellitus and decreased glucose tolerance >>> Monitor the patients!

10. Abnormal Bleeding: abnormal platelet aggregation >>> caution in co administration with Warfarin, ASA, NSAID

11. Caution is recommended when the drug is administered to patients with a history of

12. Sedation may occur in some patients >>> Avoid activities requiring complete mental alertness, judgement and physical coordination >>> Avoid Driving!

13. Used with caution in patients with raised intraocular pressure or those with narrow-angle glaucoma.

14. Mania/Hypomania: Patients with bipolar disorder may be at an increased risk of experiencing manic episodes when treated with antidepressants alone >>> Use with Caution.

15. Notify physician if conception occurred.

16. May potentiate the effects of alcohol and increase the level of psychomotor impairment.

17. Propronolol: cautious dose titration is recommend >>> Reduction in initial dose may be required.

18. Ropinirole (Anti-Parkinson Agent): Careful monitoring+ reduction in the dosage of Ropinirole in concomitant use.

19. Overdosage : most common symptoms: nausea, vomiting and diarrhea, somnolence + dizziness, tachycardia, bradycardia, hypotension, liver function disturbances, convulsions and coma >>> Treatment: No specific antidote, supportive therapy.