Vortioxetine

Yes

To avoid the risk of serotonin syndrome, a rare but serious disorder caused by abnormally high levels of serotonin in the body, vortioxetine should not be used in combination or within 14 days of treatment with monoamine oxidase inhibitors (MOAI). Conversely, treatment with MAOI should not be started until 21 days have passed after stopping vortioxetine.

The potential risk of serotonin syndrome also exists when vortioxetine is co-administered with other drugs that also affect serotonin levels in the brain. Examples of such drugs include:

• Several classes of commonly used antidepressants such as:
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin norepinephrine reuptake inhibitors (SNRIs)
  • Tricyclic antidepressants (TCAs)
• Triptans used to treat migraine headaches
• Products containing (this is not a complete list):
  • tryptophan
  • tramadol (Ultram, Ultram ER, Conzip),
  • St. John's Wort,
  • Amphetamines,
  • methylphenidate (Concerta, Ritalin, Daytrana, Metadate)
  • buspirone (BuSpar)

Serotonin plays an important role in forming blood clots. Use of vortioxetine may increase the risk of bleeding, especially if taken with:

• the blood thinner warfarin (Coumadin or Jantoven),
• aspirin, or
• nnon-steroidal anti-inflammatory drugs (NSAIDS) such as:
  • ibuprofen (Motrin),
  • naproxen (Naprosyn), and
  • indomethacin (Indocin).

Vortioxetine is extensively metabolized or broken down by the CYP2D6 liver enzymes. Strong CYP2D6 inhibitors may increase the blood levels of vortioxetine, and consequently increase the risk for side effects. Examples of strong CYP2D6 inhibitors are bupropion (Wellbutrin), paroxetine (Paxil), and quinidine (Quin-Tab). The dose of vortioxetine should be reduced by half when co-administered with such agents.

Conversely, strong CYP2D6 inducers may decrease the blood levels of vortioxetine, resulting in poor treatment outcomes. Dose of vortioxetine should be increased when administered with strong CYP2D6 inducers such as rifampin (Rimactane), carbamazepine (Tegretol), and phenytoin (Dilantin).

Pregnancy

A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy; the women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants; consider risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum

Exposure to serotonergic antidepressants in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN); monitor neonates who were exposed to therapy in the third trimester of pregnancy for PPHN and drug discontinuation syndrome

Lactation

There is no information regarding presence of vortioxetine in human milk, effects on the breastfed infant, or effects on milk production; vortioxetine is present in rat milk; developmental and health benefits of breastfeeding should be considered along with mother's clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal condition

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Vortioxetine is an antidepressant that affects chemicals in the brain that may become unbalanced.

Vortioxetine is used to treat major depressive disorder in adults.

Vortioxetine may also be used for purposes not listed in this medication guide.

You should not use vortioxetine if you are being treated with linezolid or methylene blue injection.

Do not use an MAO inhibitor within 14 days before you take vortioxetine. A dangerous drug interaction could occur. MAO inhibitors include isocarboxazid, phenelzine, rasagiline, selegiline, tranylcypromine, and others. After you stop taking vortioxetine you must wait at least 21 days before you start taking an MAO inhibitor.

Some young people have thoughts about suicide when first taking an antidepressant. Your doctor will need to check your progress at regular visits while you are using vortioxetine. Your family or other caregivers should also be alert to changes in your mood or symptoms.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Do not give vortioxetine to anyone younger than 18 years old without the advice of a doctor. Vortioxetine is not approved for use in children.

You should not use this medicine if you are allergic to vortioxetine, or if you are being treated with linezolid or methylene blue injection.

Do not use an MAO inhibitor within 14 days before you take vortioxetine. A dangerous drug interaction could occur. MAO inhibitors include isocarboxazid, phenelzine, rasagiline, selegiline, tranylcypromine, and others. After you stop taking vortioxetine you must wait at least 21 days before you start taking an MAO inhibitor.

Do not give vortioxetine to anyone younger than 18 years old without the advice of a doctor. Vortioxetine is not approved for use in children.

To make sure vortioxetine is safe for you, tell your doctor if you have:

• bipolar disorder (manic depression), or a history of drug abuse or suicidal thoughts;
• liver disease;
• narrow-angle glaucoma;
• seizures or epilepsy;
• bleeding or blood clotting disorder;
• low levels of sodium in your blood;
• if you take aspirin or a blood thinner (warfarin, Coumadin, Jantoven); or
• if you use a "triptan" migraine headache medicine.

Some young people have thoughts about suicide when first taking an antidepressant. Your doctor will need to check your progress at regular visits while you are using vortioxetine. Your family or other caregivers should also be alert to changes in your mood or symptoms.

Taking an SSRI antidepressant during pregnancy may cause heart defects, serious lung problems, or other complications in the baby. However, you may have withdrawal symptoms or a relapse of depression if you stop taking your antidepressant. Tell your doctor right away if you become pregnant while taking vortioxetine. Do not start or stop taking this medicine during pregnancy without your doctor's advice.

It is not known whether vortioxetine passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take vortioxetine with or without food.

Do not stop using vortioxetine suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using vortioxetine.

