DRUGS & SUPPLEMENTS
1 INDICATIONS AND USAGE
Luvox tablets USP are indicated for the treatment of obsessions and compulsions in patients with obsessive compulsive disorder .
1.1 Obsessive-Compulsive Disorder
Luvox tablets USP 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 Luvox tablets USP 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 14 CLINICAL STUDIES ).
2 DOSAGE AND ADMINISTRATION
The recommended starting dose for Luvox tablets in adult patients is 50 mg, administered as a single daily dose at bedtime. In the controlled clinical trials establishing the effectiveness of Luvox tablets in OCD, patients were titrated within a dose range of 100 mg/day 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
The recommended starting dose for Luvox 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 Luvox tablets in OCD, pediatric patients (ages 8 to 17) were titrated within a dose range of 50 mg/day 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 Luvox. 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 Luvox 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 (see USE IN SPECIFIC POPULATIONS, 8.1 Pregnancy ). When treating pregnant women with Luvox tablets during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering Luvox 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 Luvox tablets. Similarly, at least 14 days should be allowed after stopping Luvox tablets before starting an MAOI.
2.7 Discontinuation of Treatment with Luvox Tablets
Symptoms associated with discontinuation of other SSRIs or SNRIs have been reported (see WARNINGS AND PRECAUTIONS, 5.9 Discontinuation of Treatment with Luvox ). 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
Luvox Tablets are available as:
25 mg: Off-white, round, biconvex, film-coated, debossed “E” over “17” on one side and plain on the other side.
50 mg: Yellow, round, biconvex, film-coated, debossed “E” over “27” on one side and bisected on the other side.
100 mg: Beige, round, biconvex, film-coated, debossed “E” over “157” on one side and bisected on the other side.
Co-administration of tizanidine, thioridazine, alosetron or pimozide with Luvox is contraindicated (see WARNINGS AND PRECAUTIONS, 5.4 Potential Thioridazine Interaction, 5.5 Potential Tizanidine Interaction, 5.6 Potential Pimozide Interaction and 5.7 Potential Alosetron Interaction ).
The use of MAOIs concomitantly with or within 14 days of treatment with Luvox is contraindicated (see WARNINGS AND PRECAUTIONS, 5.2 Potential for Monoamine Oxidase Inhibitors Interaction.)
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 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.
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, 5.9 Discontinuation of Treatment with Luvox , for a description of the risks of discontinuation of Luvox 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 Luvox 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 Luvox is 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, 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, Luvox 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 Luvox before starting an MAOI (see DOSAGE AND ADMINISTRATION, 2.5 Switching Patients To or From a Monoamine Oxidase Inhibitor and 4 CONTRAINDICATIONS ).
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 Luvox 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 Luvox with MAOIs intended to treat depression is contraindicated.
If concomitant treatment of Luvox 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 Luvox with serotonin precursors (such as tryptophan) is not recommended.
Treatment with Luvox 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.
5.4 Potential Thioridazine Interaction
The effect of fluvoxamine 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 three-fold 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 torsades 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 (see 4 CONTRAINDICATIONS ).
5.5 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 male 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 the psychomotor task was significantly impaired. Fluvoxamine and tizanidine should not be used together (see 4 CONTRAINDICATIONS ).
5.6 Potential Pimozide Interaction
Pimozide is metabolized by the cytochrome P4503A4 isoenzyme and it has been demonstrated that ketoconazole, a potent inhibitor of CYP3A4, blocks the metabolism of this drug, resulting in increased plasma concentrations of parent drug. An increased plasma concentration of pimozide causes QT prolongation and has 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 CYP3A4. Although it has not been definitively demonstrated that fluvoxamine is a potent CYP3A4 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 pimozide.
5.7 Potential Alosetron Interaction
Because alosetron is metabolized by a variety of hepatic CYP drug metabolizing enzymes, inducers or inhibitors of these enzymes may change the clearance of alosetron. Fluvoxamine is a known potent inhibitor of CYP1A2 and also inhibits CYP3A4, CYP2C9 and CYP2C19. In a pharmacokinetic study, 40 healthy female subjects received fluvoxamine in escalating doses from 50 mg to 200 mg a day for 16 days, with co-administration of alosetron 1 mg on the last day. Fluvoxamine increased mean alosetron plasma concentration (AUC) approximately 6-fold and prolonged the half-life by approximately 3-fold (see 4 CONTRAINDICATIONS and LotronexTM (alosetron) package insert).
5.8 Other Potentially Important Drug Interactions
Benzodiazepines: Benzodiazepines metabolized by hepatic oxidation should be used with caution because the clearance of these drugs is likely to be reduced by fluvoxamine. The clearance of benzodiazepines metabolized by glucuronidation (e.g., lorazepam, oxazepam, temazepam) is unlikely to be affected by fluvoxamine.
Alprazolam: When Luvox (100 mg q.d.) and alprazolam (1 mg q.i.d.) were co-administered to steady state, plasma concentrations and other pharmacokinetic parameters (AUC, Cmax, T½) of alprazolam were approximately twice those observed when alprazolam was administered alone; oral clearance was reduced by about 50%. The elevated plasma alprazolam concentrations resulted in decreased psychomotor performance and memory. This interaction, which has not been investigated using higher doses of fluvoxamine, may be more pronounced if a 300 mg daily dose is co-administered, particularly since fluvoxamine exhibits non-linear pharmacokinetics over the dosage range 100 mg to 300 mg. If alprazolam is co-administered with Luvox, the initial alprazolam dosage should be at least halved and titration to the lowest effective dose is recommended. No dosage adjustment is required for Luvox.
