Brexpiprazole - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

Overview:

Brexpiprazole is an atypical antipsychotic drug, a dopamine D2 receptor partial antagonist. The drug was approved by (FDA) Food and Drug Administration for schizophrenia on 10 July 2015. Brexpiprazole causes various dose-related side effects. Therefore, it is prescribed starting with a lower dose and later titrated according to the patient's response to the treatment.

Uses of Brexpiprazole

• Used in the adjunctive treatment to antidepressants to treat (MDD) major depressive disorder.

• Treatment of schizophrenia in adults and pediatric patients (13 years and above).

Dose and Administration

Adults:

The recommended starting dosage of Brexpiprazole is one tablet of 1 mg daily on days 1 to 4. It can be taken with or without food.

Titration - The recommended target dose of Brexpiprazole is one tablet of 2 mg to 4 mg daily. The dose is titrated to 2 mg once per day on days 5 to 7 and later to 4 mg on day 8, depending on the drug’s effectiveness and tolerance by the patient. The maximum recommended dose is 4 mg per day.

For Pediatric Patients:

The recommended starting dosage of Brexpiprazole is one tablet of 0.5 mg daily on days 1 to 4 for pediatric patients of 13 years and above. It can be taken with or without food.

Titration - The dose is titrated to one tablet of 1 mg daily on days 5 to 7 and later titrated to 2 mg on day 8, depending on the drug’s effectiveness and tolerance by the patient. The recommended dose of Brexpiprazole is 2 mg to 4 mg once daily.

Warning and Precautions

• Suicidal Behavior and Thoughts in Young Adults, Children, and Adolescents: The controlled trials on these patients have not revealed any long-term risk of suicidal behavior or thoughts arising from Brexpiprazole, but the drug is not approved in pediatric patients with major depressive disorders (MDD).

• Increased Mortality in Elderly Patients With Dementia-related Psychosis: Patients treated with antidepressants suffering from dementia-related psychosis are at risk of death. However, the cause of death in patients was due to other conditions, such as cardiovascular or lung infections. But the drug is not approved for patients with dementia-related psychosis.

• Neuroleptic Neuralgia Syndrome (NMS): The syndrome has been associated with administering antipsychotic drugs, such as Brexpiprazole. The drug causes altered mental status, hyperpyrexia, autonomic instability, and muscle rigidity in neuroleptic neuralgia syndrome patients. In addition, the drug may also cause acute renal failure, myoglobinuria, and elevated creatinine phosphokinase. Therefore, if any of these symptoms are experienced in NMS patients, discontinue Brexpiprazole immediately and seek immediate treatment and monitoring.

• Cerebrovascular Adverse Reactions, Including Stroke in Elderly People With Dementia-Related Psychosis: Brexpiprazole is strictly contraindicated in elderly patients with dementia-related psychosis as the drug can cause transient ischemia to attach and fatal stroke.

• Tardive Dyskinesia: Patients treated with antipsychotic drugs, such as Brexpiprazole, often develop tardive dyskinesia, which causes potentially irreversible and involuntary dyskinesia movements. The risk of tardive dyskinesia can develop at a small dose of antipsychotic treatment. Therefore, doctors should prescribe Brexpiprazole in a manner that can reduce the risk of tardive dyskinesia. Also, sometimes, a person may develop tardive dyskinesia due to the discontinuation of the treatment with Brexpiprazole. Such cases should be reconsidered as they may require treatment despite the occurrence of tardive dyskinesia symptoms.

• Metabolic Changes: Brexpiprazole, an atypical antipsychotic drug, can cause various metabolic changes in the body. These include dyslipidemia, hyperglycemia, body weight gain, and diabetes mellitus. In controlled trials, adult patients with schizophrenia showed a shift in fasting glucose from <100 mg/dL (normal) to >126 mg/dL (high) or borderline to high ( >100 mg/dL to <126 mg/dL) when treated with Brexpiprazole. In pediatric patients, a shift in fasting glucose from <100 mg/dL (normal) to >126 mg/dL (high) was observed while taking Brexpiprazole.

Use in Specific Populations

• Pregnancy: Women exposed to or treated with antipsychotic drugs like Brexpiprazole during the third trimester are at risk of developing withdrawal and extrapyramidal symptoms. Also, the drug affects the neonate and causes symptoms such as hypotonia, agitation, hypertonia, feeding disorders, respiratory distress, and tremors. Therefore, Brexpiprazole should be cautiously used in this population, and proper treatment of withdrawals and monitoring must be done.

• Lactation: The study on lactation to assess the presence of Brexpiprazole in human milk has yet to be established. Therefore, the mother’s clinical needs for Brexpiprazole and the adverse effects on breastfeeding should be carefully analyzed.

• Pediatric Use: The effectiveness and safety of Brexpiprazole are established in patients with schizophrenia in well-controlled studies. Therefore, the drug is recommended for pediatric patients of 13 years and above.

