Fetzima Titration Pack

Levomilnacipran is a selective serotonin and norepinephrine reuptake inhibitor (SNRI). It potently inhibits the reuptake of both serotonin (5-HT) and norepinephrine (NE) into presynaptic neurons, with greater potency for norepinephrine reuptake inhibition (NE:5-HT reuptake inhibition ratio of approximately 1:2). This dual action is thought to enhance the availability of these neurotransmitters in the synaptic cleft, thereby modulating mood and behavior.

Urgent Side Effects: Seek Medical Help Right Away

Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:

Signs of an allergic reaction, such as:
+ Rash or hives
+ Itching or red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing or tightness in the chest or throat
+ Difficulty breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of bleeding, including:
+ Vomiting or coughing up blood
+ Vomit that resembles coffee grounds
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding from the gums
+ Abnormal vaginal bleeding
+ Unexplained bruises or bruises that increase in size
+ Uncontrollable bleeding
Signs of low sodium levels, such as:
+ Headache
+ Difficulty focusing or memory problems
+ Feeling confused or weak
+ Seizures or changes in balance
Signs of high blood pressure, including:
+ Severe headache or dizziness
+ Fainting or changes in vision
Fast or abnormal heartbeat
Seizures
Feeling extremely tired or weak
Difficulty urinating
Sex-related problems, such as:
+ Decreased interest in sex
+ Difficulty having an orgasm
+ Ejaculation problems
+ Trouble getting or maintaining an erection
A potentially life-threatening condition called serotonin syndrome, which may be more likely to occur if you are taking certain other medications. Symptoms include:
+ Agitation
+ Changes in balance or coordination
+ Confusion
+ Hallucinations
+ Fever
+ Fast or abnormal heartbeat
+ Flushing
+ Muscle twitching or stiffness
+ Seizures
+ Shivering or shaking
+ Excessive sweating
+ Severe diarrhea, stomach upset, or vomiting
+ Severe headache

Other Possible Side Effects

Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it is essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor:

Upset stomach or vomiting
Constipation
* Excessive sweating

This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.

Before Taking This Medication: Important Information to Share with Your Doctor

It is essential to inform your doctor about the following:

Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced.
If you have kidney disease, as this may affect how your body processes the medication.
If you have narrow angle glaucoma or are at risk of developing it.
If you are currently taking or have recently taken certain medications, including:
+ Linezolid or methylene blue, as these can interact with this medication.
+ Drugs for depression or Parkinson's disease, such as isocarboxazid, phenelzine, tranylcypromine, selegiline, or rasagiline, within the last 14 days. Combining these medications can lead to very high blood pressure.
* Other health problems or medications you are taking, including prescription and over-the-counter drugs, natural products, and vitamins. This is not an exhaustive list, and it is crucial to discuss all your medications and health issues with your doctor.

To ensure your safety, it is vital to consult with your doctor and pharmacist about all your medications and health problems before taking this medication. Do not start, stop, or change the dose of any medication without first consulting your doctor to confirm it is safe to do so.

It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.

Before engaging in activities that require your full attention, such as driving, wait until you understand how this medication affects you.

To minimize the risk of side effects, do not abruptly stop taking this medication without first consulting your doctor. If you need to discontinue use, your doctor will provide guidance on how to gradually taper off the medication.

As directed by your doctor, regularly schedule blood tests and other laboratory exams to monitor your condition. Additionally, check your blood pressure and heart rate as instructed by your doctor.

While taking this medication, it is recommended that you avoid consuming alcohol. Before using marijuana, cannabis products, or prescription and over-the-counter medications that may cause drowsiness, consult with your doctor.

Be aware that this medication may increase the risk of bleeding, which can be life-threatening in some cases. Discuss this risk with your doctor.

Certain individuals may be at a higher risk of developing eye problems while taking this medication. Your doctor may recommend an eye exam to assess your risk. If you experience eye pain, changes in vision, or swelling and redness around the eye, contact your doctor immediately.

This medication can cause low sodium levels, which can be life-threatening and lead to seizures, loss of consciousness, breathing difficulties, or death.

If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.

If you are pregnant, planning to become pregnant, or may be pregnant, discuss the benefits and risks of taking this medication with your doctor. Using this medication during the third trimester of pregnancy may increase the risk of bleeding after delivery and potentially cause health problems in the newborn.

If you are breastfeeding, consult with your doctor to discuss any potential risks to your baby.

