INDICATION AND USES:
Fluvoxamine Maleate Tablets are indicated for the treatment of obsessions and compulsions in patients with obsessive compulsive disorder (OCD) (1).
DOSAGE AND ADMINISTRATION
- Adults: Recommended starting dose is 50 mg at bedtime, with increases of 50 mg every 4 to 7 days as tolerated to maximum effect, not to exceed 300 mg/day. Daily doses over 100 mg should be divided (2.1).
- Children and adolescents (8-17 years): Recommended starting dose is 25 mg at bedtime, with increases of 25 mg every 4 to 7 days as tolerated to maximum effect, not to exceed 200 mg/day (8-11 years) or 300 mg/day (12-17 years). Daily doses over 50 mg should be divided (2.2).
- Hepatically impaired: Decreased clearance may require modified dose and titration (2.3).
- Extended treatment: Adjust dose to maintain lowest effective dose; reassess patients periodically (2.6).
- Discontinuation: Gradual dose reduction is recommended (2.7, 5.9).
SIDE EFFECTS:
Most common reactions in controlled trials with adult OCD and depression patients (incidence ³5% and at least twice that for placebo) were nausea, somnolence, insomnia, asthenia, nervousness, dyspepsia, abnormal ejaculation, sweating, anorexia, tremor, and vomiting (6.2). Using the above rule, the following events were also identified: anorgasmia, decreased libido, dry mouth, rhinitis, taste perversion, and urinary frequency in patients with OCD; and agitation, depression, dysmenorrhea, flatulence, hyperkinesia, and rash in pediatric patients with OCD.
CONTRAINDICATIONS:
- Coadministration of tizanidine, thioridazine, alosetron, pimozide (4)
- Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with Fluvoxamine Maleate Tablets or within 14 days of stopping treatment with Fluvoxamine Maleate Tablets. Do not use Fluvoxamine Maleate Tablets within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start Fluvoxamine Maleate Tablets in a patient who is being treated with linezolid or intravenous methylene blue (4)
WARNINGS AND PRECAUTIONS:
- Suicidality: Monitor for clinical worsening and suicide risk (5.1).
- Bipolar disorder: Screen for bipolar disorder (5.1).
- Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including Fluvoxamine Maleate Tablets, both when taken alone, but especially when co-administered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort). If such symptoms occur, discontinue Fluvoxamine Maleate Tablets and initiate supportive treatment. If concomitant use of Fluvoxamine Maleate Tablets with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases. (5.2).
- Angle Closure Glaucoma: Angle closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants (5.3).
- Other potentially important drug interactions. Benzodiazepines: Use with caution. Coadministration with diazepam is generally not advisable (5.8). Clozapine: Clozapine levels may be increased and produce orthostatic hypotension or seizures (5.8). Methadone: Coadministration may produce opioid intoxication. Discontinuation of fluvoxamine may produce opioid withdrawal (5.8). Mexiletine: Monitor serum mexiletine levels (5.8). Ramelteon: Should not be used in combination with fluvoxamine (5.8). Theophylline: Clearance decreased; reduce theophylline dose by one-third (5.8). Warfarin: Plasma concentrations increased and prothrombin times prolonged; monitor prothrombin time and adjust warfarin dose accordingly (5.8). Other Drugs Affecting Hemostasis: Increased risk of bleeding with concomitant use of NSAIDs, aspirin, or other drugs affecting coagulation (5.8, 5.10). See Contraindications (4).
- Discontinuation: Symptoms associated with discontinuation have been reported (5.9). Abrupt discontinuation not recommended. See Dosage And Administration (2.7).
- Activation of mania/hypomania has occurred (5.11).
- Seizures: Avoid administering fluvoxamine in patients with unstable epilepsy; monitor patients with controlled epilepsy; discontinue treatment if seizures occur or frequency increases (5.12).