Diazepam: The co-administration of Luvox 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 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 co-administered.
Clozapine: Elevated serum levels of clozapine have been reported in patients taking Luvox and clozapine. Since clozapine-related seizures and orthostatic hypotension appear to be dose related, the risk of these adverse events may be higher when fluvoxamine and clozapine are co-administered. Patients should be closely monitored when Luvox and clozapine are used concurrently.
Methadone: Significantly increased methadone (plasma level:dose) ratios have been reported when Luvox was administered to patients receiving maintenance methadone treatment, with symptoms of opioid intoxication in one patient. Opioid withdrawal symptoms were reported following Luvox discontinuation in another patient.
Mexiletine: The effect of steady-state fluvoxamine (50 mg b.i.d. for 7 days) on the single dose pharmacokinetics of mexiletine (200 mg) was evaluated in 6 healthy Japanese males. The clearance of mexiletine was reduced by 38% following co-administration with fluvoxamine compared to mexiletine alone. If fluvoxamine and mexiletine are co-administered, serum mexiletine levels should be monitored.
Ramelteon: When fluvoxamine 100 mg twice daily was administered for 3 days prior to single-dose co-administration of ramelteon 16 mg and fluvoxamine, the AUC for ramelteon increased approximately 190-fold and the Cmax increased approximately 70-fold compared to ramelteon administered alone. Ramelteon should not be used in combination with fluvoxamine.
Theophylline: The effect of steady-state fluvoxamine (50 mg bid) on the pharmacokinetics of a single dose of theophylline (375 mg as 442 mg aminophylline) was evaluated in 12 healthy nonsmoking, male volunteers. The clearance of theophylline was decreased approximately 3-fold. Therefore, if theophylline is co-administered with Luvox, 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 Luvox.
Warfarin and Other Drugs That Interfere With Hemostasis (NSAIDs, Aspirin, etc.): Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. These studies have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding. Thus, patients should be cautioned about the use of such drugs concurrently with fluvoxamine (see WARNINGS AND PRECAUTIONS, 5.10 Abnormal Bleeding ).
Warfarin: When Luvox (50 mg t.i.d.) was administered concomitantly with warfarin for two weeks, warfarin plasma concentrations increased by 98% and prothrombin times were prolonged. Thus patients receiving oral anticoagulants and Luvox tablets should have their prothrombin time monitored and their anticoagulant dose adjusted accordingly. No dosage adjustment is required for Luvox.
5.9 Discontinuation of Treatment with Luvox
During marketing of Luvox 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 Luvox 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 DOSAGE AND ADMINISTRATION, 2.7 Discontinuation of Treatment with Luvox Tablets ).
5.10 Abnormal Bleeding
SSRIs and SNRIs, including Luvox, may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, warfarin and other anticoagulants may add to this risk. Case reports and epidemiological studies 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 Luvox and NSAIDs, aspirin or other drugs that affect coagulation (see WARNINGS AND PRECAUTIONS, 5.8 Other Potentially Important Drug Interactions ).
5.11 Activation of Mania/Hypomania
During pre-marketing studies involving primarily depressed patients, hypomania or mania occurred in approximately 1% of patients treated with fluvoxamine. In a ten week pediatric OCD study, 2 out of 57 patients (4%) treated with fluvoxamine experienced manic reactions, compared to none of 63 placebo patients. Activation of mania/hypomania has also been reported in a small proportion of patients with major affective disorder who were treated with other marketed antidepressants. As with all antidepressants, Luvox should be used cautiously in patients with a history of mania.
During pre-marketing studies, seizures were reported in 0.2% of fluvoxamine-treated patients. Caution is recommended when the drug is administered to patients with a history of convulsive disorders. Fluvoxamine should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be carefully monitored. Treatment with fluvoxamine should be discontinued if seizures occur or if seizure frequency increases.
Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including Luvox. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone. 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 USE IN SPECIFIC POPULATION, 8.5 Geriatric Use ). Also, patients taking diuretics or who are otherwise volume depleted may be at greater risk. Discontinuation of Luvox 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.
5.14 Use in Patients with Concomitant Illness
Closely monitored clinical experience with Luvox in patients with concomitant systemic illness is limited. Caution is advised in administering Luvox to patients with diseases or conditions that could affect hemodynamic responses or metabolism.
Luvox has 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 pre-marketing testing. Evaluation of the electrocardiograms for patients with depression or OCD who participated in pre-marketing studies revealed no differences between fluvoxamine and placebo in the emergence of clinically important ECG changes.
Patients with Hepatic Impairment: In patients with liver dysfunction, fluvoxamine clearance was decreased by approximately 30%. Patients with liver dysfunction should begin with a low dose of Luvox and increase it slowly with careful monitoring.
5.15 Laboratory Tests
There are no specific laboratory tests recommended.
