Fetzima (Levomilnacipran) - Uses, Dose, Side effects, Brands

An inhibitor of serotonin-norepinephrine reuptake is Fetzima (Levomilnacipran) (SNRI). 

It is employed to treat severe depression.

Fetzima (Levomilnacipran) Uses:

  • Major depressive disorder:

    • Treatment of major depressive disorder (MDD)

Fetzima (Levomilnacipran) Dose in Adults:

Fetzima (Levomilnacipran) Dose in the treatment of Depression:

  • Oral:
    • Initial: 20 mg once daily for 2 days, then increase to 40 mg once daily.
    • Subsequently, the dosage may be increased by increments of 40 mg every two or more days.
    • Maintenance: 40 to 120 mg once daily.
    • Maximum: 120 mg per day.

  • Discontinuation of Levomilnacipran therapy:

    • To mitigate withdrawal symptoms and detect reemerging symptoms, it's advisable to gradually decrease the dose of antidepressant medication over a period of 2 to 4 weeks after discontinuation, especially if the medication has been used for more than 3 weeks.

    • Factors such as using a medication with a half-life of less than 24 hours (e.g., paroxetine or venlafaxine), previous history of antidepressant withdrawal symptoms, or high doses of antidepressants may necessitate a slower titration, such as over 4 weeks.

    • If unacceptable withdrawal symptoms occur, restarting the previously prescribed dose or reducing the dose at a more gradual rate is recommended.

    • For individuals receiving long-term treatment (over 6 months), such as those with a history of discontinuation syndrome, tapering over more than three months may be beneficial.

    • It's important to note that there is limited evidence available to support ideal taper rates, and individualized approaches may be necessary.

MAO inhibitor recommendations:

  • A psychiatric condition is treated by using an MAO inhibitor, and switching to or from one:

    • Levomilnacipran should be initiated 14 days after discontinuing the use of an MAO inhibitor used to treat psychiatric disorders.

    • Conversely, it is advised to wait 7 days after stopping levomilnacipran before starting an MAO inhibitor.

Use in Children:

Not indicated

Pregnancy Risk Factor C

  • Late in the third trimester, SSRI/SNRI medications may have nonteratogenic effects on the infant, which can include symptoms such as hyperreflexia, hypoglycemia, hypo- or hypertonia, vomiting, feeding problems, seizures, and respiratory distress.

  • These effects may be due to toxic effects of SSRIs and SNRIs or a withdrawal syndrome, and they could also align with serotonin syndrome associated with SSRI use.

  • Women with major depression who were euthymic before pregnancy are more likely to discontinue antidepressant medication compared to women who continue taking it.

  • ACOG recommends individualized treatment using SSRIs and SNRIs during pregnancy, with consideration of the obstetrician's and primary care provider's clinical expertise in managing depression during pregnancy.

  • The American Psychiatric Association notes that medication treatment for depression during pregnancy carries risks, but these should be weighed against the risks of untreated depression.

  • Women who have stopped antidepressant medication during pregnancy and are at high risk of postpartum depression may consider reintroducing their medications.

  • Both ACOG and APA have developed treatment algorithms for managing depression in women before conception and during pregnancy.

Use of levomilnacipran while breastfeeding

  • The presence of levomilnacipran in breast milk is currently unknown.
  • In light of this uncertainty, the manufacturer advises that mothers make an informed decision regarding whether to discontinue breastfeeding or cease using the medication due to the potential for serious adverse reactions in the infant.

Fetzima (Levomilnacipran) Dose in Kidney Disease:

  • For individuals with different levels of renal function:

  • Creatinine clearance (CrCl) ≥60 mL/minute: No dose adjustment necessary.
  • CrCl 30 to 59 mL/minute: A maximum dose of 80 mg once daily is recommended.
  • CrCl 15 to 29 mL/minute: A maximum dose of 40 mg once daily is recommended.
  • End-stage renal disease (ESRD): Not recommended.

