levomilnacipran

Action and Spectrum

Actions and spectrum: 

levomilnacipran is a medication used to treat major depressive disorder (MDD) in adults. It belongs to serotonin-norepinephrine reuptake inhibitors (SNRIs), which acts by increasing the levels of serotonin and norepinephrine in the brain. 

levomilnacipran is selective serotonin and norepinephrine reuptake inhibitor (SSNRI), meaning it selectively inhibits the reuptake of serotonin and norepinephrine from the synaptic cleft, leading to increased levels of these neurotransmitters in the brain. It has a higher affinity for the serotonin transporter than for the norepinephrine transporter. 

Drug Interaction

Adverse Reaction

Frequency defined:  

>10% 

Nausea (17%)  

1-10% 

Increased heart rate (1%) 

Hot flush (1%) 

Decreased appetite (1%) 

Increased blood pressure (1%) 

Hypotension (1%) 

Hyperhidrosis (2%) 

Urinary hesitation, dose-related (4-6%) 

Vomiting (5%) 

Palpitations (5%) 

Tachycardia (6%) 

Erectile dysfunction (6-10%) 

Constipation (9%)  

<1% 

Ejaculation disorder 

Testicular pain  

Post marketing Results 

Takotsubo cardiomyopathy 

Black Box Warning

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Known hypersensitivity to levomilnacipran or its ingredients. 
• Concomitant use of Monoamine Oxidase Inhibitors (MAOIs) 
• Uncontrolled narrow-angle glaucoma. 

Caution: 

• Suicidal thoughts and behaviour: levomilnacipran increases the risk of suicidal thoughts and behavior, particularly in children, adolescents, and young adults. Close monitoring of patients for clinical worsening, suicidal thoughts or behavior, and unusual changes in behavior is recommended. 
• Serotonin syndrome: levomilnacipran can cause serotonin syndrome, a potentially life-threatening condition that occurs when there is an excess of serotonin in the body. Symptoms may include agitation, hallucinations, confusion, rapid heartbeat, high blood pressure, fever, sweating, tremors, muscle rigidity, and diarrhea. Concurrent use of other serotonergic drugs should be avoided. 
• Hypertension: levomilnacipran can increase blood pressure. Patients should monitor their blood pressure regularly, and dose adjustments may be necessary for those with hypertension or a history of cardiovascular disease. 
• Seizures: levomilnacipran can lower the seizure threshold, and in patients having seizures or conditions should be used with caution that lower the seizure threshold. 
• Hepatic impairment: levomilnacipran is metabolized in the liver, and dose adjustment is necessary in patients with hepatic impairment. 
• Renal impairment: levomilnacipran is excreted primarily in the urine, and dose adjustments may be necessary in patients with renal impairment. 
• Hyponatremia: levomilnacipran can cause hyponatremia (low sodium levels in the blood), particularly in elderly patients. Sodium levels should be monitored regularly, and dose adjustments may be necessary in patients with hyponatremia. 
• Glaucoma: levomilnacipran can increase intraocular pressure and in patients with narrow-angle glaucoma should be used with caution. 
• Pregnancy and breastfeeding: The safety of levomilnacipran during pregnancy and breastfeeding is not known.

Comorbidities: 

• Hypertension: levomilnacipran can increase blood pressure, so in patients with a history of hypertension or those who are currently receiving treatment for hypertension . 
• Seizures: levomilnacipran can increase the risk of seizures, so in patients with a history of seizures or those at risk for seizures it should be used with caution. 
• Suicidal thoughts or behaviours: levomilnacipran, like other antidepressants, can increase the risk of suicidal behaviors or thoughts, especially in young adults. 
• Mania or hypomania: levomilnacipran can cause mania or hypomania in patients with a history of bipolar disorder. 
• Bleeding disorders: levomilnacipran can increase the risk of bleeding, so it should be used with caution in patients with bleeding disorders or those taking anticoagulant medications. 
• Glaucoma: levomilnacipran can increase intraocular pressure, hence, it has to be used with caution in patients with glaucoma. 
• Hepatic impairment: levomilnacipran is metabolized in the liver, hence, it has to be used with caution in patients with hepatic impairment. 

Pregnancy / Lactation

Pregnancy consideration: Pregnancy Category C 

Lactation: not recommended as it gets excreted into human milk.  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

levomilnacipran is selective serotonin and norepinephrine reuptake inhibitor (SNRI). It acts by inhibiting the reuptake of serotonin and norepinephrine in the brain, increasing their concentration in the synaptic cleft and improving neurotransmission. 

The drug has a higher affinity for the serotonin transporter than the norepinephrine transporter. However, it still has a significant effect on the reuptake of norepinephrine, which is believed to contribute to its antidepressant effect.  

Pharmacodynamics: 

levomilnacipran is serotonin and norepinephrine reuptake inhibitor (SNRI) used as an antidepressant. It acts by inhibit the reuptake of both serotonin and norepinephrine into the presynaptic neurons, thereby increasing their availability in the synaptic cleft and enhancing neurotransmission. This leads to increased mood and decreased anxiety and depression symptoms in patients with major depressive disorder. 

levomilnacipran is a selective inhibitor of the serotonin and norepinephrine transporters, with minimal effects on other monoamine transporters such as dopamine and histamine. It is the levo-isomer of milnacipran and has greater selectivity for the serotonin and norepinephrine transporters than its parent compound.  

Pharmacokinetics: 

Absorption 

levomilnacipran is rapidly absorbed after oral administration with peak plasma concentration (Cmax) reached within 2 hours. 

Distribution 

levomilnacipran has a high volume of distribution (Vd) of approximately 1000 L, indicating extensive tissue distribution. It is highly bound to plasma proteins, with a protein binding of approximately 98%. 

Metabolism 

levomilnacipran is primarily metabolized in the liver via glucuronidation by uridine diphosphate glucuronosyltransferase (UGT) 1A3 and 2B7. The major metabolite is an inactive glucuronide conjugate. It is also a substrate of cytochrome P450 (CYP) 3A4, but to a lesser extent. 

Elimination and excretion 

levomilnacipran is eliminated primarily through the kidneys with approximately 70% of the administered dose excreted in the urine as unchanged drug or glucuronide conjugate. The elimination half-life (t1/2) is approximately 12 hours. 

Adminstartion

Administration: 

levomilnacipran is available in the form of an extended-release capsule for oral administration. The recommended dosage of levomilnacipran is 20 mg once daily, which can be increased to 40 mg once daily after two or more weeks of treatment if needed. The maximum recommended daily dosage is 120 mg.

The capsules should be administered whole and not crushed, chewed or dissolved. The dose should be tapered based on the patient’s response to treatment and tolerability. It is important to follow the instructions provided by the healthcare provider while taking levomilnacipran. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: levomilnacipran 

Pronounced: [ lee-voe-mil-na-si-pran ]  

Why do we use levomilnacipran? 

levomilnacipran is selective serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressant that is used to treat major depressive disorder (MDD) in adults. It is used to treat other psychiatric disorders such as anxiety disorders and neuropathic pain