brexpiprazole

Brexpiprazole is an oral atypical antipsychotic used to treat schizophrenia, major depressive disorder, and agitation associated with dementia due to Alzheimer's disease. Other atypical antipsychotic drugs include olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), and aripiprazole (Abilify).

Atypical antipsychotics differ from typical antipsychotics because they cause a lesser degree of movement (extrapyramidal) side effects and constipation.

The exact mechanism of action of brexpiprazole is not known, but, like other anti-psychotics, it is believed that brexpiprazole affects the way the brain works by interfering with communication among the brain's nerves.

Nerves communicate with each other by making and releasing chemicals called neurotransmitters. The neurotransmitters travel to other nearby nerves where they attach to receptors on the nerves. The attachment of the neurotransmitters either stimulates or inhibits the function of the nearby nerves. Brexpiprazole blocks several of the receptors on nerves including dopamine type 2, serotonin type 2, and alpha 2 adrenergic receptors. It is believed that many psychotic illnesses are caused by abnormal communication among nerves in the brain and that by altering communication through neurotransmitters, brexpiprazole can alter the psychotic state.

The FDA approved Rexulti in December, 2006.

Increased Mortality in Elderly Patients with Dementia-Related Psychosis; and Suicidal Thoughts and Behaviors

• Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Rexulti is not approved for the treatment of patients with dementia-related psychosis without agitation associated with dementia due to Alzheimer's disease.

Suicidal Thoughts and Behaviors

• Antidepressants increased the risk of suicidal thoughts and behaviors in patients aged 24 years and younger in short-term studies.
• Monitor closely for clinical worsening and for emergence of suicidal thoughts and behaviors.
• The safety and efficacy of Rexulti have not been established in pediatric patients with MDD.

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.

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Administer Rexulti orally, once daily with or without food

Recommended Dosage for Adjunctive Treatment of Major Depressive Disorder (Adults)

The recommended starting Rexulti dosage for the adjunctive treatment of MDD in adults is 0.5 mg or 1 mg once daily. Titrate to 1 mg once daily, then titrate to the target dosage of 2 mg once daily (based on the patient’s clinical response and tolerability, increase the dosage at weekly intervals). The maximum recommended daily dosage is 3 mg. Periodically reassess to determine the continued need and appropriate dosage for treatment.

Recommended Dosage for Schizophrenia (Adults and Pediatric Patients 13 to 17 Years)

Adults

The recommended starting Rexulti dosage for the treatment of schizophrenia in adults is 1 mg once daily on Days 1 to 4. Titrate to 2 mg once daily on Day 5 through Day 7. On Day 8, the dosage can be increased to the maximum recommended daily dosage of 4 mg based on clinical response and tolerability. The recommended target dosage is 2 mg to 4 mg once daily.

Pediatric Patients (13 to 17 Years Of Age)

The recommended starting Rexulti dosage for the treatment of schizophrenia in pediatric patients 13 to 17 years of age is 0.5 mg taken orally once daily on Days 1 to 4. On Days 5 through 7, titrate to 1 mg per day and on Day 8 titrate to 2 mg based on clinical response and tolerability. Weekly dose increases can be made in 1 mg increments. A recommended target dosage is 2 to 4 mg once daily. The maximum recommended daily dosage is 4 mg.

Recommended Dosage for Agitation Associated with Dementia Due to Alzheimer’s Disease

The recommended starting Rexulti dosage for the treatment of agitation associated with dementia due to Alzheimer’s disease is 0.5 mg taken once daily on Days 1 to 7. Increase the dosage on Days 8 through 14 to 1 mg once daily, and on Day 15 to 2 mg once daily. The recommended target dose is 2 mg once daily. The dosage can be increased to the maximum recommended daily dosage of 3 mg once daily after at least 14 days, based on clinical response and tolerability.

Recommended Dosage in Patients with Hepatic Impairment

The maximum recommended dosage in patients with moderate to severe hepatic impairment (Child-Pugh score ≥7) is.

• 2 mg once daily in patients with MDD or agitation associated with dementia due to Alzheimer’s disease, and
• 3 mg orally once daily in patients with schizophrenia

Recommended Dosage in Patients with Renal Impairment

The maximum recommended dosage in patients with creatinine clearance CrCl<60 mL/minute is.

• 2 mg orally once daily in patients with MDD or agitation associated with dementia due to Alzheimer’s disease and
• 3 mg orally once daily in patients with schizophrenia

Dosage Modifications for CYP2D6 Poor Metabolizers and for Concomitant Use with CYP Inhibitors or Inducers

Dosage modifications are recommended in patients who are known cytochrome P450 (CYP) 2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors, CYP2D6 inhibitors, or strong CYP3A4 inducers (see Table 1). If the concomitant drug is discontinued, adjust the Rexulti dosage to its original level. If the concomitant CYP3A4 inducer is discontinued, reduce the Rexulti dosage to the original level over 1 to 2 weeks.

Table 1 Dosage Modifications of Rexulti for CYP2D6 Poor Metabolizers and for Concomitant Use with CYP3A4 Inhibitors, CYP2D6 Inhibitors, or CYP3A4 Inducers

Brexpiprazole can cause low blood pressure especially when standing up from a sitting down or laying down position (orthostatic hypotension). Therefore, brexpiprazole should be used cautiously with other drugs also associated with causing orthostatic hypotension.

Brexpiprazole is metabolized or broken down by liver enzymes. Drugs that induce these enzymes will increase their activity and consequently decrease blood levels of brexpiprazole. The dose of brexpiprazole should be increased in people also taking carbamazepine (Tegretol), rifampin (Rifadin), St. John's Wort, and other drugs that may decrease its blood levels.

Drugs that block the action of enzymes that breakdown brexpiprazole will increase blood levels and side effects of brexpiprazole. The dose of brexpiprazole should be reduced in people who are also taking itraconazole (Sporanox), clarithromycin (Biaxin), ketoconazole, paroxetine (Paxil), fluoxetine (Prozac), quinidine, and other drugs that may increase its blood levels. The dose of brexpiprazole also should be reduced in people whose liver enzymes are less active than the general population.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.”

Unborn babies exposed to antipsychotics during the third trimester of pregnancy are at risk for extrapyramidal and withdrawal symptoms after birth. Symptoms reported included agitation, hypertonia, hypotonia, tremor, somnolence, depressed breathing, and feeding disorder. Currently there is no data on the use of brexpiprazole during pregnancy. Brexpiprazole should only be used during pregnancy if the potential benefit outweighs the potential for side effects in the unborn baby.

A pregnancy exposure registry has been established to monitor the use of atypical antipsychotics, including brexpiprazole, during pregnancy. If you are pregnant and taking atypical antipsychotics, you are advised to enroll in this pregnancy registry and report any side effects.

Brexpiprazole is known to enter human milk but its effects on the breastfeeding infant or milk production is not yet known.