  • It's important to adhere to these dosage recommendations to ensure safe and effective use of the medication in individuals with varying degrees of renal impairment.

Fetzima (Levomilnacipran) Dose in Liver disease:

  • Dose adjustment not necessary.

Common Side Effects of Fetzima (Levomilnacipran):

  • Cardiovascular:

    • Orthostatic hypotension

  • Gastrointestinal:

    • Nausea

Less Common Side Effects of Fetzima (Levomilnacipran):

  • Cardiovascular:

    • Increased Heart Rate
    • Tachycardia
    • Palpitations
    • Hypertension
    • Hypotension
    • Increased Blood Pressure
    • Angina Pectoris
    • Chest Pain
    • Supraventricular Extrasystole
    • Syncope
    • Ventricular Premature Contractions

  • Central Nervous System:

    • Aggressive Behavior
    • Agitation
    • Extrapyramidal Reaction
    • Migraine
    • Outbursts Of Anger
    • Panic Attack
    • Paresthesia
    • Tension
    • Yawning

  • Dermatologic:

    • Hyperhidrosis
    • Skin Rash
    • Pruritus
    • Urticaria
    • Xeroderma

  • Endocrine & Metabolic:

    • Hot Flash
    • Hypercholesterolemia
    • Increased Thirst

  • Gastrointestinal:

    • Constipation
    • Vomiting
    • Decreased Appetite
    • Abdominal Pain
    • Bruxism
    • Flatulence

  • Genitourinary:

    • Erectile Dysfunction
    • Urinary Hesitancy
    • Ejaculatory Disorder
    • Testicular Pain
    • Hematuria
    • Pollakiuria
    • Proteinuria

  • Hepatic:

    • Abnormal Hepatic Function Tests

  • Ophthalmic:

    • Blurred Vision
    • Conjunctival Hemorrhage
    • Dry Eye Syndrome

Contraindications to Fetzima (Levomilnacipran):

  • MAO inhibitors should not be used concurrently with levomilnacipran or within seven days of discontinuing levomilnacipran.

  • Hypersensitivity to milnacipran, levomilnacipran, or any other ingredient in the formulation is a contraindication to its use.

  • Additionally, patients who have received intravenous linezolid or intravenous methylene blue should not start levomilnacipran.

  • These medications can interact with levomilnacipran and lead to serotonin syndrome or hypertensive crisis.

Canadian labeling: Additional contraindications:

  • Patients who have undergone a cardiac procedure or experienced a myocardial infarction (MI) within the last year may use this medication, provided that their healthcare provider determines it to be appropriate for their individual case.

  • Additionally, patients with heart failure (NYHA Class I or II), uncontrolled tachyarrhythmia, uncontrolled hypertension, or a history of cerebrovascular accidents (CVA's) may also use this medication, but close monitoring and careful management of their condition are essential.

Warnings and precautions

  • Bleeding Risk:

    • The concurrent use of aspirin, NSAIDs, or warfarin with SNRIs can lead to impaired platelet aggregation, potentially increasing the risk of bleeding events.

    • Reports suggest that SNRI use may cause bleeding ranging from minor bruising and nosebleeds to more serious hemorrhages.

    • Therefore, caution is advised when using these medications together, and patients should be closely monitored for signs of bleeding.

  • Cardiovascular effects

    • The medication may increase blood pressure and heart rate.

    • Therefore, it's crucial to evaluate your blood pressure and heart rate before starting therapy and regularly thereafter.

    • Patients with sustained hypertension and tachycardia should be considered for dose reductions or gradual discontinuation of therapy.

    • Additionally, individuals with hypertension or tachyarrhythmias (such as atrial fibrillation) should approach the medication with caution.

