(lee-voe-mil-na-si-pran ) ,


(trade name)


Therapeutic: antidepressants
Pharmacologic: selective serotonin norepinephrine reuptake inhibitors
Pregnancy Category: C


Treatment of Major Depressive Disorder (MDD)


Inhibits neuronal reuptake of norepinephrine and serotonin in the CNS (SNRI).

Therapeutic effects

Decrease in depressive symptomatology, with fewer relapses/recurrences


Absorption: Well absorbed (92%) following oral administration
Distribution: Widely distributed
Metabolism and Excretion: 58% eliminated unchanged in urine; 42% metabolized, primarily by the CYP3A4 enzyme system; metabolites are renally eliminated
Half-life: 12 hr

Time/action profile

POUnk6–8 hr (blood level)Unk


Contraindicated in: Hypersensitivity to levomilnacipran or milnacipranUncontrolled narrow-angle glaucomaConcurrent use of or in close temporal proximity to MAO inhibitors, linezolid or methylene blue (risk of serotonin syndrome)Concurrent use of alcohol
Use Cautiously in: History of hypertension, cardiovascular or cerebrovascular disease (blood pressure should be controlled prior to treatment)History of bipolar disorder (may activate mania/hypomania)Renal impairment (dosage reduction required for CCr< 60 mL/min) Geriatric: Consider age-related ↓ in renal function, chronic disease state and concurrent drug therapy; may have ↑ risk of hyponatremia; Obstetric: Use only if clearly required during pregnancy weighing benefit to mother versus potential harm to fetus; Lactation: Potential for serious adverse reactions in infant; discontinue drug or discontinue breast feeding; Pediatric: ↑ risk of suicidal thinking and behavior (suicidality) in adolescents and young adults up to 24 yrs with MDD
Exercise Extreme Caution in: Concurrent use with other serotonergic drugs (↑ risk of serotonin syndrome especially during initiation and dose adjustment).

Adverse Reactions/Side Effects

Central nervous system

  • activation of mania/hypomania

Ear, Eye, Nose, Throat

  • mydrasis


  • hypertension
  • hypotension
  • palpitations
  • tachycardia


  • nausea (most frequent)
  • ↓ appetite
  • constipation
  • vomiting


  • ejaculation disorder
  • erectile dysfunction
  • testicular pain
  • urinary hesitation/retention


  • hot flush
  • hyperhydrosis
  • rash

Fluid and Electrolyte

  • hyponatremia (in association with syndrome of inappropriate antidiuretic hormone [SIADH])


  • bleeding


  • serotonin syndrome (life-threatening)


Drug-Drug interaction

Concurrent use with MAO inhibitors used for psychiatric disorders may result in serious, potentially fatal reactions; wait at least 14 days following discontinuation of MAO inhibitor before initiation of levomilnacipran. Wait at least 7 days after discontinuing levomilnacipran before initiation of MAO inhibitorConcurrent use of serotonergic drugs (including triptans, lithium, buspirone, fentanyl, tricyclics and tramadol ) may ↑ the risk of serotinin syndrome, especially during initiation and dose adjustment; also ↑ risk of coronary vasoconstriction and hypertension.Concurrent use with methylene blue or linezolid is contraindicated due to risk of serotonin syndromeConcurrent use of NSAIDs, aspirin, warfarin or otherdrugs that affect coagulation may ↑ the risk of bleeding.Blood levels and risk of toxicity ↑ by concurrent use of CYP3A4 inhitors including ketoconazole, clarithromycin, ritonavir ; daily dose should not exceed 80 mgConcurrent use of other medications that may ↑ blood pressure may ↑ risk of hypertensionConcurrent use with alcohol may cause a rapid release of drug and should be avoidedConcurrent use with other CNS-active medications, especially other NSRIs Concurrent use with St. John's wort or tryptophan may ↑ the risk of serotinin syndrome; also ↑ risk of coronary vasoconstriction and hypertension.


Oral (Adults) 20 mg once daily for two days, then increase to 40 mg once daily, may then be increased by 40 mg every two or more days; may be increased up to 120 mg/day; concurrent use of CYP3A4 inhibitors (including ketoconazole, clarithromycin, ritonavir)—not to exceed 80 mg/day.

Renal Impairment

Oral (Adults) CCr 30–59 mL/minnot to exceed 80 mg/day; CCr 15–29 mL/minnot to exceed 40 mg/day


Extended-release capsules: 20 mg, 40 mg, 80 mg, 120 mg

Nursing implications

Nursing assessment

  • Monitor blood pressure and heart rate before and periodically during therapy. Treat per-existing hypertension and cardiac disease prior to therapy. Sustained hypertension may require discontinuation of therapy.
  • Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
  • Lab Test Considerations: May cause hyponatremia.

Potential Nursing Diagnoses

Ineffective coping (Indications)
Risk for suicide (Adverse Reactions)


  • Oral: Administer daily without regard to food. Swallow capsule whole; do not open, crush, or chew.