- Hyponatremia: May occur with SSRIs and SNRIs, including Fluvoxamine Maleate Tablets. The elderly may be at increased risk. Consider discontinuing in patients with symptomatic hyponatremia (5.13).
- Concomitant illness: Use caution in patients with diseases or conditions that affect hemodynamic responses or metabolism (5.14). Patients with impaired liver function may require a lower starting dose and slower titration (2.3).
DRUG INTERACTIONS:
- Drug Interactions (not described in Contraindications or Warnings And Precautions) include the following: Drugs Inhibiting or Metabolized by Cytochrome P450: Fluvoxamine inhibits several cytochrome P450 isoenzymes (CYP1A2, CYP2C9, CYP3A4, and CYP2C19).
- Carbamazepine: Elevated carbamazepine levels and symptoms of toxicity with coadministration (7.2).
- Sumatriptan: Rare post marketing reports of weakness, hyperreflexia, and incoordination following use of an SSRI and sumatriptan. Monitor appropriately if concomitant treatment is clinically warranted (7.2).
- Tacrine: Coadministration increased tacrine Cmax and AUC five- and eight-fold and caused nausea, vomiting, sweating, and diarrhea (7.2).
- Tricyclic Antidepressants (TCAs): Coadministration significantly increased plasma TCA levels. Use caution; monitor plasma TCA levels; reduce TCA dose if indicated (7.2).
- Tryptophan: Severe vomiting with coadministration (7.2).
- Diltiazem: Bradycardia with coadministration (7.3).
- Propranolol or metoprolol: Reduce dose if co-administered and titrate more cautiously (7.3)
OVERDOSE:
Worldwide exposure to fluvoxamine includes over 45,000 patients treated in clinical trials and an estimated exposure of 50,000,000 patients treated during worldwide marketing experience (end of 2005). Of the 539 cases of deliberate or accidental overdose involving fluvoxamine reported from this population, there were 55 deaths. Of these, 9 were in patients thought to be taking fluvoxamine alone and the remaining 46 were in patients taking fluvoxamine along with other drugs. Among non-fatal overdose cases, 404 patients recovered completely. Five patients experienced adverse sequelae of overdosage, to include persistent mydriasis, unsteady gait, hypoxic encephalopathy, kidney complications (from trauma associated with overdose), bowel infarction requiring a hemicolectomy, and vegetative state. In 13 patients, the outcome was provided as abating at the time of reporting. In the remaining 62 patients, the outcome was unknown. The largest known ingestion of fluvoxamine involved 12,000 mg (equivalent to 2 to 3 months’ dosage). The patient fully recovered. However, ingestions as low as 1,400 mg have been associated with lethal outcome, indicating considerable prognostic variability.
Commonly (³5%) observed adverse events associated with fluvoxamine maleate overdose include gastrointestinal complaints (nausea, vomiting and diarrhea), coma, hypokalemia, hypotension, respiratory difficulties, somnolence, and tachycardia. Other notable signs and symptoms seen with fluvoxamine maleate overdose (single or multiple drugs) include bradycardia, ECG abnormalities (such as heart arrest, QT interval prolongation, first degree atrioventricular block, bundle branch block, and junctional rhythm), convulsions, dizziness, liver function disturbances, tremor, and increased reflexes.
Management of Overdosage: Treatment should consist of those general measures employed in the management of overdosage with any antidepressant. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients. Activated charcoal should be administered. Due to the large volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit. No specific antidotes for fluvoxamine are known. A specific caution involves patients taking, or recently having taken, fluvoxamine who might ingest excessive quantities of a tricyclic antidepressant. In such a case, accumulation of the parent tricyclic and/or an active metabolite may increase the possibility of clinically significant sequelae and extend the time needed for close medical observation [see Drug Interactions (7.2)]. In managing overdosage, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Telephone numbers for certified poison control centers are listed in the Physicians’ Desk Reference (PDR).
