Usage
Asenapine is prescribed for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults, both as monotherapy and adjunctive therapy with lithium or valproate. It is also indicated for the treatment of schizophrenia in adults. Asenapine belongs to the pharmacological class of atypical antipsychotics. Its mechanism of action involves antagonism of dopamine D2 and serotonin 5-HT2A receptors, along with activity at other receptors including 5-HT1A, 5-HT2C, 5-HT6, 5-HT7, alpha2-adrenergic, and histamine H1 receptors.
Alternate Names
Asenapine is also known as its maleate salt form, asenapine maleate. It is marketed under the brand names Saphris (sublingual tablets) and Secuado (transdermal patch). Sycrest is another brand name used internationally.
How It Works
Pharmacodynamics: Asenapine exerts its therapeutic effects primarily through antagonism of dopamine D2 and serotonin 5-HT2A receptors. The precise mechanism by which this receptor blockade leads to its antipsychotic and mood-stabilizing effects is not fully understood but likely involves modulation of dopaminergic and serotonergic neurotransmission in the brain. Asenapine also exhibits varying affinities for other receptors, including adrenergic, histaminergic and serotonergic subtypes, which might contribute to its clinical profile and side effects.
Pharmacokinetics: Asenapine administered sublingually is rapidly absorbed, reaching peak plasma concentrations within 0.5 to 1.5 hours. Sublingual administration bypasses first-pass metabolism, leading to a higher bioavailability (35%) compared to oral administration (<2%). Asenapine is extensively metabolized in the liver, mainly via direct glucuronidation by UGT1A4 and also by CYP1A2 to a lesser extent. The primary route of elimination is renal excretion (via urine). Asenapine’s elimination half-life is approximately 24 hours, allowing for twice-daily dosing.
Dosage
Standard Dosage
Adults:
- Schizophrenia: 5 mg sublingually twice daily. The dose may be increased to 10 mg twice daily after one week if tolerated. The maximum dose is 20 mg/day.
- Bipolar I Disorder (Monotherapy): 5 to 10 mg sublingually twice daily. The maximum dose is 20 mg/day.
- Bipolar I Disorder (Adjunctive Therapy with Lithium or Valproate): 5 mg sublingually twice daily initially. May be increased to 10 mg twice daily based on clinical response and tolerability. The maximum dose is 20 mg/day.
Children:
- Bipolar I Disorder (ages 10-17 years): 2.5 mg sublingually twice daily initially. May be increased to 5 mg twice daily after 3 days and up to 10 mg twice daily after another 3 days, based on response and tolerability. The safety and efficacy of doses greater than 10 mg twice daily haven’t been established. Asenapine is not recommended for children younger than 10 years due to a lack of data on safety and efficacy.
Special Cases:
- Elderly Patients: Although no specific dosage adjustment is routinely recommended, caution is advised due to potential increased sensitivity to side effects. Start with the lower end of the dose range and titrate cautiously.
- Patients with Renal Impairment: No dosage adjustment is needed.
- Patients with Hepatic Dysfunction: No dosage adjustment is necessary for mild to moderate hepatic impairment. Asenapine is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C).
- Patients with Comorbid Conditions: Careful monitoring and potential dose adjustment may be necessary in patients with cardiovascular disease, diabetes, or other conditions that could be exacerbated by asenapine’s side effects.
Clinical Use Cases
Asenapine’s use is limited to the treatment of schizophrenia and bipolar I disorder. It is not specifically indicated for conditions like intubation, surgical procedures, mechanical ventilation, or in the intensive care unit (ICU) setting, nor for emergency situations such as status epilepticus or cardiac arrest.
Dosage Adjustments
Dosage adjustments are not typically necessary for renal impairment. However, dose adjustments should be considered for moderate hepatic impairment, based on patient’s tolerability to the drug. Asenapine is contraindicated in severe hepatic impairment. For elderly patients, dose adjustments might be necessary based on clinical response and tolerability.
Side Effects
Common Side Effects:
- Somnolence/Sedation
- Dizziness
- Oral hypoesthesia (numbness in or around the mouth)
- Akathisia (restlessness)
- Weight gain
- Dysgeusia (altered sense of taste)
- Increased appetite
Rare but Serious Side Effects:
- Neuroleptic Malignant Syndrome (NMS)
- Tardive dyskinesia
- Orthostatic hypotension
- Seizures
- Neutropenia/leukopenia
- Hyperprolactinemia
Long-Term Effects:
Tardive dyskinesia, a movement disorder characterized by involuntary and repetitive movements, can be a long-term side effect of asenapine. Weight gain and associated metabolic changes can also occur with prolonged use.
