Brexpiprazole

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

High doses or long-term use of brexpiprazole can cause a serious movement disorder that may not be reversible. Symptoms of this disorder include uncontrollable muscle movements of your lips, tongue, eyes, face, arms, or legs. The longer you take brexpiprazole, the more likely you are to develop a serious movement disorder. The risk of this side effect is higher in women and older adults.

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.

Call your doctor at once if you have:

• severe agitation, distress, or restless feeling;
• a light-headed feeling, like you might pass out;
• trouble swallowing;
• feelings of warmth, intolerance to heat;
• thoughts about suicide or hurting yourself;
• twitching or uncontrolled muscle movements;
• a seizure (convulsions);
• high blood sugar--increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, weight loss;
• low blood cell counts--sudden weakness or ill feeling, fever, chills, sore throat, swollen gums, painful mouth sores, red or swollen gums, skin sores, cold or flu symptoms, cough, trouble breathing; or
• a severe nervous system reaction--very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out.

Common side effects may include:

• weight gain;
• dizziness, drowsiness; or
• agitation, feeling restless.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

The most common side effects include

• drowsiness,
• weight gain,
• headache,
• upper respiratory tract infection,
• constipation,
• feeling restless or difficulty sitting still (akathisia), and
• tremors.

Brexpiprazole may increase blood levels of prolactin.

Less common but serious side effects include:

• Increased risk of stroke and death in elderly patients with dementia-related psychosis.
• Neuroleptic malignant syndrome (NMS). NMS is a rare but serious side effect associated with the use of antipsychotics. NMS may result in death and must be treated in the hospital. Signs and symptoms of NMS may include
  • high fever,
  • sweating (diaphoresis),
  • severe muscle stiffness or rigidity,
  • confusion,
  • loss of consciousness,
  • high blood pressure,
  • rapid heartbeat, and
  • changes in breathing.

Extrapyramidal side effects (EPS) including:

• Dystonia: painful spasms of the oral, throat, or neck muscles that may cause problems with speech, swallowing, and stiff neck.
• Pseudoparkinsonism: drug induced Parkinson's symptoms.
• Tardive dyskinesia (TD). Tardive dyskinesia usually occurs after long-term use of antipsychotics and usually presents with abnormal uncontrollable movement problems affecting the tongue, lips, jaw, face, and extremities.
• Metabolic changes including high blood sugar (hyperglycemia), diabetes, increase in blood cholesterol, and weight gain.
• High blood levels of prolactin. Prolactin is a hormone that allows the production of breast milk. High levels of prolactin may cause menstrual abnormalities, leakage of milk from the breast, development of breasts in males (gynecomastia), and erection problems in men.
• Brexpiprazole may increase risk of seizures.

Tablets: 0.25, 0.5, 1, 2, 3, and 4 mg

Brexpiprazole should be stored at room temperature, between 15 C and 30 C (59 F and 86 F).

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Brexpiprazole is a prescription medication used to treat the symptoms of major depressive disorder (MDD) and schizophrenia in adults. It belongs to a group of drugs called atypical antipsychotics. These medications work by altering the activity of certain natural substances in the brain.

This medication comes in tablet form and is usually taken once a day, with or without food.

Common side effects of brexpiprazole include weight gain, headache, and restlessness.

Brexpiprazole can also cause drowsiness. Do not drive or operate heavy machinery until you know how brexpiprazole affects you.

Before taking brexpiprazole, tell your healthcare provider if you: 

• have diabetes or high blood sugar or a family history of diabetes or high blood sugar. Your healthcare provider should check your blood sugar before you start brexpiprazole and during your treatment. 
• have high levels of cholesterol, triglycerides, LDL-cholesterol, or low levels of HDL cholesterol 
• have or had seizures (convulsions)
• have or had abnormal thyroid tests
• have or had low or high blood pressure
• have or had heart problems or a stroke
• have or had low white blood cell count 
• are pregnant or plan to become pregnant. It is not known if brexpiprazole may harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if brexpiprazole passes into your breast milk. You and your healthcare provider should decide if you will take brexpiprazole or breastfeed. 

Tell your healthcare provider about all the medicines you take or recently have taken, including prescription medicines, non-prescription medicines, vitamins and herbal supplements. 

• Store brexpiprazole at room temperature
• Keep this and all medicines out of the reach of children

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

High doses or long-term use of brexpiprazole can cause a serious movement disorder that may not be reversible. Symptoms of this disorder include uncontrollable muscle movements of your lips, tongue, eyes, face, arms, or legs. The longer you take brexpiprazole, the more likely you are to develop a serious movement disorder. The risk of this side effect is higher in women and older adults.

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.