6 ADVERSE REACTIONS
To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Adverse Reactions Leading to Treatment Discontinuation
Of the 1,087 OCD and depressed patients treated with Luvox 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).
6.2 Incidence in Controlled Trials
Commonly Observed Adverse Reactions in Controlled Clinical Trials: Luvox has been studied in 10-week short-term controlled trials of OCD 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 Luvox 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 Luvox 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.
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.
6.3 Other Adverse Reactions in OCD Pediatric Population
In pediatric patients (N=57) treated with Luvox, 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 Luvox than with placebo: cough increase, dysmenorrhea, ecchymosis, emotional lability, epistaxis, hyperkinesia, manic reaction, rash, sinusitis and weight decrease.
6.4 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, 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 Luvox in placebo-controlled trials in depression and OCD.
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.
6.5 Vital Sign Changes
Comparisons of Luvox 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 Luvox and placebo.
6.6 Laboratory Changes
Comparisons of Luvox and placebo groups in separate pools of short-term OCD and depression trials on 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 Luvox and placebo.
6.7 ECG Changes
Comparisons of Luvox 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 Luvox and placebo.
6.8 Other Events Observed During Pre-marketing Evaluation of Luvox
During pre-marketing clinical trials conducted in North America and Europe, multiple doses of Luvox were administered for a combined total of 2,737 patient exposures in patients suffering OCD or Major Depressive Disorder. Untoward reactions associated with this exposure were recorded by clinical investigators using descriptive terminology of their own choosing.
Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse reactions without first grouping similar types of untoward reactions into a limited number of standard reaction categories.
In the tabulations which follow, a standard COSTART-based Dictionary terminology has been used to classify reported adverse reactions. If the COSTART term for a reaction was so general as to be uninformative, it was replaced with a more informative term. The frequencies presented, therefore, represent the proportion of the 2,737 patient exposures to multiple doses of Luvox who experienced a reaction of the type cited on at least one occasion while receiving Luvox. All reported reactions are included in the list below, with the following exceptions: 1) those reactions already listed in Table 2, which tabulates incidence rates of common adverse experiences in placebo-controlled OCD and depression clinical trials, are excluded; 2) those reactions for which a drug cause was not considered likely are omitted; 3) reactions for which the COSTART term was too vague to be clinically meaningful and could not be replaced with a more informative term; and 4) reactions which were reported in only one patient and judged to not be potentially serious are not included. It is important to emphasize that, although the reactions reported did occur during treatment with Luvox, a causal relationship to Luvox has not been established.
Reactions are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse reactions are defined as those occurring on one or more occasions in at least 1/100 patients; infrequent adverse reactions are those occurring between 1/100 and 1/1,000 patients; and rare adverse reactions are those occurring in less than 1/1,000 patients.
Body as a Whole: Frequent: malaise; Infrequent: photosensitivity reaction and suicide attempt.
Cardiovascular System: Frequent: syncope.
Digestive System: Infrequent: gastrointestinal hemorrhage and melena; Rare: hematemesis.
Hemic and Lymphatic Systems: Infrequent: anemia and ecchymosis; Rare: purpura.
Metabolic and Nutritional Systems: Frequent: weight gain and weight loss.
Nervous System: Frequent: hyperkinesia, manic reaction and myoclonus; Infrequent: abnormal dreams, akathisia, convulsion, dyskinesia, dystonia, euphoria, extrapyramidal syndrome and twitching; Rare: withdrawal syndrome.
Respiratory System: Infrequent: epistaxis. Rare: hemoptysis and laryngismus.
Skin: Infrequent: urticaria.
Urogenital System*: Infrequent: hematuria, menorrhagia and vaginal hemorrhage; Rare: hematospermia.
* Based on the number of males or females, as appropriate.
6.9 Post-marketing Reports
Voluntary reports of adverse reactions in patients taking Luvox that have been received since market introduction and are of unknown causal relationship to Luvox use include: acute renal failure, agranulocytosis, amenorrhea, anaphylactic reaction, angioedema, aplastic anemia, bullous eruption, Henoch-Schoenlein purpura, hepatitis, ileus, pancreatitis, porphyria, Stevens-Johnson syndrome, toxic epidermal necrolysis, vasculitis and ventricular tachycardia (including torsades de pointes).
7 DRUG INTERACTIONS
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 5 WARNINGS AND PRECAUTIONS ). 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 Cmax, 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 Luvox 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 4 CONTRAINDICATIONS and 5 WARNINGS AND PRECAUTIONS ).
7.2 CNS Active Drugs
Antipsychotics: See WARNINGS AND PRECAUTIONS, 5.3 Serotonin Syndrome or Neuroleptic Malignant Syndrome -like Reactions .
Benzodiazepines: See WARNINGS AND PRECAUTIONS, 5.8 Other Potentially Important Drug Interactions .
Alprazolam: See WARNINGS AND PRECAUTIONS, 5.8 Other Potentially Important Drug Interactions .
Diazepam: See WARNINGS AND PRECAUTIONS, 5.8 Other Potentially Important Drug Interactions .
Lorazepam : A study of multiple doses of Luvox (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 co-administration 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 Luvox (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 Luvox tablets.
Carbamazepine: Elevated carbamazepine levels and symptoms of toxicity have been reported with the co-administration of Luvox and carbamazepine.
