loxapine inhaled

Action and Spectrum

Actions and spectrum: 

• Antipsychotic Effect: loxapine inhalation exerts an antipsychotic effect by blocking dopamine receptors in the brain, particularly the D2 and D3 receptors. By reducing the activity of dopamine, it helps to alleviate symptoms of psychosis such as delusions, hallucinations, and disorganized thinking. 
• Rapid Onset of Action: loxapine inhalation is designed for rapid relief of acute agitation. When inhaled, the medication is quickly absorbed into the bloodstream, allowing for a faster onset of action compared to oral or injectable forms of loxapine. 
• Anxiolytic Effect: loxapine inhalation also possesses anxiolytic properties, helping to reduce anxiety and tension in patients experiencing acute agitation. 
• Sedative Effect: loxapine inhalation has mild sedative effects, which can contribute to calming and relaxation in individuals with agitation. 
• Broad Spectrum of Activity: loxapine inhalation has demonstrated efficacy in the treatment of acute agitation associated with schizophrenia and bipolar I disorder. It is effective in reducing symptoms such as aggression, hostility, excitement, and uncooperativeness. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Throat irritation (3%)  

>10% 

Dysgeusia (14%) 

Respiratory adverse effects with COPD (19%) 

Sedation (12%)  

<1% 

Akathisia (0.4%) 

Bronchospasm (0.8%) 

Neck oculogyration and dystonia (0.4%) 

Black Box Warning

Black Box Warning 

The black box warning for loxapine inhalation states that it should be reserved for patients with schizophrenia or bipolar I disorder who require rapid control of acute agitation.

It warns of an increased risk of bronchospasm, including potentially fatal outcomes, and emphasizes the need for careful patient selection and monitoring for respiratory symptoms. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Known hypersensitivity: loxapine inhalation should not be used in individuals who have a known hypersensitivity or allergic reaction to loxapine or any of its components. 
• Asthma or chronic obstructive pulmonary disease (COPD): loxapine inhalation is contraindicated in individuals with a history of asthma or COPD, as it may cause bronchospasm and worsen respiratory symptoms. 
• Acute respiratory conditions: loxapine inhalation should not be used in patients with acute respiratory conditions, such as acute bronchospasm, acute respiratory distress syndrome (ARDS), or acute respiratory infection. 
• Concurrent use of certain medications: loxapine inhalation is contraindicated when used concomitantly with other medications that may increase the risk of respiratory depression, sedation, or interact with the drug’s metabolism. 

Caution: 

• Respiratory conditions: Use with caution in patients with a history of respiratory conditions, such as asthma or COPD, as loxapine inhalation can potentially cause bronchospasm and worsen respiratory symptoms. 
• Cardiovascular conditions: loxapine inhalation may cause changes in blood pressure and heart rate. Use with caution in patients with cardiovascular conditions, including heart disease, hypertension, or arrhythmias. 
• Central nervous system depression: loxapine inhalation may cause sedation and impairment of cognitive and motor functions. Caution should be used when operating machinery or driving until the individual’s response to the medication is known. 
• Hypersensitivity reactions: Monitor for signs of allergic reactions, such as rash, itching, swelling, or difficulty breathing. Discontinue use if an allergic reaction occurs. 
• Use in the elderly: Elderly patients may be more sensitive to the effects of loxapine inhalation, including sedation and orthostatic hypotension. Dose adjustments and close monitoring may be necessary. 

Comorbidities: 

• Respiratory conditions: loxapine inhalation may exacerbate respiratory symptoms in individuals with asthma or COPD. Close monitoring of respiratory function is necessary in these individuals. 
• Cardiovascular conditions: loxapine inhalation can have cardiovascular effects, including changes in blood pressure and heart rate. It should be used cautiously in individuals with cardiovascular conditions, such as heart disease, hypertension, or a history of cardiac arrhythmias. 
• Epilepsy or seizure disorders: loxapine inhalation may reduce the seizure threshold and may have an increased risk of seizures. It should be used with caution in individuals with a history of epilepsy or seizure disorders. 
• Diabetes: loxapine inhalation may affect glucose metabolism and insulin sensitivity. patients with diabetes or those who are at risk for diabetes should be closely monitored for changes in blood sugar levels during treatment. 
• Neurological disorders: loxapine inhalation may have central nervous system effects and can worsen symptoms in individuals with pre-existing neurological disorders, such as Parkinson’s disease or dementia. 
• Hepatic or renal impairment: loxapine is primarily metabolized in liver and gets excreted through kidneys. Individuals with hepatic or renal impairment may require dosage adjustments and closer monitoring due to potential changes in drug metabolism and elimination. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: C 

