FLUVOXAMINE MALEATE 100 MG TABLET | RED RECTANGLE APO FLU100 PD-RX PHARMACEUTICALS, INC. 7278922130

Suicidality:Monitor for clinical worsening and suicide risk ( 5.1). Bipolar disorder:Screen for bipolar disorder ( 5.1). S erotonin 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. 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/hypomaniahas 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). Sexual Dysfunction: Fluvoxamine Maleate Tablets may cause symptoms of sexual dysfunction ( 5.16).

Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4,400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1,000 patients treated) are provided in Table 1. TABLE 1 DRUG-PLACEBO DIFFERENCES IN NUMBER OF CASES OF SUICIDALITY PER 1,000 PATIENTS TREATED Age Range Increases Compared to Placebo <18 14 Additional Cases 18-24 5 Additional Cases Age Range Decreases Compared to Placebo 25-64 1 Fewer Case 65 6 Fewer Cases No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about the drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient s presenting symptoms. If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms and risks [see Dosage and Administration ( 2.7)]. Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers.Prescriptions for fluvoxamine maleate tablets should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose. Screening Patients for Bipolar Disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that fluvoxamine maleate tablets are not approved for use in treating bipolar depression.

Selective serotonin reuptake inhibitors (SSRIs), including Fluvoxamine Maleate Tablets, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, meperidine, methadone, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John's Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications ( 4), Drug Interactions ( 7.1)]. Serotonin syndrome can also occur when these drugs are used alone. Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome. The concomitant use of fluvoxamine maleate tablets with MAOIs is contraindicated. In addition, do not initiate Fluvoxamine Maleate Tablets in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking fluvoxamine maleate tablets, discontinue Fluvoxamine maleate tablets before initiating treatment with the MAOI [see Contraindications ( 4), Drug Interactions ( 7.2)]. Monitor all patients taking Fluvoxamine Maleate Tablets for the emergence of serotonin syndrome. Discontinue treatment with Fluvoxamine Maleate Tablets and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of fluvoxamine maleate tablets with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.

Benzodiazepines: Benzodiazepines metabolized by hepatic oxidation (e.g., alprazolam, midazolam, triazolam, etc.) should be used with caution because the clearance of these drugs is likely to be reduced by fluvoxamine. The clearance of benzodiazepines metabolized by glucuronidation (e.g., lorazepam, oxazepam, temazepam) is unlikely to be affected by fluvoxamine. Alprazolam - When fluvoxamine maleate (100 mg q.d.) and alprazolam (1 mg q.i.d.) were coadministered to steady state, plasma concentrations and other pharmacokinetic parameters (AUC, C max, T ) of alprazolam were approximately twice those observed when alprazolam was administered alone; oral clearance was reduced by about 50%. The elevated plasma alprazolam concentrations resulted in decreased psychomotor performance and memory. This interaction, which has not been investigated using higher doses of fluvoxamine, may be more pronounced if a 300 mg daily dose is coadministered, particularly since fluvoxamine exhibits non-linear pharmacokinetics over the dosage range 100 to 300 mg. If alprazolam is coadministered with fluvoxamine maleate tablets, the initial alprazolam dosage should be at least halved and titration to the lowest effective dose is recommended. No dosage adjustment is required for fluvoxamine maleate tablets. Diazepam -The coadministration of fluvoxamine maleate tablets and diazepam is generally not advisable. Because fluvoxamine reduces the clearance of both diazepam and its active metabolite, N-desmethyldiazepam, there is a strong likelihood of substantial accumulation of both species during chronic coadministration. Evidence supporting the conclusion that it is inadvisable to coadminister fluvoxamine and diazepam is derived from a study in which healthy volunteers taking 150 mg/day of fluvoxamine were administered a single oral dose of 10 mg of diazepam. In these subjects (N=8), the clearance of diazepam was reduced by 65% and that of N-desmethyldiazepam to a level that was too low to measure over the course of the 2 week long study. It is likely that this experience significantly underestimates the degree of accumulation that might occur with repeated diazepam administration. Moreover, as noted with alprazolam, the effect of fluvoxamine may even be more pronounced when it is administered at higher doses. Accordingly, diazepam and fluvoxamine should not ordinarily be coadministered. Clozapine -Elevated serum levels of clozapine have been reported in patients taking fluvoxamine maleate and clozapine. Since clozapine-related seizures and orthostatic hypotension appear to be dose related, the risk of these adverse events may be higher when fluvoxamine and clozapine are coadministered. Patients should be closely monitored when fluvoxamine maleate and clozapine are used concurrently. Methadone: Significantly increased methadone (plasma level:dose) ratios have been reported when fluvoxamine maleate was administered to patients receiving maintenance methadone treatment, with symptoms of opioid intoxication in one patient. Opioid withdrawal symptoms were reported following fluvoxamine maleate discontinuation in another patient. Mexiletine: The effect of steady-state fluvoxamine (50 mg b.i.d. for 7 days) on the single dose pharmacokinetics of mexiletine (200 mg) was evaluated in 6 healthy Japanese males. The clearance of mexiletine was reduced by 38% following coadministration with fluvoxamine compared to mexiletine alone. If fluvoxamine and mexiletine are coadministered, serum mexiletine levels should be monitored. Ramelteon: When fluvoxamine 100 mg twice daily was administered for 3 days prior to single-dose coadministration of ramelteon 16 mg and fluvoxamine, the AUC for ramelteon increased approximately 190-fold and the C maxincreased approximately 70-fold compared to ramelteon administered alone. Ramelteon should not be used in combination with fluvoxamine. Theophylline: The effect of steady-state fluvoxamine (50 mg bid) on the pharmacokinetics of a single dose of theophylline (375 mg as 442 mg aminophylline) was evaluated in 12 healthy non-smoking, male volunteers. The clearance of theophylline was decreased approximately 3-fold. Therefore, if theophylline is coadministered with fluvoxamine maleate, its dose should be reduced to one-third of the usual daily maintenance dose and plasma concentrations of theophylline should be monitored. No dosage adjustment is required for fluvoxamine maleate tablets. Warfarin and Other Drugs That Interfere With Hemostasis (NSAIDs, Aspirin, etc.): Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. These studies have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding. Thus, patients should be cautioned about the use of such drugs concurrently with fluvoxamine [see Warnings and Precautions ( 5.10)]. Warfarin - When fluvoxamine maleate (50 mg t.i.d.) was administered concomitantly with warfarin for two weeks, warfarin plasma concentrations increased by 98% and prothrombin times were prolonged. Thus patients receiving oral anticoagulants and fluvoxamine maleate tablets should have their prothrombin time monitored and their anticoagulant dose adjusted accordingly. No dosage adjustment is required for fluvoxamine maleate tablets.

