Fluvoxamine

⚠️ 3. Warnings & Possible Side Effects

conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Most common reactions in controlled trials with OCD patients and patients from another studied population (incidence ≥5% and at least twice that for placebo) were abnormal ejaculation, anorexia, anorgasmia, asthenia, diarrhea, nausea, somnolence, sweating and tremor ( 6.2 ) . The following additional reactions occurred: anxiety, decreased libido, myalgia, pharyngitis, and vomiting in the OCD population; and dyspepsia, dizziness, insomnia, and yawning in another studied population. To report SUSPECTED ADVERSE REACTIONS, contact Ajanta Pharma USA Inc., at 855-664-7744 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Data Sources Fluvoxamine maleate extended-release capsules were studied in one 12-week controlled trial in patients with OCD (N = 124; mean exposure 66.6 days) and in two 12-week controlled trials for another condition (N = 279; mean exposure 59.2 days). Patients in these trials were initiated on 100 mg/day and were titrated in 50 mg increments over the first 6 weeks to within a range of 100 mg/day to 300 mg/day. The reactions listed in Table 2 show reactions from the two populations separately. Table 3 shows reactions from the three controlled studies combined. 6.2 Adverse Reactions Observed in Controlled Trials Adverse Reactions Associated with Discontinuation of Treatment : Of the 124 patients with OCD and 279 patients in other studies treated with fluvoxamine maleate extended-release capsules in controlled clinical trials, 19% and 26% discontinued treatment due to an adverse reaction. The most common reactions (≥1%) associated with discontinuation and considered to be drug related (i.e., those reactions associated with dropout at a rate at least twice that of placebo) were anorexia (including, but not limited to, loss of appetite and decreased appetite) (1%), anxiety (3%), asthenia (3%), diarrhea (2%), dizziness (4%), headache (2%), insomnia (5%), nausea (7%), nervousness (1%), somnolence (5%), and thinking abnormal (1%). Commonly Observed Adverse Reactions: Fluvoxamine maleate extended-release capsules have been studied in one controlled trial in patients with OCD (N = 124) and two controlled trials for another condition (N = 279). In general, adverse reaction rates were similar in the two data sets as well as in a study of pediatric patients with OCD treated with immediate-release fluvoxamine maleate tablets. The most commonly observed treatment-emergent adverse reactions associated with the use of fluvoxamine maleate extended-release capsules and likely to be drug- related (incidence of 5% or greater and at least twice that for placebo) and derived from Table 2 were: abnormal ejaculation, anorexia, anorgasmia, asthenia, diarrhea, nausea, somnolence, sweating, and tremor . In the one controlled trial in patients with OCD, the following additional reactions occurred at an incidence of 5% or greater and at least twice that for placebo: anxiety, decreased libido, myalgia, pharyngitis, and vomiting . The following additional reactions occurred in another studied population: dyspepsia, dizziness, insomnia, and yawning . In a study evaluating immediate-release fluvoxamine maleate tablets in 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 ≥ 2%: Table 2 enumerates adverse reactions that occurred in adults at a frequency of 2% or more, and were more frequent than in the placebo group, among patients treated with fluvoxamine maleate extended-release capsules in two short-term, placebo-controlled trials (12 weeks) in another population and one short-term placebo-controlled OCD trial (12 weeks) and in which patients were dosed once-a-day in a range of 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 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 health care provider with some basis for estimating the relative contribution of drug and non-drug factors to the side-effect incidence rate in the population studied. TABLE 2: TREATMENT-EMERGENT ADVERSE REACTION INCIDENCE RATES BY BODY SYSTEM IN ADULT OCD PATIENTS AND ANOTHER STUDIED POPULATION 1 1 Events for which fluvoxamine maleate incidence was equal to or less than placebo include the following for OCD patients: abdominal pain, flu syndrome, infection, palpitation, flatulence, increased appetite, weight gain, abnormal dreams, amnesia, hypertonia, nervousness, paresthesia, increased cough, dyspnea, rhinitis, and ear pain. In the other studied population the following events were seen: abdominal pain, accidental injury, back pain, flu syndrome, infection, pain, flatulence, pharyngitis, rhinitis, rash, and dysmenorrhea. 2 Term includes body aches/pains, dental pain, pain from surgery, unspecified pain, and general pain secondary to injuries (sprains, fractures). 