Fluvoxamine Maleate Information
Fluvoxamine maleate (Fluvoxamine maleate) Dosage Forms And Strengths
Fluvoxamine maleate (Fluvoxamine maleate) tablets USP are available as:
Tablets 25 mg: white, film-coated capsule-shaped tablets debossed “93” on one side and “72” on the other side
Tablets 50 mg: yellow, film-coated capsule-shaped tablets debossed “93” on one side and scored between the two numbers, and debossed “56” on the other side
Tablets 100 mg: pink to light-brick, film-coated capsule-shaped tablets debossed “93” on one side and scored between the two numbers, and debossed “57” on the other side
Fluvoxamine maleate (Fluvoxamine maleate) Contraindications
Coadministration of tizanidine, thioridazine, alosetron, or pimozide with Fluvoxamine maleate (Fluvoxamine maleate) tablets is contraindicated (see [to ]).
The use of MAOIs concomitantly with or within 14 days of treatment with Fluvoxamine maleate (Fluvoxamine maleate) tablets is contraindicated (see []).
Fluvoxamine maleate (Fluvoxamine maleate) Warnings And Precautions
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 .
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 ,
[], for a description of the risks of discontinuation of Fluvoxamine maleate (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.
Screening Patients for Bipolar Disorder:
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 (Fluvoxamine maleate) tablet 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 (Fluvoxamine maleate) tablets with MAOIs intended to treat depression is contraindicated.
If concomitant treatment of Fluvoxamine maleate (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 (Fluvoxamine maleate) tablets with serotonin precursors (such as tryptophan) is not recommended.
Treatment with Fluvoxamine maleate (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.
The effect of fluvoxamine (25 mg b.i.d. 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 coadministration of fluvoxamine.
Thioridazine administration produces a dose-related prolongation of the QT 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 coadministered (see []).
Alprazolam
Diazepam
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.
max
5.10
Warfarin
During marketing of Fluvoxamine maleate (Fluvoxamine maleate) tablets and other SSRIs and SNRIs (serotonin and norepinephrine reuptake inhibitors), there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias, such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, and hypomania. While these events are generally self-limiting, there have been reports of serious discontinuation symptoms.
Patients should be monitored for these symptoms when discontinuing treatment with Fluvoxamine maleate (Fluvoxamine maleate) tablets. 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 (see []).
SSRIs and SNRIs, including Fluvoxamine maleate (Fluvoxamine maleate) tablets, may increase the risk of bleeding events. Concomitant use of aspirin, non-steroidal anti-inflammatory drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to SSRIs and SNRIs have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages.
Patients should be cautioned about the risk of bleeding associated with the concomitant use of Fluvoxamine maleate (Fluvoxamine maleate) tablets and NSAIDs, aspirin, or other drugs that affect coagulation [see section ].
Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including Fluvoxamine maleate (Fluvoxamine maleate) tablets. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone (SIADH). Cases with serum sodium lower than 110 mmol/L have been reported. Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs (see ,
[]). Also, patients taking diuretics or who are otherwise volume depleted may be at greater risk. Discontinuation of Fluvoxamine maleate (Fluvoxamine maleate) tablets should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted.
Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death.
Closely monitored clinical experience with Fluvoxamine maleate (Fluvoxamine maleate) tablets in patients with concomitant systemic illness is limited. Caution is advised in administering Fluvoxamine maleate (Fluvoxamine maleate) tablets to patients with diseases or conditions that could affect hemodynamic responses or metabolism.
Fluvoxamine maleate (Fluvoxamine maleate) tablets have not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were systematically excluded from many clinical studies during the product's premarketing testing. Evaluation of the electrocardiograms for patients with depression or OCD who participated in premarketing studies revealed no differences between fluvoxamine and placebo in the emergence of clinically important ECG changes.
Patients with Hepatic Impairment
Fluvoxamine maleate (Fluvoxamine maleate) Adverse Reactions
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.
The reactions in OCD studies with a two-fold increase in rate compared to reaction rates in OCD and depression studies were:
and . These reactions are listed in order of decreasing rates in the OCD trials.
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
There are no adequate and well-controlled studies examining sexual dysfunction 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.
During premarketing clinical trials conducted in North America and Europe, multiple doses of Fluvoxamine maleate (Fluvoxamine maleate) were administered for a combined total of 2737 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 2737 patient exposures to multiple doses of Fluvoxamine maleate (Fluvoxamine maleate) who experienced a reaction of the type cited on at least one occasion while receiving Fluvoxamine maleate (Fluvoxamine maleate) . All reported reactions are included in the list below, with the following exceptions: 1) those reactions already listed in , 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 (Fluvoxamine maleate) , a causal relationship to Fluvoxamine maleate (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 1/1000 patients; and rare adverse reactions are those occurring in less than 1/1000 patients.