Commonly Observed Adverse Reactions in Controlled Clinical Trials: Fluvoxamine maleate tablets have been studied in 10-week short-term controlled trials of OCD (N=320) and depression (N=1,350). In general, adverse reaction rates were similar in the two data sets as well as in the pediatric OCD study. The most commonly observed adverse reactions associated with the use of fluvoxamine maleate tablets and likely to be drug-related (incidence of 5% or greater and at least twice that for placebo) derived from Table 2were: nausea, somnolence, insomnia, asthenia, nervousness, dyspepsia, abnormal ejaculation, sweating, anorexia, tremor,and vomiting.In a pool of two studies involving only patients with OCD, the following additional reactions were identified using the above rule: anorgasmia, decreased libido, dry mouth, rhinitis, taste perversion,and urinary frequency.In a study of pediatric patients with OCD, the following additional reactions were identified using the above rule: agitation, depression, dysmenorrhea, flatulence, hyperkinesia,and rash. Adverse Reactions Occurring at an Incidence of 1%: Table 2enumerates adverse reactions that occurred in adults at a frequency of 1% or more, and were more frequent than in the placebo group, among patients treated with fluvoxamine maleate tablets in two short-term placebo controlled OCD trials (10 week) and depression trials (6 week) in which patients were dosed in a range of generally 100 to 300 mg/day. This table shows the percentage of patients in each group who had at least one occurrence of a reaction at some time during their treatment. Reported adverse reactions were classified using a standard COSTART-based Dictionary terminology. The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors may differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the side-effect incidence rate in the population studied. TABLE 2 TREATMENT-EMERGENT ADVERSE REACTION INCIDENCE RATES BY BODY SYSTEM IN ADULT OCD AND DEPRESSION POPULATIONS COMBINED 1 BODY SYSTEM/ ADVERSE REACTION Percentage of Patients Reporting Reaction FLUVOXAMINE N=892 PLACEBO N=778 BODY AS WHOLE Headache 22 20 Asthenia 14 6 Flu Syndrome 3 2 Chills 2 1 CARDIOVASCULAR Palpitations 3 2 DIGESTIVE SYSTEM Nausea 40 14 Diarrhea 11 7 Constipation 10 8 Dyspepsia 10 5 Anorexia 6 2 Vomiting 5 2 Flatulence 4 3 Tooth Disorder 2 3 1 Dysphagia 2 1 NERVOUS SYSTEM Somnolence 22 8 Insomnia 21 10 Dry Mouth 14 10 Nervousness 12 5 Dizziness 11 6 Tremor 5 1 Anxiety 5 3 Vasodilatation 3 3 1 Hypertonia 2 1 Agitation 2 1 Decreased Libido 2 1 Depression 2 1 CNS Stimulation 2 1 RESPIRATORY SYSTEM Upper Respiratory Infection 9 5 Dyspnea 2 1 Yawn 2 0 SKIN Sweating 7 3 SPECIAL SENSES Taste Perversion 3 1 Amblyopia 4 3 2 UROGENITAL Abnormal Ejaculation 5,6 8 1 Urinary Frequency 3 2 Impotence 6 2 1 Anorgasmia 2 0 Urinary Retention 1 0 1Reactions for which fluvoxamine maleate incidence was equal to or less than placebo are not listed in the table above. 2Includes "toothache," "tooth extraction and abscess," and "caries." 3Mostly feeling warm, hot, or flushed. 4"Mostly "blurred vision." 5"Mostly "delayed ejaculation." 6Incidence based on number of male patients. Adverse Reactions in OCD Placebo Controlled Studies Which are Markedly Different (defined as at least a two-fold difference) in Rate from the Pooled Reaction Rates in OCD and Depression Placebo Controlled Studies: The reactions in OCD studies with a two-fold decrease in rate compared to reaction rates in OCD and depression studies were dysphagia and amblyopia (mostly blurred vision). Additionally, there was an approximate 25% decrease in nausea. The reactions in OCD studies with a two-fold increase in rate compared to reaction rates in OCD and depression studies were: asthenia, abnormal ejaculation (mostly delayed ejaculation), anxiety, rhinitis, anorgasmia (in males), depression, libido decreased, pharyngitis, agitation, impotence, myoclonus/twitch, thirst, weight loss, leg cramps, myalgia,and urinary retention.These reactions are listed in order of decreasing rates in the OCD trials.

