FETZIMA® (levomilnacipran) extended-release capsules are indicated for the treatment of Major Depressive Disorder (MDD) in adults.
FETZIMA is not approved for the management of fibromyalgia, and its efficacy and safety have not been
established for that use.
IMPORTANT SAFETY INFORMATION
WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult
patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical
worsening and for emergence of suicidal thoughts and behaviors.
FETZIMA is not approved for use in pediatric patients.
FETZIMA is contraindicated in patients with a hypersensitivity to levomilnacipran, milnacipran HCl, or to
any excipient in the formulation.
The use of monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders with FETZIMA
or within 7 days of stopping treatment with FETZIMA is contraindicated due to an increased risk of
serotonin syndrome. The use of FETZIMA within 14 days of stopping an MAOI intended to treat
psychiatric disorders is also contraindicated.
Starting FETZIMA in a patient who is being treated with MAOIs, such as linezolid or intravenous
methylene blue, is also contraindicated due to an increased risk of serotonin syndrome.
Warnings and Precautions
Suicidal Thoughts and Behavior in Adolescents and Young Adults: Monitor all antidepressant-treated
patients for any indication of clinical worsening and emergence of suicidal thoughts and
behaviors, especially during the initial few months of drug therapy and at times of dosage changes.
Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the
healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing
FETZIMA, in patients whose depression is persistently worse or who are experiencing emergent
suicidal thoughts or behaviors.
Serotonin Syndrome: selective-serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine
reuptake inhibitors (SNRIs), including FETZIMA, can precipitate serotonin syndrome, a potentially life-threatening
condition. The risk is increased with concomitant use of other serotonergic drugs (including
triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines,
and St. John’s Wort) and with drugs that impair metabolism of serotonin, ie, MAOIs. Symptoms of
serotonin syndrome may include mental status changes (eg, agitation, hallucinations, delirium, and
coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing,
hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination),
seizures, and/or gastrointestinal symptoms. If symptoms of serotonin syndrome occur, discontinue
FETZIMA immediately and initiate supportive treatment. If concomitant use of FETZIMA with other
serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome
and monitor for symptoms.
Elevated Blood Pressure: SNRIs, including FETZIMA, have been associated with increases in blood
pressure. Blood pressure should be measured prior to initiating treatment and periodically throughout
FETZIMA treatment. Preexisting hypertension should be controlled before initiating treatment with
FETZIMA. Use with caution in patients with preexisting hypertension or cardiovascular or
cerebrovascular conditions that might be compromised by increases in blood pressure. Concomitant
use of FETZIMA with drugs that increase blood pressure and heart rate has not been evaluated and
such combinations should be used with caution. For patients who experience a sustained increase in
blood pressure, discontinuation or other appropriate medical intervention should be considered.
Elevated Heart Rate: SNRIs, including FETZIMA, have been associated with an increase in heart rate.
Heart rate should be measured prior to initiating treatment and periodically throughout FETZIMA
treatment. Preexisting tachyarrhythmias and other cardiac disease should be treated before starting
therapy with FETZIMA. For patients who experience a sustained increase in heart rate, discontinuation
or other appropriate medical intervention should be considered.
Increased Risk of Bleeding: Drugs that interfere with serotonin reuptake inhibition, including
FETZIMA, may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory
drugs (NSAIDs), warfarin, and other anticoagulants may add to this risk.
Angle-closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated
anatomically narrow angles treated with antidepressants. The pupillary dilation that occurs following
use of many antidepressant drugs, including FETZIMA, may trigger an angle closure attack in a patient
with anatomically narrow angles who does not have a patent iridectomy.
Urinary Hesitation or Retention: FETZIMA can affect urethral resistance. In clinical studies, urinary
hesitation occurred in 4%, 5%, and 6% of FETZIMA-treated patients receiving doses of 40, 80, and 120
mg, respectively, compared to no patients in the placebo group. Caution is advised when using
FETZIMA in patients prone to obstructive urinary disorders.
Activation of Mania/Hypomania: Symptoms of mania/hypomania were reported in 0.2% of FETZIMA-treated
patients and 0.2% of placebo-treated patients in clinical studies. As with all antidepressants,
FETZIMA should be used cautiously in patients with a history or family history of bipolar disorder,
mania, or hypomania. Prior to initiating treatment with FETZIMA, patients should be adequately
screened to determine if they are at risk for bipolar disorder.
FETZIMA is not approved for use in treating bipolar depression.
- Seizures: FETZIMA should be prescribed with caution in patients with a seizure disorder.
Discontinuation Syndrome: Discontinuation symptoms, some serious, have been reported with
discontinuation of serotonergic antidepressants such as FETZIMA. Gradual dose reduction is
recommended, instead of abrupt discontinuation, whenever possible. Monitor patients when
discontinuing FETZIMA. If intolerable symptoms occur following a dose decrease or upon
discontinuation of treatment, consider resuming the previously prescribed dose and decreasing the
dose at a more gradual rate.
Hyponatremia: Advise patients that if they are treated with diuretics or are otherwise volume depleted,
or are elderly, they may be at greater risk of developing hyponatremia while taking FETZIMA. Although
no adverse events of hyponatremia resulting from FETZIMA treatment were reported in the clinical
studies, hyponatremia has occurred as a result of treatment with SSRIs and SNRIs. FETZIMA should
be discontinued in patients with symptomatic hyponatremia and appropriate medical intervention should
Sexual Dysfunction: FETZIMA may cause symptoms of sexual dysfunction. Discuss potential
management strategies to support patients in making informed decisions about treatment.
Concomitant use of FETZIMA with strong CYP3A4 inhibitors increases levomilnacipran exposure. The
dose of FETZIMA should not exceed 80 mg once daily when used with strong CYP3A4 inhibitors.
Alcohol should be avoided while taking FETZIMA.
Use in Specific Populations
Pregnancy: Third trimester use may increase risk of postpartum hemorrhage and may increase the risk of
neonatal complications requiring prolonged hospitalizations, respiratory support, and tube feeding.
Lactation: Breastfeeding women should monitor infants for sedation, agitation, irritability, poor feeding,
and poor weight gain and should seek medical care if they notice these signs.
The most commonly observed adverse reactions in MDD patients treated with FETZIMA in placebo-controlled
studies (incidence ≥5% and at least twice the rate of placebo) were nausea (17% vs 6%),
constipation (9% vs 3%), hyperhidrosis (9% vs 2%), heart rate increased (6% vs 1%), erectile dysfunction
(6% vs 1%), tachycardia (6% vs 2%), vomiting (5% vs 1%), and palpitations (5% vs 1%).
Please also see the full Prescribing Information, including Boxed Warning.