Clozapine: See WARNINGS AND PRECAUTIONS, 5.8 Other Potentially Important Drug Interactions .
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 co-administration of Luvox and lithium.
Methadone: See WARNINGS AND PRECAUTIONS, 5.8 Other Potentially Important Drug Interactions .
Monoamine Oxidase Inhibitors: See 4 CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS, 5.2 Potential for Monoamine Oxidase Inhibitors Interaction .
Pimozide: See 4 CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS, 5.6 Potential Pimozide Interaction .
Ramelteon: See WARNINGS AND PRECAUTIONS, 5.8 Other Potentially Important Drug Interactions .
Serotonergic Drugs: See WARNINGS AND PRECAUTIONS, 5.3 Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions .
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 Cmax and AUC, respectively, compared to the administration of tacrine alone.
Five subjects experienced nausea, vomiting, sweating and diarrhea following co-administration, consistent with the cholinergic effects of tacrine.
Thioridazine: See 4 CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS [5.4].
Tizanidine: See 4 CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS, 5.5 Potential Tizanidine Interaction .
Tricyclic Antidepressants (TCAs): Significantly increased plasma TCA levels have been reported with the co-administration of Luvox and amitriptyline, clomipramine or imipramine. Caution is indicated with the co-administration of Luvox 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, 5.3 Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions ).
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 co-administration of Luvox and tryptophan (see WARNINGS AND PRECAUTIONS, 5.3 Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions ).
7.3 Other Drugs
Alosetron: See 4 CONTRAINDICATIONS , WARNINGS AND PRECAUTIONS, 5.7 Potential Alosetron Interaction and LotronexTM (alosetron) package insert.
Digoxin: Administration of Luvox 100 mg daily for 18 days (N=8) did not significantly affect the pharmacokinetics of a 1.25 mg single intravenous dose of digoxin.
Diltiazem: Bradycardia has been reported with the co-administration of Luvox and diltiazem.
Mexiletine: See WARNINGS AND PRECAUTIONS, 5.8 Other Potentially Important Drug Interactions .
Propranolol and Other Beta-Blockers: Co-administration of Luvox 100 mg per day and propranolol 160 mg per day in normal volunteers resulted in a mean five-fold increase (range 2 to 17) in minimum propranolol plasma concentrations. In this study, there was a slight potentiation of the propranolol-induced reduction in heart rate and reduction in the exercise diastolic pressure.
One case of bradycardia and hypotension and a second case of orthostatic hypotension have been reported with the co-administration of Luvox and metoprolol.
If propranolol or metoprolol is co-administered with Luvox, a reduction in the initial beta-blocker dose and more cautious dose titration are recommended. No dosage adjustment is required for Luvox.
Co-administration of Luvox 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.
Theophylline: See WARNINGS AND PRECAUTIONS, 5.8 Other Potentially Important Drug Interactions .
Warfarin and Other Drugs That Interfere With Hemostasis (NSAIDs, Aspirin, etc.): See WARNINGS AND PRECAUTIONS, 5.8 Other Potentially Important Drug Interactions and 5.10 Abnormal Bleeding ).
7.4 Effects of Smoking on Fluvoxamine Metabolism
Smokers had a 25% increase in the metabolism of fluvoxamine compared to nonsmokers.
7.5 Electroconvulsive Therapy
There are no clinical studies establishing the benefits or risks of combined use of ECT and Luvox.
8 USE IN SPECIFIC POPULATIONS
Specific populations not discussed in DOSAGE AND ADMINISTRATION or WARNINGS AND PRECAUTIONS include:
Teratogenic Effects: Pregnancy Category C: When pregnant rats were given oral doses of fluvoxamine (60 mg/kg, 120 mg/kg 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. Decreased fetal body weight was seen at the high dose. The no effect dose for developmental toxicity in this study was 60 mg/kg (approximately 2 times the MRHD on a mg/m2 basis).
In a study in which pregnant rabbits were administered doses of up to 40 mg/kg (approximately 2 times the MRHD on a mg/m2 basis) during 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 mg/kg, 20 mg/kg, 80 mg/kg or 160 mg/kg), increased pup mortality at birth was seen at doses of 80 mg/kg or greater and decreases in pup body weight and survival were observed at all doses (low effect dose approximately 0.1 times the MRHD on a mg/m2 basis).
Nonteratogenic Effects: Neonates exposed to Luvox and other SSRIs or serotonin and norepinephrine reuptake inhibitors (SNRIs) late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support and tube feeding. These findings are based on post-marketing reports. 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 or 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, 5.3 Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions ).
Infants exposed to SSRIs in late pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN is associated with substantial neonatal morbidity and mortality. In a case-control study of 377 women whose infants were born with PPHN and 836 women whose infants were born healthy, the risk for developing PPHN was approximately six-fold higher for infants exposed to SSRIs after the 20th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy. PPHN occurs in 1 to 2 per 1,000 live births in the general population.
When treating a pregnant woman with Luvox during the third trimester, the physician should carefully consider both the potential risks and benefits of treatment (see DOSAGE AND ADMINISTRATION, 2.4 Pregnant Women During the Third Trimester ). Physicians should note that in a prospective longitudinal study of 201 women with a history of major depression who were euthymic at the beginning of pregnancy, women who discontinued antidepressant medication during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant medication.