During premarketing clinical trials conducted in North America and Europe, multiple doses of fluvoxamine maleate were administered for a combined total of 2,737 patient exposures in patients suffering OCD or Major Depressive Disorder. Untoward reactions associated with this exposure were recorded by clinical investigators using descriptive terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse reactions without first grouping similar types of untoward reactions into a limited (i.e., reduced) number of standard reaction categories. In the tabulations which follow, a standard COSTART-based Dictionary terminology has been used to classify reported adverse reactions. If the COSTART term for a reaction was so general as to be uninformative, it was replaced with a more informative term. The frequencies presented, therefore, represent the proportion of the 2,737 patient exposures to multiple doses of fluvoxamine maleate who experienced a reaction of the type cited on at least one occasion while receiving fluvoxamine maleate. All reported reactions are included in the list below, with the following exceptions: 1) those reactions already listed in Table 2, which tabulates incidence rates of common adverse experiences in placebo-controlled OCD and depression clinical trials, are excluded; 2) those reactions for which a drug cause was not considered likely are omitted; 3) reactions for which the COSTART term was too vague to be clinically meaningful and could not be replaced with a more informative term; and 4) reactions which were reported in only one patient and judged to not be potentially serious are not included. It is important to emphasize that, although the reactions reported did occur during treatment with fluvoxamine maleate, a causal relationship to fluvoxamine maleate has not been established. Reactions are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse reactions are defined as those occurring on one or more occasions in at least 1/100 patients; infrequent adverse reactions are those occurring between 1/100 and 1/1,000 patients; and rare adverse reactions are those occurring in less than 1/1,000 patients. Body as a Whole - Frequent:malaise; Infrequent:photosensitivity reaction and suicide attempt. Cardiovascular System - Frequent:syncope. Digestive System - Infrequent:gastrointestinal hemorrhage and melena; Rare:hematemesis. Hemic and Lymphatic Systems - Infrequent:anemia and ecchymosis; Rare:purpura. Metabolic and Nutritional Systems - Frequent:weight gain and weight loss. Nervous System - Frequent:hyperkinesia, manic reaction, and myoclonus; Infrequent:abnormal dreams, akathisia, convulsion, dyskinesia, dystonia, euphoria, extrapyramidal syndrome, and twitching; Rare:withdrawal syndrome. Respiratory System - Infrequent:epistaxis. Rare:hemoptysis and laryngismus. Skin - Infrequent:urticaria. Urogenital System * - Infrequent:hematuria, menorrhagia, and vaginal hemorrhage; Rare:hematospermia. * Based on the number of males or females, as appropriate.

Multiple hepatic cytochrome P450 isoenzymes are involved in the oxidative biotransformation of a large number of structurally different drugs and endogenous compounds. The available knowledge concerning the relationship of fluvoxamine and the cytochrome P450 isoenzyme system has been obtained mostly from pharmacokinetic interaction studies conducted in healthy volunteers, but some preliminary in vitrodata are also available. Based on a finding of substantial interactions of fluvoxamine with certain of these drugs[see later parts of this section and also Warnings and Precautions ( 5)] and limited in vitrodata for CYP3A4, it appears that fluvoxamine inhibits several cytochrome P450 isoenzymes that are known to be involved in the metabolism of other drugs such as: CYP1A2 (e.g., warfarin, theophylline, propranolol, tizanidine), CYP2C9 (e.g., warfarin), CYP3A4 (e.g., alprazolam), and CYP2C19 (e.g., omeprazole). In vitrodata suggest that fluvoxamine is a relatively weak inhibitor of CYP2D6. Approximately 7% of the normal population has a genetic code that leads to reduced levels of activity of CYP2D6. Such individuals have been referred to as "poor metabolizers" (PM) of drugs such as debrisoquin, dextromethorphan, and tricyclic antidepressants. While none of the drugs studied for drug interactions significantly affected the pharmacokinetics of fluvoxamine, an in vivostudy of fluvoxamine single-dose pharmacokinetics in 13 PM subjects demonstrated altered pharmacokinetic properties compared to 16 "extensive metabolizers" (EM): mean C max, AUC, and half-life were increased by 52%, 200%, and 62%, respectively, in the PM compared to the EM group. This suggests that fluvoxamine is metabolized, at least in part, by CYP2D6. Caution is indicated in patients known to have reduced levels of CYP2D6 activity and those receiving concomitant drugs known to inhibit this cytochrome P450 isoenzyme (e.g., quinidine). The metabolism of fluvoxamine has not been fully characterized and the effects of potent cytochrome P450 isoenzyme inhibition, such as the ketoconazole inhibition of CYP3A4, on fluvoxamine metabolism have not been studied. A clinically significant fluvoxamine interaction is possible with drugs having a narrow therapeutic ratio such as pimozide, warfarin, theophylline, certain benzodiazepines, omeprazole and phenytoin. If fluvoxamine maleate tablets are to be administered together with a drug that is eliminated via oxidative metabolism and has a narrow therapeutic window, plasma levels and/or pharmacodynamic effects of the latter drug should be monitored closely, at least until steady-state conditions are reached [see Contraindications (4), Warnings and Precautions ( 5)].

