Atypical Antipsychotic Linked to Life-Threatening Reactions

Caroline Cassels


September 01, 2011

September 1, 2011 (UPDATED September 30, 2011) — The US Food and Drug Administration (FDA) has issued a warning about possible severe allergic reactions, including anaphylaxis and angioedema, to the atypical antipsychotic asenapine maleate (Saphris, Merck).

A search of the FDA's Adverse Event Reporting System (AERS) identified 52 cases of allergic reactions with the drug's use. Of these cases, 15 reported a resolution of symptoms after discontinuation of asenapine maleate, whereas 2 of these cases reported a reappearance of symptoms after reintroduction of the drug. There were 19 cases that resulted in hospitalization or emergency department visits, and therapeutic interventions were reported in 7 cases.

According to the FDA warning, reported signs and symptoms included anaphylaxis, angioedema, hypotension, tachycardia, swollen tongue, dyspnea, wheezing, and rash. Some of the cases reported the occurrence of more than 1 hypersensitivity reaction after use of asenapine maleate. Eight cases reported hypersensitivity reactions after just 1 dose of asenapine maleate. The reactions reported after use of a single dose included possible angioedema, respiratory distress, and possible anaphylaxis.

"Although many of the cases have limited information, the findings from the cases are consistent with hypersensitivity reactions, including anaphylaxis, and support a temporal association between the onset of the reactions and Saphris use," the FDA reports.

The FDA also notes that the drug's label has been revised to include information about this risk and advises healthcare professionals not to use it in patients with a known hypersensitivity to asenapine maleate.

In addition, clinicians should counsel patients receiving the drug about the signs and symptoms of a serious allergic reaction.

A previously issued boxed warning for asenapine maleate indicates increased risk for death in elderly patients with dementia-related psychosis treated with antipsychotic drugs. Therefore, asenapine maleate is not approved for the treatment of patients with dementia-related psychosis.

Indications, Administration of Drug

Used to treat symptoms of schizophrenia and bipolar disorder, asenapine maleate was approved in 2009. It is estimated that as of June 2011, approximately 235,000 prescriptions were dispensed for asenapine maleate, and approximately 87,000 patients received a dispensed prescription for the drug from US outpatient retail pharmacies.

Asenapine maleate is indicated for treatment and maintenance therapy of schizophrenia in adults, and for acute treatment, either as monotherapy or as adjunctive therapy, of manic or mixed episodes associated with bipolar I disorder in adults. It is supplied as sublingual tablets, plain or black-cherry flavor, 5 mg and 10 mg, to be placed under the tongue and allowed to dissolve completely, which will occur within seconds. The patient should not eat or drink for 10 minutes after administration, and the tablet should not be swallowed.

For acute treatment of schizophrenia in adults, starting dose and recommended dose of asenapine maleate are 5 mg twice daily, and maximal dose is 10 mg twice daily. For maintenance, starting dose is 5 mg twice daily for 1 week, with recommended dose and maximal dose of 10 mg twice daily. For monotherapy of bipolar mania in adults, the starting dose is 10 mg twice daily, with a recommended dose of 5 to 10 mg twice daily and maximal dose 10 mg twice daily. As an adjunct to lithium or valproate in adults with bipolar mania, the starting dose is 5 mg twice daily, with recommended dose of 5 to 10 mg twice daily and maximal dose of 10 mg twice daily.

Additional Adverse Reactions

Commonly observed adverse reactions, occurring at an incidence of at least 5% and at least twice that for placebo, with asenapine maleate used to treat schizophrenia were akathisia, decreased oral sensation, and sleepiness. When asenapine maleate is used as monotherapy for bipolar disorder, common adverse events are sleepiness, dizziness, extrapyramidal symptoms other than akathisia, and weight gain. When asenapine maleate is used as adjunctive therapy for bipolar disorder, common adverse events are somnolence and oral hypoesthesia.

Adverse events related to asenapine maleate can be communicated to MedWatch, the FDA's adverse event and reporting program, by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.

More information on safety changes to asenapine maleate is available on the FDA MedWatch site.

Laurie Barclay, MD, contributed to this synopsis.


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