Lactation: Excreted into human milk: Unknown  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or 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

Pharmacology: 

loxapine inhalation is an antipsychotic medication that acts as a dopamine D2 receptor antagonist and a serotonin 5-HT2 receptor antagonist. It exerts its pharmacological effects by blocking the postsynaptic dopamine receptors in the brain, thereby reducing the excessive dopaminergic activity associated with psychosis.

The blockade of 5-HT2 receptors also contributes to its antipsychotic properties. loxapine also exhibits moderate affinity for other receptors, including adrenergic, cholinergic, and histaminergic receptors, which may contribute to its side effect profile.

The inhaled formulation allows for rapid absorption of the medication into the bloodstream, leading to faster onset of action. loxapine is metabolized in the liver, primarily by the cytochrome P450 enzyme system, and is eliminated primarily via renal excretion.  

Pharmacodynamics: 

• Dopamine D2 receptor blockade: loxapine acts as a potent antagonist at the dopamine D2 receptors, reducing excessive dopaminergic activity. This helps alleviate positive symptoms of psychosis, such as hallucinations and delusions. 
• Serotonin 5-HT2 receptor blockade: loxapine also blocks the serotonin 5-HT2 receptors, which contributes to its antipsychotic effects. This receptor blockade helps improve negative symptoms of psychosis and may have mood-stabilizing properties. 
• Alpha-adrenergic receptor blockade: loxapine exhibits moderate affinity for alpha-adrenergic receptors, which may contribute to its sedative and hypotensive effects. 
• Anticholinergic effects: loxapine has anticholinergic properties, resulting in the blockade of muscarinic acetylcholine receptors. This can lead to side effects such as dry mouth, blurred vision, constipation, and urinary retention. 
• Histamine H1 receptor blockade: loxapine also blocks histamine H1 receptors, which can contribute to sedation and weight gain. 

Pharmacokinetics: 

Absorption 

When inhaled, loxapine is rapidly absorbed through the respiratory system and enters the bloodstream. This allows for a quick onset of action. 

Distribution 

loxapine is widely distributed throughout the body, including the central nervous system (CNS). It crosses blood-brain barrier and binds to its target receptors in the brain. 

Metabolism 

loxapine undergoes extensive metabolism in the liver primarily by the cytochrome P450 enzyme system, specifically CYP1A2 and CYP3A4. This metabolism results in the formation of active metabolites, including amoxapine, which also contributes to the drug’s pharmacological effects. 

Elimination and excretion 

The elimination of loxapine and its metabolites occurs primarily through urine. The exact proportions of excretion for unchanged loxapine versus metabolites may vary. 

Adminstartion

Administration: 

• Prepare the inhaler: Before use, ensure that the inhaler device is assembled and ready for administration.  
• Prime the inhaler: If required, prime the inhaler as per the manufacturer’s instructions. This step helps ensure that the device is ready to deliver the appropriate dose of loxapine. 
• Breathe out: Before inhaling, exhale fully to empty your lungs. 
• Inhale the medication: Place the mouthpiece of the inhaler in your mouth and form a tight seal around it. Take a slow, deep breath through mouth, and simultaneously press down on the canister to release a dose of loxapine. Inhale the medication deeply into your lungs. 
• Hold breath and exhale: After inhaling, hold breath for a few seconds to allow medication to reach deeper into the lungs. Then, exhale slowly. 
• Clean the inhaler: After use, clean the inhaler device as instructed by the manufacturer to maintain its functionality and prevent contamination. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: loxapine inhaled 

Pronounced: (loh-ZAP-een in-HAYLD)  

Why do we use loxapine inhaled? 

loxapine inhaled is primarily used for the treatment of schizophrenia or bipolar disorder agitation in adults. It is specifically indicated for the acute treatment of mild to moderate agitation in these patients. loxapine inhaled provides rapid relief of agitation symptoms, helping to calm and stabilize individuals experiencing acute episodes of agitation. It is typically used in controlled clinical settings under healthcare professional supervision due to the risks associated with the use of antipsychotic medications.