Patient/Family Teaching

  • Instruct patient to take levomilnacipran as directed at the same time each day. Take missed doses as soon as possible unless time for next dose; do not double dose. Do not stop abruptly; must be decreased gradually. Abrupt discontinuation may cause dysphoric mood, irritability, agitation, dizziness, paresthesia, electric shock sensation, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus and seizures. Advise patient to read Medication Guide prior to therapy and with each Rx refill in case of changes.
  • May cause drowsiness and may affect ability to make decisions or react quickly. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
  • Advise patient, family, and caregivers to look for activation of mania/hypomania and suicidality, especially during early therapy or dose changes. Notify health care professional immediately if thoughts about suicide or dying, attempts to commit suicide; new or worse depression or anxiety; agitation or restlessness; panic attacks; insomnia; new or worse irritability; aggressiveness; acting on dangerous impulses, mania, or other changes in mood or behavior or if symptoms of serotonin syndrome occur.
  • Caution patient of the risk or serotonin syndrome (agitation, hallucinations, changes in mental status, muscle twitching, fast heartbeat, high or low blood pressure, sweating or fever, nausea or vomiting, diarrhea, muscle stiffness or tightness), especially when taking triptans, tramadol, tryptophan supplements and other serotonergic or antipsychotic agents.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to avoid concurrent use of Rx, OTC, and herbal products, especially NSAIDs, aspirin, and warfarin, without consulting health care professional; may increase bleeding.
  • Instruct patient to notify health care professional if signs of hyponatremia (headache, difficulty concentrating, memory impairment, confusion, weakness, unsteadiness) occur.
  • Advise patient to avoid taking alcohol during levomilnacipran therapy.
  • Instruct patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.
  • Encourage patient to maintain routine follow-up visits with health care provider to determine effectiveness.

Evaluation/Desired Outcomes

  • Increased sense of well-being
    • Renewed interest in surroundings. Need for therapy should be periodically reassessed.
Drug Guide, © 2015 Farlex and Partners
References in periodicals archive ?
* SNRIs are a newer option, and include desvenlafaxine (Pristiq[R], Khedezla[R]), duloxetine (Cymbalta[R]), levomilnacipran (Fetzima[R]), and venlafaxine (Effexor, Effexor XR[R]).
Presently too few double-blind RCTs have been conducted to assess the pain-mitigating effects of other antidepressants (eg, bupropion and newer SNRIs such as desvenlafaxine and levomilnacipran).
The National Pregnancy Registry for Antidepressants (844-405-6185) is studying amitriptyline (Elavil), amoxapine (Asendin), bupropion (Forfivo XL and Wellbutrin), Citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), desvenlafaxine (Prisiq), doxepin (Sinequan), escitalopram (Lexapro), fluvoxamine (Luvox), fluoxetine (Prozac), imipramine (Tofranil), isocarboxazid (Marplan), levomilnacipran (Fetzima), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Pamelor), paroxetine (Paxil), phenelzine (Nardill), protriptyline (Vivactil), selegiline (Emsam), sertraline (Zoloft), tranylcypromine (Parnate), trazodone (Desyrel), trimipramine (Surmontil), venlafaxine (Effexor), and vilazodone (Viibryd).
Doris, "Enantioselective synthesis of levomilnacipran," Chemical Communications, vol.
Based on this approach, in the past three years the US Food and Drug Administration (USFDA) approved the marketing of three new combination agents: vilazodone, levomilnacipran, and vortioxetine.
That list includes vilazodone, desvenlafaxine, levomilnacipran, vortioxetine, as well as the less-traditional choices of I-methylfolate and ketamine.
There are no pediatric safety or efficacy data on the new antidepressants vilazodone, desvenlafaxine, levomilnacipran, or vortioxetine, and the lesstraditional choices of L-methylfolate and ketamine.
M2 EQUITYBITES-September 28, 2012-Forest Laboratories Inc submits NDA to FDA for Levomilnacipran for MDD in adults(C)2012 M2 COMMUNICATIONS http://www.m2.com
M2 PHARMA-September 28, 2012-Forest Laboratories Inc submits NDA to FDA for Levomilnacipran for MDD in adults(C)2012 M2 COMMUNICATIONS
Table 1 Medications that can cause serotonin syndrome Action Medications Increases serotonin Tryptophan formation Increases release of Amphetamines and amphetamine derivatives serotonin Cocaine MDMA Impairs serotonin Cocaine, MDMA, meperidine, reuptake tramadol, pentazocine SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) SNRIs (desvenlafaxine, duloxetine, milnacipran, venlafaxine, levomilnacipran) Dopamine-norepinephrine reuptake inhibitors (bupropion) Serotonin modulators (nefazodone, trazodone, vilazodone, vortioxetine) TCAs (amitriptyline, amoxapine, clomipramine, desipramine, doxepin) St.
-- Levomilnacipran SR resulted in significant improvement in cognitive measures of attention and information processing in a phase III trial conducted in patients with major depressive disorder; the drug was approved in late July by the Food and Drug Administration under the trade name Fetzima.
M2 EQUITYBITES-September 27, 2012-Forest Laboratories Inc submits NDA to US FDA for levomilnacipran for MDD in adult patients(C)2012 M2 COMMUNICATIONS http://www.m2.com