Fluvoxamine maleate tablets are indicated for the treatment of obsessions and compulsions in patients with obsessive compulsive disorder (OCD) ( 1 ).
1.1Obsessive-Compulsive Disorder
Fluvoxamine maleate tablets are indicated for the treatment of obsessions and compulsions in patients with obsessive compulsive disorder (OCD), as defined in DSM-III-R or DSM-IV. The obsessions or compulsions cause marked distress, are time-consuming, or significantly interfere with social or occupational functioning. Obsessive compulsive disorder is characterized by recurrent and persistent ideas, thoughts, impulses or images (obsessions) that are ego-dystonic and/or repetitive, purposeful, and intentional behaviors (compulsions) that are recognized by the person as excessive or unreasonable.
The efficacy of fluvoxamine maleate tablets was established in four trials in outpatients with OCD: two 10-week trials in adults, one 10-week trial in pediatric patients (ages 8 to 17), and one maintenance trial in adults [see Clinical Studies (14) ] .
Contraindications
Coadministration of tizanidine, thioridazine, alosetron, pimozide ( 4 ) Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with fluvoxamine maleate tablets or within 14 days of stopping treatment with fluvoxamine maleate tablets. Do not use fluvoxamine maleate tablets within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start fluvoxamine maleate tablets in a patient who is being treated with linezolid or intravenous methylene blue ( 4 ).
Coadministration Coadministration of tizanidine, thioridazine, alosetron, or pimozide with fluvoxamine maleate tablets are contraindicated [see Warnings and Precautions (5.4 , 5.5 , 5.6 , 5.7) ] . Serotonin Syndrome and Monoamine Oxidase Inhibitors (MAOIs) The use of MAOIs intended to treat psychiatric disorders with fluvoxamine maleate tablets or within 14 days of stopping treatment with fluvoxamine maleate is contraindicated because of an increased risk of serotonin syndrome.
The use of fluvoxamine maleate tablets within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration (2.4) , Warnings and Precautions (5.2) ] . Starting fluvoxamine maleate tablets in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see Dosage and Administration (2.5) , Warnings and Precautions (5.2) ] .
Suicidality: Monitor for clinical worsening and suicide risk ( 5.1 ). Bipolar disorder: Screen for bipolar disorder ( 5.1 ). Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including fluvoxamine maleate tablets, both when taken alone, but especially when coadministered with other serotonergic-agents. If such symptoms occur, discontinue fluvoxamine maleate tablets and serotonergic agents and initiate supportive treatment.
If concomitant use of fluvoxamine maleate tablets with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases ( 5.2 ). Angle Closure Glaucoma: Angle closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants ( 5.3 ). Other potentially important drug interactions.
Benzodiazepines: Use with caution. Coadministration with diazepam is generally not advisable ( 5.8 ). Clozapine: Clozapine levels may be increased and produce orthostatic hypotension or seizures ( 5.8 ). Methadone: Coadministration may produce opioid intoxication. Discontinuation of fluvoxamine may produce opioid withdrawal ( 5.8 ). Mexiletine: Monitor serum mexiletine levels ( 5.8 ). Ramelteon: Should not be used in combination with fluvoxamine ( 5.8 ).
Theophylline: Clearance decreased; reduce theophylline dose by one-third ( 5.8 ). Warfarin: Plasma concentrations increased and prothrombin times prolonged; monitor prothrombin time and adjust warfarin dose accordingly ( 5.8 ). Other Drugs Affecting Hemostasis: Increased risk of bleeding with concomitant use of NSAIDs, aspirin, or other drugs affecting coagulation ( 5.8 , 5.10 ) [see Contraindications (4) ] . Discontinuation: Symptoms associated with discontinuation have been reported ( 5.9 ).
Abrupt discontinuation not recommended [see Dosage and Administration (2.7) ] . Activation of mania/hypomania has occurred ( 5.11 ). Seizures: Avoid administering fluvoxamine in patients with unstable epilepsy; monitor patients with controlled epilepsy; discontinue treatment if seizures occur or frequency increases ( 5.12 ). Hyponatremia: May occur with SSRIs and SNRIs, including fluvoxamine maleate tablets. The elderly may be at increased risk.
Consider discontinuing in patients with symptomatic hyponatremia ( 5.13 ). Concomitant Illness: Use caution in patients with diseases or conditions that affect hemodynamic responses or metabolism ( 5.14 ). Patients with impaired liver function may require a lower starting dose and slower titration ( 2.3 ). Sexual Dysfunction: Fluvoxamine maleate tablets may cause symptoms of sexual dysfunction ( 5.16 ).
5.1Clinical Worsening and Suicide Risk 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 less than 18 14 Additional cases 18 to 24 5 Additional cases Age Range Decreases Compared to Placebo 25 to 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 ta
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Interactions
Drug Interactions [not described in Contraindications or Warnings and Precautions] include the following: Drugs Inhibiting or Metabolized by Cytochrome P450: Fluvoxamine inhibits several cytochrome P450 isoenzymes (CYP1A2, CYP2C9, CYP3A4 and CYP2C19). Carbamazepine: Elevated carbamazepine levels and symptoms of toxicity with coadministration ( 7.2 ). Sumatriptan: Rare post-marketing reports of weakness, hyperreflexia and incoordination following use of an SSRI and sumatriptan.