Adverse Drug Reactions (ADR):
Clinically significant ADRs include NMS, anaphylaxis, severe orthostatic hypotension, and agranulocytosis. These events warrant immediate medical intervention.
Contraindications
- Known hypersensitivity to asenapine
- Severe hepatic impairment (Child-Pugh Class C)
Drug Interactions
Asenapine is metabolized by UGT1A4 and to a lesser extent CYP1A2. Therefore, interactions can occur with strong inducers or inhibitors of these enzymes. Concomitant use of CNS depressants (e.g., alcohol, benzodiazepines, opioids) can potentiate sedation. Use with caution in patients receiving drugs known to prolong the QT interval.
Pregnancy and Breastfeeding
Asenapine’s safety during pregnancy has not been definitively established. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Its presence in breast milk is unknown; therefore, caution is advised when administering to breastfeeding mothers. Consider the risks and benefits for both the mother and infant.
Drug Profile Summary
- Mechanism of Action: Dopamine D2 and serotonin 5-HT2A receptor antagonist
- Side Effects: Somnolence, dizziness, oral hypoesthesia, akathisia, weight gain, dysgeusia
- Contraindications: Hypersensitivity, severe hepatic impairment
- Drug Interactions: CYP1A2 and UGT1A4 inducers/inhibitors, CNS depressants, QT prolonging drugs
- Pregnancy & Breastfeeding: Use with caution. Potential for fetal risk and unknown effects on breastfed infants.
- Dosage: See detailed dosage guidelines above.
- Monitoring Parameters: Weight, blood glucose, lipids, extrapyramidal symptoms, complete blood count (especially during initial months), signs of NMS
Popular Combinations
Asenapine can be used in combination with lithium or valproate in the treatment of bipolar mania when monotherapy is inadequate.
Precautions
- Monitor for NMS, tardive dyskinesia, orthostatic hypotension, seizures, metabolic changes, and blood dyscrasias.
- Pre-screening for hepatic and renal impairment, cardiovascular disease, and seizure history is crucial.
- Use cautiously in the elderly, in patients with a history of seizures or conditions that lower the seizure threshold, and in patients at risk for falls.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Asenapine?
A: See the detailed dosage guidelines provided above, which includes specific dosages for adults, children, and special populations.
Q2: What is the mechanism of action of Asenapine?
A: Asenapine primarily acts as an antagonist at dopamine D2 and serotonin 5-HT2A receptors. It also interacts with other receptors, including 5-HT1A, 5-HT2C, 5-HT6, 5-HT7, alpha2-adrenergic, and histamine H1 receptors.
Q3: What are the common side effects of Asenapine?
A: Common side effects include somnolence, dizziness, oral hypoesthesia, akathisia, weight gain, and dysgeusia.
Q4: What are the serious side effects of Asenapine?
A: Serious side effects can include neuroleptic malignant syndrome (NMS), tardive dyskinesia, orthostatic hypotension, seizures, neutropenia/leukopenia, and hyperprolactinemia.
Q5: Is Asenapine safe to use during pregnancy?
A: The safety of asenapine during pregnancy hasn’t been fully established. Use only if the potential benefit outweighs the potential risk to the fetus. Neonates exposed to antipsychotics during the third trimester are at risk for extrapyramidal symptoms (EPS) or withdrawal symptoms after delivery.
Q6: Can Asenapine be used in patients with renal impairment?
A: Yes, no dose adjustment is generally needed for patients with renal impairment.
Q7: Can Asenapine be used in patients with hepatic impairment?
A: Dose adjustment may be needed for patients with moderate hepatic dysfunction. Asenapine is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C).
Q8: How should Asenapine be administered?
A: Asenapine sublingual tablets should be placed under the tongue and allowed to dissolve completely. Do not chew or swallow the tablet. No food or drink should be consumed for 10 minutes after administration.
Q9: What monitoring parameters are essential for patients on Asenapine?
A: Monitor weight, blood glucose, lipids, extrapyramidal symptoms, and complete blood count (especially during the initial months of treatment). Watch for any signs of neuroleptic malignant syndrome.
Q10: Are there any drug interactions I should be aware of with Asenapine?
A: Asenapine is metabolized by UGT1A4 and, to a lesser extent, CYP1A2. Co-administration with strong inducers or inhibitors of these enzymes could alter asenapine concentrations. Concomitant use of CNS depressants can increase sedation. Monitor closely when used with drugs that prolong the QT interval.