Antipsychotics: See Warnings and Precautions ( 5.2). Benzodiazepines: S arnings and Precautions ( 5.8). Alprazolam: See Warnings and Precautions ( 5.8). Diazepam: See Warnings and Precautions ( 5.8). Lorazepam: A study of multiple doses of fluvoxamine maleate (50 mg b.i.d.) in healthy male volunteers (N=12) and a single dose of lorazepam (4 mg single dose) indicated no significant pharmacokinetic interaction. On average, both lorazepam alone and lorazepam with fluvoxamine produced substantial decrements in cognitive functioning; however, the coadministration of fluvoxamine and lorazepam did not produce larger mean decrements compared to lorazepam alone. Alcohol: Studies involving single 40 g doses of ethanol (oral administration in one study and intravenous in the other) and multiple dosing with fluvoxamine maleate (50 mg b.i.d.) revealed no effect of either drug on the pharmacokinetics or pharmacodynamics of the other. As with other psychotropic medications, patients should be advised to avoid alcohol while taking fluvoxamine maleate tablets. Carbamazepine: Elevated carbamazepine levels and symptoms of toxicity have been reported with the coadministration of fluvoxamine maleate and carbamazepine. Clozapine: See Warnings and Precautions ( 5.8). Lithium: As with other serotonergic drugs, lithium may enhance the serotonergic effects of fluvoxamine and, therefore, the combination should be used with caution. Seizures have been reported with the coadministration of fluvoxamine maleate and lithium. Methadone: See Warnings and Precautions ( 5.8). Monoamine Oxidase Inhibitors: See Dosage and Administration ( 2.4, 2.5), Contraindications ( 4),Warnings and Precautions (5.2). Pimozide: See Contraindications ( 4),Warnings and Precautions (5.6). Ramelteon: See Warnings and Precautions ( 5.8). Other Serotonergic Drugs: The concomitant use of serotonergic drugs (including other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St. John's Wort) with Fluvoxamine Maleate Tablets increases the risk of serotonin syndrome. Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of Fluvoxamine Maleate Tablets and/or concomitant serotonergic drugs [see Warnings and Precautions ( 5.2)] . Tacrine: In a study of 13 healthy, male volunteers, a single 40 mg dose of tacrine added to fluvoxamine 100 mg/day administered at steady-state was associated with five-and eight-fold increases in tacrine C maxand AUC, respectively, compared to the administration of tacrine alone. Five subjects experienced nausea, vomiting, sweating, and diarrhea following coadministration, consistent with the cholinergic effects of tacrine. Thioridazine: See Contraindications ( 4), Warnings and Precautions ( 5.4) . Tizanidine: See Contraindications ( 4), Warnings and Precautions (5.5). Tricyclic Antidepressants (TCAs): Significantly increased plasma TCA levels have been reported with the coadministration of fluvoxamine maleate and amitriptyline, clomipramine or imipramine. Caution is indicated with the coadministration of fluvoxamine maleate tablets and TCAs; plasma TCA concentrations may need to be monitored, and the dose of TCA may need to be reduced. Triptans: There have been rare postmarketing reports of serotonin syndrome with use of an SSRI and a triptan. If concomitant treatment of fluvoxamine with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases [see Warnings and Precautions ( 5.2)]. Sumatriptan: There have been rare postmarketing reports describing patients with weakness, hyperreflexia, and incoordination following the use of a selective serotonin reuptake inhibitor (SSRI) and sumatriptan. If concomitant treatment with sumatriptan and an SSRI (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline) is clinically warranted, appropriate observation of the patient is advised. Tryptophan: Tryptophan may enhance the serotonergic effects of fluvoxamine, and the combination should, therefore, be used with caution. Severe vomiting has been reported with the coadministration of fluvoxamine maleate and tryptophan [ see Warnings and Precautions( 5.2)].

Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/. Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions ( 5.10) and Clinical Considerations]. Prolonged experience with fluvoxamine in pregnant women over decades, based on published observational studies, have not identified a clear drug-associated risk of major birth defects or miscarriage (see Data). There are risks associated with untreated depression in pregnancy and risks of persistent pulmonary hypertension of the newborn (PPHN) and poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including fluvoxamine, during pregnancy (see Clinical Considerations). When pregnant rats were treated orally with fluvoxamine throughout the period of organogenesis, increased embryofetal death and increased incidences of fetal eye abnormalities (folded retinas) was observed at doses 3 times the maximum recommended human dose (MRHD) of 300 mg/day given to adolescents on a mg/m 2basis. In addition, decreased fetal body weight was seen at a dose 6 times the MRHD given to adolescents on a mg/m 2basis. There were no adverse developmental effects in rabbits treated with fluvoxamine during the period of organogenesis up to a dose 2 times the MRHD given to adolescents on a mg/m 2basis. When fluvoxamine was administered orally to rats during pregnancy and lactation, increased pup mortality at birth was seen at a dose 2 times the MRHD given to adolescents on a mg/m 2basis. In addition, decreases in pup body weight and survival were observed at doses that are 0.13 times the MRHD given to adolescents (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. This finding is from a prospective, longitudinal study that followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Maternal Adverse Reactions Use of Fluvoxamine Maleate Tablets in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions ( 5.10)] . Fetal/Neonatal adverse reactions Neonates exposed to Fluvoxamine Maleate Tablets and other SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions ( 5.2)] . Data Human Data Exposure during late pregnancy to SSRIs may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1 to 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Animal Data When pregnant rats were given oral doses of fluvoxamine (60, 120, or 240 mg/kg) throughout the period of organogenesis, developmental toxicity in the form of increased embryofetal death and increased incidences of fetal eye abnormalities (folded retinas) was observed at doses of 120 mg/kg or greater (3 times the MRHD of 300 mg/day, given to adolescents on a mg/m 2basis). Decreased fetal body weight was seen at the high dose of 240 mg/kg/day (6 times the MRHD given to adolescents on a mg/m 2basis). The no effect dose for developmental toxicity in this study was 60 mg/kg/day (1.6 times the MRHD given to adolescents on a mg/m 2basis). In a study in which pregnant rabbits were administered doses of up to 40 mg/kg (approximately 2.1 times the MRHD given to adolescents on a mg/m 2basis) during the period of organogenesis, no adverse effects on embryofetal development were observed. In other reproduction studies in which female rats were dosed orally during pregnancy and lactation (5, 20, 80, or 160 mg/kg), increased pup mortality at birth was seen at doses of 80 mg/kg/day (2 times the MRHD given to adolescents on a mg/m 2basis) or greater and decreases in pup body weight and survival were observed at all doses (low effect dose approximately 0.13 times the MRHD given to adolescents on a mg/m 2basis).