  • Fractures

    • Antidepressant treatment has been linked to an increased risk of bone fractures.
    • Therefore, individuals undergoing antidepressant therapy should be aware of potential signs indicating a fragility fracture, such as unexplained bone pain, tenderness, swelling, or bruising.
    • Prompt medical attention is advisable if any of these symptoms occur while on antidepressant treatment.

  • Ocular effects

    • Mild pupillary dilation may occur with this medication, and in some cases, it can increase the risk of narrow-angle glaucoma.
    • Therefore, patients who have not undergone an iridectomy to reduce this risk should be evaluated before starting treatment.
    • This evaluation helps to assess the individual's risk factors and determine the most appropriate course of action to minimize the potential for developing narrow-angle glaucoma.

  • Serotonin syndrome

    • Serotonin syndrome (SS), a potentially life-threatening condition, has been reported with the use of serotonergic drugs, including SSRIs and SNRIs.

    • This risk is particularly heightened when these medications are combined with other serotonergic agents such as triptans, TCAs, fentanyls, buspirones, tramadols, St. John's Wort, tryptophan, MAO inhibitors, intravenous methylene blue, and linezolid.

      Symptoms of serotonin syndrome include:

    • Mental status changes (e.g., agitation, hallucinations, delirium)
    • Autonomic instability (e.g., tachycardia, labile blood pressure, diaphoresis)
    • Neuromuscular changes (e.g., tremors, rigidity, myoclonus)
    • Gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea)
    • Seizures

    • If you notice any signs or symptoms of serotonin syndrome, it's crucial to stop taking any serotonergic medication or treatment immediately and seek medical attention.

  • SIADH and Hyponatremia

    • SSRIs, SNRIs, and SIADH (syndrome of inappropriate antidiuretic hormone secretion) have been associated with the development of hyponatremia, which is a condition characterized by low sodium levels in the blood.

    • While severe cases with serum sodium levels as low as 110 mmol/L are rare, it's essential to be aware of this potential complication.

    • Certain factors, including advanced age (especially in the elderly), volume loss, and concurrent use of diuretics, increase the risk of developing hyponatremia in individuals taking these medications.

    • Patients who develop hyponatremia while on SSRIs or SNRIs should discontinue the medication and seek medical attention promptly.

    • Managing hyponatremia may involve addressing the underlying cause and correcting sodium levels under medical supervision.

  • Retention or urinary hesitancy:

    • Patients taking certain medications, including those for psychiatric conditions, should promptly report any symptoms of increased urinary resistance or hesitation to their healthcare provider.

    • This is particularly important for individuals with obstructive bladder conditions, as these symptoms may indicate a worsening of their condition or potential adverse effects of the medication.

    • Close monitoring and communication with healthcare providers are essential for managing any urinary symptoms and ensuring appropriate care.

  • Hypomania and mania:

    • Mania and hypomania can manifest in individuals with bipolar disorder.

    • Due to the risk of inducing manic episodes, monotherapy with certain antidepressants, including levomilnacipran, is generally not recommended for patients with bipolar disorder.

    • It's important to conduct testing for bipolar disorder in patients presenting with depressive symptoms, as this can help guide appropriate treatment decisions and prevent potential adverse outcomes associated with antidepressant use in bipolar disorder.

    • It's worth noting that the FDA has not approved levomilnacipran for the treatment of bipolar disorder. Therefore, it should not be used as a sole treatment option for individuals with this condition.

    • Instead, treatment decisions for bipolar disorder should be made in consultation with a qualified healthcare provider and may involve a combination of mood stabilizers, antipsychotics, and other appropriate interventions.

  • Renal impairment

    • It's essential to exercise caution when prescribing medications that are cleared less efficiently by the kidneys, as higher plasma concentrations can result.

    • Patients with severe or mild renal impairment may require lower doses of such medications to avoid potential adverse effects associated with elevated plasma concentrations.

    • In cases of end-stage renal disease (ESRD), treatment with certain medications may not be advisable due to the significantly impaired renal function.