- Uses
-
INDICATION AND USES:
Fluvoxamine Maleate Tablets are indicated for the treatment of obsessions and compulsions in patients with obsessive compulsive disorder (OCD) (1).
DOSAGE AND ADMINISTRATION
- Adults: Recommended starting dose is 50 mg at bedtime, with increases of 50 mg every 4 to 7 days as tolerated to maximum effect, not to exceed 300 mg/day. Daily doses over 100 mg should be divided (2.1).
- Children and adolescents (8-17 years): Recommended starting dose is 25 mg at bedtime, with increases of 25 mg every 4 to 7 days as tolerated to maximum effect, not to exceed 200 mg/day (8-11 years) or 300 mg/day (12-17 years). Daily doses over 50 mg should be divided (2.2).
- Hepatically impaired: Decreased clearance may require modified dose and titration (2.3).
- Extended treatment: Adjust dose to maintain lowest effective dose; reassess patients periodically (2.6).
- Discontinuation: Gradual dose reduction is recommended (2.7, 5.9).
- Side Effects
-
SIDE EFFECTS:
Most common reactions in controlled trials with adult OCD and depression patients (incidence ³5% and at least twice that for placebo) were nausea, somnolence, insomnia, asthenia, nervousness, dyspepsia, abnormal ejaculation, sweating, anorexia, tremor, and vomiting (6.2). Using the above rule, the following events were also identified: anorgasmia, decreased libido, dry mouth, rhinitis, taste perversion, and urinary frequency in patients with OCD; and agitation, depression, dysmenorrhea, flatulence, hyperkinesia, and rash in pediatric patients with OCD.
- Precautions
-
CONTRAINDICATIONS:
- Coadministration of tizanidine, thioridazine, alosetron, pimozide (4)
- Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with Fluvoxamine Maleate Tablets or within 14 days of stopping treatment with Fluvoxamine Maleate Tablets. Do not use Fluvoxamine Maleate Tablets within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start Fluvoxamine Maleate Tablets in a patient who is being treated with linezolid or intravenous methylene blue (4)
WARNINGS AND PRECAUTIONS:
- Suicidality: Monitor for clinical worsening and suicide risk (5.1).
- Bipolar disorder: Screen for bipolar disorder (5.1).
- Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including Fluvoxamine Maleate Tablets, both when taken alone, but especially when co-administered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort). If such symptoms occur, discontinue Fluvoxamine Maleate Tablets and initiate supportive treatment. If concomitant use of Fluvoxamine Maleate Tablets with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases. (5.2).
- Angle Closure Glaucoma: Angle closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants (5.3).
- Other potentially important drug interactions. Benzodiazepines: Use with caution. Coadministration with diazepam is generally not advisable (5.8). Clozapine: Clozapine levels may be increased and produce orthostatic hypotension or seizures (5.8). Methadone: Coadministration may produce opioid intoxication. Discontinuation of fluvoxamine may produce opioid withdrawal (5.8). Mexiletine: Monitor serum mexiletine levels (5.8). Ramelteon: Should not be used in combination with fluvoxamine (5.8). Theophylline: Clearance decreased; reduce theophylline dose by one-third (5.8). Warfarin: Plasma concentrations increased and prothrombin times prolonged; monitor prothrombin time and adjust warfarin dose accordingly (5.8). Other Drugs Affecting Hemostasis: Increased risk of bleeding with concomitant use of NSAIDs, aspirin, or other drugs affecting coagulation (5.8, 5.10). See Contraindications (4).
- Discontinuation: Symptoms associated with discontinuation have been reported (5.9). Abrupt discontinuation not recommended. See Dosage And Administration (2.7).
- Activation of mania/hypomania has occurred (5.11).
- Seizures: Avoid administering fluvoxamine in patients with unstable epilepsy; monitor patients with controlled epilepsy; discontinue treatment if seizures occur or frequency increases (5.12).