The efficacy of fluvoxamine maleate for the treatment of obsessive compulsive disorder was demonstrated in a 10-week multicenter placebo controlled study with 120 outpatients ages 8 to 17. In addition, 99 of these outpatients continued open-label fluvoxamine maleate treatment for up to another one to three years, equivalent to 94 patient years. The adverse event profile observed in that study was generally similar to that observed in adult studies with fluvoxamine [ see Adverse Reactions (6.3),Dosage and Administration (2.2)]. Decreased appetite and weight loss have been observed in association with the use of fluvoxamine as well as other SSRIs. Consequently, regular monitoring of weight and growth is recommended if treatment of a child with an SSRI is to be continued long term. The risks, if any, that may be associated with fluvoxamine s extended use in children and adolescents with OCD have not been systematically assessed. The prescriber should be mindful that the evidence relied upon to conclude that fluvoxamine is safe for use in children and adolescents derives from relatively short term clinical studies and from extrapolation of experience gained with adult patients. In particular, there are no studies that directly evaluate the effects of long term fluvoxamine use on the growth, cognitive behavioral development, and maturation of children and adolescents. Although there is no affirmative finding to suggest that fluvoxamine possesses a capacity to adversely affect growth, development or maturation, the absence of such findings is not compelling evidence of the absence of the potential of fluvoxamine to have adverse effects in chronic use [see Warnings and Precautions (5.1)]. Safety and effectiveness in the pediatric population other than pediatric patients with OCD have not been established [see Boxed Warning; Warnings and Precautions (5.1)] . Anyone considering the use of fluvoxamine maleate tablets in a child or adolescent must balance the potential risks with the clinical need.

Absorption: The absolute bioavailability of fluvoxamine maleate is 53%. Oral bioavailability is not significantly affected by food. In a dose proportionality study involving fluvoxamine maleate at 100, 200 and 300 mg/day for 10 consecutive days in 30 normal volunteers, steady state was achieved after about a week of dosing. Maximum plasma concentrations at steady state occurred within 3 to 8 hours of dosing and reached concentrations averaging 88, 283 and 546 ng/mL, respectively. Thus, fluvoxamine had nonlinear pharmacokinetics over this dose range, i.e., higher doses of fluvoxamine maleate produced disproportionately higher concentrations than predicted from the lower dose. Distribution: The mean apparent volume of distribution for fluvoxamine is approximately 25 L/kg, suggesting extensive tissue distribution. Approximately 80% of fluvoxamine is bound to plasma protein, mostly albumin, over a concentration range of 20 to 2,000 ng/mL. Metabolism: Fluvoxamine maleate is extensively metabolized by the liver; the main metabolic routes are oxidative demethylation and deamination. Nine metabolites were identified following a 5 mg radiolabelled dose of fluvoxamine maleate, constituting approximately 85% of the urinary excretion products of fluvoxamine. The main human metabolite was fluvoxamine acid which, together with its N-acetylated analog, accounted for about 60% of the urinary excretion products. A third metabolite, fluvoxethanol, formed by oxidative deamination, accounted for about 10%. Fluvoxamine acid and fluvoxethanol were tested in an in vitroassay of serotonin and norepinephrine reuptake inhibition in rats; they were inactive except for a weak effect of the former metabolite on inhibition of serotonin uptake (1 to 2 orders of magnitude less potent than the parent compound). Approximately 2% of fluvoxamine was excreted in urine unchanged [See Drug Interactions ( 7)]. Elimination: Following a 14C-labelled oral dose of fluvoxamine maleate (5 mg), an average of 94% of drug-related products was recovered in the urine within 71 hours. The mean plasma half-life of fluvoxamine at steady state after multiple oral doses of 100 mg/day in healthy, young volunteers was 15.6 hours. Elderly Subjects: In a study of fluvoxamine maleate tablets at 50 and 100 mg comparing elderly (ages 66 to 73) and young subjects (ages 19 to 35), mean maximum plasma concentrations in the elderly were 40% higher. The multiple dose elimination half-life of fluvoxamine was 17.4 and 25.9 hours in the elderly compared to 13.6 and 15.6 hours in the young subjects at steady state for 50 and 100 mg doses, respectively. In elderly patients, the clearance of fluvoxamine was reduced by about 50% and, therefore, fluvoxamine maleate tablets should be slowly titrated during initiation of therapy [see Dosage and Administration ( 2.3)]. Pediatric Subjects: The multiple-dose pharmacokinetics of fluvoxamine were determined in male and female children (ages 6 to 11) and adolescents (ages 12 to 17). Steady-state plasma fluvoxamine concentrations were 2 to 3-fold higher in children than in adolescents. AUC and C maxin children were 1.5- to 2.7-fold higher than that in adolescents. (See Table 4.) As in adults, both children and adolescents exhibited nonlinear multiple-dose pharmacokinetics. Female children showed significantly higher AUC (0-12) and C maxcompared to male children and, therefore, lower doses of fluvoxamine maleate tablets may produce therapeutic benefit. (See Table 5.) No gender differences were observed in adolescents. Steady-state plasma fluvoxamine concentrations were similar in adults and adolescents at a dose of 300 mg/day, indicating that fluvoxamine exposure was similar in these two populations. (See Table 4.) Dose adjustment in adolescents (up to the adult maximum dose of 300 mg) may be indicated to achieve therapeutic benefit [see Dosage and Administration ( 2.2)]. TABLE 4 COMPARISON OF MEAN (SD) FLUVOXAMINE PHARMACOKINETIC PARAMETERS BETWEEN CHILDREN, ADOLESCENTS, AND ADULTS Pharmacokinetic Parameter (body weight corrected) Dose = 200 mg/day (100 mg b.i.d.) Dose = 300 mg/day (150 mg b.i.d.) Children (N=10) Adolescent (N=17) Adolescent (N=13) Adult (N=16) AUC 0-12 (ng h/mL/kg) 155.1 (160.9) 43.9 (27.9) 69.6 (46.6) 59.4 (40.9) C max(ng/mL/kg) 14.8 (14.9) 4.2 (2.6) 6.7 (4.2) 5.7 (3.9) C min(ng/mL/kg) 11 (11.9) 2.9 (2) 4.8 (3.8) 4.6 (3.2) TABLE 5 COMPARISON OF MEAN (SD) FLUVOXAMINE PHARMACOKINETIC PARAMETERS BETWEEN MALE AND FEMALE CHILDREN (6-11 YEARS) Pharmacokinetic Parameter (body weight corrected) Dose = 200 mg/day (100 mg b.i.d.) Male Children (N=7) Female Children (N=3) AUC 0-12 (ng h/mL/kg) 95.8 (83.9) 293.5 (233) C max(ng/mL/kg) 9.1 (7.6) 28.1 (21.1) C min(ng/mL/kg) 6.6 (6.1) 21.2 (17.6) Hepatic and Renal Disease: A cross study comparison (healthy subjects versus patients with hepatic dysfunction) suggested a 30% decrease in fluvoxamine clearance in association with hepatic dysfunction. The mean minimum plasma concentrations in renally impaired patients (creatinine clearance of 5 to 45 mL/min) after 4 and 6 weeks of treatment (50 mg b.i.d., N=13) were comparable to each other, suggesting no accumulation of fluvoxamine in these patients [see Warnings and Precautions ( 5.14)].

