Saphris (Asenapine) Dosing and Monitoring for Schizophrenia and Bipolar Disorder
For adults with schizophrenia, start asenapine at 5 mg sublingually twice daily, and for bipolar I disorder manic or mixed episodes, start at 5-10 mg sublingually twice daily, with a maximum dose of 10 mg twice daily for both indications. 1
Administration Requirements
The sublingual administration is critical and non-negotiable:
- Place the tablet under the tongue and allow complete dissolution—do not swallow the tablet 1
- The tablet dissolves in saliva within seconds 1
- Patients must avoid eating and drinking for 10 minutes after administration 1
- Bioavailability is only 35% when taken sublingually but drops to less than 2% if swallowed, making proper administration essential 2
Specific Dosing by Indication
Schizophrenia
- Start at 5 mg sublingually twice daily 1, 3
- Maximum dose: 10 mg twice daily 1
- Efficacy was demonstrated primarily at the 5 mg twice daily dose in registration trials 2
Bipolar I Disorder (Manic or Mixed Episodes)
- Start at 5 mg sublingually twice daily when used as monotherapy or adjunct to lithium/valproate 1
- Titrate to 5-10 mg twice daily based on response 1
- Maximum dose: 10 mg twice daily 1
- The 10 mg twice daily dose was tested in bipolar registration trials 4, 2
Monitoring Requirements
Movement Disorders
- Monitor specifically for akathisia during the first weeks of treatment, as this is the most common movement-related side effect 5
- The placebo-subtracted rate of extrapyramidal symptoms (excluding akathisia) is 5%, while akathisia occurs at a 2% placebo-subtracted rate 6
- Somnolence is common (24% vs 6% placebo) and should be monitored 6
Weight and Metabolic Parameters
- Monitor weight at baseline and regularly during treatment 4, 6
- During 3-week acute trials, the placebo-subtracted rate of clinically significant weight gain (≥7%) was approximately 5% 6
- In 9-week extension trials, 19% of patients experienced clinically significant weight gain 6
- Asenapine has minimal effects on plasma glucose and lipid levels, making it favorable compared to olanzapine 3, 4, 2
Cardiovascular Monitoring
- Baseline ECG is prudent given mild QT interval effects similar to quetiapine 2
- Monitor for orthostatic hypotension due to alpha-1 adrenergic receptor binding 2
- Asenapine has little pro-arrhythmogenic potential 4
Other Monitoring
- Prolactin levels: effects are similar to olanzapine and generally mild 2
- Oral hypoesthesia (numbness) occurs commonly and should be discussed with patients 3, 2
Common Pitfalls to Avoid
The most critical error is improper administration—patients who swallow the tablet will receive virtually no therapeutic benefit due to <2% bioavailability 2. Emphasize the 10-minute restriction on food and drink, as this significantly impacts absorption 1.
The twice-daily dosing requirement and administration restrictions represent obstacles to adherence that require explicit patient education 2. The mean elimination half-life is approximately 75 hours, but twice-daily dosing is still required for optimal efficacy 7.