Usage
- Levomilnacipran is prescribed for the treatment of Major Depressive Disorder (MDD) in adults.
- Pharmacological classification: Serotonin-Norepinephrine Reuptake Inhibitor (SNRI).
- Mechanism of action: Levomilnacipran inhibits the reuptake of serotonin and norepinephrine in the central nervous system, increasing the levels of these neurotransmitters in the synaptic cleft, which are believed to be deficient in patients with MDD. It has a greater effect on norepinephrine reuptake compared to serotonin.
Alternate Names
- (S)-Milnacipran
- Brand name: Fetzima
How It Works
- Pharmacodynamics: Levomilnacipran increases the synaptic concentrations of serotonin and norepinephrine, leading to enhanced neurotransmission in areas of the brain implicated in mood regulation.
- Pharmacokinetics:
- Absorption: Well-absorbed orally. Food does not significantly affect absorption.
- Metabolism: Extensively metabolized in the liver, primarily by CYP3A4.
- Elimination: Excreted primarily in the urine (approximately 50% as unchanged drug) with a half-life of about 12 hours.
- Mode of action: Binds to serotonin and norepinephrine transporters, inhibiting their reuptake into presynaptic neurons.
- Receptor binding/Enzyme inhibition/Neurotransmitter modulation: Inhibits serotonin and norepinephrine transporters.
- Elimination pathways: Primarily renal excretion, with some hepatic metabolism via CYP3A4.
Dosage
Standard Dosage
Adults:
- Initial: 20 mg once daily for 2 days, then increase to 40 mg once daily.
- Maintenance: 40 mg to 120 mg once daily.
- Maximum: 120 mg/day. Dose adjustments should be made at intervals of 2 or more days, based on individual patient response and tolerability.
Children:
- Not approved for use in pediatric patients.
Special Cases:
- Elderly Patients: No specific dose adjustment needed, but monitor for hyponatremia.
- Patients with Renal Impairment:
- Moderate (CrCl 30-59 mL/min): Maximum dose 80 mg/day.
- Severe (CrCl 15-29 mL/min): Maximum dose 40 mg/day.
- End-stage renal disease: Not recommended.
- Patients with Hepatic Dysfunction: No dose adjustment necessary.
- Patients with Comorbid Conditions: Caution should be exercised in patients with hypertension, cardiovascular disease, seizures, or a history of mania/hypomania.
Clinical Use Cases
- Levomilnacipran is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its sole indication is for MDD in adults.
Dosage Adjustments
- Coadministration with strong CYP3A4 inhibitors: Maximum dose 80 mg/day.
Side Effects
Common Side Effects
- Nausea, constipation, hyperhidrosis, dizziness, insomnia, headache, dry mouth, decreased appetite, erectile dysfunction/ejaculation disorder, urinary hesitation.
Rare but Serious Side Effects
- Serotonin syndrome, suicidal thoughts/behaviors (especially in young adults), hyponatremia, mania, angle-closure glaucoma, increased blood pressure, increased heart rate, abnormal bleeding, urinary retention, seizures.
Long-Term Effects
- Potential for withdrawal symptoms upon discontinuation (e.g., irritability, nausea, dizziness, headache, paresthesia).
Adverse Drug Reactions (ADR)
- Severe allergic reactions (e.g., hives, difficulty breathing, swelling of face/tongue/throat).
- Serotonin Syndrome (e.g., fever, altered mental status, muscle rigidity).
Contraindications
- Hypersensitivity to levomilnacipran or milnacipran.
- Concurrent use of MAOIs or within 7 days of stopping MAOIs. Do not start MAOI within 14 days of stopping levomilnacipran.
- Concurrent use of linezolid or intravenous methylene blue.
Drug Interactions
- MAOIs: Risk of serotonin syndrome.
- CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): Increased levomilnacipran levels.
- CYP3A4 inducers (e.g., rifampin): Decreased levomilnacipran levels.
