Fluvoxamine Maleate (Luvox, Faverin), Page 1

Fluvoxamine maleate (Luvox) tablets are indicated for the treatment of obsessions and compulsions in patients with obsessive compulsive disorder (OCD).

FLUVOXAMINE MALEATE- fluvoxamine maleate tablet, film coated
Barr Laboratories Inc.

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 psychiatric 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 compulsive disorder (OCD) [see Warnings and Precautions, Clinical Worsening and Suicide Risk (5.1)].

1 INDICATIONS AND USAGE

1.1 Obsessive-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 three trials in outpatients with OCD: two 10 week trials in adults, one 10-week trial in pediatric patients (ages 8 to 17) [see Clinical Studies (14)].

2 DOSAGE AND ADMINISTRATION

2.1 Adults

The recommended starting dose for fluvoxamine maleate tablets in adult patients is 50 mg, administered as a single daily dose at bedtime. In the controlled clinical trials establishing the effectiveness of fluvoxamine maleate tablets in OCD, patients were titrated within a dose range of 100 to 300 mg/day. Consequently, the dose should be increased in 50 mg increments every 4 to 7 days, as tolerated, until maximum therapeutic benefit is achieved, not to exceed 300 mg per day. It is advisable that a total daily dose of more than 100 mg should be given in two divided doses. If the doses are not equal, the larger dose should be given at bedtime.

2.2 Pediatric Population (children and adolescents)

The recommended starting dose for fluvoxamine maleate tablets in pediatric populations (ages 8 to 17 years) is 25 mg, administered as a single daily dose at bedtime. In a controlled clinical trial establishing the effectiveness of fluvoxamine maleate tablets in OCD, pediatric patients (ages 8 to 17) were titrated within a dose range of 50 to 200 mg/day. Physicians should consider age and gender differences when dosing pediatric patients. The maximum dose in children up to age 11 should not exceed 200 mg/day. Therapeutic effect in female children may be achieved with lower doses. Dose adjustment in adolescents (up to the adult maximum dose of 300 mg) may be indicated to achieve therapeutic benefit. The dose should be increased in 25 mg increments every 4 to 7 days, as tolerated, until maximum therapeutic benefit is achieved. It is advisable that a total daily dose of more than 50 mg should be given in two divided doses. If the two divided doses are not equal, the larger dose should be given at bedtime.

2.3 Elderly or Hepatically Impaired Patients

Elderly patients and those with hepatic impairment have been observed to have a decreased clearance of fluvoxamine maleate. Consequently, it may be appropriate to modify the initial dose and the subsequent dose titration for these patient groups.

2.4 Pregnant Women During the Third Trimester

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 and may be at risk for persistent pulmonary hypertension of the newborn (PPHN) [see Use in Specific Populations (8.1)]. When treating pregnant women with fluvoxamine maleate tablets during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering fluvoxamine maleate tablets in the third trimester.

2.5 Switching Patients To or From a Monoamine Oxidase Inhibitor

At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with Fluvoxamine Maleate Tablets. Similarly, at least 14 days should be allowed after stopping Fluvoxamine Maleate Tablets before starting an MAOI.

2.7 Discontinuation of Treatment with Fluvoxamine Maleate Tablets

Symptoms associated with discontinuation of other SSRIs or SNRIs have been reported [see Warnings and Precautions (5.9)]. Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.

3 DOSAGE FORMS AND STRENGTHS

Fluvoxamine Maleate Tablets, USP are available as:

Tablets 25 mg: Off-white, oval, film-coated, biconvex, unscored tablet. Debossed with stylized b on one side and 967 on the other side.

Tablets 50 mg: Yellow, oval, film-coated, biconvex, scored tablet. Debossed with stylized b on one side and 968/50 on the scored side.

Tablets 100 mg: Brown, oval, film-coated, biconvex, scored tablet. Debossed with stylized b on one side and 969/100 on the scored side.

4 CONTRAINDICATIONS

Coadministration of tizanidine, thioridazine, alosetron, or pimozide with fluvoxamine maleate tablets is contraindicated [see Warnings and Precautions (5.4 to 5.7)].

The use of MAOIs concomitantly with or within 14 days of treatment with fluvoxamine maleate tablets is contraindicated [see Warnings and Precautions (5.2)].

5 WARNINGS AND PRECAUTIONS

5.1 Clinical 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 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 DRUG-PLACEBO DIFFERENCES IN NUMBER OF CASES OF SUICIDALITY PER 1000 PATIENTS TREATED
Age Range Increases Compared to Placebo
< 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 [see Dosage and Administration, Discontinuation of Treatment with Fluvoxamine Maleate Tablets (5.9)], 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 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.

5.2 Potential for Monoamine Oxidase Inhibitors Interaction

In patients receiving another serotonin reuptake inhibitor drug in combination with monoamine oxidase inhibitors (MAOIs), 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 an MAOI. Some cases presented with features resembling a serotonin syndrome or neuroleptic malignant syndrome. Therefore, fluvoxamine maleate tablets should not be used in combination with an MAOI, or within 14 days of discontinuing treatment with an MAOI. Similarly, at least 14 days should be allowed after stopping fluvoxamine maleate tablets before starting an MAOI [see Dosage and Administration (2.5) and Contraindications (4)].

5.3 Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions

The development of a potentially life-threatening serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions have been reported with SNRIs and SSRIs alone, including fluvoxamine maleate tablets treatment, but particularly with concomitant use of serotonergic drugs (including triptans) with drugs which impair metabolism of serotonin (including MAOIs), or with antipsychotics or other dopamine antagonists. 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). Serotonin syndrome, in its most severe form can resemble Neuroleptic Malignant Syndrome, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of serotonin syndrome or NMS-like signs and symptoms.

The concomitant use of fluvoxamine maleate tablets with MAOIs intended to treat depression is contraindicated.

If concomitant treatment of fluvoxamine maleate tablets with a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.

The concomitant use of fluvoxamine maleate tablets with serotonin precursors (such as tryptophan) is not recommended.

Treatment with fluvoxamine maleate tablets and any concomitant serotonergic or antidopaminergic agents, including antipsychotics, should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.

All medication material on this site is included in as near-original form as possible: information as supplied by the FDA has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent. This page was originally published by on and was last reviewed or updated by Site Editor on .

This site is brought to you by the team behind counselling and psychotherapy site CounsellingResource.com. Our mental health medication information is not intended as a substitute for direct consultation with a qualified health professional. The graphic portion of our unofficial logo was created by the talented Ukrainian artist and illustrator Iaroslav Lazunov and is used under license, copyright © Depositphotos.com/Iaroslav Lazunov.

Copyright © 2002-2019. All Rights Reserved.