aripiprazole lauroxil

Actions and Spectrum: 

aripiprazole lauroxil is an antipsychotic medication used to treat schizophrenia and bipolar disorder. It is a long-acting injectable form of aripiprazole, a partial agonists of the dopamine D2 receptors and the serotonin 5-HT1A receptor, and an antagonist of the serotonin 5-HT2A receptor. 

The action of aripiprazole lauroxil is believed to be linked to its ability to modify the activity of dopamine, serotonin in the brain. By working as partial agonist at the D2 receptor, it can help regulate the levels of dopamine, which is a neurotransmitter that is generally associated with the symptoms of schizophrenia and bipolar disorder. By working as an antagonist at the 5-HT2A receptor, it can help reduce the activity of serotonin, which is also implicated in the development of these disorders. 

The spectrum of aripiprazole lauroxil refers to the range of symptoms and conditions that it is effective in treating. aripiprazole lauroxil is primarily used to treat the positive symptoms of schizophrenia, like delusions and also hallucinations, as well as the manic and mixed episodes of bipolar disorder. It may also be generally used to treat the negative symptoms of schizophrenia, like social withdrawal and apathy, although its effectiveness is less well-established. 

DRUG INTERACTION

Contraindicated  

Serious Use Alternative  

Monitor Closely  

Minor  

Frequency defined 

>10% 

Akathisia (11%) 

1-10% 

Weight gain 

headache  

Dystonia 

Injection site reaction 

insomnia  

extrapyramidal reaction 

parkinsonism  

Enhanced creatine phosphokinase 

Orthostatic hypotension 

Erythema 

Frequency not defined 

Angina pectoris 

Tachycardia 

Palpitations 

Xerostomia 

Black Box Warning: 

The black box warning for aripiprazole lauroxil is related to an enhanced risk of death in elderly patients with dementia-related psychosis. aripiprazole lauroxil is not approved for treatment of patients with dementia-related psychosis. Still, older patients with dementia-related psychosis treated with antipsychotic drugs are at an enhanced risk of death compared to placebo. 

The warning states that aripiprazole lauroxil is not approved for treating patients with dementia-related psychosis and that older patients with dementia-related psychosis generally treated with antipsychotic drugs are at an enhanced risk of death. The warning also advises healthcare providers to consider the risks and benefits of aripiprazole lauroxil before prescribing it to elderly patients with other conditions, such as schizophrenia or bipolar disorder.

Healthcare providers are also advised to monitor these patients for symptoms such as fever, muscle stiffness, and changes in mental status, which may indicate the development of a potentially life-threatening condition generally known as neuroleptic malignant syndrome (NMS). 

Contraindication/Caution: 

Contraindication 

aripiprazole lauroxil has several contraindications, including conditions or situations where the medication should not be used. These include: 

• Hypersensitivity: aripiprazole lauroxil should not be used in patients who have a known hypersensitivity/allergy to aripiprazole or any of the other ingredients in the medication. 
• Cerebrovascular disease: aripiprazole lauroxil should not be used in patients with a stroke history or transient ischemic attack (TIA). 
• Cardiovascular disease: aripiprazole lauroxil should not be used in patients with previous history of heart attack, heart failure, or other significant cardiovascular disease. 
• QT prolongation: aripiprazole lauroxil should not be used in patients with a known prior history of QT prolongation. This condition affects the heart’s electrical activity and can enhance the risk of abnormal heart rhythms. 
• Uncontrolled hypertension: aripiprazole lauroxil should not be used in uncontrolled hypertension patients (high blood pressure). 
• Severe renal impairment: aripiprazole lauroxil should not be used in patients with severe renal impairment (serum creatinine clearance less than 30 mL/min). 
• Severe hepatic impairment: aripiprazole lauroxil should not be typically used in patients with severe hepatic impairment (Child-Pugh Class C). 

Caution 

aripiprazole lauroxil has several cautions, which are conditions or situations where the medication should be used with caution and careful monitoring. These include: 

• Elderly patients: Elderly patients with dementia-related psychosis are at an enhanced risk of death when treated with antipsychotic drugs, including aripiprazole lauroxil. The drug should be generally used with caution in this population. 
• Neuroleptic Malignant Syndrome: It is a rare but potentially life-threatening condition that can occur with antipsychotic drugs, including aripiprazole lauroxil. The medication should be discontinued immediately if symptoms of NMS develop. 
• Tardive dyskinesia: It is a movement disorder condition that can generally occur with the long-term use of antipsychotic drugs. aripiprazole lauroxil should be used cautiously in patients at risk for tardive dyskinesia. 
• Seizures: aripiprazole lauroxil can lower the seizure threshold and should be generally used cautiously in patients with a prior history of seizures or other conditions that lower the seizure threshold. 
• Hyperglycemia and diabetes mellitus: aripiprazole lauroxil can cause hyperglycemia (high blood sugar) and should be used cautiously in patients with diabetes mellitus or at risk for developing diabetes. 
• Hypotension: aripiprazole lauroxil can cause hypotension (low bp) and should be generally used cautiously in patients with a history of cardiovascular disease or taking medications that lower blood pressure. 
• Pregnancy and breastfeeding: aripiprazole lauroxil should be used cautiously in pregnant or breastfeeding women, as the effects on the fetus or nursing infant are unknown. 

