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Saphris Side Effects

Generic Name: asenapine

Note: This document contains side effect information about asenapine. Some of the dosage forms listed on this page may not apply to the brand name Saphris.

In Summary

Common side effects of Saphris include: akathisia, drowsiness, extrapyramidal reaction, headache, and dizziness. Other side effects include: gastric hypersecretory conditions, hypoesthesia, sialorrhea, and weight gain. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to asenapine: sublingual tablet

Along with its needed effects, asenapine (the active ingredient contained in Saphris) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking asenapine:

More common
  • Abnormal or decreased touch sensation
  • inability to move the eyes
  • inability to sit still
  • increase in body movements
  • increased blinking or spasms of the eyelid
  • lip smacking or puckering
  • need to keep moving
  • puffing of the cheeks
  • rapid or worm-like movements of the tongue
  • restlessness
  • shakiness in the legs, arms, hands, or feet
  • sticking out of tongue
  • trembling or shaking of the hands or feet
  • trouble with breathing, speaking, or swallowing
  • twitching, twisting, uncontrolled repetitive movements of the tongue, lips, face, arms, or legs
  • uncontrolled chewing movements
  • uncontrolled twisting movements of the neck, trunk, arms, or legs
  • unusual facial expressions
  • weakness of the arms and legs
Less common Rare
  • Black, tarry stools
  • bleeding gums
  • blood in the urine or stools
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • changes in patterns and rhythms of speech
  • coma
  • confusion
  • convulsions
  • decreased urine output
  • fast, pounding, or irregular heartbeat or pulse
  • increased thirst
  • muscle pain or cramps
  • nausea or vomiting
  • pale skin
  • pinpoint red spots on the skin
  • slurred speech
  • swelling of the face, ankles, or hands
  • troubled breathing with exertion
  • unusual bleeding or bruising
  • unusual tiredness or weakness

Some side effects of asenapine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Constipation
  • sleepiness or unusual drowsiness
  • trouble sleeping
  • unusually deep sleep
  • unusually long duration of sleep
Less common
  • Acid or sour stomach
  • belching
  • depression
  • difficulty with moving
  • dry mouth
  • fear or nervousness
  • heartburn
  • increased appetite
  • increased watering of the mouth
  • increased weight
  • indigestion
  • irritability
  • muscle pain or stiffness
  • pain in the arms or legs
  • pain in the joints
  • stomach discomfort, upset, or pain
  • toothache

For Healthcare Professionals

Applies to asenapine: sublingual tablet


The most commonly reported adverse reactions in adults included akathisia, dizziness, extra pyramidal symptoms other than akathisia, oral hypoesthesia, somnolence, and increased weight. The most commonly reported adverse reactions in pediatric patients included somnolence, dizziness, dysgeusia, oral paresthesia, nausea, increased appetite, fatigue, and increased weight.[Ref]


In a dedicated QT study in patients with schizophrenia, doses of 5, 10, 15, and 20 mg twice a day were compared with placebo. QTc interval increases ranged from 2 to 5 msec. No patients had QTc increases of 60 msec or greater, nor did any patient experience a QTc of 500 msec or greater.

Orthostatic hypotension was reported in 4.1% of elderly subjects compared with 0.3% in the combined study populations.[Ref]

Common (1% to 10%): Hypertension, edema
Uncommon (0.1% to 1%): Syncope, sinus bradycardia, bundle branch block, QT prolongation on ECG, sinus tachycardia, orthostatic hypotension, hypotension
Rare (less than 0.1%): Tachycardia[Ref]


While all atypical antipsychotics have been associated with metabolic changes including hyperglycemia, dyslipidemia, and weight gain, the degree of metabolic change differs for each agent.

In clinical trials with this drug, changes from baseline in fasting glucose ranged from -0.6 to 3.8 mg/dL in adults and -0.45 to 1.43 mg/dL in pediatric patients treated with this drug for 3 to 6 weeks compared with -0.2 and -2.24 mg/dL in adults and pediatric patients receiving placebo, respectively. In a 52-week double-blind, comparator-controlled trial in primarily schizophrenic patients, the mean increase in fasting glucose from baseline was 2.4 mg/dL.