Store at room temperature away from moisture and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Serious side effects have been reported with vortioxetine including the following:

• Hypersensitivity. Tell your healthcare provider right away if you have some or all of the following symptoms of hypersensitivity.
  • chest pain
  • swelling of the face, eyes, lips, tongue, arms, or legs
  • difficulty breathing or swallowing
  • rash
• Angioedema. Tell your healthcare provider right away if you have signs or symptoms of angioedema, which include the following:
  • swelling of face, eyes, lips, tongue, larynx and extremities
  • difficulty in swallowing or breathing
  • hoarseness (having difficulty making sounds when trying to speak)

• Low levels of salt (sodium) in your blood. Symptoms of this may include the following:
  • headache
  • difficulty concentrating
  • memory changes
  • confusion
  • weakness and unsteadiness on your feet

• Serotonin syndrome. Tell your healthcare provider right away if you have signs or symptoms of serotonin syndrome, which include the following:
  • agitation, hallucinations, coma or other changes in mental status
  • problems controlling your movements or muscle twitching
  • fast heartbeat
  • high or low blood pressure
  • sweating or fever
  • nausea or vomiting
  • diarrhea
  • muscle stiffness or tightness
• Abnormal bleeding. Tell your healthcare provider right away if you have signs or symptoms of bleeding.
• Suicide risk. Tell your healthcare provider right away if you have sudden changes in mood, behavior, thoughts, or feelings, which may include the following:
  • attempts to commit suicide
  • acting aggressive, being angry or violent
  • thoughts about suicide or dying
  • new or worse depression
• Hypomania (manic episodes). Tell your healthcare provider right away if you have any of the following signs or symptoms:
  • greatly increased energy
  • severe problems sleeping
  • racing thoughts
  • reckless behavior
  • unusually grand ideas
  • excessive happiness or irritability
  • talking more or faster than usual

Vortioxetine can cause dizziness. Do not drive or operate heavy machinery until you know how vortioxetine affects you.

Do not take vortioxetine if you:

• are allergic to vortioxetine or to any of its ingredients
• take a monoamine oxidase inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid
• if you stopped taking an MAOI in the last 14 days

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if vortioxetine crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using vortioxetine.

If you take too much vortioxetine, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

 If vortioxetine is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

• Store vortioxetine at room temperature between 59°F to 86°F (15°C to 30°C).
• Keep vortioxetine and all medicines out of the reach of children.

Do not use this medicine if you have used an MAO inhibitor in the past 14 days, such as isocarboxazid, methylene blue injection, phenelzine, rasagiline, selegiline, or tranylcypromine. After you stop taking vortioxetine you must wait at least 21 days before you start taking an MAO inhibitor.

Some young people have thoughts about suicide when first taking an antidepressant. Stay alert to changes in your mood or symptoms. Report any new or worsening symptoms to your doctor.

In the U.S.

• Trintellix

Available Dosage Forms:

• Tablet

Therapeutic Class: Antidepressant

Chemical Class: Piperazine (class)

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time vortioxetine is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take vortioxetine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to vortioxetine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Inhibits reuptake of serotonin (5-HT); also has agonist activity at the 5-HT1A receptor and antagonist activity at the 5-HT3 receptor.

Distribution

Vd: 2,600 L

Metabolism

Hepatic primarily through oxidation via CYP450 isoenzymes, primarily CYP2D6, and subsequent glucuronic acid conjugation to an inactive carboxylic acid metabolite.

Excretion

Urine (59%); feces (26%)

Therapeutic: 2 to 4 weeks

Time to Peak

7 to 11 hours

Half-Life Elimination

~66 hours

Protein Binding

98%

>10%:

Central nervous system: Female sexual disorder (self-reporting: 1% to 2%; Arizona Sexual Experience Scale: 22% to 34%), male sexual disorder (self-reporting: 3% to 5%; Arizona Sexual Experience Scale: 16% to 29%)

Gastrointestinal: Nausea (dose-related, females > males, 21% to 32%; commonly occurs within the first week of treatment, then decreases in frequency but can persist in some patients)

1% to 10%:

Central nervous system: Dizziness (8% to 9%), abnormal dreams (2% to 3%)

Dermatologic: Pruritus (2% to 3%)

Gastrointestinal: Diarrhea (7% to 10%), xerostomia (7% to 8%), constipation (5% to 6%), vomiting (3% to 6%), flatulence (2% to 3%)

<1%, postmarketing, and/or case reports: Acute pancreatitis, angle-closure glaucoma, dysgeusia, dyspepsia, flushing, hypomania, hyponatremia, mania, seizure, serotonin syndrome, skin rash, vertigo, weight gain, withdrawal syndrome

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, dry mouth, dizziness, diarrhea, or constipation. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of low sodium (headache, difficulty focusing, memory impairment, confusion, weakness, seizures, or change in balance), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), behavioral changes, agitation, irritability, panic attacks, insomnia, severe dizziness, passing out, sexual dysfunction, vision changes, eye pain, eye irritation, or signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, severe diarrhea) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Mild renal dysfunction to end stage renal disease: No adjustment recommended.

Mild to moderate hepatic dysfunction: No adjustment recommended.
Severe hepatic dysfunction: Not recommended.