• Geriatric Use: No specific case study recommends a specific Brexpiprazole dose for geriatric patients. However, caution must be taken before prescribing Brexpiprazole to the geriatric population. The initial dose should be low and not affect renal, hepatic, and cardiac functions. Also, the treatment with antipsychotic drugs can cause a risk of death in geriatric patients with dementia-related psychosis; therefore, Brexpiprazole is not recommended in this condition. Necessary precautions should be taken before prescribing Berxpiprazole.

• Renal Impairment: The maximum recommended dose of Brexpiprazole should be reduced in patients with moderate, severe, and end-stage renal failure. These patients may risk higher exposure to Brexpiprazole than people with normal kidney (renal function).

• Hepatic Impairment: Brexpiprazole can cause adverse drug reactions in people with hepatic impairment. It is advised to reduce the maximum recommended dose of Brexpiprazole in patients with moderate to severe hepatic impairment. These patients develop higher drug exposure than people with sound hepatic function.

• Hypotension and Syncope: Brexpiprazole causes hypotension and syncope during the initial titration of the dose during treatment. Therefore, the patients treated with Brexpiprazole should be continuously monitored for vital symptoms. Also, patients with already existing cardiovascular disease, dehydration, etc., should be carefully prescribed this drug.

• Neutropenia, Leukopenia, and Agranulocytes: Antipsychotic drugs can cause neutropenia and leukopenia. In addition, the drug may also cause fatal cases of agranulocytes. The risk factors for neutropenia and leukopenia include low WBC (white blood cells), drug-induced neutropenia and leukopenia, etc.

• Seizures: Brexpiprazole can cause seizures like other antipsychotic drugs, and the risk may increase due to any history of seizures.

• Dysphagia: Brexpiprazole can cause aspiration and dysmotility in patients, especially in high-risk patients for aspirations.

• Falls: Brexpiprazole also causes postural hypotension, sensory instability, and falls, leading to injuries and fractures. Therefore, the medication should be carefully prescribed for long-term use.

• Body Temperature Dysregulation: Brexpiprazole disruptions the body’s cooling mechanism. Exposure to heat, exercise, and dehydration can increase body temperature. Therefore, drugs should be used cautiously if a person experiences such a condition.

• Other Specific Populations: No recommended dose adjustment is suggested in patients depending on their smoking habits, sex, or race.

For Patients

What Is Brexpiprazole?

Brexpiprazole is a prescription drug for treating schizophrenia, a mental illness causing unusual and disturbed thinking, loss of interest in life, and inappropriate and strong emotions. The drug can be given to adults and children of 13 years and above. It is an atypical antipsychotic drug that can also be used to treat depression along with other antidepressant medications.

How Should Brexpiprazole Be Used?

Brexpiprazole is taken orally once a day or as prescribed by the doctor. The drug should be taken at fixed times every day, and the doctor’s directions should be strictly followed. Do not alter the drug dose and frequency without consulting the doctor.

Brexpiprazole is usually prescribed by the doctor, starting in low doses. The drug dose is gradually increased depending on its effectiveness on a person and the side effects that it may cause. The drug is prescribed to control schizophrenia but cannot treat this condition's symptoms. A person should continue taking the drug even after feeling better and not stop it without a doctor’s advise.

What Precautions Should Be Taken Before Starting Brexpiprazole?

• Inform the doctor about allergic reactions to Brexpiprazole or any of the ingredients in the tablet.

• The doctor should also be informed about all the non-prescription, prescription, nutritional supplements, vitamins, and herbal products a person consumes. This helps the doctor prescribe or change the dose accordingly and monitor the person for any related side effects.

• In addition, the doctor should also be informed about past or present medical conditions, such as diabetes, heart disease, liver disease, or kidney disease. The healthcare provider should also know if a person has ever had any history of stroke, heart failure, low or high blood pressure, irregular heartbeat, swallowing difficulties, or seizures.

• Inform the doctor about the pregnancy or if a person plans to get pregnant or breastfeed. Brexpiprazole can cause effects on delivery if taken during the last phase of pregnancy.

• Brexpiprazole can make a person feel drowsy and dizzy. Therefore, car driving and handling of heavy machines should be restricted while taking this drug.

• Brexpiprazole can cause side effects, such as lightheadedness, fainting, and dizziness during the initial dose intake. Therefore, a person should get out of bed slowly and cautiously.

• A person may also experience an increase in weight caused by Brexpiprazole. Therefore, weight should be checked periodically.

• A person’s body temperature may also increase, and it takes longer to cool down. Therefore, planning for extreme hot exposure and exercising should be informed the doctor.