Monitor appropriately if concomitant treatment is clinically warranted ( 7.2 ). Tacrine: Coadministration increased tacrine C max and AUC five- and eight-fold and caused nausea, vomiting, sweating and diarrhea ( 7.2 ). Tricyclic Antidepressants (TCAs): Coadministration significantly increased plasma TCA levels. Use caution; monitor plasma TCA levels; reduce TCA dose if indicated ( 7.2 ). Tryptophan: Severe vomiting with coadministration ( 7.2 ).
Diltiazem: Bradycardia with coadministration ( 7.3 ). Propranolol or metoprolol: Reduce dose if coadministered and titrate more cautiously ( 7.3 ).
7.1 Potential Interactions with Drugs that Inhibit or are Metabolized by Cytochrome P450 Isoenzymes 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-vitro data 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-vitro data 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-vitro data 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-vivo study 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) ] .
7.2CNS Active Drugs Antipsychotics: See Warnings and Precautions
(5.2) . Benzodiazepines: See Warnings 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) . Serotonergic Drugs: See Dosage and Administration (2.4 , 2.5) , Contraindications (4) , 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 max and 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 post-marketing 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) ] .
7.3Other Drugs Alosetron: See Contraindications
(4) , Warnings and Precautions (5.7) , and Lotronex ® (alosetron) package insert. Digoxin: Administration o
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Pregnancy and breastfeeding
8.1Pregnancy 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 2 basis. In addition, decreased fetal body weight was seen at a dose 6 times the MRHD given to adolescents on a mg/m 2 basis.
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 2 basis. 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 2 basis. 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 2 basis). 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 2 basis).
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 2 basis). 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 2 basis) 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 2 basis) 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 2 basis).
Adverse reactions
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Most common reactions in controlled trials with adult OCD and depression patients (incidence ≥5% and at least twice that for placebo) were nausea, somnolence, insomnia, asthenia, nervousness, dyspepsia, abnormal ejaculation, sweating, anorexia, tremor and vomiting ( 6.2 ).
Using the above rule, the following events were also identified: anorgasmia, decreased libido, dry mouth, rhinitis, taste perversion and urinary frequency in patients with OCD; and agitation, depression, dysmenorrhea, flatulence, hyperkinesia and rash in pediatric patients with OCD. To report SUSPECTED ADVERSE REACTIONS, contact Upsher-Smith Laboratories, LLC at 1-855-899-9180 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Adverse Reactions Leading to Treatment Discontinuation Of the 1,087 OCD
and depressed patients treated with fluvoxamine maleate in controlled clinical trials in North America, 22% discontinued due to an adverse reaction. Adverse reactions that led to discontinuation in at least 2% of fluvoxamine maleate-treated patients in these trials were: nausea (9%), insomnia (4%), somnolence (4%), headache (3%), and asthenia, vomiting, nervousness, agitation, and dizziness (2% each).
6.2Incidence in Controlled Trials 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 2 were: 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 2 enumerates 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 mg/day 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 Reactions for which fluvoxamine maleate incidence was equal to or less than placebo are not listed in the table above.
Body System/ Adverse Reaction Percentage of Patients Reporting Reaction Fluvoxamine N=892 Placebo N=778 Body as a 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 Includes "toothache," "tooth extraction and abscess," and "caries." 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 Mostly feeling warm, hot, or flushed. 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 Mostly "blurred vision." 3 2 Urogenital Abnormal Ejaculation Mostly "delayed ejaculation." , Incidence based on number of male patients. 8 1 Urinary Frequency 3 2 Impotence 2 1 Anorgasmia 2 0 Urinary Retention 1 0 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.
6.3Other Adverse Reactions in OCD Pediatric Population
In pediatric patients (N=57) treated with fluvoxamine maleate tablets, the overall profile of adverse reactions was generally similar to that seen in adult studies, as shown in Table 2. However, the following adverse reactions, 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: cough increase, dysmenorrhea, ecchymosis, emotional lability, epistaxis, hyperkinesia, manic reaction, rash, sinusitis, and weight decrease.
6.4Male 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. Table 3 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 3: Percentage of Patients Reporting Sexual Adverse Reactions in Adult Placebo-Controlled Trials in OCD and Depression Fluvoxamine maleate tablets N=892 Placebo N=778 Abnormal Ejaculation Based on the number of male patients. 8% 1% Impotence 2% 1% Decreased Libido 2% 1% Anorgasmia 2% 0% There are no adequate and well-controlled studies examining sexual dysfunction with fluvoxamine treatment.
Fluvoxam
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Composition
Active ingredients
FLUVOXAMINE MALEATE 100MG
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
Sumatriptan: There have been rare post-marketing 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) ] .