Call your doctor at once if you have:

• severe agitation, distress, or restless feeling;

• a light-headed feeling, like you might pass out;

• trouble swallowing;

• feelings of warmth, intolerance to heat;

• thoughts about suicide or hurting yourself;

• twitching or uncontrolled muscle movements;

• a seizure (convulsions);

• high blood sugar--increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, weight loss;

• low blood cell counts--sudden weakness or ill feeling, fever, chills, sore throat, swollen gums, painful mouth sores, red or swollen gums, skin sores, cold or flu symptoms, cough, trouble breathing; or

• a severe nervous system reaction--very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out.

Common side effects may include:

• weight gain; or

• feeling restless or being unable to sit still.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Atypical or second-generation antipsychotic agent.1 6 7 8

General

• Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments.1 92 93 94 (See Worsening of Depression and Suicidality Risk under Cautions.)

Administration

Oral Administration

Administer tablets orally once daily without regard to meals.1 (See Food under Pharmacokinetics.)

Dosage

If used with a CYP2D6 and/or CYP3A4 inhibitor or a CYP3A4 inducer, dosage adjustment may be required.1 (See Interactions.)

Adults

As adjunctive treatment with antidepressants, initially, 0.5 or 1 mg once daily.1 Increase dosage to 1 mg once daily, then up to the target dosage of 2 mg once daily.1 Adjust dosage at weekly intervals based on individual patient response and tolerability.1

Periodically reassess need for continued therapy and appropriate dosage.1

Initially, 1 mg once daily on days 1–4, followed by 2 mg once daily on days 5–7.1 May increase dosage to 4 mg once daily on day 8 based on individual patient response and tolerability.1 Recommended target dosage is 2–4 mg once daily.1

In patients with remitted first or multiple episodes, APA recommends either indefinite maintenance therapy or gradual discontinuance of the antipsychotic with close follow-up and a plan to reinstitute treatment upon symptom recurrence.28 Consider antipsychotic therapy discontinuance only after ≥1 year of symptom remission or optimal response while receiving the drug.28 Indefinite maintenance treatment recommended if patient has experienced multiple previous psychotic episodes or 2 episodes within 5 years.28

Prescribing Limits

Adults

Maximum 3 mg daily.1

Maximum 4 mg daily.1

Special Populations

Hepatic Impairment

Mild hepatic impairment: Manufacturer makes no specific dosage adjustment recommendations.1

Moderate to severe hepatic impairment (Child-Pugh score ≥7): Do not exceed 2 mg once daily.1

Mild hepatic impairment: Manufacturer makes no specific dosage adjustment recommendations.1

Moderate to severe hepatic impairment (Child-Pugh score ≥7): Do not exceed 3 mg once daily.1

Renal Impairment

Moderate, severe, or end-stage renal impairment (Clcr <60 mL/minute): Do not exceed 2 mg once daily.1

Moderate, severe, or end-stage renal impairment (Clcr <60 mL/minute): Do not exceed 3 mg once daily.1

Geriatric Patients

Cautious dosage selection recommended, usually starting at the lower end of the recommended dosage range, reflecting the greater frequency of decreased hepatic, renal, and cardiac function and concomitant illnesses and other drug therapy in this population.1

Gender, Race, or Smoking Status

Dosage adjustment not required based on gender, race, or smoking status.1

Poor Metabolizers of CYP2D6

Reduce brexpiprazole dosage by 50%.1 (See Special Populations under Pharmacokinetics.) In poor CYP2D6 metabolizers who are also taking moderate or potent CYP3A4 inhibitors, reduce brexpiprazole dosage to 25% of the usual dosage.1 (See Interactions.)

Storage

Oral

20–25°C (may be exposed to 15–30°C).1

• Exact mechanism of action in major depressive disorder and schizophrenia unknown; efficacy may be mediated through a combination of partial agonist activity at dopamine type 2 (D2) and serotonin type 1 (5-hydroxytryptamine [5-HT1A]) receptors and antagonist activity at serotonin type 2 (5-HT2A) receptors.1

• Demonstrates partial agonist activity at D2 and D3 receptors and 5-HT1A receptors and antagonist activity at 5-HT2A, 5-HT2B, and 5-HT7 receptors and α1A-, α1B-, α1D-, and α2C-adrenergic receptors.1 6 7 8 9

• Compared with aripiprazole, brexpiprazole appears to have lower intrinsic activity at D2 receptors and higher activity at 5-HT1A and 5-HT1B receptors and demonstrates stronger antagonism at 5-HT2A receptors.2 4 7 8 9

• Exhibits moderate affinity for histamine (H1) receptors, which are associated with sedation, and very low affinity for muscarinic (M1) receptors.1 4 9

• OPC-34712

• Rexulti

Initial dose: 0.5 mg or 1 mg orally once a day
Titration: Based on clinical response and tolerability, dose increases should be done at weekly intervals; titrate to 1 mg once a day, then up 2 mg once a day.
Target dose: 2 mg orally once a day
Maximum dose: 3 mg per day

Use: Adjunctive treatment of major depressive disorder.

Dose selection should be cautious, usually starting at the low end of the dosing range.