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

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. Continue reading for a comprehensive list of adverse effects.

Applies to asenapine: sublingual tablet. Other dosage forms:

• transdermal patch extended release

Serious side effects of Saphris

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

• Blurred vision
• dizziness
• headache
• nervousness
• pounding in the ears
• slow or fast heartbeat

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

Other side effects of Saphris

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, transdermal film extended release.

General

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]

Nervous system

Very common (10% or greater): Somnolence (up to 53%), extrapyramidal symptoms (up to 25%), sedation (up to 19.2%), akathisia (up to 15%), headache (up to 11%), dizziness (up to 10.1%)

Common (1% to 10%): Dysgeusia, dyskinesia, dystonia/acute dystonia, extrapyramidal disorder, parkinsonism, tremor

Uncommon (0.1% to 1%): Dysarthria, restless leg syndrome, seizure, syncope

Rare (less than 0.1%): Neuroleptic malignant syndrome

Frequency not reported: Bradykinesia, cerebrovascular events, hyperkinesia, hypersomnia, lethargy, motor impairment, myoclonus, resting tremor, tardive dyskinesia^[Ref]

Somnolence occurred in up to 53% of patients aged 10 to 17 years given 5 mg orally 2 times a day.

Extrapyramidal symptoms occurred in 25% of patients given 10 mg, compared to 11% of patients given 5 mg.^[Ref]

Gastrointestinal

Very common (10% or greater): Oral hypoesthesia (up to 30%), oral paresthesia (up to 11%)

Common (1% to 10%): Abdominal pain, constipation, dry mouth, dyspepsia, glossodynia, nausea, oropharyngeal pain, salivary hypersecretion, stomach discomfort, toothache, vomiting

Uncommon (0.1% to 1%): Dysphagia, gastroesophageal reflux disease (GERD/GORD), oromucosal lesions (ulcerations, blustering, inflammation), swollen tongue

Postmarketing reports: Abdominal discomfort, abdominal pain lower, abdominal pain upper, oral dysesthesia, oral peeling/sloughing, oromandibular dystonia, oropharyngeal muscular dysfunction, pharyngeal edema, swallowing difficulty, swollen throat, tongue disorder, tongue protrusion^[Ref]

Oral hypoesthesia occurred in up to 30% of pediatric patients and up to 24% of adults.

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]

Psychiatric

Very common (10% or greater): Insomnia (up to 16%)

Common (1% to 10%): Agitation, anger, anxiety, bipolar disorder, bipolar I disorder, depression, depressive symptoms, irritability, mania, schizophrenia, suicidal ideation

Frequency not reported: Cognitive impairment^[Ref]

Other

Very common (10% or greater): Fatigue (up to 14%)

Uncommon (0.1% to 1%): Fall

Rare (less than 0.1%): Idiosyncratic drug reaction

Frequency not reported: Body temperature dysregulation, neonatal drug withdrawal syndrome^[Ref]

Metabolic

Very common (10% or greater): Weight gain of at least 7% (up to 13.1%)

Common (1% to 10%): Dehydration, hyperinsulinemia, increased appetite, new-onset metabolic syndrome, weight increased

Uncommon (0.1% to 1%): Hyperglycemia, hyponatremia

Frequency not reported: Blood insulin increased, diabetes mellitus, dyslipidemia, metabolic changes^[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]

Musculoskeletal

Very common (10% or greater: Creatine kinase elevations (up to 11.1%)

Common (1% to 10%): Arthralgia, muscle rigidity, muscle strain, myalgia

Frequency not reported: Involuntary muscle contractions, muscle spasms, muscle twitching, musculoskeletal stiffness, neck muscle spasm^[Ref]

Cardiovascular

Common (1% to 10%): Edema, hypertension, orthostatic hypotension, peripheral edema, tachycardia

Uncommon (0.1% to 1%): Bundle branch block, hypotension, QT prolongation on ECG, sinus bradycardia, sinus tachycardia, temporary bundle branch block

Frequency not reported: Heart rate increased^[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]

Hepatic

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 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 treated patients versus 1.3% for placebo treated patients. In short-term, placebo-controlled bipolar mania trials, the mean increase in transaminase levels for 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 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%): ALT increased, AST increased, angioedema, transient asymptomatic elevations in hepatic transaminases^[Ref]

Respiratory

Common (1% to 10%): Dyspnea, nasal congestion, nasopharyngitis

Rare (less than 0.1%): Pulmonary embolism

Frequency not reported: Difficulty breathing, throat tightness, upper respiratory tract infection

Postmarketing reports: Choking, wheezing^[Ref]

Genitourinary

Common (1% to 10%): Dysmenorrhea

Uncommon (0.1% to 1%): Amenorrhea, enuresis, sexual dysfunction

Rare (less than 0.1%): Galactorrhea^[Ref]

Dermatologic

Common (1% to 10%): Rash

Uncommon (0.1% to 1%): Photosensitivity reaction^[Ref]

Ocular

Uncommon (0.1% to 1%): Accommodation disorder, blurred vision, diplopia

Frequency not reported: Blepharospasm, oculogyration^[Ref]

Hematologic

Uncommon (0.1% to 1%): Anemia

Rare (less than 0.1%): Neutropenia, thrombocytopenia

Frequency not reported: Agranulocytosis, leukopenia^[Ref]

Endocrine

Uncommon (0.1% to 1%): Decreased prolactin levels

Rare (less than 0.1%): Gynecomastia

Frequency not reported: Hyperprolactinemia^[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Allergic reactions

Postmarketing reports: Anaphylactic/anaphylactoid reactions, serious hypersensitivity reactions^[Ref]

Local

Postmarketing reports: Sublingual application site reactions^[Ref]