FETZIMA SIDE EFFECTS
- Generic Name: levomilnacipran) extended-release capsules
- Brand Name: Fetzima
SIDE 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
- Abnormal Bleeding
- Angle Closure Glaucoma
- Urinary Hesitation or Retention
- Activation of Mania/Hypomania
- Seizure
- Discontinuation Syndrome
- Hyponatremia
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 Exposure
The safety of FETZIMA was evaluated in 2,673 patients (18-78 years of age) diagnosed with MDD who participated in clinical studies, representing 942 patient-years of exposure. Among the 2,673 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 2,673 patients exposed to at least one dose of FETZIMA, 737 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.
Adverse Reactions 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. 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 Adverse Reactions In Placebo-Controlled MDD Studies
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, constipation, hyperhidrosis, heart rate increased, erectile dysfunction, tachycardia, vomiting, and palpitations.
Table 1 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 1: Adverse Reactions Occurring in ≥ 2% of FETZIMA-treated Patients and at Least Twice the rate of Placebo-treated Patients
| System Organ Class Preferred Term |
Placebo (N =1040) % |
FETZIMA 40-120 mg/d (N = 1583) % |
| Gastrointestinal disorders | ||
| Nausea | 6 | 17 |
| Constipation | 3 | 9 |
| Vomiting | 1 | 5 |
| Cardiac disorders | ||
| Tachycardiaa | 2 | 6 |
| Palpitations | 1 | 5 |
| Reproductive system and breast disordersb | ||
| Erectile dysfunctionc | 1 | 6 |
| Testicular paind | <1 | 4 |
| Ejaculation disordere | <1 | 5 |
| Investigations | ||
| Heart rate increasedf | 1 | 6 |
| Blood pressure increasedg | 1 | 3 |
| Renal and urinary disorders | ||
| Urinary hesitation | 0 | 4 |
| Skin and subcutaneous tissue disorders | ||
| Hyperhidrosis | 2 | 9 |
| Rashh | 0 | 2 |
| Vascular disorders | ||
| Hot flush | 1 | 3 |
| Hypotensioni | 1 | 3 |
| Hypertensionj | 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 |
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Dose-Related Adverse Reactions
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 40-120 mg once daily, with the exception of erectile dysfunction and urinary hesitation (see Table 2).
Table 2: Dose-Related Adverse Reactions
| System Organ Class Preferred Term |
Placebo (N = 362) % |
FETZIMA | ||
| 40 mg/d (N = 366) % |
80 mg/d (N = 367) % |
120 mg/d (N = 180) % |
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| Urinary hesitation | 0 | 4 | 5 | 6 |
| Erectile dysfunctiona | 2 | 6 | 8 | 10 |
| a Percentage is relative to the number of male patients. N = number of patients in the Safety Population |
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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
Postmarketing Experience
Besides these reactions reported under treatment with FETZIMA, other potentially severe adverse events have been reported from the post-marketing experience with milnacipran. Since levomilnacipran is the principal pharmacologically active component of milnacipran, one should take into account the fact that the following adverse event could also potentially occur under treatment with FETZIMA.
This adverse reaction includes: Takotsubo cardiomyopathy.
SRC: NLM .