FLUVOXAMINE MALEATE tablet

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

FLUVOXAMINE MALEATE (UNII: 5LGN83G74V) (FLUVOXAMINE - UNII:O4L1XPO44W)

Available from:

Apotex Corp

INN (International Name):

FLUVOXAMINE MALEATE

Composition:

FLUVOXAMINE MALEATE 25 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Fluvoxamine maleate tablets are indicated for the treatment of obsessions and compulsions in patients with obsessive compulsive disorder (OCD), as defined in DSM-III-R or DSM-IV. The obsessions or compulsions cause marked distress, are time-consuming, or significantly interfere with social or occupational functioning. Obsessive compulsive disorder is characterized by recurrent and persistent ideas, thoughts, impulses or images (obsessions) that are ego-dystonic and/or repetitive, purposeful, and intentional behaviors (compulsions) that are recognized by the person as excessive or unreasonable. The efficacy of fluvoxamine maleate tablets was established in four trials in outpatients with OCD: two 10-week trials in adults, one 10-week trial in pediatric patients (ages 8 to 17), and one maintenance trial in adults [see Clinical Studies (14)]. Coadministration Coadministration of tizanidine, thioridazine, alosetron, or pimozide with Fluvoxamine Maleate Tablets is contraindicated [see Warnings and Precautions (5.4, 5.5, 5.6, 5.7)]. Serotonin Syndrome and Monoamine Oxidase Inhibitors (MAOIs)   The use of MAOIs intended to treat psychiatric disorders with Fluvoxamine Maleate Tablets or within 14 days of stopping treatment with Fluvoxamine Maleate Tablets is contraindicated because of an increased risk of serotonin syndrome. The use of Fluvoxamine Maleate Tablets within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration (2.4), Warnings and Precautions (5.2)]. Starting Fluvoxamine Maleate Tablets in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see Dosage and Administration (2.5), Warnings and Precautions (5.2)]. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/.   Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions (5.10) and Clinical Considerations]. Prolonged experience with fluvoxamine in pregnant women over decades, based on published observational studies, have not identified a clear drug-associated risk of major birth defects or miscarriage (see Data). There are risks associated with untreated depression in pregnancy and risks of persistent pulmonary hypertension of the newborn (PPHN) and poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including fluvoxamine, during pregnancy (see Clinical Considerations).   When pregnant rats were treated orally with fluvoxamine throughout the period of organogenesis, increased embryofetal death and increased incidences of fetal eye abnormalities (folded retinas) was observed at doses ≥3 times the maximum recommended human dose (MRHD) of 300 mg/day given to adolescents on a mg/m2 basis. In addition, decreased fetal body weight was seen at a dose 6 times the MRHD given to adolescents on a mg/m2 basis. There were no adverse developmental effects in rabbits treated with fluvoxamine during the period of organogenesis up to a dose 2 times the MRHD given to adolescents on a mg/m2 basis. When fluvoxamine was administered orally to rats during pregnancy and lactation, increased pup mortality at birth was seen at a dose 2 times the MRHD given to adolescents on a mg/m2 basis. In addition, decreases in pup body weight and survival were observed at doses that are ≥0.13 times the MRHD given to adolescents (see Data).   The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.   Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. This finding is from a prospective, longitudinal study that followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum.   Maternal Adverse Reactions Use of Fluvoxamine Maleate Tablets in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions (5.10)] . Fetal/Neonatal adverse reactions Neonates exposed to Fluvoxamine Maleate Tablets and other SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions (5.2)] .   Data Human Data Exposure during late pregnancy to SSRIs may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1 to 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality.   