    • Therefore, patients with ESRD should avoid treatment with medications that are primarily eliminated by the kidneys, unless otherwise directed by a healthcare professional.

  • Seizure disorders

    • Being cautious with medication use is paramount.
    • It's crucial to follow prescribed dosages, adhere to medical advice, and promptly report any concerning symptoms to healthcare providers.
    • Additionally, discussing any potential risks or concerns with your healthcare provider can help ensure safe and effective treatment. Your well-being is the top priority.

Levomilnacipran: Drug Interaction

Risk Factor C (Monitor therapy)

Acalabrutinib

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.)

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Almotriptan

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Alosetron

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Alpha2-Agonists

The antihypertensive action of Alpha2-Agonists may be diminished by  Serotonin/Norepinephrine Reuptake Inhibitors.Exceptions: Apraclonidine.

Amphetamines

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Anticoagulants

Agents with antiplatelet properties may have an enhanced antiplatelet impact.Exceptions: Bemiparin; Enoxaparin; Heparin.

Antiemetics (5HT3 Antagonists)

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Antipsychotic Agents

Antipsychotic Agents' negative or toxic effects may be exacerbated by  Serotonergic Agents (High Risk). Particularly, serotonergic drugs may  intensify  the  effects of  dopamine blocking,  thus raising the danger  of  neuroleptic malignant syndrome. Serotonergic agents' serotonergic action  may be enhanced by antipsychotic  drugs (High Risk). Serotonin syndrome  might occur from this.

Apixaban

Antiplatelet agents may intensify the toxic/unfavorable effects of apixaban.  In particular, there may be an elevated risk of bleeding. Management:  Carefully weigh the advantages and disadvantages  of this pairing, and keep  a tight eye on things.

Aprepitant

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Aspirin

Serotonin/Norepinephrine Reuptake Inhibitors may improve aspirin's ability to reduce  blood clots.

Bemiparin

Bemiparin's anticoagulant impact may be strengthened by substances with antiplatelet  properties. Management: Avoid taking bemiparin at the same time as antiplatelet  medications. If concurrent use is unavoidable, keep a cautious eye out for bleeding  signs and symptoms.

Brexanolone

Serotonin/Norepinephrine Reuptake Inhibitors may increase Brexanolone's ability to  depress the central nervous system.

BusPIRone

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Cephalothin

Agents having antiplatelet properties may intensify cephalothin's harmful or hazardous  effects. In particular, there may be an elevated risk of bleeding.

Clofazimine

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Collagenase (Systemic)

Collagenase's harmful or toxic effects may be enhanced by substances with antiplatelet  properties (Systemic). In particular, there may be an increased risk of bruising and/or bleeding  at  the injection site.

Cyclobenzaprine

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

CYP3A4 Inhibitors (Moderate)

May slow down CYP3A4 substrate metabolism (High risk with Inhibitors).

Dabigatran Etexilate

Dabigatran Etexilate's anticoagulant activity may be strengthened by substances with  antiplatelet properties. Dabigatran Etexilate's serum levels may rise in response to  substances with  antiplatelet properties. The drug clopidogrel is especially covered by this  mechanism. Management: Carefully weigh the advantages and disadvantages of  this combination, and keep a  tight eye on things; Canadian labelling advises against  using prasugrel or ticagrelor.

Dasatinib

Agents having antiplatelet properties may strengthen their anticoagulant effects.  Management: Separate drug interaction monographs go into further detail about  the medications indicated as exceptions to this book.

Deoxycholic Acid

Deoxycholic Acid's harmful or toxic effects may be increased by substances with  antiplatelet properties. In particular, there may be a higher chance of bleeding or bruising  in the treatment region.

Dexmethylphenidate-Methylphenidate

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Dextromethorphan

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Duvelisib

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Edoxaban

Antiplatelet agents may intensify the toxic/unfavorable effects of edoxaban. In  particular, there may be an elevated risk of bleeding.