- Serotonergic drugs (e.g., SSRIs, triptans, tramadol): Increased risk of serotonin syndrome.
- Alcohol: May increase the rate of levomilnacipran release from the extended-release capsules.
- CNS depressants: Additive sedative effects.
- Antiplatelet/anticoagulants: Increased bleeding risk.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (Data in pregnant women are insufficient. Animal data show reduced fetal weight and delayed skeletal ossification, but no malformations. Use only if the potential benefit outweighs potential fetal risks.)
- Breastfeeding: Levomilnacipran is likely present in breast milk. Use with caution, especially with newborns or preterm infants. Monitor infant for sedation, poor feeding, and weight gain. Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for levomilnacipran and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition.
Drug Profile Summary
- Mechanism of Action: SNRI - inhibits serotonin and norepinephrine reuptake.
- Side Effects: Nausea, constipation, dizziness, hyperhidrosis, insomnia, sexual dysfunction, serotonin syndrome, suicidal ideation.
- Contraindications: Hypersensitivity, MAOIs, linezolid, intravenous methylene blue.
- Drug Interactions: MAOIs, CYP3A4 inhibitors/inducers, serotonergic drugs, alcohol.
- Pregnancy & Breastfeeding: Use with caution. Monitor infant if breastfeeding.
- Dosage: 40-120 mg once daily (adjustments for renal impairment).
- Monitoring Parameters: Blood pressure, heart rate, mental status, suicidal ideation, symptoms of serotonin syndrome, sodium levels.
Popular Combinations
No information about popular drug combinations involving levomilnacipran was found in the provided materials.
Precautions
- General Precautions: Monitor for suicidality, worsening of depression, serotonin syndrome, hyponatremia, bleeding, mania/hypomania, blood pressure changes, and angle-closure glaucoma. Avoid abrupt discontinuation. Screen for bipolar disorder.
- Specific Populations: See “Dosage - Special Cases.”
- Lifestyle Considerations: Limit or avoid alcohol. Avoid driving or operating machinery until effects are known.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Levomilnacipran?
A: Initial: 20 mg once daily for 2 days, then 40 mg once daily. Maintenance: 40-120 mg once daily. Maximum: 120 mg/day. Adjust for renal impairment and drug interactions.
Q2: What are the common side effects of Levomilnacipran?
A: Nausea, constipation, hyperhidrosis, dizziness, insomnia, headache, dry mouth, decreased appetite, sexual dysfunction.
Q3: What are the serious side effects of Levomilnacipran?
A: Serotonin syndrome, suicidal thoughts, hyponatremia, mania/hypomania, increased blood pressure/heart rate, abnormal bleeding, seizures, angle-closure glaucoma, urinary retention.
Q4: Can Levomilnacipran be used in children?
A: No, levomilnacipran is not approved for use in pediatric patients.
Q5: What are the contraindications for Levomilnacipran?
A: Hypersensitivity, concurrent MAOI use, concurrent linezolid or intravenous methylene blue use.
Q6: What are the major drug interactions with Levomilnacipran?
A: MAOIs, CYP3A4 inhibitors/inducers, serotonergic medications, alcohol, CNS depressants.
Q7: Can Levomilnacipran be used during pregnancy and breastfeeding?
A: Use with caution. Consult a healthcare professional to weigh the potential risks and benefits. Monitor infants who are breastfed.
Q8: Is it necessary to adjust the dose of Levomilnacipran for patients with liver disease?
A: No, dose adjustment is not required for patients with hepatic impairment.
Q9: How should Levomilnacipran be discontinued?
A: Taper the dose gradually to minimize the risk of withdrawal symptoms. Do not discontinue abruptly.
Q10: What is the mechanism of action of Levomilnacipran?
A: It’s an SNRI that inhibits the reuptake of serotonin and norepinephrine, primarily norepinephrine. This increases the levels of these neurotransmitters in the brain, which are believed to play a crucial role in mood regulation.