- Hyponatremia: May occur with SSRIs and SNRIs, including Fluvoxamine Maleate Tablets. The elderly may be at increased risk. Consider discontinuing in patients with symptomatic hyponatremia (5.13).
- Concomitant illness: Use caution in patients with diseases or conditions that affect hemodynamic responses or metabolism (5.14). Patients with impaired liver function may require a lower starting dose and slower titration (2.3).
- Interactions
-
DRUG INTERACTIONS:
- Drug Interactions (not described in Contraindications or Warnings And Precautions) include the following: Drugs Inhibiting or Metabolized by Cytochrome P450: Fluvoxamine inhibits several cytochrome P450 isoenzymes (CYP1A2, CYP2C9, CYP3A4, and CYP2C19).
- Carbamazepine: Elevated carbamazepine levels and symptoms of toxicity with coadministration (7.2).
- Sumatriptan: Rare post marketing reports of weakness, hyperreflexia, and incoordination following use of an SSRI and sumatriptan. Monitor appropriately if concomitant treatment is clinically warranted (7.2).
- Tacrine: Coadministration increased tacrine Cmax and AUC five- and eight-fold and caused nausea, vomiting, sweating, and diarrhea (7.2).
- Tricyclic Antidepressants (TCAs): Coadministration significantly increased plasma TCA levels. Use caution; monitor plasma TCA levels; reduce TCA dose if indicated (7.2).
- Tryptophan: Severe vomiting with coadministration (7.2).
- Diltiazem: Bradycardia with coadministration (7.3).
- Propranolol or metoprolol: Reduce dose if co-administered and titrate more cautiously (7.3)
- Overdose
-
OVERDOSE:
Worldwide exposure to fluvoxamine includes over 45,000 patients treated in clinical trials and an estimated exposure of 50,000,000 patients treated during worldwide marketing experience (end of 2005). Of the 539 cases of deliberate or accidental overdose involving fluvoxamine reported from this population, there were 55 deaths. Of these, 9 were in patients thought to be taking fluvoxamine alone and the remaining 46 were in patients taking fluvoxamine along with other drugs. Among non-fatal overdose cases, 404 patients recovered completely. Five patients experienced adverse sequelae of overdosage, to include persistent mydriasis, unsteady gait, hypoxic encephalopathy, kidney complications (from trauma associated with overdose), bowel infarction requiring a hemicolectomy, and vegetative state. In 13 patients, the outcome was provided as abating at the time of reporting. In the remaining 62 patients, the outcome was unknown. The largest known ingestion of fluvoxamine involved 12,000 mg (equivalent to 2 to 3 months’ dosage). The patient fully recovered. However, ingestions as low as 1,400 mg have been associated with lethal outcome, indicating considerable prognostic variability.
Commonly (³5%) observed adverse events associated with fluvoxamine maleate overdose include gastrointestinal complaints (nausea, vomiting and diarrhea), coma, hypokalemia, hypotension, respiratory difficulties, somnolence, and tachycardia. Other notable signs and symptoms seen with fluvoxamine maleate overdose (single or multiple drugs) include bradycardia, ECG abnormalities (such as heart arrest, QT interval prolongation, first degree atrioventricular block, bundle branch block, and junctional rhythm), convulsions, dizziness, liver function disturbances, tremor, and increased reflexes.
Management of Overdosage: Treatment should consist of those general measures employed in the management of overdosage with any antidepressant. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients. Activated charcoal should be administered. Due to the large volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit. No specific antidotes for fluvoxamine are known. A specific caution involves patients taking, or recently having taken, fluvoxamine who might ingest excessive quantities of a tricyclic antidepressant. In such a case, accumulation of the parent tricyclic and/or an active metabolite may increase the possibility of clinically significant sequelae and extend the time needed for close medical observation [see Drug Interactions (7.2)]. In managing overdosage, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Telephone numbers for certified poison control centers are listed in the Physicians’ Desk Reference (PDR).