FDA label 3fe319c7-7001-1995-e054-00144ff88e88

BOXED WARNING Suicidality and Antidepressant Drugs Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of fluvoxamine maleate tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. 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 in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psyctiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Fluvoxamine Maleate tablets are not approved for use in pediatric patients except for patients with obsessive complusive disorder (OCD)(SeeWarnings: Clinical Worsening and Suicide Risk,Precautions: Information for Patients, andPrecautions: Pediatric Use)

WARNINGS Potential for Interaction with Monoamine Oxidase Inhibitors In patients receiving another serotonin reuptake inhibitor drug in combination with monoamine oxidase inhibitors (MAOI), there have been reports of serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. These reactions have also been reported in patients who have discontinued that drug and have been started on a MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Therefore, it is recommended that Fluvoxamine MaleateTablets not be used in combination with a MAOI, or within 14 days of discontinuing treatment with a MAOI. After stopping Fluvoxamine MaleateTablets, at least 2 weeks should be allowed before starting a MAOI. Potential Interaction with Thioridazine The effect of fluvoxamine (25 mg bid for one week) on thioridazine steady-state concentrations was evaluated in 10 male inpatients with schizophrenia. Concentrations of thioridazine and its two active metabolites, mesoridazine and sulforidazine, increased threefold following co-administration of fluvoxamine. Thioridazine administration produces a dose-related prolongation of the QTc interval, which is associated with serious ventricular arrhythmias, such as torsade de pointes-type arrhythmias, and sudden death. It is likely that this experience underestimates the degree of risk that might occur with higher doses of thioridazine. Moreover, the effect of fluvoxamine may be even more pronounced when it is administered at higher doses. Therefore, fluvoxamine and thioridazine should not be co-administered (seeCONTRAINDICATIONSandPRECAUTIONS). Potential Terfenadine, Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P4503A4 isozyme, and it has been demonstrated that ketoconazole, a potent inhibitor of 3A4, blocks the metabolism of these drugs, resulting in increased plasma concentrations of parent drug. Increased plasma concentrations of terfenadine, astemizole, cisapride, and pimozide cause QT prolongation and have been associated with torsades de pointes-type ventricular tachycardia, sometimes fatal. As noted below, a substantial pharmacokinetic interaction has been observed for fluvoxamine in combination with alprazolam, a drug that is known to be metabolized by the 3A4 isozyme. Although, it has not been definitively demonstrated that fluvoxamine is a potent 3A4 inhibitor, it is likely to be, given the substantial interaction of fluvoxamine with alprazolam. Consequently, it is recommended that fluvoxamine not be used in combination with either terfenadine, astemizole, cisapride, or pimozide (seeCONTRAINDICATIONSandPRECAUTIONS). Potential Tizanidine Interaction Fluvoxamine is a potent inhibitor of CYP1A2 and tizanidine is a CYP1A2 substrate. The effect of fluvoxamine (100 mg daily for 4 days) on the pharmacokinetics and pharmacodynamics of a single 4 mg dose of tizanidine has been studied in 10 healthy subjects. Tizanidine Cmax was increased approximately 12-fold (range 5-fold to 32-fold), elimination half-life was increased by almost 3-fold, and AUC increased 33-fold (range 14-fold to 103-fold). The mean maximal effect on blood pressure was a 35 mm Hg decrease in systolic blood pressure, a 20 mm Hg decrease in diastolic blood pressure, and a 4 beat/min decrease in heart rate. Drowsiness was significantly increased and performance on a psychomotor task was significantly impaired. Fluvoxamine and tizanidine should not be used together. (SeeContraindicationsandPrecautions). Potential Alosetron Interaction Fluvoxamine, an inhibitor of several CYP isozymes, has been shown to increase mean alosetron plasma concentrations (AUC) approximately 6-fold and prolonged the half-life by approximately 3-fold. Consequently, it is recommended that fluvoxamine not be used in combination with alosetron (SeeContraindications,Precautions, and Lotronex(alosetron) package insert). Clinical Worsening and Suicide Risk 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 4400 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 1000 patients treated) are provided in Table 1. Table 1 Age RangeDrug-Placebo Difference in Number of Cases of Suicidality per 1000 Patients Treated Increases Compared to Placebo<1814 additional cases18-245 additional casesDecreases Compared to Placebo25-641 fewer case6 fewer casesNo 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 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 (see PRECAUTIONS and DOSAGE AND ADMINISTRATION - Discontinuation of Treatment with Fluvoxamine Maleate Tablets , for a description of the risks of discontinuation of Fluvoxamine Maleate Tablets). 