Advise the patient to read the FDA-approved patient labeling (Medication Guide). Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with fluvoxamine maleate tablets and should counsel them in the appropriate use. A patient Medication Guide about Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions is available for fluvoxamine maleate tablets. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document. Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking fluvoxamine maleate tablets. Clinical Worsening and Suicide Risk Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient s prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient s presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate the need for very close monitoring and possibly changes in the medication [see Boxed Warning,Warnings and Precautions ( 5.1)]. Serotonin Syndrome Patients should be cautioned about the risk of serotonin syndrome particularly with the concomitant use of fluvoxamine with other serotonergic agents (including triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St. John's Wort) [see Warnings and Precautions ( 5.2)]. Angle Closure Glaucoma Patients should be advised that taking Fluvoxamine Maleate Tablets can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle closure glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible [see Warnings and Precautions ( 5.3)]. Interference with Cognitive or Motor Performance Since any psychoactive drug may impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are certain that fluvoxamine maleate tablets therapy does not adversely affect their ability to engage in such activities. Pregnancy Advise pregnant women to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with Fluvoxamine Maleate Tablets. Advise patients that Fluvoxamine Maleate Tablets use late in pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN). Advise women that there is a risk of relapse with discontinuation of antidepressants. Advise women that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Fluvoxamine Maleate Tablets during pregnancy [see Use in Specific Populations ( 8.1)]. Lactation Advise breastfeeding women using Fluvoxamine Maleate Tablets to monitor infants for diarrhea, vomiting, decreased sleep, and agitation and to seek medical care if they notice these signs [see Use in Specific Populations ( 8.2)]. Concomitant Medication Patients should be advised to notify their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for clinically important interactions with fluvoxamine maleate tablets. Patients should be cautioned about the concomitant use of fluvoxamine and NSAIDs, aspirin, or other drugs that affect coagulation since the combined use of psychotropic drugs that interfere with serotonin reuptake and these agents has been associated with an increased risk of bleeding [see Warnings and Precautions ( 5.8)]. Because of the potential for the increased risk of serious adverse reactions including severe lowering of blood pressure and sedation when fluvoxamine and tizanidine are used together, fluvoxamine should not be used with tizanidine [see Warnings and Precautions ( 5.5)]. Because of the potential for the increased risk of serious adverse reactions when fluvoxamine and alosetron are used together, fluvoxamine should not be used with Lotronex TM (alosetron) [see Warnings and Precautions ( 5.7)]. Sexual Dysfunction Advise patients that use of fluvoxamine maleate tablets may cause symptoms of sexual dysfunction in both male and female patients. Inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider [see Warnings and Precautions ( 5.16)]. Alcohol As with other psychotropic medications, patients should be advised to avoid alcohol while taking fluvoxamine maleate tablets. Allergic Reactions Patients should be advised to notify their physicians if they develop a rash, hives, or a related allergic phenomenon during therapy with fluvoxamine maleate tablets. All registered trademarks in this document are the property of their respective owners. Dispense with Medication Guide available at https://www.apotex.com/products/us/mg.asp APOTEX INC. FLUVOXAMINE MALEATE TABLETS, USP 25 mg, 50 mg and 100 mg Manufactured by Manufactured for Apotex Inc. Apotex Corp. Toronto, Ontario Weston, Florida Canada M9L1T9 USA 33326 Revision: 17

MEDICATION GUIDE Fluvoxamine (Flu VOX ah meen) Maleate Tablets, USP Medication Guide available at https://www.apotex.com/products/us/mg.asp Read the Medication Guide that comes with fluvoxamine maleate tablets before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. Talk with your healthcare provider if there is something you do not understand or want to learn more about. What is the most important information I should know about fluvoxamine maleate tablets? Fluvoxamine is the same kind of medicine as those used to treat depression and may cause serious side effects, including: 1. Suicidal thoughts or actions: Fluvoxamine maleate tablets and antidepressant medicines may increase suicidal thoughts or actionsin some children, teenagers, or young adults within the first few months of treatment or when the dose is changed . Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. Watch for these changes and call your healthcare provider right away if you notice: New or sudden changes in mood, behavior, actions, thoughts, or feelings, especially if severe. Pay particular attention to such changes when fluvoxamine maleate tablets is started or when the dose is changed. Keep all follow-up visits with your healthcare provider and call between visits if you are worried about symptoms. Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency, especially if they are new, worse, or worry you: attempts to commit suicide acting on dangerous impulses acting aggressive or violent thoughts about suicide or dying new or worse depression new or worse anxiety or panic attacks feeling agitated, restless, angry or irritable trouble sleeping an increase in activity or talking more than what is normal for you other unusual changes in behavior or mood Tell your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency. Fluvoxamine maleate tablets may be associated with these serious side effects: 2. Serotonin Syndrome: This condition can be life-threatening and may include: agitation, hallucinations, coma or other changes in mental status coordination problems or muscle twitching (overactive reflexes) racing heartbeat, high or low blood pressure sweating or fever nausea, vomiting, or diarrhea muscle rigidity 3. Visual problems eye pain changes in vision swelling or redness in or around the eye Only some people are at risk for these problems. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are. 4. Severe allergic reactions: trouble breathing swelling of the face, tongue, eyes, or mouth rash, itchy welts (hives) or blisters, alone or with fever or joint pain 5. Abnormal bleeding: fluvoxamine maleate tablets and antidepressant medicines may increase your risk of bleeding or bruising, especially if you take the blood thinner warfarin (Coumadin , Jantoven ), or a non-steroidal anti-inflammatory drug (NSAIDs, like ibuprofen, naproxen, or aspirin). 6. Seizures or convulsions 7. Manic episodes: greatly increased energy severe trouble sleeping racing thoughts reckless behavior unusually grand ideas excessive happiness or irritability talking more or faster than usual 8. Changes in appetite or weight.Children and adolescents should have height and weight monitored during treatment. 9. Low salt (sodium) levels in the blood.Elderly people may be at greater risk for this. Symptoms may include: headache weakness or feeling unsteady confusion, problems concentrating or thinking or memory problems 10. Sexual problems (dysfunction).Taking selective serotonin reuptake inhibitors (SSRIs), including fluvoxamine maleate tablets, may cause sexual problems. Symptoms in males may include: Delayed ejaculation or inability to have an ejaculation Decreased sex drive Problems getting or keeping an erection Symptoms in females may include: Decreased sex drive Delayed orgasm or inability to have an orgasm Talk to your healthcare provider if you develop any changes in your sexual function or if you have any questions or concerns about sexual problems during treatment with fluvoxamine maleate tablets. There may be treatments your healthcare provider can suggest. Do not stop fluvoxamine maleate tablets without first talking to your healthcare provider. Stopping fluvoxamine maleate tablets too quickly may cause serious symptoms including: anxiety, irritability, high or low mood, feeling restless or changes in sleep habits headache, sweating, nausea, dizziness electric shock-like sensations, shaking, confusion What are fluvoxamine maleate tablets? Fluvoxamine maleate tablets are a prescription medicine used to treat obsessive compulsive disorder (OCD). It is important to talk with your healthcare provider about the risks of treating OCD and also the risks of not treating it. You should discuss all treatment choices with your healthcare provider. Talk to your healthcare provider if you do not think that your condition is getting better with fluvoxamine maleate tablets treatment. Who should not take fluvoxamine maleate tablets? Do not take fluvoxamine maleate tablets if you: are allergic to fluvoxamine maleate or any of the ingredients in fluvoxamine maleate tablets. See the end of this Medication Guide for a complete list of ingredients in fluvoxamine maleate tablets. take a Monoamine Oxidase Inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid. Do not take an MAOI within 2 weeks of stopping fluvoxamine maleate tablets unless directed to do so by your physician. Do not start fluvoxamine maleate tablets if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician. People who take fluvoxamine maleate tablets close in time to an MAOI may have serious or even life-threatening side effects. Get medical help right away if you have any of these symptoms: high fever uncontrolled muscle spasms stiff muscles rapid changes in heart rate or blood pressure confusion loss of consciousness (pass out) take Mellaril (thioridazine). Do not take Mellaril within 2 weeks of stopping Fluvoxamine Maleate Tabletsbecause this can cause serious heart rhythm problems or sudden death. take Orap (pimozide) because taking this drug with Fluvoxamine Maleate Tablets can cause serious heart rhythm problems or sudden death. take Zanaflex (tizanidine). Fluvoxamine maleate tablets could increase the amount of Zanaflex in your body, which could increase its actions and side effects. This could include drowsiness and a drop in blood pressure and affecting how well you do things that require alertness. Take Lotronex (alosetron). Fluvoxamine maleate tablets may increase the amount of Lotronex in your body, which could increase its actions and side effects. What should I tell my healthcare provider before taking fluvoxamine maleate tablets? Ask if you are not sure. Before starting fluvoxamine maleate tablets, tell your healthcare provider if you: Are taking certain drugs such as: Monoamine oxidase inhibitors (MAOIs) such as Emsam (selegiline), Nardil (phenelzine), or Parnate (tranylcypromine) Mellaril (thioridazine): used to treat mental or mood problems Zanaflex (tizanidine): used to treat spasticity (a condition in which muscles keep tightening and cramping) Orap (pimozide): used to treat Tourette Syndrome (a brain condition causing tics) Lotronex (alosetron): used to treat a condition with diarrhea, continuing stomach pain, cramps, and bloating Triptans: used to treat migraine headache Medicines used to treat mood, anxiety, psychotic