*
Fluvoxamine maleate (Fluvoxamine maleate) Drug Interactions
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 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 []) and limited 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
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 study of fluvoxamine single-dose pharmacokinetics in 13 PM subjects demonstrated altered pharmacokinetic properties compared to 16 "extensive metabolizers" (EM): mean C, 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 (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 [] and []).
5.3
5.8
5.8
5.8
5.8
5.8
5.8
5.3
max
5.3
Sumatriptan
5.3
One case of bradycardia and hypotension and a second case of orthostatic hypotension have been reported with the coadministration of Fluvoxamine maleate (Fluvoxamine maleate) and metoprolol.
If propranolol or metoprolol is coadministered with Fluvoxamine maleate (Fluvoxamine maleate) tablets, a reduction in the initial beta-blocker dose and more cautious dose titration are recommended. No dosage adjustment is required for Fluvoxamine maleate (Fluvoxamine maleate) tablets.
Coadministration of Fluvoxamine maleate (Fluvoxamine maleate) 100 mg per day with atenolol 100 mg per day (N = 6) did not affect the plasma concentrations of atenolol. Unlike propranolol and metoprolol which undergo hepatic metabolism, atenolol is eliminated primarily by renal excretion.
Fluvoxamine maleate (Fluvoxamine maleate) Use In Specific Populations
The efficacy of Fluvoxamine maleate (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 (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 [] and []).
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 , []).
Safety and effectiveness in the pediatric population other than pediatric patients with OCD have not been established (see BOXED WARNING and , []). Anyone considering the use of Fluvoxamine maleate (Fluvoxamine maleate) tablets in a child or adolescent must balance the potential risks with the clinical need.
Fluvoxamine maleate (Fluvoxamine maleate) Overdosage
Worldwide exposure to fluvoxamine includes over 45,000 patients treated in clinical trials and an estimated exposure of 50,000,000 patients treated during worldwide marketing experience (end of 2005). Of the 539 cases of deliberate or accidental overdose involving fluvoxamine reported from this population, there were 55 deaths. Of these, 9 were in patients thought to be taking fluvoxamine alone and the remaining 46 were in patients taking fluvoxamine along with other drugs. Among non-fatal overdose cases, 404 patients recovered completely. Five patients experienced adverse sequelae of overdosage, to include persistent mydriasis, unsteady gait, hypoxic encephalopathy, kidney complications (from trauma associated with overdose), bowel infarction requiring a hemicolectomy, and vegetative state. In 13 patients, the outcome was provided as abating at the time of reporting. In the remaining 62 patients, the outcome was unknown. The largest known ingestion of fluvoxamine involved 12,000 mg (equivalent to 2 to 3 months' dosage). The patient fully recovered. However, ingestions as low as 1,400 mg have been associated with lethal outcome, indicating considerable prognostic variability.
Commonly (≥ 5%) observed adverse events associated with Fluvoxamine maleate (Fluvoxamine maleate) overdose include gastrointestinal complaints (nausea, vomiting and diarrhea), coma, hypokalemia, hypotension, respiratory difficulties, somnolence, and tachycardia. Other notable signs and symptoms seen with Fluvoxamine maleate (Fluvoxamine maleate) overdose (single or multiple drugs) include bradycardia, ECG abnormalities (such as heart arrest, QT interval prolongation, first degree atrioventricular block, bundle branch block, and junctional rhythm), convulsions, dizziness, liver function disturbances, tremor, and increased reflexes.
Treatment should consist of those general measures employed in the management of overdosage with any antidepressant.
Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients.
Activated charcoal should be administered. Due to the large volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit. No specific antidotes for fluvoxamine are known.
A specific caution involves patients taking, or recently having taken, fluvoxamine who might ingest excessive quantities of a tricyclic antidepressant. In such a case, accumulation of the parent tricyclic and/or an active metabolite may increase the possibility of clinically significant sequelae and extend the time needed for close medical observation (see []).
In managing overdosage, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Telephone numbers for certified poison control centers are listed in the (PDR).
Fluvoxamine maleate (Fluvoxamine maleate) Description
Fluvoxamine maleate (Fluvoxamine maleate) is a selective serotonin (5-HT) reuptake inhibitor (SSRI) belonging to the chemical series, the 2-aminoethyl oxime ethers of aralkylketones.
