Fluvoxamine Maleate (Page 4 of 12)

5.10 Discontinuation of Treatment with Fluvoxamine Maleate Extended-Release Capsules

During marketing of immediate-release fluvoxamine maleate tablets and other SSRIs and SNRIs (serotonin and norepinephrine reuptake inhibitors), there have been spontaneous reports of adverse reactions 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 reactions are generally self-limiting, there have been reports of serious discontinuation symptoms.

Patients should be monitored for these symptoms when discontinuing treatment with fluvoxamine maleate extended-release capsules. 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 health care provider may continue decreasing the dose but at a more gradual rate (see Dosage and Administration [2.7]).

5.11 Abnormal Bleeding

SSRIs and SNRIs, including fluvoxamine maleate extended-release capsules, 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 (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to SSRIs and SNRIs use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages.

Patients should be cautioned about the risk of bleeding associated with the concomitant use of fluvoxamine maleate extended-release capsules and NSAIDs, aspirin, or other drugs that affect coagulation (see Warnings and Precautions [5.9]).

5.12 Activation of Mania/Hypomania

During premarketing studies of immediate-release fluvoxamine maleate tablets involving primarily depressed patients, hypomania or mania occurred in approximately 1% of patients treated with fluvoxamine. In a 10-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, fluvoxamine maleate extended-release capsules should be used cautiously in patients with a history of mania.

5.13 Seizures

During premarketing studies with immediate-release fluvoxamine maleate tablets, 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.

5.14 Hyponatremia

Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including fluvoxamine maleate extended-release capsules. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Cases with serum sodium lower than 110 mmol/L have been reported. Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs (see Use in Specific Populations, Geriatric Use [8.5]). Also, patients taking diuretics or who are otherwise volume depleted may be at greater risk. Discontinuation of fluvoxamine maleate extended-release capsules 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.

5.15 Use in Patients with Concomitant Illness

Closely monitored clinical experience with fluvoxamine maleate extended-release capsules in patients with concomitant systemic illness is limited. Caution is advised in administering fluvoxamine maleate extended-release capsules to patients with diseases or conditions that could affect hemodynamic responses or metabolism.

Fluvoxamine maleate extended-release capsules or immediate-release fluvoxamine maleate tablets have not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were systematically excluded from many clinical studies during premarketing testing of these products. Evaluation of the electrocardiograms for patients with depression or OCD who participated in premarketing studies revealed no differences between fluvoxamine and placebo in the emergence of clinically important ECG changes.

Patients with Hepatic Impairment — In patients with liver dysfunction, following administration of immediate-release fluvoxamine maleate tablets, fluvoxamine clearance was decreased by approximately 30%. Patients with liver dysfunction should begin with a low dose of fluvoxamine maleate extended-release capsules and increase it slowly with careful monitoring.

5.16 Laboratory Tests

There are no specific laboratory tests recommended.


Because clinical trials are conducted under widely varying 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.

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 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 (greater than or equal to 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 Greater Than or Equal To 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 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 Population1
ADVERSE REACTION N = 124 N = 124 N = 279 N = 276
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.
Headache 32 31 35 30
Asthenia 26 8 24 10
Pain2 10 8
Abdominal Pain 5 4
Accidental Injury 5 3
Chest Pain 3 1
Viral Infection 2 <1
Palpitation 3 1
Vasodilatation 2 <1
Hypertension 2 <1
Nausea 34 13 39 11
Diarrhea 18 8 14 5
Anorexia3 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
Ecchymosis 4 2
Weight Loss 2 <1
Myalgia 5 2
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
Pharyngitis 6 <1
Yawn 2 0 5 <1
Laryngitis 3 0
Bronchitis 2 1
Epistaxis 2 0
Sweating 7 <1 6 2
Acne 2 0
Taste Perversion 2 <1 2 <1
Amblyopia 2 <1
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

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2023. All Rights Reserved.