or thought disorders, including tricyclics, lithium, SSRIs, SNRIs, or antipsychotics Tramadol, fentanyl, meperidine, methadone, or other opioids Benzodiazepines: used to reduce anxiety, stress, emotional upset, or seizures; helps you sleep; helps with alcohol withdrawal; reduces restlessness; and relaxes muscles Clozapine: used to treat mental disorders Mexiletine: used to treat abnormalities in heart rhythm Theophylline: used to treat swollen air passages in your lungs, to relax the muscles in your chest to ease shortness of breath, often to treat asthma Warfarin and other drugs that affect how your blood clots Diuretics to treat high blood pressure, congestive heart failure, or swelling Over-the-counter supplements such as tryptophan or St. John s Wort have liver problems have kidney problems have heart problems have or had seizures or convulsions have bipolar disorder or mania have low sodium levels in your blood have a history of a stroke have high blood pressure have or had bleeding problems are pregnant or plan to become pregnant. Talk to your healthcare provider about the risk to your unborn baby if you take Fluvoxamine Maleate Tablets. Talk to your healthcare provider about the benefits and risks of treating OCD during pregnancy. If you become pregnant during treatment with Fluvoxamine Maleate Tablets, talk to your healthcare provider about registering with the National Pregnancy Registry for Antidepressants. You can register by calling 1- 844-405-6185. are breast-feeding or plan to breast-feed. Some fluvoxamine maleate tablets may pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby while taking fluvoxamine maleate tablets. Tell your healthcare provider about all the medicines that you take,including prescription and non-prescription medicines, vitamins, and herbal supplements. fluvoxamine maleate tablets and some medicines may interact with each other, may not work as well, or may cause serious side effects. Your healthcare provider or pharmacist can tell you if it is safe to take fluvoxamine maleate tablets with your other medicines. Do not start or stop any medicine while taking fluvoxamine maleate tablets without talking to your healthcare provider first. If you take fluvoxamine maleate tablets, you should not take any other medicines that contain fluvoxamine including: Fluvoxamine maleate extended-release capsules. How should I take fluvoxamine maleate tablets? Take fluvoxamine maleate tablets exactly as prescribed. Your healthcare provider may need to change the dose of fluvoxamine maleate tablets until it is the right dose for you. Fluvoxamine maleate tablets may be taken with or without food. If you miss a dose of fluvoxamine maleate tablets, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of fluvoxamine maleate tablets at the same time. If you take too much fluvoxamine maleate tablets, call your healthcare provider or poison control center right away, or get emergency treatment. What should I avoid while taking fluvoxamine maleate tablets? Fluvoxamine maleate tablets can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly. You should not drive, operate heavy machinery, or do other dangerous activities until you know how fluvoxamine maleate tablets affects you. Do not drink alcohol while using fluvoxamine maleate tablets. What are the possible side effects of fluvoxamine maleate tablets? Fluvoxamine maleate tablets may cause serious side effects, including: See What is the most important information I should know about fluvoxamine maleate tablets? Feeling anxious or trouble sleeping Common possible side effects in people who take fluvoxamine maleate Tablets include: nausea sleepiness weakness indigestion sweating loss of appetite shaking vomiting delayed ejaculation inability to have an orgasm decreased sex drive dry mouth stuffy nose unusual taste frequent urination Other side effects in children and adolescents include: agitation or abnormal increase in activity feeling depressed or sad excessive gas heavy menstrual periods rash possible slowed growth rate and weight change. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of fluvoxamine maleate tablets. For more information, ask your healthcare provider or pharmacist. CALL YOUR DOCTOR FOR MEDICAL ADVICE ABOUT SIDE EFFECTS. YOU MAY REPORT SIDE EFFECTS TO APOTEX AT 1-800-706-5575 OR FDA AT 1-800-FDA-1088. How should I store fluvoxamine maleate tablets? Store fluvoxamine maleate tablets at 20 C to 25 C (68 F to 77 F); excursions permitted from 15 C to 30 C (59 F to 86 F) [see USP Controlled Room Temperature]. Keep Fluvoxamine Maleate Tablets away from high humidity. Keep Fluvoxamine Maleate Tablets in a tight, light-resistant container. Keep fluvoxamine maleate tablets and all medicines out of the reach of children. General information about fluvoxamine maleate Tablets Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use fluvoxamine maleate tablets for a condition for which it was not prescribed. Do not give fluvoxamine maleate tablets to other people, even if they have the same condition. It may harm them. This Medication Guide summarizes the most important information about fluvoxamine maleate tablets. If you would like more information, talk with your healthcare provider. You may ask your healthcare provider or pharmacist for information about fluvoxamine maleate tablets that is written for healthcare professionals. For more information about Fluvoxamine Maleate Tablets call toll free at 1-800-706-5575 or go to www.apotex.com What are the ingredients in fluvoxamine maleate tablets? Active ingredient: Fluvoxamine maleate Inactive ingredients: hydroxyethyl cellulose (25 mg and 50 mg), hydroxypropyl cellulose (100 mg), hypromellose (100 mg), iron oxide black (100 mg), iron oxide red (100 mg), iron oxide yellow (50 mg and 100 mg), magnesium stearate, mannitol, polyethylene glycol and titanium dioxide. All registered trademarks in this document are the property of their respective owners. APOTEX INC. FLUVOXAMINE MALEATE TABLETS, USP 25 mg, 50 mg and 100 mg Manufactured by Manufactured for Apotex Inc. Apotex Corp. Toronto, Ontario Weston, Florida Canada M9L1T9 USA 33326 Revised: February 2024 This Medication Guide has been approved by the U.S. Food and Drug Administration.

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