• Brexpiprazole causes high blood sugar levels or hyperglycemia even if they do not have diabetes. Schizophrenia often causes diabetes, and the drug Brexpiprazole further increases the risk of developing a diabetic condition in a person. Therefore, inform the doctor if a person experiences any symptoms of diabetes, such as extreme hunger, frequent urination, extreme thirst, weakness, or blurred vision. The doctor should be consulted immediately, as high blood sugar can cause life-threatening conditions, such as ketoacidosis. Symptoms of ketoacidosis are nausea and vomiting, dry mouth, shortness of breath, and decreased consciousness.

What Are the Side Effects of Brexpiprazole?

Common Side Effects:

Consult the doctor immediately if these symptoms persist for longer.

• Constipation.

• Headaches.

• Tiredness.

• Heartburn.

• Dizziness and difficulty in balancing the body.

• Uncontrollable body shaking.

Severe Side Effects:

• Breathing and swallowing problems.

• Itching.

• Rash.

• Hives.

• Seizures.

• Chills, cough, and sore throat.

• Shortness of breath (dyspnea).

• Unusual and uncontrollable body and face movements.

• Irregular heartbeats, sweating, fever, severe muscle stiffness.

• Tightness of throat and neck muscles.

• Fainting.

What Happens With the Overdose of Brexpiprazole?

In case of an overdose from Brexpiprazole, call the emergency if a person has seizures, trouble breathing, cannot be awakened, or collapses.

What Should Be Done if the Brexpiprazole Dose Is Missed?

The missed dose should be taken as soon as the person remembers it. It is advisable to skip the missed dose if the timing is almost for the next dose and follow the regular dose schedule. Do not make up for the missed dose by taking a double dose of Brexpiprazole.

Drug Storage and Disposal

The drug should be kept away from the children and stored in a tightly closed container. The drug should be stored at room temperature and away from excess moisture and heat.

The drug should be disposed of carefully by following FDA’s (Food and Drug Administration) safe disposal methods for drugs. Do not flush the medicine in the toilets.

For Doctors

Clinical Pharmacology

Mechanism of Action

The mechanism of action of Brexpiprazole in treating schizophrenia is still unclear. But the drug's efficacy is believed to be caused by antagonist activity at serotonin 2A receptors and the partial agonist activity at dopamine D2 and serotonin receptors.

Pharmacodynamics

Brexpiprazole has efficacy for various monoaminergic receptors such as nonadrenergic, dopamine, and serotonin. The drug also has efficacy for the muscarinic M1 receptor and histamine H1 receptor.

Pharmacokinetics

Absorption:

After taking a single dose of the Brexpiprazole tablet, the peak plasma concentration occurs within four hours, and the oral bioavailability is almost 95 percent. In addition, the steady-state concentration is achieved between 10 to 12 days of regular dosing.

Distribution:

The drug's (Brexpiprazole) distribution volume is high when administered intravenously as compared to oral intake, indicating the extravascular distribution.

Elimination:

The single oral dose of Brexpiprazole is excreted 25 percent in urine and 46 percent in feces.

Approximately 1 to 14 percent of unchanged Brexpiprazole are excreted in urine and feces. Regular once-daily administration or intake of Brexpiprazole has a half-life of 91 hours.

Ingredients

Active Ingredients: Brexpiprazole

Passive Ingredients: Hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, ferrosoferric oxide, titanium dioxide, hypromellose, microcrystalline cellulose, iron oxide, corn starch, and talc.

Dosage Forms and Strength

Strength: Brexpiprazole is available in 6 strengths.

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

Administration of the Drug

The recommended dose of Brexpiprazole is 1 mg once daily in adults and 0.5 mg once daily in children above 13 years of age for the treatment of schizophrenia.

Consideration of the Administration

Brexpiprazole is given to a patient in tablet form to treat schizophrenia. The initial dose is started with 1 mg in adults for days 1 to 4 and later titrated to 2 mg to 4 mg on days 5 to 7 and 8, respectively. The titration is done according to the patient's response, effectiveness, and working of Brexpiprazole.

Contraindications

Brexpiprazole is contraindicated in people with known hypersensitivity to Brexpiprazole and to any of its ingredients. Side effects include facial swelling, rashes, anaphylaxis, and urticaria.

Adverse Effects

The adverse effects of Brexpiprazole include

• Convulsions or seizures.

• Metabolic changes.

• High blood sugar levels.

• Troubled breathing and swallowing.

• Severe nervous system disorders include high fever, sweating, irregular heartbeats, and rigid muscles.

• Uncontrolled muscle movements in the face.

• Low white blood cell counts cause sore throat, skin sores, fever, and trouble breathing.

• Blood clots cause numbness, vision defects, redness and swelling in limbs, and weakness.

• Lightheadedness and fall.

• Intolerance to heat.

Drug Interactions

• Brexpiprazole does not require dose adjustment when administered with Ticlopidine (CYP2B6 inhibitors).

• Brexpiprazole does not require dose adjustment with Dextromethorphan (CYP2B6 substrate), Lovastatin, BCRP or Rosuvastatin, CYP2B6 or Bupropion, or P-gp or Fexofenadine.