• Monoamine Oxidase Inhibitors (MAOIs) (concurrent use or within 14 days of discontinuing MAOI or levomilnacipran)
• Linezolid (an antibiotic with MAOI activity)
• Methylene Blue (intravenous, with MAOI activity)

• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir, saquinavir, telithromycin, nefazodone) - may significantly increase levomilnacipran exposure.
• Other serotonergic drugs (e.g., SSRIs, other SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, St. John's Wort) - increased risk of serotonin syndrome.
• Drugs that impair platelet aggregation (e.g., NSAIDs, aspirin, warfarin) - increased risk of bleeding.

• Moderate CYP3A4 inhibitors (e.g., erythromycin, diltiazem, verapamil, grapefruit juice) - may increase levomilnacipran exposure.
• Alcohol - may increase CNS depressant effects.

• Not specifically listed for minor interactions, but general caution with other CNS depressants.

• Worsening depression
• Suicidal thoughts or behavior (especially in young adults)
• Unusual changes in behavior (e.g., agitation, irritability, anxiety, panic attacks, insomnia, impulsivity, aggression, akathisia, hypomania, mania)
• Signs of serotonin syndrome (e.g., agitation, hallucinations, delirium, coma, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia, tremor, rigidity, myoclonus, hyperreflexia, incoordination, gastrointestinal symptoms)
• Signs of hyponatremia (e.g., headache, difficulty concentrating, memory impairment, confusion, weakness, unsteadiness, falls, severe and more acute symptoms include hallucinations, syncope, seizure, coma, respiratory arrest)
• Increased blood pressure or heart rate
• Abnormal bleeding or bruising
• Urinary hesitation or retention
• Visual disturbances (e.g., angle-closure glaucoma symptoms like eye pain, vision changes, swelling or redness in or around the eye)

Use during pregnancy should be avoided unless the potential benefit outweighs the potential risk to the fetus. Exposure during the third trimester may lead to complications in the neonate requiring prolonged hospitalization, respiratory support, and tube feeding. These complications can arise immediately upon delivery.

Levomilnacipran is excreted into human milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother and the potential for adverse reactions in the breastfed infant.

Safety and effectiveness have not been established in pediatric patients. Fetzima is not approved for use in pediatric patients. Antidepressants carry a Black Box Warning for increased risk of suicidal thoughts and behavior in children, adolescents, and and young adults (up to 24 years of age).

No overall differences in safety or effectiveness were observed between elderly subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients may be at increased risk for hyponatremia and falls. Dose adjustments for renal impairment are particularly important in this population.

• Fetzima Titration Pack is designed to help patients initiate therapy with a lower dose (20 mg) for 2 days before increasing to the standard 40 mg dose, which may help improve tolerability.
• Levomilnacipran has a higher affinity for norepinephrine reuptake inhibition compared to serotonin, which may differentiate its clinical profile from other SNRIs.
• Monitor blood pressure and heart rate regularly, especially during dose escalation, as dose-dependent increases can occur.
• Counsel patients on the importance of not abruptly stopping the medication to avoid withdrawal symptoms.
• Be vigilant for signs of serotonin syndrome, especially when co-administered with other serotonergic agents.
• Advise patients to report any unusual bleeding or bruising, particularly if they are also taking NSAIDs, aspirin, or anticoagulants.

• Other SNRIs (e.g., Venlafaxine, Desvenlafaxine, Duloxetine)
• SSRIs (e.g., Fluoxetine, Sertraline, Escitalopram, Paroxetine, Citalopram)
• Atypical antidepressants (e.g., Bupropion, Mirtazapine, Vortioxetine, Vilazodone)
• Tricyclic Antidepressants (TCAs)
• MAOIs (reserved for refractory cases)
• Psychotherapy (e.g., Cognitive Behavioral Therapy - CBT)
• Electroconvulsive Therapy (ECT)
• Transcranial Magnetic Stimulation (TMS)

If your symptoms or health problems do not improve or worsen over time, it is essential to contact your doctor for further evaluation and guidance. To ensure your safety and the effectiveness of your treatment, never share your medication with others or take someone else's medication.

This medication is accompanied by a Medication Guide, which is a comprehensive patient fact sheet. It is crucial to read this guide carefully and review it again whenever your prescription is refilled. If you have any questions or concerns about your medication, do not hesitate to consult with your doctor, pharmacist, or other healthcare provider.

In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide detailed information, including the name of the medication taken, the amount consumed, and the time it occurred.