8.2 Labor and Delivery
The effect of fluvoxamine on labor and delivery in humans is unknown.
8.3 Nursing Mothers
As for many other drugs, fluvoxamine is secreted in human breast milk. The decision of whether to discontinue nursing or to discontinue the drug should take into account the potential for serious adverse effects from exposure to fluvoxamine in the nursing infant as well as the potential benefits of Luvox therapy to the mother.
8.4 Pediatric Use
The efficacy of Luvox 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 Luvox 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 ).
Decreased appetite and weight loss have been observed in association with the use of fluvoxamine as well as other SSRIs. Consequently, regular monitoring of weight and growth is recommended if treatment of a child with an SSRI is to be continued long term.
The risks, if any, that may be associated with fluvoxamine’s extended use in children and adolescents with OCD have not been systematically assessed. The prescriber should be mindful that the evidence relied upon to conclude that fluvoxamine is safe for use in children and adolescents derives from relatively short term clinical studies and from extrapolation of experience gained with adult patients. In particular, there are no studies that directly evaluate the effects of long term fluvoxamine use on the growth, cognitive behavioral development and maturation of children and adolescents. Although there is no affirmative finding to suggest that fluvoxamine possesses a capacity to adversely affect growth, development or maturation, the absence of such findings is not compelling evidence of the absence of the potential of fluvoxamine to have adverse effects in chronic use (see WARNINGS AND PRECAUTIONS, 5.1 Clinical Worsening and Suicide Risk ).
Safety and effectiveness in the pediatric population other than pediatric patients with OCD have not been established (see BOXED WARNING and WARNINGS AND PRECAUTIONS, 5.1 Clinical Worsening and Suicide Risk ). Anyone considering the use of Luvox in a child or adolescent must balance the potential risks with the clinical need.
8.5 Geriatric Use
Approximately 230 patients participating in controlled pre-marketing studies with Luvox were 65 years of age or over. No overall differences in safety were observed between these patients and younger patients. Other reported clinical experience has not identified differences in response between the elderly and younger patients. However, SSRIs and SNRIs, including Luvox, have been associated with several cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event (see WARNINGS AND PRECAUTIONS, 5.13 Hyponatremia ). Furthermore, the clearance of fluvoxamine is decreased by about 50% in elderly compared to younger patients (see CLINICAL PHARMACOLOGY, 12.3 Pharmacokinetics ) and greater sensitivity of some older individuals also cannot be ruled out. Consequently, a lower starting dose should be considered in elderly patients and Luvox should be slowly titrated during initiation of therapy.
9 DRUG ABUSE AND DEPENDENCE
9.1 Controlled Substance Class
Luvox is not a controlled substance.
9.2 Physical and Psychological Dependence
The potential for abuse, tolerance and physical dependence with Luvox has been studied in a nonhuman primate model. No evidence of dependency phenomena was found. The discontinuation effects of Luvox was not systematically evaluated in controlled clinical trials. Luvox was not systematically studied in clinical trials for potential for abuse, but there was no indication of drug-seeking behavior in clinical trials. It should be noted, however, that patients at risk for drug dependency were systematically excluded from investigational studies of Luvox. Generally, it is not possible to predict on the basis of preclinical or pre-marketing clinical experience the extent to which a CNS active drug will be misused, diverted and/or abused once marketed. Consequently, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of Luvox misuse or abuse (i.e., development of tolerance, incrementation of dose, drug-seeking behavior). atrioventricular block, bundle branch block and junctional rhythm), convulsions, dizziness, liver function disturbances, tremor and increased reflexes.
10.1 Human Experience
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. 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 Luvox overdose include gastrointestinal complaints (nausea, vomiting and diarrhea), coma, hypokalemia, hypotension, respiratory difficulties, somnolence and tachycardia. Other notable signs and symptoms seen with Luvox 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.
10.2 Management of Overdosage
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 DRUG INTERACTIONS, 7.2 CNS Active Drugs ).
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 Physicians’ Desk Reference (PDR).
Luvox USP 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-(E)-O-(2-aminoethyl)oxime maleate (1:1) and has the empirical formula C15H21O2N2F3-C4H4O4. Its molecular weight is 434.4.
The structural formula is:
Luvox USP is a white to off-white, odorless, crystalline powder which is sparingly soluble in water, freely soluble in ethanol and chloroform and practically insoluble in diethyl ether.
Luvox tablets USP are available in 25 mg, 50 mg and 100 mg strengths for oral administration. In addition to the active ingredient, Luvox USP, each tablet contains the following inactive ingredients: carnauba wax, corn starch, hypromellose, magnesium stearate, mannitol, methylcellulose, polyethylene glycol, polysorbate, pregelatinized starch, sodium starch glycolate, titanium dioxide and yellow iron oxide. The 100 mg tablets also contains red iron oxide.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The mechanism of action of Luvox in obsessive compulsive disorder is presumed to be linked to its specific serotonin reuptake inhibition in brain neurons. Fluvoxamine has been shown to be a potent inhibitor of the serotonin reuptake transporter in preclinical studies, both in vitro and in vivo.