Animal Data When pregnant rats were given oral doses of fluvoxamine (60, 120, or 240 mg/kg) throughout the period of organogenesis, developmental toxicity in the form of increased embryofetal death and increased incidences of fetal eye abnormalities (folded retinas) was observed at doses of 120 mg/kg or greater (3 times the MRHD of 300 mg/day, given to adolescents on a mg/m2 basis). Decreased fetal body weight was seen at the high dose of 240 mg/kg/day (6 times the MRHD given to adolescents on a mg/m2 basis). The no effect dose for developmental toxicity in this study was 60 mg/kg/day (1.6 times the MRHD given to adolescents on a mg/m2 basis).   In a study in which pregnant rabbits were administered doses of up to 40 mg/kg (approximately 2.1 times the MRHD given to adolescents on a mg/m2 basis) during the period of organogenesis, no adverse effects on embryofetal development were observed.   In other reproduction studies in which female rats were dosed orally during pregnancy and lactation (5, 20, 80, or 160 mg/kg), increased pup mortality at birth was seen at doses of 80 mg/kg/day (2 times the MRHD given to adolescents on a mg/m2 basis) or greater and decreases in pup body weight and survival were observed at all doses (low effect dose approximately 0.13 times the MRHD given to adolescents on a mg/m2 basis). Data from published literature report the presence of fluvoxamine is in human milk (see Data). No adverse effects on the breastfed infant have been reported in most cases of maternal use of fluvoxamine during breastfeeding. However, there are reports of diarrhea, vomiting, decreased sleep, and agitation (see Clinical Considerations). There are no data on the effect of fluvoxamine on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for fluvoxamine and any potential adverse effects on the breastfed child from fluvoxamine or from the underlying maternal condition.   Clinical Considerations Monitor infants exposed to fluvoxamine through breast milk for diarrhea, vomiting, decreased sleep, and agitation.   Data Milk drug concentrations ≤ 425 ng/mL were observed following maternal dosing of fluvoxamine 25 mg/day to 300 mg/day in published case reports and case series. Infertility Animal findings suggest fertility may be impaired while taking fluvoxamine [see Nonclinical Toxicology (13.1)]. The efficacy of 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 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 Adverse Reactions (6.3), Dosage and Administration (2.2)]. 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)].   Safety and effectiveness in the pediatric population other than pediatric patients with OCD have not been established [see Boxed Warning; Warnings and Precautions (5.1)] . Anyone considering the use of fluvoxamine maleate tablets in a child or adolescent must balance the potential risks with the clinical need. Approximately 230 patients participating in controlled premarketing studies with fluvoxamine maleate tablets 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 fluvoxamine maleate tablets, 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)] . Furthermore, the clearance of fluvoxamine is decreased by about 50% in elderly compared to younger patients [see Clinical Pharmacology (12.3)], and greater sensitivity of some older individuals also cannot be ruled out. Consequently, a lower starting dose should be considered in elderly patients and fluvoxamine maleate tablets should be slowly titrated during initiation of therapy. Fluvoxamine maleate tablets are not a controlled substance. The potential for abuse, tolerance and physical dependence with fluvoxamine maleate has been studied in a nonhuman primate model. No evidence of dependency phenomena was found. The discontinuation effects of fluvoxamine maleate tablets were not systematically evaluated in controlled clinical trials. Fluvoxamine maleate tablets were 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 fluvoxamine maleate. Generally, it is not possible to predict on the basis of preclinical or premarketing 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 fluvoxamine maleate misuse or abuse (i.e., development of tolerance, incrementation of dose, drug-seeking behavior).