Eletriptan

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Erdafitinib

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Ergot Derivatives

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Fat Emulsion (Fish Oil Based)

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

FentaNYL

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Fosaprepitant

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Fosnetupitant

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Glucosamine

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Ibritumomab Tiuxetan

Antiplatelet agents may intensify the toxic/unfavorable effects of ibritumomab tiuxetan.  Both substances may raise the risk of bleeding and compromise platelet function.

Ibrutinib

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Inotersen

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Ioflupane I 123

Ioflupane I 123's ability to serve as a diagnostic tool may be diminished by  serotonin/norepinephrine reuptake inhibitors.

Larotrectinib

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Lasmiditan

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Limaprost

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Lorcaserin

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Meperidine

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Metaxalone

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Mirtazapine

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Multivitamins/Fluoride (with ADE)

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Multivitamins/Minerals (with ADEK, Folate, Iron)

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Multivitamins/Minerals (with AE, No Iron)

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Netupitant

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Nonsteroidal Anti-Inflammatory Agents (Nonselective)

Nonsteroidal Anti-Inflammatory Drugs may have a stronger antiplatelet impact when used  with Serotonin/Norepinephrine Reuptake Inhibitors (Nonselective).

Obinutuzumab

Agents with antiplatelet properties may intensify Obinutuzumab's toxic/unfavorable effects.  In particular, there may be an increased risk of life-threatening bleeding-related incidents.

Omega-3 Fatty Acids

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Ondansetron

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Opioid Agonists

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.Exceptions: FentaNYL; Meperidine; TraMADol.

Oxitriptan

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Palbociclib

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Pentosan Polysulfate Sodium

Agents with poisonous or harmful effects may intensify their negative or hazardous effects.  In particular, the concurrent use of several drugs may raise the risk of bleeding.

Pentoxifylline

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Prostacyclin Analogues

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Ramosetron

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Rivaroxaban

Rivaroxaban's anticoagulant impact may be increased by substances with antiplatelet properties.  Management: Carefully weigh the advantages and disadvantages of this combination,  and keep a tight eye on things; Canadian labelling advises against using prasugrel or ticagrelor.

Salicylates

The harmful or toxic effect of salicylates may be increased by substances with antiplatelet  properties. Bleeding risk could rise as a result.

Selective Serotonin Reuptake Inhibitors

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status. Exceptions: Dapoxetine.

Serotonergic Agents (High Risk, Miscellaneous)

Tricyclic Antidepressants' serotonergic effects may be strengthened by  serotonin/norepinephrine reuptake inhibitors. Serotonin syndrome might  occur from this. When using these drugs together, watch out for any  changes in mental  status and indicators of serotonin syndrome, such as  hyperreflexia, clonus, hyperthermia, diaphoresis, tremor,  and  autonomic  instability.

Serotonin 5-HT1D Receptor Agonists (Triptans)

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Serotonin/Norepinephrine Reuptake Inhibitors

Tricyclic Antidepressants' serotonergic effects may be strengthened by  serotonin/norepinephrine reuptake inhibitors. Serotonin syndrome might  occur from this. When using these drugs together, watch out for any  changes in mental  status and indicators of serotonin syndrome, such as  hyperreflexia, clonus, hyperthermia, diaphoresis, tremor,  and  autonomic  instability.

Simeprevir

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

St John's Wort

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Syrian Rue

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Thrombolytic Agents

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Tipranavir

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

TraMADol

Tricyclic Antidepressants' serotonergic effects may be strengthened by  serotonin/norepinephrine reuptake inhibitors. Serotonin syndrome might  occur from this. When using these drugs together, watch out for any  changes in mental  status and indicators of serotonin syndrome, such as  hyperreflexia, clonus, hyperthermia, diaphoresis, tremor,  and  autonomic  instability.