In in vitro studies, Luvox had no significant affinity for histaminergic, alpha or beta adrenergic, muscarinic or dopaminergic receptors. Antagonism of some of these receptors is thought to be associated with various sedative, cardiovascular, anticholinergic and extrapyramidal effects of some psychotropic drugs.
Absorption: The absolute bioavailability of Luvox is 53%. Oral bioavailability is not significantly affected by food.
In a dose proportionality study involving Luvox at 100 mg/day, 200 mg/day 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 ng/mL, 283 ng/mL and 546 ng/mL, respectively. Thus, fluvoxamine had nonlinear pharmacokinetics over this dose range, i.e., higher doses of Luvox produced disproportionately higher concentrations than predicted from the lower dose.
Distribution: The mean apparent volume of distribution for fluvoxamine is approximately 25 L/kg, suggesting extensive tissue distribution.
Approximately 80% of fluvoxamine is bound to plasma protein, mostly albumin, over a concentration range of 20 ng/mL to 2000 ng/mL.
Metabolism: Luvox is extensively metabolized by the liver; the main metabolic routes are oxidative demethylation and deamination. Nine metabolites were identified following a 5 mg radiolabelled dose of Luvox, constituting approximately 85% of the urinary excretion products of fluvoxamine. The main human metabolite was fluvoxamine acid which, together with its N-acetylated analog, accounted for about 60% of the urinary excretion products. A third metabolite, fluvoxethanol, formed by oxidative deamination, accounted for about 10%. Fluvoxamine acid and fluvoxethanol were tested in an in vitro assay of serotonin and norepinephrine reuptake inhibition in rats; they were inactive except for a weak effect of the former metabolite on inhibition of serotonin uptake (1 to 2 orders of magnitude less potent than the parent compound). Approximately 2% of fluvoxamine was excreted in urine unchanged (see 7 DRUG INTERACTIONS ).
Elimination: Following a 14C-labelled oral dose of Luvox (5 mg), an average of 94% of drug-related products was recovered in the urine within 71 hours.
The mean plasma half-life of fluvoxamine at steady state after multiple oral doses of 100 mg/day in healthy, young volunteers was 15.6 hours.
Elderly Subjects: In a study of Luvox at 50 mg and 100 mg comparing elderly (ages 66 to 73) and young subjects (ages 19 to 35), mean maximum plasma concentrations in the elderly were 40% higher. The multiple dose elimination half-life of fluvoxamine was 17.4 and 25.9 hours in the elderly compared to 13.6 and 15.6 hours in the young subjects at steady state for 50 mg and 100 mg doses, respectively. In elderly patients, the clearance of fluvoxamine was reduced by about 50% and, therefore, Luvox should be slowly titrated during initiation of therapy (see DOSAGE AND ADMINISTRATION, 2.3 Elderly or Hepatically Impaired Patients ).
Pediatric Subjects: The multiple-dose pharmacokinetics of fluvoxamine were determined in male and female children (ages 6 to 11) and adolescents (ages 12 to 17). Steady-state plasma fluvoxamine concentrations were 2- to 3-fold higher in children than in adolescents. AUC and Cmax in children were 1.5- to 2.7-fold higher than that in adolescents. As in adults, both children and adolescents exhibited nonlinear multiple-dose pharmacokinetics. Female children showed significantly higher AUC (0-12) and Cmax compared to male children and, therefore, lower doses of Luvox may produce therapeutic benefit. No gender differences were observed in adolescents. Steady-state plasma fluvoxamine concentrations were similar in adults and adolescents at a dose of 300 mg/day, indicating that fluvoxamine exposure was similar in these two populations. Dose adjustment in adolescents (up to the adult maximum dose of 300 mg) may be indicated to achieve therapeutic benefit (see DOSAGE AND ADMINISTRATION, 2.2 Pediatric Population (children and adolescents) ).
Hepatic and Renal Disease: A cross study comparison (healthy subjects versus patients with hepatic dysfunction) suggested a 30% decrease in fluvoxamine clearance in association with hepatic dysfunction. The mean minimum plasma concentrations in renally impaired patients (creatinine clearance of 5 to 45 mL/min) after 4 and 6 weeks of treatment (50 mg b.i.d., 26 N=13) were comparable to each other, suggesting no accumulation of fluvoxamine in these patients (see WARNINGS AND PRECAUTIONS, 5.13 Hyponatremia .)
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis: There was no evidence of carcinogenicity in rats treated orally with Luvox for 30 months or hamsters treated orally with Luvox for 20 (females) or 26 (males) months. The daily doses in the high dose groups in these studies were increased over the course of the study from a minimum of 160 mg/kg to a maximum of 240 mg/kg in rats and from a minimum of 135 mg/kg to a maximum of 240 mg/kg in hamsters. The maximum dose of 240 mg/kg is approximately 6 times the maximum human daily dose on a mg/m2 basis.
Mutagenesis: No evidence of genotoxic potential was observed in a mouse micronucleus test, an in vitro chromosome aberration test or the Ames microbial mutagen test with or without metabolic activation.