Product summary:

Fluvoxamine maleate tablets, USP are available in the following strengths, colors, imprints, and presentations:   Tablets 25 mg: White to off-white, round, unscored, film coated tablets, engraved “APO” on one side and “F25” on the other side. Bottles of 100...........................................................................NDC 60505-0164-1 Tablets 50 mg: Golden, round, scored, film coated tablets, engraved “APO” on one side and “F50” with a partial bisect on the other side. Bottles of 100...........................................................................NDC 60505-0165-1   Tablets 100 mg: Reddish-brown, pillow shaped, scored, film coated tablets, engraved “APO” on one side and “FLU” bisect “100” on the other side. Bottles of 100...........................................................................NDC 60505-0166-1 Keep out of reach of children.   Fluvoxamine maleate tablets, USP should be protected from high humidity and stored at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].   Dispense in a tight, light-resistant container.

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

FLUVOXAMINE MALEATE- FLUVOXAMINE MALEATE TABLET
Apotex Corp
----------
MEDICATION GUIDE
Fluvoxamine (Flu VOX ah meen) Maleate Tablets, USP
Medication Guide available at
https://www.apotex.com/products/us/mg.asp
Read the Medication Guide that comes with fluvoxamine maleate 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 fluvoxamine
maleate 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:
•
Fluvoxamine maleate tablets and antidepressant medicines may increase
suicidal thoughts or
actions in some children, teenagers, or young adults within the first
few months of treatment or
when the dose is changed.
•
Depression or other serious mental illnesses are the most important
causes of suicidal thoughts or
actions.
•
Watch for these changes and call your healthcare provider right away
if you notice:
•
New or sudden changes in mood, behavior, actions, thoughts, or
feelings, especially if severe.
•
Pay particular attention to such changes when fluvoxamine maleate
tablets is started or when the
dose is changed.
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:
•
attempts to commit suicide
•
acting on dangerous impulses
•
acting aggressive or violent
•
thoughts about suicide or dying
•
new or worse depression
•
new or worse anxiety or panic attacks
•
feeling agitated, restless, angry or irritable
•
trouble sleeping
•
an incre

Summary of Product characteristics

FLUVOXAMINE MALEATE- FLUVOXAMINE MALEATE TABLET
APOTEX CORP
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
FLUVOXAMINE MALEATE
TABLETS SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
FLUVOXAMINE MALEATE
TABLETS.
FLUVOXAMINE MALEATE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 1994
WARNING: SUICIDALITY AND ANTIDEPRESSANTS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
INCREASED RISK OF SUICIDAL THINKING AND BEHAVIOR IN CHILDREN,
ADOLESCENTS, AND YOUNG
ADULTS TAKING ANTIDEPRESSANTS FOR MAJOR DEPRESSIVE DISORDER AND OTHER
PSYCHIATRIC
DISORDERS. FLUVOXAMINE MALEATE TABLETS ARE NOT APPROVED FOR USE IN
PEDIATRIC PATIENTS
EXCEPT THOSE WITH OBSESSIVE COMPULSIVE DISORDER (5.1).
RECENT MAJOR CHANGES
Warnings and Precautions (5.2, 5.10) 8/2023
INDICATIONS AND USAGE
Fluvoxamine maleate tablets are indicated for the treatment of
obsessions and compulsions in patients
with obsessive compulsive disorder (OCD) (1).
DOSAGE AND ADMINISTRATION
Adults: Recommended starting dose is 50 mg at bedtime, with increases
of 50 mg every 4 to 7 days as
tolerated to maximum effect, not to exceed 300 mg/day. Daily doses
over 100 mg should be divided
(2.1).
Children and adolescents (8 to 17 years): Recommended starting dose is
25 mg at bedtime, with
increases of 25 mg every 4 to 7 days as tolerated to maximum effect,
not to exceed 200 mg/day (8 to
11 years) or 300 mg/day (12 to 17 years). Daily doses over 50 mg
should be divided (2.2).
Hepatically impaired: Decreased clearance may require modified dose
and titration (2.3).
Extended treatment: Adjust dose to maintain lowest effective dose;
reassess patients periodically (2.6).
Discontinuation: Gradual dose reduction is recommended (2.7, 5.9).
DOSAGE FORMS AND STRENGTHS
25 mg tablets, 50 mg tablets, and 100 mg tablets (3)
CONTRAINDICATIONS
Coadministration of tizanidine, thioridazine, alosetron, pimozide (4)
SEROTONIN SYNDROME AND MAOIS: Do not use MAOIs intended to treat
psychiatric disorders with
flu