1 Adverse Reaction Overview The safety of FETZIMA was evaluated in 3317 patients (18-78 years of age) diagnosed with MDD who participated in clinical studies. Among the 3317 FETZIMA-treated patients, 1,583 were exposed to FETZIMA in short-term, placebo-controlled studies.
A total of 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 40-120 mg once daily and was given without regard to food. The most commonly observed adverse events in FETZIMA-treated MDD patients in placebo-controlled studies (incidence ≥ 5% and at least twice the rate of placebo) were: nausea, heart rate increased, erectile dysfunction, hyperhidrosis, constipation, tachycardia, vomiting, and palpitations.
Adverse Events Reported as Reasons for Discontinuation of Treatment In the short-term placebo-controlled pre-marketing studies for MDD, 9% of the 1,583 patients who received FETZIMA (40-120 mg) discontinued treatment due to an adverse event, compared with 3% of the 1,040 placebo-treated patients in those studies.
5%). Blood Pressure and Heart Rate In placebo-controlled clinical studies for change from baseline to endpoint, FETZIMA treatment was associated with mean increases in blood pressure and heart rate. See Cardiovascular. The most commonly reported cardiovascular adverse events among FETZIMA-treated patients in the short-term clinical studies included heart rate increased, tachycardia, palpitations, hypertension, hypotension, and blood pressure increased (see Table 3).
2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. FETZIMA (levomilnacipran) Page 18 of 44 Table 3 shows the incidence of adverse events that occurred in ≥ 2% of FETZIMA-treated MDD patients (and greater than placebo-treated patients) in the short-term, placebo-controlled studies.
Table 3 - Adverse Events Occurring in ≥ 2% of FETZIMA-Treated Patients and Greater than Placebo Treated Patients in Five, Short-term, Phase 3 Placebo-Controlled Studies FETZIMA 40-120 mg/day N = 1583 (%) Placebo N =1040 (%) Gastrointestinal disorders Nausea Dry mouth Constipation Vomiting Abdominal Pain 17 10 9 5 5 6 7 3 1 3 Nervous system disorders Headachea Dizziness 17 8 14 5 Skin and subcutaneous tissue disorders Hyperhidrosis Rash 9 2 2 <1 Cardiac disorders Tachycardiaa Palpitations 6 5 2 1 Reproductive system and breast disordersb Erectile dysfunctionb Testicular painb Ejaculation disorderb 6 4 5 1 <1 <1 Investigations Heart rate increaseda Blood pressure increaseda 6 3 1 1 FETZIMA (levomilnacipran) Page 19 of 44 FETZIMA 40-120 mg/day N = 1583 (%) Placebo N =1040 (%) Psychiatric disorders Insomniaa Anxiety 6 2 4 1 Infections and infestations Upper respiratory tract infectiona Nasopharyngitis 5 4 4 3 Renal and urinary disorders Urinary hesitation 4 0 Vascular disorders Hot flush Hypertensiona Hypotension 3 3 3 1 1 1 Metabolism and nutrition disorders Decreased appetite 3 1 a Similar adverse event terms were grouped together b Percentage is relative to the number of patients in the associated demographic sex category.
N = number of patients in the Safety Population Dose-Related Adverse Events In pooled data from the short-term placebo-controlled fixed-dose studies, there were no dose-related adverse events (greater than 2% overall incidence) in patients treated with FETZIMA across the dose range 40-120 mg/day, with the exception of erectile dysfunction and urinary hesitation (see Table 4).
Table 4 - Dose-Related Adverse Events in Two Fixed-Dose, Phase 3, Placebo-Controlled Studies FETZIMA Placebo N = 362 (%) 40 mg/day N = 366 (%) 80 mg/day N = 367 (%) 120 mg/day N = 180 (%) Urinary hesitation 4 5 6 0 Erectile dysfunctiona 6 8 10 2 a Percentage is relative to the number of patients in the associated demographic sex category.
N = number of patients in the Safety Population FETZIMA (levomilnacipran) Page 20 of 44 Sexual Function While sexual dysfunction is often part of depression and other psychiatric disorders, there is increasing evidence that treatment with selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine-reuptake inhibitors (SNRIs) may induce sexual side effects.
This is a difficult area to study because patients may not spontaneously report symptoms of this nature. Table 5 shows the incidence of adverse events associated with sexual dysfunction in FETZIMA-treated patients in placebo controlled short-term studies.
1 Clinical Trial Adverse Reactions – Pediatrics Pediatrics (<18 years): Based on the data submitted and reviewed by Health Canada, the safety and efficacy of FETZIMA in pediatric patients has not been established; therefore Health Canada has not authorized an indication for pediatric use.
Two adequate and well-controlled 8-week studies were conducted in pediatric MDD patients, one in patients 7 to 17 years and the […]