Impairment of Fertility: In a study in which male and female rats were administered fluvoxamine (60 mg/kg, 120 mg/kg or 240 mg/kg) prior to and during mating and gestation, fertility was impaired at oral doses of 120 mg/kg or greater, as evidenced by increased latency to mating, decreased sperm count, decreased epididymal weight and decreased pregnancy rate. In addition, the numbers of implantations and embryos were decreased at the highest dose. The no effect dose for fertility impairment was 60 mg/kg (approximately 2 times the maximum recommended human dose [MRHD] on a mg/m2 basis).
14 CLINICAL STUDIES
14.1 Adult OCD Studies
The effectiveness of Luvox for the treatment of obsessive compulsive disorder was demonstrated in two 10-week multicenter, parallel group studies of adult outpatients. Patients in these trials were titrated to a total daily Luvox dose of 150 mg/day over the first two weeks of the trial, following which the dose was adjusted within a range of 100 mg/day 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 Luvox 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 provides the outcome classification by treatment group on the Global Improvement item of the Clinical Global Impressions (CGI) scale for both studies combined.
Exploratory analyses for age and gender effects on outcomes did not suggest any differential responsiveness on the basis of age or sex.
14.3 Pediatric OCD Study
The effectiveness of Luvox 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 mg/day 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 Luvox experienced mean reductions of approximately six units on the CY-BOCS total score, compared to a three-unit reduction for placebo patients.
Table 7 provides the outcome classification by treatment group on the Global Improvement item of the Clinical Global Impression (CGI) scale for the pediatric study.
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 CLINICAL PHARMACOLOGY, 12.3 Pharmacokinetics ) 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.
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
Luvox Tablets USP, for oral administration, are available as:
25 mg: Off-white, round, biconvex, film-coated, debossed “E” over “17” on one side and plain on the other side and supplied as:
NDC 0185-0017-30 bottles of 30
NDC 0185-0017-01 bottles of 100
50 mg: Yellow, round, biconvex, film-coated, debossed “E” over “27” on one side and bisected on the other side and supplied as:
NDC 0185-0027-30 bottles of 30
NDC 0185-0027-01 bottles of 100
NDC 0185-0027-05 bottles of 500
100 mg: Beige, round, biconvex, film-coated, debossed “E” over “157” on one side and bisected on the other side and supplied as:
NDC 0185-0157-30 bottles of 30
NDC 0185-0157-01 bottles of 100
NDC 0185-0157-05 bottles of 500
Keep this and all medications out of the reach of children. Luvox tablets USP should be protected from high humidity and stored at 20° to 25°C (68° to 77°F). Dispense in a tight, light-resistant container as defined in the USP with a child-resistant closure, as required.
17 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 Luvox tablets and should counsel them in the appropriate use. A patient Medication Guide about “Antidepressant Medicines, Depression and other Serious Mental Illnesses and Suicidal Thoughts or Actions” is available for Luvox 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 Luvox tablets.
17.1 Clinical Worsening and Suicide Risk
Patients, their families and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, other unusual changes in behavior, worsening of depression and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient’s prescriber or health professional, especially if they are severe, abrupt in onset or were not part of the patient’s presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate the need for very close monitoring and possibly changes in the medication (see BOXED WARNING and WARNINGS AND PRECAUTIONS, 5.1 Clinical Worsening and Suicide Risk ).
17.2 Serotonin Syndrome
Patients should be cautioned about the risk of serotonin syndrome with the concomitant use of fluvoxamine and triptans, tramadol or other serotonergic agents (see WARNINGS AND PRECAUTIONS, 5.3 Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions ).
17.3 Interference with Cognitive or Motor Performance
Since any psychoactive drug may impair judgment, thinking or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are certain that Luvox tablets therapy does not adversely affect their ability to engage in such activities.
Patients should be advised to notify their physicians if they become pregnant or intend to become pregnant during therapy with Luvox tablets.
Patients receiving Luvox tablets should be advised to notify their physicians if they are breast-feeding an infant (see USE IN SPECIFIC POPULATIONS, 8.3 Nursing Mothers ).
17.6 Concomitant Medication
Patients should be advised to notify their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for clinically important interactions with Luvox tablets.
Patients should be cautioned about the concomitant use of fluvoxamine and NSAIDs, aspirin or other drugs that affect coagulation since the combined use of psychotropic drugs that interfere with serotonin reuptake and these agents has been associated with an increased risk of bleeding.
Because of the potential for the increased risk of serious adverse reactions including severe lowering of blood pressure and sedation when fluvoxamine and tizanidine are used together, fluvoxamine should not be used with tizanidine (see WARNINGS AND PRECAUTIONS, 5.5 Potential Tizanidine Interaction ).
Because of the potential for the increased risk of serious adverse reactions when fluvoxamine and alosetron are used together, fluvoxamine should not be used with LotronexTM (alosetron) (see WARNINGS AND PRECAUTIONS, 5.7 Potential Alosetron Interaction ).
As with other psychotropic medications, patients should be advised to avoid alcohol while taking Luvox tablets.
17.8 Allergic Reactions
Patients should be advised to notify their physicians if they develop a rash, hives or a related allergic phenomenon during therapy with Luvox tablets.
LotronexTM is a registered trademark of GlaxoSmithKline.
