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 OD for 2 days; increase to 40 mg OD
- After that, the dosage may be increased by increments of 40 mg every two or more days.
- Maintenance: 40 to 120 mg OD
- Maximum: 120 mg/day
- Initial:
-
Discontinuation of Levomilnacipran therapy:
- To reduce withdrawal symptoms and identify reemerging symptoms, the dose should be progressively decreased (for example, over a period of 2 to 4 weeks) after stopping antidepressant medication that has lasted for more than 3 weeks.
- The usage of a medication with a half life of less than 24 hours (such as paroxetine or venlafaxine), a prior history of antidepressant withdrawal symptoms, or large doses of antidepressants are causes for a slower titration (for example, over 4 weeks).
- The previously prescribed dose should be restarted and/or the dose should be lowered at a more gradual rate if unacceptable withdrawal symptoms develop.
- Tapering over more than three months may be beneficial for some individuals receiving long term treatment (>6 months), such as those with a history of discontinuation syndrome.
- Limited evidence is available that supports ideal taper rates.
MAO inhibitor recommendations:
-
A psychiatric condition is treated by using an MAO inhibitor, and switching to or from one:
- Levomilnacipran should be started 14 days after an MAO inhibitor used to treat psychiatric disorders has been stopped.
- It is recommended to wait 7 days before starting an MAO inhibitor after stopping Levomilnacipran.
Use in Children:
Not indicated
Pregnancy Risk Factor C
- Late in the third trimester, SSRI/SNRI may have nonteratogenic effects on the infant.
- These include hyperreflexia, hypoglycemia, hypo- or hypertonia, vomiting, feeding problems, seizures, and respiratory distress.
- The toxic effects of SSRIs and SNRIs or a withdrawal syndrome may be to blame for the symptoms. They might also be in line with the serotonin syndrome connected to SSRI use.
- Women with major depression and euthymic before pregnancy are more likely than women who continue to take antidepressant medication.
- Individualized treatment utilising SSRIs and SNRIs is advised by ACOG during pregnancy.
- The obstetrician's and primary care provider's clinical skills can be used to address depression during pregnancy.
- The American Psychiatric Association states that medication treatment has risks, but should be weighed against untreated depression.
- Women who have stopped taking antidepressant medication during pregnancy and are at high risk of developing postpartum depression can have their medications reintroduced.
- The ACOG & APA have developed treatment algorithms for women suffering from depression before conception and during pregnancy.
Use of levomilnacipran while breastfeeding
- It is unknown if breast milk contains levomilnacipran.
- The manufacturer recommends that the mother decide whether to stop nursing the infant or discontinue using the drug.
- This is in consideration of the possibility of serious adverse reactions in the infant.
Fetzima (Levomilnacipran) Dose in Kidney Disease:
- CrCl ≥60 mL/minute:
- Dose adjustment not necessary.
- CrCl 30 to 59 mL/minute:
- 80 mg OD (maximum).
- CrCl 15 to 29 mL/minute:
-
- 40 mg OD (maximum).
-
- End-stage renal disease (ESRD):
- Not recommended.
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):
- Use MAO inhibitors to treat mental illnesses concurrently, within seven days of quitting levomilnacipran, or within two weeks. Hypersensitivity to milnacipran, levomilnacipran, or any other ingredient of the formulation.
- A patient who has had intravenous linezolid or intravenous Methylene Blue starting levomilnacipran
Canadian labeling: Additional contraindications:
- Patients who have had a cardiac procedure or MI within the last year may use this medication.
- HF (NYHA Class I or II)
- Tachyarrhythmia uncontrolled
- Hypertension uncontrolled
- CVA's history.
Warnings and precautions
-
Bleeding Risk:
- Use of aspirin, NSAIDs or warfarin together can cause impaired platelet aggregation. This may increase the risk of bleeding events.
- Reports indicate that SNRI use can cause bleeding from minor to severe bruising and epistaxis to serious hemorhage.
-
Cardiovascular effects
- May increase BP & heart beat
- Before starting therapy, it is important to evaluate your BP and heart rate. This should also be done periodically.
- Patients with sustained hypertension and tachycardia should be considered for dose reductions or gradual discontinuation of therapy
- Patients with hypertension or tachyarrhythmias (eg atrial fibrillation) should be cautious.
-
Fractures
- Antidepressant treatment has been shown to be associated with bone fractures.
- Unexplained bone pain, tenderness, swelling or bruising in an antidepressant-treated person may indicate a fragility fracture.
-
Ocular effects
- Mild pupillary dilation may occur, which can in some cases lead to narrow-angle glaucoma.
- Patients who have not undergone an iridectomy to reduce the risk of narrow-angle glaucoma should be evaluated.
-
Serotonin syndrome
- Serotonin syndrome (SS), which can be life-threatening, has been reported with serotonergic drugs (eg SSRIs, SNRIs), especially when combined with other serotonergic medications (eg triptans TCAs, fentanyls, buspirones, tramadols, fentanyls, fentanyls, fentanyls, fentanyls, fentanyls, buspirones wort, tryptophan, MAOs to treat psychid, intravenous methyleneblue blue and linezolid]
- Serotonin syndrome symptoms such as:
- Mental status changes (eg. agitation, hallucinations and delirium)
- Autonomic instability (eg tachycardia or labile blood pressure, diaphoresis, etc.)
- Neuromuscular changes (eg tremors, rigidity, myoclonus, etc.)
- GI symptoms (eg nausea, vomiting, diarrhea)
- Seizures
- Stop taking any serotoninrgic medication or treatment if you notice signs or symptoms.
-
SIADH and Hyponatremia
- SSRIs, SNRIs, and SIADH have been linked to the development of hyponatremia. Hyponatremia is rare (including severe cases with serum salt 110 mmol/L).
- Age (the elderly), volume loss &/or concurrent diuretics use are all risk factors.
- Patients with hyponatremia should stop taking medication.
-
Retention or urinary hesitancy:
- Patients should report any symptoms of increased urinary resistance or hesitation.
- Patients with obstructive bladder conditions should be cautious.
-
Hypomania and mania:
- Mania and hypomania can occur in bipolar patients.
- Monotherapy is not advised for those with bipolar disorder.
- Bipolar disorder testing should be performed on patients who have depressed symptoms.
- The FDA has not authorised levomilnacipran for the treatment of bipolar disorder.
-
Renal impairment
- Be careful
- Plasma concentrations are higher when there is less clearance
- Patients with severe or mild renal impairment need to take less medication.
- Patients with ESRD should not be treated.
-
Seizure disorders
- Be careful.
Levomilnacipran: Drug Interaction
|
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:
- Clinically indicated serum sodium for at-risk populations
- Suicidal ideation, depression and mental status (especially when starting therapy or when dosages are increased/lowered).
- Serotonin syndrome symptoms
- Dosing purposes: Renal function
- Heart rate and blood pressure
- Patients at high risk of glaucoma or with baseline elevations should have intraocular pressure
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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 is the active enantiomer to milnacipran and is a powerful inhibitor of serotonin and norepinephrine reuptake.
Protein binding:
- 22%
Metabolism:
- Hepatic to inactive metabolites
Bioavailability:
- 92%
Half-life elimination:
- 12 hours
Time to peak:
- 6 to 8 hours
Excretion:
- Urine (58% as unchanged drug)
International Brands of Levomilnacipran:
- Fetzima
- Fetzima Titration
Levomilnacipran Brand Names in Pakistan:
No Brands Available in Pakistan.