Fluvoxamine Maleate (Page 5 of 12)

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 manifestations of a psychiatric disorder and with aging, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that selective serotonin reuptake inhibitors (SSRIs) can cause such untoward sexual experiences.

Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and 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	Placebo
	N = 403	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 3219 patient exposures in patients suffering OCD or other studied disorders. These exposures include 482 patient exposures with fluvoxamine maleate extended-release capsules and 2737 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. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse reactions without first grouping similar types of untoward reactions into a limited (i.e., reduced) number of standard reaction categories.

In the tabulations that follow, a 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 when possible. The frequencies presented, therefore, represent the proportion of the total patient exposures to multiple doses of fluvoxamine maleate who experienced a reaction of the type cited on at least one occasion while receiving fluvoxamine maleate. 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. It is important to emphasize that, although the events reported did occur during treatment with fluvoxamine maleate, a causal relationship to fluvoxamine maleate has not been established.

For fluvoxamine maleate extended-release capsules, all reported events are included in the list below, with the following exclusions: 1) those events already listed in Table 2 or previous sections of this prescribing information; 2) those events for which there is no basis to suspect a causal relationship; and 3) events that were reported in only one patient and judged not to be potentially serious.

Body as a Whole: Infrequent: chills, malaise, photosensitivity reaction, suicide attempt.

Cardiovascular System: Infrequent: syncope.

Digestive System: Infrequent: eructation, increased salivation.

Metabolic and Nutritional Disorders: Frequent: weight gain.

Nervous System: Infrequent: confusion, incoordination, sleep disorder, suicidal tendency.

Skin and Appendages: Infrequent: eczema, urticaria.

Special Senses: Infrequent: dry eyes, photophobia, taste loss.

Urogenital System: Infrequent: vaginal hemorrhage¹.

¹ Based on the number of females.

For immediate-release fluvoxamine tablets, all reported events are included in the list below, with the following exclusions: 1) those events already listed in Table 2, in previous sections of this prescribing information, or in the fluvoxamine maleate extended-release capsules list of Other Reactions Observed During Premarketing Evaluation; 2) those events for which there is no basis to suspect a causal relationship; and 3) events that were reported in only one patient and judged not to be potentially serious.

Body as a Whole: Infrequent: allergic reaction, neck pain, neck rigidity, overdose; Rare: sudden death.

Cardiovascular System: Frequent: hypotension; Infrequent: angina pectoris, bradycardia, cardiomyopathy, cardiovascular disease, cold extremities, conduction delay, myocardial infarction, pallor, pulse irregular, ST segment changes; Rare: AV block, cerebrovascular accident, embolus, pericarditis, phlebitis, pulmonary infarction, supraventricular extrasystoles.

Digestive System: Frequent: elevated liver transaminases; Infrequent: colitis, esophagitis, gastritis, gastroenteritis, gastrointestinal hemorrhage, gastrointestinal ulcer, glossitis, hemorrhoids, melena, rectal hemorrhage, stomatitis; Rare: biliary pain, cholecystitis, cholelithiasis, fecal incontinence, hematemesis, intestinal obstruction, jaundice.

Endocrine System: Infrequent: hypothyroidism; Rare: goiter.

Hemic and Lymphatic Systems: Infrequent: leukocytosis, lymphadenopathy, thrombocytopenia; Rare: leukopenia, purpura.

Metabolic and Nutritional Systems: Frequent: edema; Infrequent: dehydration, hypercholesterolemia; Rare: diabetes mellitus, hyperglycemia, hyperlipidemia, hypoglycemia, hypokalemia, lactate dehydrogenase increased.

Musculoskeletal System: Infrequent: arthralgia, arthritis, bursitis, generalized muscle spasm, myasthenia; Rare: myopathy.

Nervous System: Frequent: amnesia, apathy, hyperkinesia, hypokinesia, manic reaction, myoclonus, psychotic reaction; Infrequent: agoraphobia, akathisia, ataxia, CNS depression, convulsion, delirium, delusion, depersonalization, dyskinesia, dystonia, emotional lability, euphoria, extrapyramidal syndrome, gait unsteady, hallucinations, hemiplegia, hostility, hypersomnia, hypochondriasis, hypotonia, hysteria, increased libido, paralysis, paranoid reaction, phobia, psychosis, stupor, twitching, vertigo; Rare: akinesia, coma, fibrillations, mutism, obsessions, reflexes decreased, slurred speech, tardive dyskinesia, torticollis, trismus, withdrawal syndrome.

Respiratory System: Frequent: cough increased, sinusitis; Infrequent: asthma, bronchitis, hoarseness, hyperventilation; Rare: apnea, congestion of upper airway, hemoptysis, hiccups, laryngismus, obstructive pulmonary disease, pneumonia.

Skin: Infrequent: alopecia, dry skin, exfoliative dermatitis, furunculosis, seborrhea, skin discoloration.

Special Senses: Infrequent: accommodation abnormal, conjunctivitis, diplopia, eye pain, mydriasis, otitis media, parosmia, visual field defect; Rare: corneal ulcer.

Urogenital System: Infrequent: anuria, cystitis, delayed menstruation¹ , dysuria, female lactation¹ , hematuria, menopause¹ , metrorrhagia¹ , nocturia, premenstrual syndrome¹ , urination impaired, vaginitis¹ ; Rare: kidney calculus, hematospermia² , oliguria.

¹ Based on the number of females.

² Based on the number of males.