Usage
- Blonanserin is prescribed for the treatment of schizophrenia. It is also used in some cases for delusional disorder, treatment-resistant schizophrenia, and bipolar mania, although these are not officially approved indications.
- Pharmacological Classification: Atypical antipsychotic.
- Mechanism of Action: Blonanserin primarily acts as an antagonist at dopamine D2 and serotonin 5-HT2A receptors. It also exhibits affinity for dopamine D3 and serotonin 5-HT6 receptors. This combined action helps to alleviate both positive (e.g., hallucinations, delusions) and negative (e.g., social withdrawal, apathy) symptoms of schizophrenia.
Alternate Names
- International Nonproprietary Name (INN): Blonanserin.
- Brand Names: Lonasen, Bloniten, Blonan.
How It Works
- Pharmacodynamics: Blonanserin exerts its therapeutic effects by blocking dopamine D2 and serotonin 5-HT2A receptors in the brain. It also has an affinity for dopamine D3 and serotonin 5-HT6 receptors, which may contribute to its efficacy, particularly for negative symptoms and cognitive function. Blonanserin has a lower affinity for other receptors, such as histamine H1, muscarinic M1, and adrenergic α1, which may explain its relatively low incidence of certain side effects like sedation, weight gain, and orthostatic hypotension.
- Pharmacokinetics: Blonanserin is administered orally and is well-absorbed. It is extensively metabolized by the liver, primarily by the CYP3A4 enzyme. Elimination occurs through both renal and hepatic routes.
- Mode of Action: Blonanserin’s mode of action involves competitive binding to dopamine D2 and serotonin 5-HT2A receptors, preventing the binding of these neurotransmitters. This action modulates dopaminergic and serotonergic neurotransmission in the brain, thereby ameliorating the symptoms of schizophrenia.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: As mentioned before, blonanserin primarily acts as an antagonist of dopamine D2 and serotonin 5-HT2A receptors. The drug shows high affinity for these receptors while possessing lower affinities for adrenergic α1, histamine H1, muscarinic M1 and 5HT2C receptors and a relatively high affinity for 5-HT6 receptors.
- Elimination Pathways: Blonanserin is mainly metabolized by CYP3A4 in the liver, and its metabolites are excreted in both urine and feces.
Dosage
Standard Dosage
Adults:
- Initial dose: 8 mg/day, administered orally in two divided doses after meals.
- Maintenance dose: 8-16 mg/day, divided into two doses after meals.
- Maximum dose: 24 mg/day.
Children:
Limited data are available for adolescents (12-18 years). Doses ranging from 8-16 mg/day have been studied in clinical trials. Safety and efficacy have not been established in children younger than 12 years.
Special Cases:
- Elderly Patients: Start with a lower dose (4 mg/day) and titrate cautiously, considering age-related decline in renal and hepatic function.
- Patients with Renal Impairment: Not specifically studied, but caution is advised. Dose adjustment may be necessary.
- Patients with Hepatic Dysfunction: Use with caution. A lower dose may be required.
- Patients with Comorbid Conditions: Exercise caution in patients with cardiovascular disease, diabetes, seizures, or angle-closure glaucoma. Dose adjustments and careful monitoring may be necessary.
Clinical Use Cases
Blonanserin’s use in specific medical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations is not established. It is primarily indicated for the management of schizophrenia.
Dosage Adjustments
Dosage modifications should be based on individual patient factors, including renal and hepatic function, comorbid conditions, and potential drug interactions.
Side Effects
Common Side Effects:
- Constipation
- Drowsiness
- Dizziness
- Cough
- Rash
- Itching
- Headache
- Tremor
- Restlessness
- Nausea and vomiting
- Weight gain
- Insomnia
- Anxiety
Rare but Serious Side Effects:
- Dystonia
- Parkinsonism
- Neuroleptic malignant syndrome (NMS)
- Hyperglycemia and ketoacidosis
- QT prolongation
- Seizures
- Tardive dyskinesia
Long-Term Effects:
- Tardive dyskinesia
- Metabolic changes (e.g., weight gain, dyslipidemia, hyperglycemia)
Adverse Drug Reactions (ADR):
- NMS
- Hyperglycemia and ketoacidosis
- Severe dystonia
- Seizures
- QT prolongation
Contraindications
- Hypersensitivity to blonanserin
- Concurrent use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, HIV protease inhibitors) and inducers (e.g., rifampicin, carbamazepine, phenytoin).