17.9 FDA–Approved Medication Guide
Fluvoxamine (Flu VOX ah meen) Maleate Tablets
Read the Medication Guide that comes with Luvox Tablets before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. Talk with your healthcare provider if there is something you do not understand or want to learn more about.
What is the most important information I should know about Luvox Tablets?
Fluvoxamine is the same kind of medicine as those used to treat depression and may cause serious side effects, including:
1. Suicidal thoughts or actions:
Keep all follow-up visits with your healthcare provider and call between visits if you are worried about symptoms.
Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency, especially if they are new, worse, or worry you:
Tell your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency. Luvox Tablets may be associated with these serious side effects:
2. Serotonin Syndrome or Neuroleptic Malignant Syndrome-like reactions. This condition can be life-threatening and may include:
3. Severe allergic reactions:
4. Abnormal bleeding: Luvox Tablets and antidepressant medicines may increase your risk of bleeding or bruising, especially if you take the blood thinner warfarin (Coumadin®, Jantoven®), a non-steroidal anti-inflammatory drug (NSAID’s, like ibuprofen, naproxen, or aspirin).
5. Seizures or convulsions
6. Manic episodes:
7. Changes in appetite or weight. Children and adolescents should have height and weight monitored during treatment.
8. Low salt (sodium) levels in the blood. Elderly people may be at greater risk for this. Symptoms may include:
Do not stop Luvox Tablets without first talking to your healthcase provider.
Stopping Luvox Tablets too quickly may cause serious symptoms including:
What is Luvox Tablets?
Luvox Tablets is a prescription medicine used to treat obsessive compulsive disorder (OCD). It is important to talk with your healthcare provider about the risks of treating OCD and also the risks of not treating it. You should discuss all treatment choices with your healthcare provider.
Talk to your healthcare provider if you do not think that your condition is getting better with Luvox Tablets treatment.
Who should not take Luvox Tablets?
Do not take Luvox Tablets if you:
People who take Luvox Tablets close in time to an MAOI may have serious or even life-threatening side effects. Get medical help right away if you have any of these symptoms:
What should I tell my healthcare provider before taking Luvox Tablets? Ask if you are not sure.
Before starting Luvox Tablets, tell your healthcare provider if you:
Tell your healthcare provider about all the medicines that you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Luvox Tablets and some medicines may interact with each other, may not work as well, or may cause serious side effects.
Your healthcare provider or pharmacist can tell you if it is safe to take Luvox Tablets with your other medicines. Do not start or stop any medicine while taking Luvox Tablets without talking to your healthcare provider first.
If you take Luvox Tablets, you should not take any other medicines that contain fluvoxamine including: LUVOX CR ®
How should I take Luvox Tablets?
What should I avoid while taking Luvox Tablets?
Luvox Tablets can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly. You should not drive, operate heavy machinery, or do other dangerous activities until you know how Luvox Tablets affects you. Do not drink alcohol while using Luvox Tablets.
What are the possible side effects of Luvox Tablets?
Luvox Tablets may cause serious side effects, including:
Common possible side effects in people who take Luvox Tablets include:
Other side effects in children and adolescents include:
Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Luvox Tablets. For more information, ask your healthcare provider or pharmacist.
To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
How should I store Luvox Tablets?
Store Luvox Tablets at room temperature between 20° to 25°C (68° to 77°F).
Keep Luvox Tablets and all medicines out of the reach of children.
General information about Luvox Tablets
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Luvox Tablets for a condition for which it was not prescribed. Do not give Luvox Tablets to other people, even if they have the same condition. It may harm them.
This Medication Guide summarizes the most important information about Luvox Tablets. If you would like more information, talk with your healthcare provider. You may ask your healthcare provider or pharmacist for information about Luvox Tablets that is written for healthcare professionals.
For more information about Luvox Tablets call Sandoz Inc. at 1-800-525-8747 or go to www.us.sandoz.com
What are the ingredients in Luvox Tablets?
Active ingredient: Luvox
Inactive ingredients: carnauba wax, corn starch, hypromellose, magnesium stearate, mannitol, methylcellulose, polyethylene glycol, polysorbate, pregelatinized starch, sodium starch glycolate, titanium dioxide and yellow iron oxide.
The 100 mg tablets also contain red iron oxide.
Princeton, NJ 08540
Luvox 50mg Tablet
Luvox pharmaceutical active ingredients containing related brand and generic drugs:
Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.
Luvox available forms, composition, doses:
Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.
Luvox destination | category:
Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.
Luvox Anatomical Therapeutic Chemical codes:
A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.
Luvox pharmaceutical companies:
Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.
Frequently asked QuestionsCan i drive or operate heavy machine after consuming Luvox?
Depending on the reaction of the Luvox after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Luvox not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Luvox addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
Reviewsdrugs.com conducted a study on Luvox, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Luvox consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.
Visitor reported usefulNo survey data has been collected yet
Visitor reported side effectsNo survey data has been collected yet
Visitor reported price estimatesNo survey data has been collected yet
Visitor reported frequency of useNo survey data has been collected yet
Visitor reported dosesNo survey data has been collected yet
Visitor reported time for resultsNo survey data has been collected yet
Visitor reported administrationNo survey data has been collected yet
Visitor reported ageNo survey data has been collected yet
The information was verified by Dr. Arunabha Ray, MD Pharmacology