Highlights Of Prescribing Information hypotension or seizures (5.7). Methadone: Coadministration may produce These highlights do not include all the information needed to use opioid intoxication. Discontinuation of fluvoxamine may produce opioid Fluvoxamine Maleate Tablets safely and effectively. See full prescribing withdrawal (5.7). Mexiletine: Monitor serum mexiletine levels (5.7). information for Fluvoxamine Maleate Tablets. Ramelteon: Should not be used in combination with fluvoxamine (5.7). Theophylline: Clearance decreased; reduce theophylline dose by one-third Fluvoxamine Maleate Tablets for oral administration (5.7). Warfarin: Plasma concentrations increased and prothrombin times Initial U.S. Approval: 1994 prolonged; monitor prothrombin time and adjust warfarin dose accordingly Warning: Suicidality and Antidepressants (5.7). Other Drugs Affecting Hemostasis: Increased risk of bleeding with See full prescribing information for complete boxed warning. concomitant use of NSAIDs, aspirin, or other drugs affecting coagulation (5.7, Increased risk of suicidal thinking and behavior in children, adolescents, and 5.9). See Contraindications (4). Discontinuation: Symptoms associated with young adults taking antidepressants for major depressive disorder and other discontinuation have been reported (5.8). Abrupt discontinuation not psychiatric disorders. Fluvoxamine Maleate Tablets are not approved for use in recommended. See Dosage And Administration (2.8). pediatric patients except those with obsessive compulsive disorder (5.1). Activation of mania/hypomania has occurred (5.10). Seizures: Avoid administering fluvoxamine in patients with unstable epilepsy; ----------------------------------Recent Major Changes-------------------------------- monitor patients with controlled epilepsy; discontinue treatment if seizures Indications and Usage, Long-Term Use (1.1) 4/2008 occur or frequency increases (5.11). Dosage and Administration, Maintenance (2.7) 4/2008 Warnings and Precautions, Abnormal Bleeding (5.7, 5.9) 4/2008 Hyponatremia: May occur with SSRIs and SNRIs, including Fluvoxamine Warnings and Precautions, Serotonin Syndrome (5.2) 2/2009 Maleate Tablets. The elderly may be at increased risk. Consider discontinuing in Dosage and Administration (2.5, 2.6), Contraindications (4.2), patients with symptomatic hyponatremia (5.12). Warnings and Precautions (5.2), Use in Specific Populations (8.1) 9/2012 Concomitant illness: Use caution in patients with diseases or conditions that affect hemodynamic responses or metabolism (5.13). Patients with impaired ----------------------------------Indications And Usage--------------------------------- liver function may require a lower starting dose and slower titration (2.3). Fluvoxamine Maleate Tablets are indicated for the treatment of obsessions and compulsions in patients with obsessive compulsive disorder (OCD) (1). ------------------------------Adverse Reactions----------------------------------------­ Most common reactions in controlled trials with adult OCD and depression -------------------------------Dosage And Administration----------------------------­ patients (incidence 5% and at least twice that for placebo) were nausea, Adults: Recommended starting dose is 50 mg at bedtime, with increases of somnolence, insomnia, asthenia, nervousness, dyspepsia, abnormal 50 mg every 4 to 7 days as tolerated to maximum effect, not to exceed ejaculation, sweating, anorexia, tremor, and vomiting (6.2). Using the above 300 mg/day. Daily doses over 100mg should be divided (2.1). rule, the following events were also identified: anorgasmia, decreased Children and adolescents (8-17 years): Recommended starting dose is 25 mg at libido, dry mouth, rhinitis, taste perversion, and urinary frequency in bedtime, with increases of 25 mg every 4 to 7 days as tolerated to maximum patients with OCD; and agitation, depression, dysmenorrhea, flatulence, effect, not to exceed 200 mg/day (8-11 years) or 300 mg/day (12-17 years). Daily hyperkinesia, and rash in pediatric patients with OCD. doses over 50mg should be divided (2.2). To report Suspected Adverse Reactions, call toll free at 1-800-308-6755 Hepatically impaired: Decreased clearance may require modified dose and (phone); 1-651-641-0341 (fax); or FDA at 1-800-FDA-1088 or titration (2.3). www.fda.gov/Medwatch. Extended treatment: Adjust dose to maintain lowest effective dose; reassess -------------------------------Drug Interactions----------------------------------------­ patients periodically (2.7). Drug Interactions (not described in Contraindications or Warnings And Discontinuation: Gradual dose reduction is recommended (2.8, see Warnings Precautions) include the following: And Precautions [5.8]). Drugs Inhibiting or Metabolized by Cytochrome P450: Fluvoxamine inhibits -------------------------------Dosage Forms And Strengths -----------------------------­ several cytochrome P450 isoenzymes (CYP1A2, CYP2C9, CYP3A4, and 25 mg Tablets, 50 mg Tablets, and 100 mg Tablets (3) CYP2C19). Carbamazepine: Elevated carbamazepine levels and symptoms of toxicity with coadministration (7.2). Sumatriptan: Rare postmarketing reports ------------------------------------Contraindications---------------------------------------­ of weakness, hyperreflexia, and incoordination following use of an SSRI and Coadministration of tizanidine, thioridazine, alosetron, pimozide (4.1) sumatriptan. Monitor appropriately if concomitant treatment is clinically warranted (7.2). Tacrine: Coadministration increased tacrine Cmax and AUC Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat five- and eight-fold and caused nausea, vomiting, sweating, and diarrhea (7.2). psychiatric disorders with Fluvoxamine Maleate Tablets or within 14 days of Tricyclic Antidepressants (TCAs): Coadministration significantly increased stopping treatment with Fluvoxamine Maleate Tablets. Do not use plasma TCA levels. Use caution; monitor plasma TCA levels; reduce TCA dose Fluvoxamine Maleate Tablets within 14 days of stopping an MAOI intended if indicated (7.2). Tryptophan: Severe vomiting with coadministration (7.2). to treat psychiatric disorders. In addition, do not start Fluvoxamine Maleate Diltiazem: Bradycardia with coadministration (7.3). Propranolol or Tablets in a patient who is being treated with linezolid or intravenous metoprolol: Reduce dose if coadministered and titrate more cautiously (7.3). methylene blue (4.2) -------------------------Use In Specific Populations----------------------------------­ --------------------------------Warnings And Precautions-------------------------------­ Specific populations not discussed in Dosage and Administration or Suicidality: Monitor for clinical worsening and suicide risk (5.1). Warnings and Precautions include: Bipolar disorder: Screen for bipolar disorder (5.1). Pregnancy: Consider both potential risks and benefits when treating a pregnant woman. Infants exposed to SSRIs late in pregnancy have Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and developed various complications and may be at risk for persistent pulmonary SNRIs, including Fluvoxamine Maleate Tablets, both when taken alone, but hypertension of the newborn (PPHN) (2.4, 8.1). especially when co-administered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, Nursing mothers: Fluvoxamine is secreted in human breast milk (8.3). buspirone and St. John's Wort). If such symptoms occur, discontinue Pediatric: Monitor weight and growth; effects of long-term use on growth, Fluvoxamine Maleate Tablets and initiate supportive treatment. If concomitant congnitive behavioral development, and maturation have not been studied use of Fluvoxamine Maleate Tablets with other serotonergic drugs is clinically (8.4). warranted, patients should be made aware of a potential increased risk for Geriatric: Use of a lower starting dose may be warranted. Titrate slowly serotonin syndrome, particularly during treatment initiation and dose during initiation of therapy (2.3, 8.5). increases. (5.2). Smokers: Smokers had a 25% increase in fluvoxamine metabolism (7.4). Other potentially important drug interactions. Benzodiazepines: Use with caution. Coadministration with diazepam is generally not advisable (5.7). See 17 For Patient Counseling Information and the FDA-Approved Clozapine: Clozapine levels may be increased and produce orthostatic Medication Guide Rev MM/YY 1 Reference ID: 3223798 FULL PRESCRIBING INFORMATION: CONTENTS* 8 USE IN SPECIFIC POPULATIONS SUICIDALITY AND ANTIDEPRESSANT DRUGS 8.1 Pregnancy 1 INDICATIONS AND USAGE 8.2 Labor And Delivery 1.1 Obssesive-Compulsive Disorder 8.3 Nursing Mothers 2 DOSAGE AND ADMINISTRATION 8.4 Pediatric Use 2.1 Adults 8.5 Geriatric Use 2.2 Pediatric Population (children and adolescents) 9 DRUG ABUSE AND DEPENDENCE 2.3 Elderly or Hepatically Impaired Patients 9.1 Controlled Substance 2.4 Pregnant Women During the Third Trimester 9.2 Physical and Psychological Dependence 2.5 Switching a Patient To or From a Monoamine Oxidase Inhibitor 10 OVERDOSAGE (MAOI) Intended to Treat Psychiatric Disorders 10.1 Human Experience 2.6 Use of Fluvoxamine Maleate Tablets with Other MAOIs such as 10.2 Management of Overdosage Linezolid or Methylene Blue 11 DESCRIPTION 2.7 Maintenance/Continuation Extended Treatment 12 CLINICAL PHARMACOLOGY 2.8 Discontinuation of Treatment with Fluvoxamine Maleate Tablets 12.1 Mechanism Of Action 3 DOSAGE FORMS AND STRENGTHS 12.2 Pharmacodynamics