Drug Interactions
Blonanserin is primarily metabolized by CYP3A4, therefore concomitant medications impacting this enzyme, as those listed above, should be used cautiously or be avoided. Blonanserin can interact with other drugs affecting the central nervous system (e.g., benzodiazepines, opioids, alcohol) potentially increasing the risk of sedation and respiratory depression. Interactions with dopamine agonists (e.g., levodopa) may reduce Blonanserin’s effectiveness, and concurrent use with adrenaline is contraindicated due to the risk of severe hypotension.
Pregnancy and Breastfeeding
Blonanserin’s safety during pregnancy has not been established. It is generally not recommended unless the benefits outweigh the risks. Blonanserin is likely excreted in breast milk; hence, breastfeeding is generally not advised during treatment.
Drug Profile Summary
- Mechanism of Action: Dopamine D2 and serotonin 5-HT2A receptor antagonist.
- Side Effects: Common: constipation, drowsiness, dizziness, insomnia, anxiety. Serious: NMS, tardive dyskinesia, seizures, QT prolongation.
- Contraindications: Hypersensitivity, concurrent use of strong CYP3A4 inhibitors.
- Drug Interactions: CYP3A4 inhibitors and inducers, CNS depressants, dopamine agonists, adrenaline.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: 8-16 mg/day; Max: 24 mg/day. Elderly: Start with 4mg/day.
- Monitoring Parameters: Weight, blood glucose, lipids, ECG, extrapyramidal symptoms, mental status.
Popular Combinations
No specific popular drug combinations involving blonanserin are routinely recommended. Concomitant medication needs to be carefully evaluated based on individual needs and potential interactions.
Precautions
- Assess for allergies, cardiovascular conditions, diabetes, hepatic/renal impairment, and history of seizures before initiating therapy.
- Monitor patients for extrapyramidal symptoms, metabolic changes, and other potential side effects.
- Avoid alcohol and other CNS depressants.
- Caution is advised for driving and operating heavy machinery due to potential drowsiness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Blonanserin?
A: The standard adult dose is 8-16 mg/day, divided into two doses after meals, with a maximum dose of 24 mg/day. Elderly patients should start with a lower dose (4 mg/day).
Q2: How does Blonanserin work?
A: Blonanserin primarily blocks dopamine D2 and serotonin 5-HT2A receptors in the brain, which helps to regulate neurotransmission and improve symptoms of schizophrenia.
Q3: What are the common side effects of Blonanserin?
A: Common side effects include constipation, drowsiness, dizziness, insomnia, and anxiety.
Q4: What are the serious side effects of Blonanserin?
A: Serious side effects may include neuroleptic malignant syndrome (NMS), tardive dyskinesia, seizures, and QT prolongation.
Q5: What are the contraindications for Blonanserin?
A: Blonanserin is contraindicated in individuals with hypersensitivity to the drug and should not be used concurrently with strong CYP3A4 inhibitors.
Q6: Can Blonanserin be used during pregnancy or breastfeeding?
A: Blonanserin is generally not recommended during pregnancy and breastfeeding unless the potential benefits clearly outweigh the risks.
Q7: What are the potential drug interactions with Blonanserin?
A: Blonanserin can interact with CYP3A4 inhibitors and inducers, CNS depressants, dopamine agonists, and adrenaline.
Q8: How should Blonanserin be administered?
A: Blonanserin is administered orally, usually twice daily after meals.
Q9: What monitoring parameters are important during Blonanserin treatment?
A: Monitor weight, blood glucose, lipids, ECG, extrapyramidal symptoms, and mental status regularly.
Q10: Is Blonanserin effective for negative symptoms of schizophrenia?
A: Blonanserin has shown efficacy in treating both positive and negative symptoms of schizophrenia, possibly due to its affinity for dopamine D3 and serotonin 5-HT6 receptors.