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 health care 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 Other Potentially Important Drug Interactions (Also see PRECAUTIONS - Drug Interactions ) 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 This interaction, which has not been investigated using higher doses of fluvoxamine, may be more pronounced if a 300 mg daily dose is co-administered, particularly since fluvoxamine exhibits non-linear pharmacokinetics over the dosage range 100-300 mg. If alprazolam is co-administered 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 co-administration 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 co-administration. Evidence supporting the conclusion that it is inadvisable to co-administer 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 co-administered. Mexiletine The effect of steady-state fluvoxamine (50 mg BID for 7 days) on the single dose pharmacokinetics of mexiletene (200 mg) was evaluated in 6 healthy Japanese males. The clearance of mexiletine was reduced by 38% following co-administration with fluvoxamine compared to mexiletene alone. If fluvoxamine and mexiletene are co-administered, serum mexiletene levels should be monitored. Serotonin Syndrome The development of a potentially life-threatening serotonin syndrome may occur with fluvoxamine treatment particularly with concomitant use of serotonergic drugs (including triptans) and with drugs which impair metabolism of serotonin (including MAOIs). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of fluvoxamine with MAOIs intended to treat depression is contraindicated (see CONTRAINDICATIONS and WARNINGSPotential for Interaction with Monoamine Oxidase Inhibitors .) If concomitant treatment of fluvoxamine with 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases (see PRECAUTIONSDrug Interactions ). The concomitant use of fluvoxamine with serotonin precursors (such a tryptophan) is not recommended (see PRECAUTIONSDrug Interactions ). Neuroleptic Malignant Syndrome (NMS) or NMS-Like Events Rare instances of neuroleptic malignant syndrome (NMS) or NMS-like events have been reported in association with fluvoxamine treatment when co-administered with antipsychotic. Additionally, a small number of such cases have been reported with fluvoxamine treatment in the absence of antipsychotic co-administration. These serious and sometimes fatal events can include hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes. As these events may result in potentially life-threatening conditions, patients receiving this combination of therapy should be monitored for the emergence of NMS-like signs and symptoms. Treatment with fluvoxamine and any concomitant antipsychotic agent should be discontinued immediately if such event occurs and supportive symptomatic treatment should be initiated. 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 co-administered 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 When fluvoxamine maleate (50 mg tid) 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.

ADVERSE REACTIONS Associated with Discontinuation of Treatment Of the 1087 OCD and depressed patients treated with fluvoxamine maleate in controlled clinical trials conducted in North America, 22% discontinued treatment due to an adverse event. The most common events (associated with discontinuation and considered to be drug related (i.e., those events associated with dropout at a rate at least twice that of placebo) included: Table 2 ADVERSE EVENTS ASSOCIATED WITH DISCONTINUATION OF TREATMENT IN OCD AND DEPRESSION POPULATIONS BODY SYSTEM/ ADVERSE EVENTPERCENTAGE OF PATIENTS FLUVOXAMINEPLACEBO BODY AS A WHOLEHeadache3%1%Asthenia2%<1%Abdominal Pain1%0%DIGESTIVENausea9%1%Diarrhea1%<1%Vomiting2%<1%Anorexia1%<1%Dyspepsia1%<1%NERVOUS SYSTEMInsomnia4%1%Somnolence4%<1%Nervousness2%<1%Agitation2%<1%Dizziness2%<1%Anxiety1%<1%Dry mouth1%<1% Incidence in Controlled Trials Commonly Observed Adverse Events in Controlled Clinical Trials Fluvoxamine Maleate Tablets have been studied in controlled trials of OCD (N=320) and depression (N=1350). In general, adverse event rates were similar in the two data sets as well as in the pediatric OCD study. The most commonly observed adverse events 