TraZODone

Makes serotonergic agents more effective (High Risk). Serotonin syndrome  might  occur from this. When these medications are taken together, it is  important  to watch out for any signs and symptoms of serotonin syndrome  or serotonin poisoning,  such as hyperreflexia, clonus, hyperthermia,  diaphoresis, tremor, autonomic  instability, and changes in mental status.

Tricyclic Antidepressants

Tricyclic Antidepressants' serotonergic effects may be strengthened by  serotonin/norepinephrine reuptake inhibitors. Serotonin syndrome might  occur from this. When using these drugs together, watch out for any  changes in mental  status and indicators of serotonin syndrome, such as  hyperreflexia, clonus, hyperthermia, diaphoresis, tremor,  and  autonomic  instability.

Vitamin E (Systemic)

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Vitamin K Antagonists (eg, warfarin)

Levomilnacipran may make Vitamin K Antagonists' harmful or hazardous effects worse.  In particular, there may be an elevated risk of bleeding.

Zanubrutinib

Agents with antiplatelet properties may have an enhanced antiplatelet impact.

Risk Factor D (Consider therapy modification)

Alcohol (Ethyl)

May increase the absorption of Levomilnacipran. More specifically, Alcohol (Ethyl) may cause more rapid release of Levomilnacipran from extended-release tablets, which could accelerate absorption early post-dose. Management: Avoid administering levomilnacipran with alcohol. The use of alcohol in patients receiving levomilnacipran is not otherwise advised against, although it may theoretically modify the central effects of one or both drugs.

Alpha-/Beta-Agonists

The tachycardic action of beta- and alphaagonists may be enhanced by  serotonin/norepinephrine reuptake inhibitors. The vasopressor impact of alpha/beta  agonists may be enhanced by serotonin/norepinephrine reuptake inhibitors.

CYP3A4 Inhibitors (Strong)

Levomilnacipran's serum concentration can rise. Treatment: In patients who are  already taking  potent CYP3A4 inhibitors, a maximum adult dose of 80 mg/day of levomilnacipran should not  be exceeded. Nefazodone is an exception.

Enoxaparin

Enoxaparin's anticoagulant impact may be strengthened by substances with  antiplatelet  properties. When feasible, stop using antiplatelet medications before starting enoxaparin.  If simultaneous administration must occur, keep a cautious eye out for any bleeding  signs and symptoms.

Heparin

The anticoagulant effect of heparin may be strengthened by substances with antiplatelet  properties. If coadministration is necessary, reduce the dose of heparin or other  medications with antiplatelet characteristics.

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry)

Agents with poisonous or harmful effects may intensify their negative or hazardous effects.  Bleeding could happen. Management: When at all possible, avoid combining. If used, keep a closer eye out for signs of bleeding. Two weeks before any type of surgery, dental work,  or invasive procedure, stop using herbal  remedies that have anticoagulant or antiplatelet effects.

Metoclopramide

The negative or hazardous effects of serotonin/norepinephrine reuptake inhibitors may be increased.  Management: When possible, look for substitutions for this combination. Serotonin syndrome,  neuroleptic malignant syndrome, and extrapyramidal symptoms should be kept an eye  out for in individuals using metoclopramide along with serotonin/norepinephrine reuptake inhibitors.

MiFEPRIStone

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus.

Nefazodone

The serotonergic action of levomilnacipran may increase that of nefazodone. Serotonin syndrome  might occur from this. Levomilnacipran's serum levels may rise in response to nefazodone.  Treatment: If levomilnacipran is coupled with nefazodone, the dose should be capped  at 80 mg per  day, and patients  should be watched for any increased side effects or toxicities, such as  serotonin syndrome.

Stiripentol

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). Management:  Due to the increased potential for side effects and toxicity, stiripentol  should not be used with  CYP3A4 substrates that are thought to have a narrow therapeutic index. Use of stiripentol  with any CYP3A4 substrate necessitates closer observation.

