Levomilnacipranside effects

The following adverse reactions are discussed in greater detail in other sections of the label. Hypersensitivity Suicidal Thoughts and Behaviors in Adolescents and Young Adults Serotonin Syndrome Elevated Blood Pressure Elevated Heart Rate Increased Risk of Bleeding Angle Closure Glaucoma Urinary Hesitation or Retention Activation of Mania/Hypomania Seizure Discontinuation Syndrome Hyponatremia Sexual Dysfunction The most common adverse reactions (incidence ≥ 5% and at least twice the rate of placebo) are: nausea, constipation, hyperhidrosis, heart rate increase, erectile dysfunction, ejaculation disorder, tachycardia, vomiting, and palpitations. To report SUSPECTED ADVERSE REACTIONS, contact AbbVie at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Studies Experience 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 studies of another drug and may not reflect the rates observed in clinical practice. Patient e xposure The safety of FETZIMA was evaluated in 3,317 patients (18 to 78 years of age) diagnosed with MDD who participated in clinical studies, representing 1,186 patient-years of exposure. Among the 3,317 FETZIMA-treated patients, 1,583 were exposed to FETZIMA in short-term, placebo-controlled studies. There were 825 patients who continued from short-term studies into a one-year, open-label extension study. Of the 3,317 patients exposed to at least one dose of FETZIMA, 895 patients were exposed to FETZIMA for at least 6 months and 367 were exposed for one year. In these studies, FETZIMA was given at doses ranging from 40 mg to 120 mg once daily and was given without regard to food. Adverse r eacti ons r eported as r easons for discontinuation of t reatment In the short-term placebo-controlled pre-marketing studies for MDD, 9% of the 1,583 patients who received FETZIMA (40 mg to 120 mg) discontinued treatment due to an adverse reaction, compared with 3% of the 1,040 placebo-treated patients in those studies. The most common adverse reaction leading to discontinuation in at least 1% of the FETZIMA-treated patients in the short-term placebo-controlled studies was nausea (1.5%). Common a dverse r eactions in p lacebo- c ontrolled MDD s tudies The most commonly observed adverse reactions in FETZIMA-treated MDD patients in placebo-controlled studies (incidence ≥ 5% and at least twice the rate of placebo) were: nausea, constipation, hyperhidrosis, heart rate increased, erectile dysfunction, ejaculation disorder, tachycardia, vomiting, and palpitations. Table 3 shows the incidence of adverse reactions that occurred in ≥ 2% of FETZIMA-treated MDD patients and at least twice the rate of placebo in the placebo-controlled studies. Table 3 Adverse Reactions Occurring in ≥ 2% of FETZIMA-treated Patients and at Least Twice the rate of Placebo-treated Patients in Pooled MDD Studies System Organ Class Preferred Term Placebo (N =1040) % FETZIMA 40 mg to 120 mg per day (N = 1583) % Gastrointestinal disorders Nausea 6 17 Constipation 3 9 Vomiting 1 5 Cardiac disorders Tachycardia a 2 6 Palpitations 1 5 Reproductive system and breast disorders b Erectile dysfunction c 1 6 Testicular pain d <1 4 Ejaculation disorder e <1 5 Investigations Heart rate increased f 1 6 Blood pressure increased g 1 3 Renal and urinary disorders Urinary hesitation 0 4 Skin and s ubcutaneous t issue d isorders Hyperhidrosis 2 9 Rash h 0 2 Vascular disorders Hot flush 1 3 Hypotension i 1 3 Hypertension j 1 3 Metabolism and nutrition disorders Decreased appetite 1 3 a Tachycardia also includes: sinus tachycardia and postural orthostatic tachycardia syndrome b Percentage is relative to the number of patients in the associated demographic sex category. Fewer than 2% of FETZIMA-treated MDD female patients in placebo-controlled clinical studies reported adverse events related to sexual function. c Erectile dysfunction includes: erectile dysfunction, organic erectile dysfunction, and psychogenic erectile dysfunction d Testicular pain includes: testicular pain, epididymitis, and seminal vesiculitis e Ejaculation disorder includes: ejaculation disorder, ejaculation delayed, ejaculation failure, and premature ejaculation f Heart rate increased also includes: orthostatic heart rate response increased g Blood pressure increased also includes: blood pressure systolic increased, blood pressure diastolic increased, and blood pressure orthostatic increased h Rash also includes: rash generalized, rash maculo-papular, rash erythematous, and rash macular i Hypotension also includes: orthostatic hypotension and dizziness postural j Hypertension also includes: labile hypertension N = number of patients in the Safety Population Dose- r elated a dverse r eactions In pooled data from the short-term placebo-controlled fixed-dose studies, there were no dose-related adverse reactions (greater than 2% overall incidence) in patients treated with FETZIMA across the dose range 40 mg to 120 mg once daily, with the exception of erectile dysfunction and urinary hesitation (see Table 4). Table 4 Dose-Related Adverse Reactions System Organ Class Preferred Term Placebo (N = 362) % FETZIMA 40 mg per day (N = 366) % 80 mg per day (N = 367) % 120 mg per day (N = 180) % Urinary hesitation 0 4 5 6 Erectile dysfunction a 2 6 8 10 a Percentage is relative to the number of male patients. N = number of patients in the Safety Population Other adverse reactions observed in clinical studies Other infrequent adverse reactions, not described elsewhere in the label, occurring at an incidence of < 2% in MDD patients treated with FETZIMA were: Cardiac disorders: Angina pectoris; Supraventricular and Ventricular extrasystoles Eye disorders: Dry eye; Vision blurred;

Conjunctival hemorrhage General disorders: Chest pain;

Thirst Gastrointestinal disorders: Abdominal pain;

Flatulence Investigations disorders: Blood cholesterol increased; Liver function test abnormal Nervous System disorders: Migraine; Paraesthesia; Syncope;

Extrapyramidal disorder Psychiatric disorders: Agitation; Anger; Bruxism; Panic attack; Tension; Aggression Renal and Urinary disorder: Pollakiuria; Hematuria; Proteinuria Respiratory, thoracic and mediastinal disorders: Yawning Skin and subcutaneous tissue disorders: Dry skin; Pruritus; Urticaria

6.2 Post m arketing

Experience The following adverse reaction has been identified during post-approval use of FETZIMA or other selective serotonin and norepinephrine reuptake inhibitors. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiac disorders: Takotsubo cardiomyopathy Respiratory, thoracic and mediastinal disorders: Anosmia, Hyposmia