It is chemically designated as 5-methoxy-4′-(trifluoromethyl)valerophenone-()--(2-aminoethyl)oxime maleate (1:1).
The structural formula is:
CHONF•CHO M.W. 434.4
Fluvoxamine maleate (Fluvoxamine maleate) is a white or off-white, odorless, crystalline powder which is sparingly soluble in water, freely soluble in ethanol and chloroform and practically insoluble in diethyl ether.
Fluvoxamine maleate (Fluvoxamine maleate) tablets USP are available in 25 mg, 50 mg and 100 mg strengths for oral administration. In addition to the active ingredient, Fluvoxamine maleate (Fluvoxamine maleate) , each tablet contains the following inactive ingredients: colloidal silicon dioxide, hydroxypropyl cellulose, hypromellose, mannitol, mannitol granulate, polyethylene glycol 400, polysorbate 80, pregelatinized starch, sodium stearyl fumarate, and titanium dioxide. Additionally each 50 mg and 100 mg tablet contains: iron oxide black, iron oxide red, and iron oxide yellow.
Fluvoxamine maleate (Fluvoxamine maleate) Clinical Pharmacology
In a dose proportionality study involving Fluvoxamine maleate (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 (Fluvoxamine maleate) produced disproportionately higher concentrations than predicted from the lower dose.
Approximately 80% of fluvoxamine is bound to plasma protein, mostly albumin, over a concentration range of 20 to 2000 ng/mL.
7
14
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.
2.3
2.2
5.14
Fluvoxamine maleate (Fluvoxamine maleate) Clinical Studies
The effectiveness of Fluvoxamine maleate (Fluvoxamine maleate) tablets for the treatment of obsessive compulsive disorder (OCD) was demonstrated in two 10 week multicenter, parallel group studies of adult outpatients. Patients in these trials were titrated to a total daily Fluvoxamine maleate (Fluvoxamine maleate) dose of 150 mg/day over the first two weeks of the trial, following which the dose was adjusted within a range of 100 to 300 mg/day (on a b.i.d. schedule), on the basis of response and tolerance. Patients in these studies had moderate to severe OCD (DSM-III-R), with mean baseline ratings on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), total score of 23. Patients receiving Fluvoxamine maleate (Fluvoxamine maleate) experienced mean reductions of approximately 4 to 5 units on the Y-BOCS total score, compared to a 2 unit reduction for placebo patients.
Table 6
Exploratory analyses for age and gender effects on outcomes did not suggest any differential responsiveness on the basis of age or sex.
The effectiveness of Fluvoxamine maleate (Fluvoxamine maleate) tablets for the treatment of OCD was also demonstrated in a 10 week multicenter, parallel group study in a pediatric outpatient population (children and adolescents, ages 8 to 17). Patients in this study were titrated to a total daily fluvoxamine dose of approximately 100 mg/day over the first two weeks of the trial, following which the dose was adjusted within a range of 50 to 200 mg/day (on a b.i.d. schedule) on the basis of response and tolerance. All patients had moderate-to-severe OCD (DSM-III-R) with mean baseline ratings on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) total score of 24. Patients receiving Fluvoxamine maleate (Fluvoxamine maleate) experienced mean reductions of approximately six units on the CY-BOCS total score, compared to a three-unit reduction for placebo patients.
Table 7
Post hoc exploratory analyses for gender effects on outcomes did not suggest any differential responsiveness on the basis of gender. Further exploratory analyses revealed a prominent treatment effect in the 8 to 11 age group and essentially no effect in the 12 to 17 age group. While the significance of these results is not clear, the 2 to 3 fold higher steady-state plasma fluvoxamine concentrations in children compared to adolescents (see
, []) is suggestive that decreased exposure in adolescents may have been a factor, and dose adjustment in adolescents (up to the adult maximum dose of 300 mg) may be indicated to achieve therapeutic benefit.
Fluvoxamine maleate (Fluvoxamine maleate) How Supplied/storage And Handling
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from high humidity.
Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
Keep this and all medications out of the reach of children.
Fluvoxamine maleate (Fluvoxamine maleate) Patient Counseling Information
Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with Fluvoxamine maleate (Fluvoxamine maleate) tablets and should counsel them in the appropriate use. A patient Medication Guide about “
” is available for Fluvoxamine maleate (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 (Fluvoxamine maleate) tablets.
Fluvoxamine maleate (Fluvoxamine maleate)
Fluvoxamine maleate (Fluvoxamine maleate)
