Usage
Loxapine is prescribed for the management of schizophrenia and acute agitation associated with schizophrenia or bipolar I disorder. It is classified as a first-generation (typical) antipsychotic medication. Loxapine’s mechanism of action involves antagonism of dopamine D2 and serotonin 5-HT2A receptors in the brain, thus modulating dopaminergic and serotonergic neurotransmission to alleviate psychotic symptoms.
Alternate Names
Loxapine is also known as loxapine succinate. Brand names include Loxitane, Loxapac, and Adasuve.
How It Works
Pharmacodynamics: Loxapine primarily acts by blocking dopamine D2 and serotonin 5-HT2A receptors in the brain. This receptor antagonism helps regulate dopaminergic and serotonergic neurotransmission, reducing the positive symptoms of schizophrenia (like hallucinations and delusions) and managing agitation. Loxapine also demonstrates affinity for other receptors like histamine H1, alpha-adrenergic, and muscarinic receptors. Binding to these receptors contributes to some of the side effects associated with loxapine, such as sedation, orthostatic hypotension, and anticholinergic effects.
Pharmacokinetics:
- Absorption: Loxapine is well-absorbed after oral administration.
- Metabolism: It undergoes extensive hepatic metabolism primarily through CYP2D6 and CYP1A2 enzymes to several active and inactive metabolites.
- Elimination: Loxapine is eliminated primarily via renal excretion and partly in feces through biliary elimination.
Dosage
Standard Dosage
Adults:
- Oral (Schizophrenia): Initial dose: 10 mg twice daily. May be increased to up to 50 mg daily in severely ill patients. Usual maintenance dose is 60-100 mg/day, divided 2-4 times a day, not exceeding 250 mg/day.
- Inhalation (Agitation): 10 mg once within a 24-hour period.
Children: Loxapine is not recommended for use in children under 18.
Special Cases:
- Elderly Patients: Start with lower doses and titrate cautiously, considering age-related changes in drug clearance.
- Patients with Renal Impairment: Use with caution and monitor renal function closely. Dosage adjustment may be needed.
- Patients with Hepatic Dysfunction: Use with caution and monitor hepatic function. Dosage adjustment may be necessary.
- Patients with Comorbid Conditions: Dosage adjustments may be needed based on the specific comorbid condition.
Clinical Use Cases
Loxapine is primarily used for the management of schizophrenia and acute agitation related to schizophrenia or bipolar disorder. It is not specifically indicated for intubation, surgical procedures, mechanical ventilation, or ICU use. For emergency situations like status epilepticus or cardiac arrest, other specific treatments are generally preferred.
Dosage Adjustments
Dose modifications are based on individual patient response, tolerability, and renal/hepatic function. Genetic polymorphisms affecting CYP2D6 and CYP1A2 may influence drug metabolism. Consider dose adjustments accordingly.
Side Effects
Common Side Effects
Dizziness, drowsiness, dry mouth, blurred vision, constipation, nausea, insomnia, extrapyramidal symptoms (tremor, rigidity, restlessness), weight gain.
Rare but Serious Side Effects
Neuroleptic malignant syndrome (NMS), tardive dyskinesia, agranulocytosis, seizures, severe allergic reactions, cardiac arrhythmias (QT prolongation).
Long-Term Effects
Tardive dyskinesia, weight gain, metabolic syndrome, cardiovascular complications.
Adverse Drug Reactions (ADR)
NMS, agranulocytosis, severe allergic reactions, QTc prolongation.
Contraindications
Comatose states, severe CNS depression, hypersensitivity to loxapine or dibenzoxazepines, dementia-related psychosis.
Drug Interactions
CNS depressants (alcohol, barbiturates, benzodiazepines), anticholinergic drugs, QT-prolonging agents, CYP2D6 and CYP1A2 inhibitors/inducers.
Pregnancy and Breastfeeding
Pregnancy Safety Category: C. Use not recommended unless benefits outweigh risks. Loxapine can cross the placenta, and third-trimester exposure is associated with neonatal extrapyramidal and/or withdrawal symptoms. It is unknown if loxapine is excreted in human breast milk. Breastfeeding is generally not recommended during treatment with loxapine.
Drug Profile Summary
- Mechanism of Action: Dopamine D2 and serotonin 5-HT2A receptor antagonist.
- Side Effects: Dizziness, drowsiness, dry mouth, extrapyramidal symptoms, NMS, tardive dyskinesia.
- Contraindications: Coma, severe CNS depression, hypersensitivity to loxapine.
- Drug Interactions: CNS depressants, anticholinergics, QT-prolonging drugs.
- Pregnancy & Breastfeeding: Use with caution; risk of neonatal effects.
- Dosage: See dosage section above.
- Monitoring Parameters: Mental status, extrapyramidal symptoms, weight, blood pressure, ECG, complete blood count, liver function tests.
Popular Combinations
Loxapine is sometimes used in combination with other psychotropic medications for managing treatment-resistant schizophrenia or bipolar disorder. These may include mood stabilizers (lithium, valproate), or other antipsychotics.
Precautions
Patients with cardiovascular disease, seizure disorders, diabetes, or hepatic/renal impairment require close monitoring. Baseline ECG and regular monitoring for QTc prolongation are recommended. Monitor for NMS, especially during initial treatment or dose increases. Avoid abrupt discontinuation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Loxapine?
A: See dosage section above.
Q2: What are the common side effects of Loxapine?
A: Common side effects include dizziness, drowsiness, dry mouth, blurred vision, constipation, nausea, insomnia, and extrapyramidal symptoms.
Q3: Is Loxapine safe to use during pregnancy?
A: Loxapine is Pregnancy Category C, and its use during pregnancy is not recommended unless the potential benefits outweigh the potential risks to the fetus.
Q4: Can Loxapine be used in elderly patients?
A: Yes, but with caution. Start with a lower dose and titrate carefully due to age-related changes in drug clearance. Loxapine is contraindicated in elderly patients with dementia-related psychosis.
Q5: What are the signs and symptoms of Neuroleptic Malignant Syndrome (NMS)?
A: NMS is a rare but serious adverse reaction characterized by high fever, muscle rigidity, altered mental status, autonomic instability (irregular heart rate, labile blood pressure, excessive sweating).
Q6: What are the drug interactions with Loxapine?
A: Loxapine interacts with CNS depressants (alcohol, benzodiazepines), anticholinergic medications, QT-prolonging drugs, and CYP2D6 and CYP1A2 inhibitors/inducers.
Q7: What is the difference between oral Loxapine and inhaled Loxapine (Adasuve)?
A: Oral loxapine is used for the maintenance treatment of schizophrenia. Inhaled loxapine (Adasuve) is used for the rapid control of acute agitation in patients with schizophrenia or bipolar I disorder.
Q8: How should Loxapine be discontinued?
A: Loxapine should be tapered gradually to minimize the risk of withdrawal symptoms. Abrupt discontinuation is not recommended.
Q9: What are the monitoring parameters for patients on Loxapine?
A: Mental status, extrapyramidal symptoms, weight, blood pressure, ECG (for QTc prolongation), complete blood count (for agranulocytosis), and liver function tests should be monitored regularly.