An increase of 7% or more in body weight occurred in 8% to 12% of adults and 4.4% to 4.8% of pediatric patients treated with this drug for 3 weeks compared with 1.1% and 1.6%, respectively in adults and pediatric patients receiving placebo. In a 52-week double-blind, comparator-controlled trial in primarily schizophrenic patients, the mean increase in weight from baseline was 0.9 kg.[Ref]

Common (1% to 10%): Weight increased, increased appetite
Uncommon (0.1% to 1%): Hyponatremia, hyperglycemia[Ref]


Uncommon (0.1% to 1%): Anemia
Rare (less than 0.1%): Neutropenia, thrombocytopenia[Ref]


Common (1% to 10%): Dysmenorrhea
Uncommon (0.1% to 1%): Sexual dysfunction, amenorrhea
Rare (less than 0.1%): Gynecomastia, galactorrhea
Frequency not reported: Hyperprolactinemia[Ref]


Frequency not reported: Hypersensitivity to include anaphylaxis, angioedema, hypotension, tachycardia, swollen tongue, dyspnea, wheezing, and rash[Ref]


Common (1% to 10%): Insomnia, anxiety, agitation, depression, irritability, suicidal ideation, anger[Ref]


Transient elevations in serum transaminases (primarily ALT) in the short-term schizophrenia and bipolar mania trials were more common in treated patients but mean changes were not clinically relevant. In short-term, placebo-controlled schizophrenia trials, the mean increase in transaminase levels for asenapine (the active ingredient contained in Saphris) treated patients was 1.6 units/L compared to a decrease of 0.4 units/L for placebo treated patients. The proportion of patients with transaminase elevations three or more times the ULN (at the endpoint) was 0.9% for asenapine treated patients versus 1.3% for placebo treated patients. In short-term, placebo-controlled bipolar mania trials, the mean increase in transaminase levels for asenapine treated patients was 8.9 units/L compared to a decrease of 4.9 units/L in placebo treated patients. The proportion of patients with transaminase elevations three or more times the ULN (at the endpoint) was 2.5% for asenapine treated patients versus 0.6% for placebo treated patients. No cases of more severe liver injury were seen. In a 52 week, double-blind, comparator controlled trial of patients with schizophrenia and schizoaffective disorder, the mean increase from baseline of ALT was 1.7 units/L.[Ref]

Common (1% to 10%): Alanine aminotransferase (ALT) increased[Ref]


Common (1% to 10%): Muscle rigidity, arthralgia, extremity pain
Rare (less than 0.1%): Rhabdomyolysis[Ref]

Nervous system

Very common (10% or greater): Somnolence (pediatric patients; up to 53%)
Common (1% to 10%): Dizziness, somnolence (adults), extrapyramidal disorder, akathisia, dyskinesia, dystonia, parkinsonism, sedation, dysgeusia, tremor, headache, dysgeusia, akathisia
Uncommon (0.1% to 1%): Seizure, dysarthria,
Rare (less than 0.1%): Neuroleptic malignant syndrome
Frequency not reported: Restless leg syndrome[Ref]


Rare (less than 0.1%): Accommodation disorder[Ref]


Common (1% to 10%): Fatigue[Ref]


Uncommon (0.1% to 1%): Epistaxis, asthma, rhinorrhea, sinus congestion, nasal dryness
Rare (less than 0.1%): Pulmonary embolism
Postmarketing: Choking[Ref]


Very common (10% or greater): Oral paraesthesia (pediatrics, up to 30%)
Common (1% to 10%): Constipation, dry mouth, oral hypoesthesia (adults), salivary hypersecretion, stomach discomfort, vomiting, toothache, dyspepsia, diarrhea, nausea, abdominal pain
Uncommon (0.1% to 1%): Dysphagia, swollen tongue, glossodynia
Postmarketing reports: Oral ulcers, blisters, peeling/sloughing, and inflammation at the application site, nausea[Ref]

Application site reactions that include oral ulcers, blisters, peeling/sloughing, and inflammation primarily in the sublingual area have led to discontinuation of therapy in many cases. Oral hypoesthesia and/or oral paraesthesia may occur directly after administration and usually resolve in 1 hour.[Ref]


Common (1% to 10%): Rash[Ref]


1. "Product Information. Saphris (asenapine)." Schering-Plough Corporation, Kenilworth, NJ.

2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

3. Cerner Multum, Inc. "Australian Product Information." O 0

Some side effects of Saphris may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.