3 Includes, but is not limited to, loss of appetite and decreased appetite. PERCENTAGE OF PATIENTS REPORTING REACTION OBSESSIVE COMPULSIVE DISORDER OTHER STUDIED POPULATION BODY SYSTEM/ ADVERSE REACTION Fluvoxamine Maleate Extended-Release N = 124 PLACEBO N = 124 Fluvoxamine Maleate Extended-Release N = 279 PLACEBO N = 276 BODY AS A WHOLE Headache 32 31 35 30 Asthenia 26 8 24 10 Pain 2 10 8 – – Abdominal Pain – – 5 4 Accidental Injury 5 3 – – Chest Pain – – 3 1 Viral Infection 2 <1 – – CARDIOVASCULAR Palpitation – – 3 1 Vasodilatation – – 2 <1 Hypertension 2 <1 – – DIGESTIVE SYSTEM Nausea 34 13 39 11 Diarrhea 18 8 14 5 Anorexia 3 13 5 14 1 Dyspepsia 8 5 10 4 Constipation 4 <1 6 5 Vomiting 6 2 – – Tooth Disorder 2 <1 – – Liver Function Test Abnormal – – 2 <1 Gingivitis 2 0 – – HEMIC AND LYMPHATIC Ecchymosis 4 2 – – METABOLIC AND NUTRITIONAL DISORDERS Weight Loss 2 <1 – – MUSCULOSKELETAL Myalgia 5 2 – – NERVOUS SYSTEM Insomnia 35 20 32 13 Somnolence 27 11 26 9 Dizziness 12 10 15 7 Dry Mouth 10 9 11 8 Nervousness – – 10 9 Libido Decreased 6 2 6 4 Male 10 5 8 6 Female 4 1 4 3 Anxiety 6 2 8 5 Tremor 6 0 8 <1 Abnormal Thinking 3 <1 3 2 Abnormal Dreams – – 3 2 Agitation 2 <1 3 <1 Hypertonia – – 2 1 Apathy 3 0 – – Paresthesia – – 3 2 Neurosis 2 <1 – – Twitching 2 0 – – RESPIRATORY SYSTEM Pharyngitis 6 <1 – – Yawn 2 0 5 <1 Laryngitis 3 0 – – Bronchitis – – 2 1 Epistaxis 2 0 – – SKIN Sweating 7 <1 6 2 Acne 2 0 – – SPECIAL SENSES Taste Perversion 2 <1 2 <1 Amblyopia 2 <1 – – UROGENITAL Abnormal Ejaculation 10 0 11 2 Anorgasmia 5 0 5 1 Male 4 0 4 2 Female 5 0 5 0 Menorrhagia 3 0 – – Sexual Function Abnormal 2 <1 3 <1 Male 4 3 2 1 Female 0 0 3 0 Urinary Tract Infection – – 2 <1 Polyuria 2 <1 – – 6.3 Other Adverse Reactions in OCD Pediatric Population In pediatric patients (N=57) treated with immediate-release fluvoxamine maleate tablets, the overall profile of adverse reactions was generally similar to that seen in adult studies, as shown in Table 2. However, the following adverse reactions, not appearing in Table 2, were reported in two or more of the pediatric patients and were more frequent with immediate-release fluvoxamine maleate tablets 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 pharmacologic treatment. In particular, some evidence suggests that selective serotonin reuptake inhibitors (SSRIs) can cause such untoward sexual experiences. Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and health care providers may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling are likely to underestimate their actual incidence. Table 3 displays the incidence of sexual side effects reported by at least 2% of patients taking fluvoxamine maleate extended-release capsules in placebo controlled trials. TABLE 3: PERCENTAGE OF PATIENTS REPORTING SEXUAL ADVERSE REACTIONS IN PLACEBO-CONTROLLED TRIALS Fluvoxamine Maleate Extended-Release N = 403 Placebo N = 400 Abnormal Ejaculation 11 2 Anorgasmia Male 4 1 Female 5 0 Impotence 2 2 Libido Decreased Male 8 5 Female 4 2 Sexual Function Abnormal Male 3 1 Female 2 0 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, health care providers should routinely inquire about such possible side effects. 6.5 Weight and Vital Sign Changes No statistically significant differences in weight gain or loss were found between patients treated with fluvoxamine maleate extended-release capsules or placebo. Comparisons of immediate-release fluvoxamine maleate tablets or fluvoxamine maleate extended-release capsules versus placebo groups in separate short-term 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 measures of vital signs variables revealed no important differences between fluvoxamine maleate and placebo. 6.6 Laboratory Changes Comparisons of immediate-release fluvoxamine maleate tablets or fluvoxamine maleate extended-release capsules versus placebo groups in separate short-term trials on (1) 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 fluvoxamine maleate and placebo. 6.7 ECG Changes Comparisons of immediate-release fluvoxamine maleate tablets or fluvoxamine maleate extended-release capsules 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 fluvoxamine maleate and placebo. 6.8 Other Reactions Observed During the Premarketing Evaluation of Fluvoxamine During premarketing clinical trials conducted in North America and Europe, multiple doses of fluvoxamine maleate extended-release capsules or immediate-release fluvoxamine maleate tablets were administered for a combined total of 3,219 patient exposures in patients suffering OCD or other studied disorders. These exposures include 482 patient exposures with fluvoxamine maleate extended-release capsules and 2,737 patient exposures with immediate-release fluvoxamine maleate tablets. Untoward reactions associated with this exposure were recorded by clinical investigators using descriptive terminology of their own choosing.…