Asenapine (Saphris)


Clinical Information


HALF-LIFE: 13-39 hours

METABOLISM: Liver (primarily CYP1A2)

STARTING DOSE: 2.5mg-5mg sublingual (SL) BID



HOW TO DOSE: Initial 2.5mg-5mg sublingual (SL) twice daily and increase as needed up to 10mg SL twice daily 

PREGNANCY: Minimal data on safety

BREASTFEEDING: Minimal data on safety

Drug Interactions

  • Inhibitor of CYP2D6

Side Effects

  • Constipation, dry mouth, blurry vision, tachycardia, orthostatic hypotension, seizures (rare but may occur at high doses), sedation, weight gain, increased cardio-metabolic risk (↑triglycerides, insulin resistance), oral numbness (transient), Akathisia, Arrhythmias, Extrapyramidal Symptoms (EPS), Neuroleptic Malignant Syndrome (Rare)

FDA Indications

  1. Schizophrenia
  2. Bipolar Disorder (acute manic/mixed episodes), 10yo and older

Off Label Uses: Agitation, Insomnia, Irritability

Mechanism(s) of Action

  • Dopamine 2 receptor antagonist, 5HT2A Receptor Antagonist, 5HT2C Receptor Antagonist, 5HT7 Receptor Antagonist, Alpha-2 Receptor Antagonist

Additional Information

  • Asenapine is structurally very similar to Mirtazapine
  • Sublingual absorption (Asenapine has very low bioavailability if swallowed due to first pass metabolism in the liver)
  • Oral Cavity surface area limits size of dose and extent of absorption
  • Rapidly absorbed and has rapid peak drug levels
  • Completely dissolves within 5-10 seconds after contact with sublingual mucosa
  • Oral hypoesthesia (numbness/tingling) is common
  • No eating or drinking for 10 minutes following administration
  • Sedation is common due to antihistamine effects 
  • Akathisia may be dose related
  • Low-moderate risk for extrapyramidal symptoms (movement disorders), Weight gain, and Prolactin elevation


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