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 2 were: somnolence, insomnia, nervousness, tremor, nausea, dyspepsia, anorexia, vomiting, abnormal ejaculation, asthenia, and sweating. In a pool of two studies involving only patients with OCD, the following additional events were identified using the above rule: dry mouth, decreased libido, urinary frequency, anorgasmia, rhinitis and taste perversion. In a study of pediatric patients with OCD, the following additional events were identified using the above rule: agitation, depression, dysmenorrhea, flatulence, hyperkinesia, and rash. Adverse Events Occurring at an Incidence of 1% Table 2 enumerates adverse events 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 an event at some time during their treatment. Reported adverse events 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 3 TREATMENT-EMERGENT ADVERSE EVENT INCIDENCE RATES BY BODY SYSTEM IN ADULT OCD AND DEPRESSION POPULATIONS COMBINED * Percentage Of Patients Reporting Event BODY SYSTEM/ ADVERSE EVENTFLUVOXAMINEPLACEBO N = 892N = 778 * Events for which fluvoxamine maleate incidence was equal to or less than placebo are not listed in the table above, but include the following: abdominal pain, abnormal dreams, appetite increase, back pain, chest pain, confusion, dysmenorrhea, fever, infection, leg cramps, migraine, myalgia, pain, paresthesia, pharyngitis, postural hypotension, pruritus, rash, rhinitis, thirst and tinnitus. Includes "toothache," "tooth extraction and abscess," and "caries." Mostly feeling warm, hot, or flushed. Mostly "blurred vision." Mostly "delayed ejaculation." # Incidence based on number of male patients.BODY AS WHOLEHeadache2220Asthenia146Flu Syndrome32Chills21CARDIOVASCULARPalpitations32DIGESTIVE SYSTEMNausea4014Diarrhea117Constipation108Dyspepsia105Anorexia62Vomiting52Flatulence43Tooth Disorder 31Dysphagia21NERVOUS SYSTEMSomnolence228Insomnia2110Dry Mouth1410Nervousness125Dizziness116Tremor51Anxiety53Vasodilatation 31Hypertonia21Agitation21Decreased Libido21Depression21CNS Stimulation21RESPIRATORY SYSTEMUpper Respiratory Infection95Dyspnea21Yawn20SKINSweating73SPECIAL SENSESTaste Perversion31Amblyopia 32UROGENITALAbnormal Ejaculation , # 81Urinary Frequency32Impotence # 21Anorgasmia20Urinary Retention10 Adverse Events in OCD Placebo Controlled Studies Which are Markedly Different (defined as at least a two-fold difference) in rate from the Pooled Event Rates in OCD and Depression Placebo Controlled Studies The events in OCD studies with a two-fold decrease in rate compared to event rates in OCD and depression studies were dysphagia and amblyopia (mostly blurred vision). Additionally, there was an approximate 25% decrease in nausea. The events in OCD studies with a two-fold increase in rate compared to event rates in OCD and depression studies were: asthenia, abnormal ejaculation (mostly delayed ejaculation), anxiety, infection, rhinitis, anorgasmia (in males), depression, libido decreased, pharyngitis, agitation, impotence, myoclonus/twitch, thirst, weight loss, leg cramps, myalgia and urinary retention. These events are listed in order of decreasing rates in the OCD trials. Other Adverse Events in OCD Pediatric Population In pediatric patients (N=57) treated with Fluvoxamine Maleate Tablets, the overall profile of adverse events was generally similar to that seen in adult studies, as shown in Table 2. However, the following adverse events, not appearing in Table 2, were reported in two or more of the pediatric patients and were more frequent with Fluvoxamine Maleate Tablets than with placebo: abnormal thinking, cough increase, dysmenorrhea, ecchymosis, emotional lability, epistaxis, hyperkinesia, infection, manic reaction, rash, sinusitis, and weight decrease. Male and Female Sexual Dysfunction with SSRIs Although changes in sexual desire, sexual performance and sexual satisfaction often occur as manifestations of a psychiatric disorder and with aging, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that selective serotonin reuptake inhibitors (SSRIs) can cause such untoward sexual experiences. Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling are likely to underestimate their actual incidence. The table below displays the incidence of sexual side effects reported by at least 2% of patients taking Fluvoxamine Maleate Tablets in placebo controlled trials in depression and OCD. Table 4 PERCENTAGE OF PATIENTS REPORTING SEXUAL ADVERSE EVENTS IN ADULT PLACEBO-CONTROLLED TRIALS IN OCD AND DEPRESSION Fluvoxamine Maleate Tablets N=892Placebo N=778 * Based on the number of male patients.Abnormal Ejaculation * 8%1%Impotence * 2%1%Decreased Libido2%1%Anorgasmia2%0%There are no adequate and well-controlled studies examining sexual dysfunction associated with fluvoxamine treatment. Fluvoxamine treatment has been associated with several cases of priapism. In those cases with a known outcome, patients recovered without sequelae and upon discontinuation of fluvoxamine. While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects Vital Sign Changes Comparisons of fluvoxamine maleate and placebo groups in separate pools of short-term OCD and depression trials on (1) median change from baseline on various vital signs variables and on (2) incidence of patients meeting criteria for potentially important changes from baseline on various vital signs variables revealed no important differences between fluvoxamine maleate and placebo. Laboratory Changes Comparisons of fluvoxamine maleate and placebo groups in separate pools of short-term OCD and depression trials on (1) median change from baseline on various serum chemistry, hematology, and urinalysis variables and on (2) incidence of patients meeting criteria for potentially important changes from baseline on various serum chemistry, hematology, and urinalysis variables revealed no important differences between fluvoxamine maleate and placebo. ECG Changes Comparisons of fluvoxamine maleate and placebo groups in separate pools of short-term OCD and depression trials on (1) mean change from baseline on various ECG variables and on (2) incidence of patients meeting criteria for potentially important changes from baseline on various ECG variables revealed no important differences between fluvoxamine maleate and placebo. Other Events Observed During the Premarketing Evaluation of Fluvoxamine Maleate Tablets During premarketing clinical trials conducted in North America and Europe, multiple doses of fluvoxamine maleate were administered for a combined total of 2737 patient exposures in patients suffering OCD or Major Depressive Disorder. Untoward events 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 events without first grouping similar types of untoward events into a limited (i.e., reduced) number of standard event categories. In the tabulations which follow, a standard COSTART-based Dictionary terminology has been used to classify reported adverse events. If the COSTART term for an event was so general as to be uninformative, it was replaced with a more informative term. The frequencies presented, therefore, represent the proportion of the 2737 patient exposures to multiple doses of fluvoxamine maleate who experienced an event of the type cited on at least one occasion while receiving fluvoxamine maleate. All reported events are included in the list below, with the following exceptions: 1) those events 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 events for which a drug cause was considered remote (i.e., neoplasia, gastrointestinal carcinoma, herpes simplex, herpes zoster, application site reaction, and unintended pregnancy) are omitted; and 3) events 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 events reported did occur during treatment with fluvoxamine maleate, a causal relationship to fluvoxamine maleate has not been established. Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring between 1/100 and 1/1000 patients; and rare adverse events are those occurring in less than 1/1000 patients. Body as a Whole: Cardiovascular System: Digestive System: Endocrine System: Hemic and Lymphatic Systems: Metabolic and Nutritional Systems: Musculoskeletal System: Nervous System: Respiratory System: Skin: Infrequent: acne, alopecia, dry skin, eczema, exfoliative dermatitis, furunculosis, seborrhea, skin discoloration, urticaria. Special Senses: Urogenital System: Infrequent: anuria, breast pain, cystitis, delayed menstruation 1 , dysuria, female lactation 1 , hematuria, menopause 1 , menorrhagia 1 , metrorrhagia 1 , nocturia, polyuria, premenstrual syndrome 1 , urinary incontinence, urinary tract infection, urinary urgency, urination impaired, vaginal hemorrhage 1 , vaginitis 1 2 , oliguria. 1 Based on the number of females. 2 Based on the number of males. Postmarketing Reports Voluntary reports of adverse events in patients taking Fluvoxamine Maleate Tablets that have been received since market introduction and are of unknown causal relationship to Fluvoxamine Maleate Tablets use include: ventricular tachycardia (including torsades de pointes), porphyria, toxic epidermal necrolysis, Stevens-Johnson syndrome, Henoch-Schoenlein purpura, bullous eruption, priapism, agranulocytosis, aplastic anemia, anaphylactic reaction, angioedema, vasculitis, hyponatremia, acute renal failure, hepatitis, pancreatitis, ileus, serotonin syndrome, neuropathy, laryngismus and severe akinesia with fever when fluvoxamine was co- administered with antipsychotic medication.