Risk Factor X (Avoid combination)

Bromopride

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Conivaptan

The negative or hazardous effects of serotonin/norepinephrine reuptake inhibitors may be increased.

Dapoxetine

Makes serotonergic agents more effective (High Risk). Serotonin syndrome might occur from this.  Treatment: Avoid using highrisk serotonergic medications with dapoxetine or within 7 days after  stopping them. Within 14 days of using a monoamine oxidase inhibitor, do not take dapoxetine.  This combination is listed on the labelling for dapoxetine as being harmful.

Fusidic Acid (Systemic)

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Idelalisib

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Iobenguane Radiopharmaceutical Products

Iobenguane radiopharmaceutical products may have less of a therapeutic impact when taken  with serotonin/norepinephrine reuptake inhibitors. Treatment: Before administering iobenguane,  stop taking any medications that could impede  or interfere with catecholamine transport or  uptake for at least five biological half-lives. After each dose of iobenguane, wait at least 7 days  before administering these medications.

Linezolid

The serotonergic impact of Methylene Blue may be increased by serotonin/norepinephrine  reuptake inhibitors. Serotonin syndrome might occur from this.

Methylene Blue

Serotonin/Norepinephrine Reuptake Inhibitors may improve their serotonergic effects. Serotonin  syndrome might occur from this.

Monoamine Oxidase Inhibitors (Antidepressant)

The serotonergic impact of Methylene Blue may be increased by serotonin/norepinephrine  reuptake inhibitors. Serotonin syndrome might occur from this.

Rasagiline

The serotonergic impact of Methylene Blue may be increased by serotonin/norepinephrine  reuptake inhibitors. Serotonin syndrome might occur from this.

Safinamide

The serotonergic impact of Methylene Blue may be increased by serotonin/norepinephrine  reuptake inhibitors. Serotonin syndrome might occur from this.

Selegiline

The serotonergic impact of Methylene Blue may be increased by serotonin/norepinephrine  reuptake inhibitors. Serotonin syndrome might occur from this.

Urokinase

Urokinase's anticoagulant impact may be strengthened by substances with antiplatelet properties.

 

Monitoring parameters:

  • For at-risk populations, such as those with suicidal ideation, depression, or changes in mental status (especially when initiating or adjusting medication dosages), monitoring clinically indicated serum sodium levels is crucial.

  • Additionally, being vigilant for symptoms of serotonin syndrome is essential, especially when starting therapy or making dosage adjustments.

  • Dosing should be carefully considered based on renal function, heart rate, and blood pressure, particularly in patients with pre-existing conditions such as hypertension or impaired renal function.

  • Furthermore, individuals at high risk of glaucoma or those with baseline elevations in intraocular pressure should have their intraocular pressure monitored regularly.

  • These measures help ensure the safety and effectiveness of treatment in vulnerable populations.

How to administer Fetzima (Levomilnacipran)?

Oral:

  • Administer with or without food at approximately the same time each day.
  • Swallow whole, do not open, chew, or crush the capsule.

Mechanism of action of Fetzima (Levomilnacipran):

  • Levomilnacipran, the active enantiomer of milnacipran, acts as a potent inhibitor of serotonin and norepinephrine reuptake.

  • Here are some pharmacokinetic parameters:

  • Protein binding: Approximately 22%
  • Metabolism: Hepatic metabolism to inactive metabolites
  • Bioavailability: High bioavailability, approximately 92%
  • Half-life elimination: Approximately 12 hours
  • Time to peak concentration: 6 to 8 hours
  • Excretion: Primarily via urine, with approximately 58% of the drug excreted unchanged.

  • These parameters provide insights into the absorption, distribution, metabolism, and excretion of levomilnacipran, aiding in understanding its pharmacological profile and clinical use.

International Brands of Levomilnacipran:

  • Fetzima
  • Fetzima Titration

Levomilnacipran Brand Names in Pakistan:

No Brands Available in Pakistan.

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