Pregnancy consideration:  

US FDA pregnancy category: Not assigned 

Lactation:   

Excreted into human milk is Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.        
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.       
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.        
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.        
• Category N: There is no data available for the drug under this category 

Pharmacology: 

aripiprazole lauroxil is an atypical antipsychotic medication that is a prodrug of aripiprazole. Once injected, aripiprazole lauroxil is slowly metabolized to aripiprazole, the active ingredient responsible for the medication’s pharmacological effects. 

aripiprazole works by blocking the activity of certain neurotransmitters in the brain, including dopamine and also serotonin, which are involved in developing schizophrenia and bipolar disorder. Unlike other antipsychotic medications, aripiprazole acts as a partial agonist at dopamine D2, serotonin 5-HT1A receptors, which means both activate and inhibit the activity of these receptors depending on the level of dopamine or serotonin in the brain. This unique mechanism of action is believed to contribute to aripiprazole’s effectiveness in treating both positive and also negative symptoms of schizophrenia and bipolar disorder and reducing the risk of extrapyramidal side effects. 

Pharmacodynamics: 

Mechanism of action: The drug, aripiprazole lauroxil is a prodrug of aripiprazole, an atypical antipsychotic medication. The active ingredient, aripiprazole, works by blocking or modulating the activity of several neurotransmitters in the brain, including dopamine and serotonin. 

Pharmacokinetics: 

Absorption 

After intramuscular injection, aripiprazole lauroxil is slowly absorbed into the bloodstream. The absorption of the medication is controlled by the hydrophobicity of the molecule, which results in a slow release of aripiprazole over a period of several weeks. 

Distribution 

Once absorbed into the bloodstream, aripiprazole is distributed to many tissues in the body, like in the brain. The protein binding of aripiprazole is approximately 99%, which means that only a small quantity of the medication is unbound and available for distribution. 

Metabolism 

aripiprazole is primarily metabolized by the liver through the cytochrome P450 system, with the majority of the medication being metabolized into its active metabolite, dehydro-aripiprazole. Dehydro-aripiprazole has similar pharmacological properties to aripiprazole and is also partially responsible for the medication’s therapeutic effects. 

Elimination and Excretion 

aripiprazole and its metabolites are eliminated primarily in the feces, with a small quantity in the urine. The elimination half-life of aripiprazole is approximately 75 hours, meaning it takes approximately two weeks for the medication to be excreted from the body. 

Administration: 

aripiprazole lauroxil is a long-acting injectable medication that a healthcare provider administers. Here are some essential considerations for the administration of aripiprazole lauroxil: 

• aripiprazole lauroxil is administered by intramuscular injection into the arm’s deltoid muscle or the buttock’s gluteal muscle.  
• The recommended aripiprazole lauroxil is 441 mg, 662 mg, or 882 mg, depending on the patient’s clinical needs and previous antipsychotic treatment. 
• Before administering aripiprazole lauroxil, the healthcare provider should assess the patient’s medical history, including any allergies, previous antipsychotic treatment, and any medical conditions that may affect the patient’s response to the medication. 
• aripiprazole lauroxil should not be administered to patients currently experiencing an acute exacerbation of schizophrenia or bipolar disorder, as the medication may take several weeks to become fully effective. 
• After the initial dose of aripiprazole lauroxil, the patient should be observed in a healthcare setting for at least 3 hours to monitor for any potential adverse reactions, such as injection site reactions, hypersensitivity reactions, or changes in mental status. 
• aripiprazole lauroxil should be administered regularly as prescribed by the healthcare provider. The patient should receive the next scheduled dose immediately if a dose is missed. 

Patient information leaflet 

Generic Name: aripiprazole lauroxil 

Why do we use aripiprazole lauroxil? 

aripiprazole lauroxil is an antipsychotic medication for treating schizophrenia and bipolar I disorder in adults. Here are some details about the uses of aripiprazole lauroxil: 

• Schizophrenia: aripiprazole lauroxil is used to treat schizophrenia in adults. Schizophrenia is a severe mental disorders characterized by hallucinations, delusions, impaired thinking, and abnormal behaviors. 
• Bipolar I disorder: aripiprazole lauroxil treats manic/mixed episodes linked with bipolar I disorder in adults. Bipolar I disorder is generally a mental illness characterized by episodes of mania (elevated mood and energy) and depression. 
• Maintenance treatment: aripiprazole lauroxil is also used as a maintenance treatment to prevent relapse of symptoms in patients with schizophrenia/bipolar I disorder. 

aripiprazole lauroxil works by blocking the activity of certain types of the neurotransmitters in the brain, including dopamine, serotonin, which are involved in developing schizophrenia and bipolar disorder. 

It is important to note that aripiprazole lauroxil should only be typically used under the guidance of a physician and that the medication may not be suitable for everyone.