Saphris (asenapine maleate): Drug Safety Communication: Serious Allergic Reactions
The U.S. Food and Drug Administration (FDA) is warning the public that serious allergic reactions have been reported with the use of the antipsychotic medication Saphris (asenapine maleate). The Contraindications, Warnings and Precautions, Adverse Reactions, and Patient Counseling Information sections of the Saphris drug label have been revised to include information about this risk and to inform healthcare professionals that Saphris should not be used in patients with a known hypersensitivity to the drug.
A search of the FDA's Adverse Event Reporting System (AERS) database identified 52 cases of Type I hypersensitivity reactions (allergic reactions) with Saphris use (see Data Summary below). Hypersensitivity reactions can be classified into four categories (Type I to Type IV). Signs and symptoms of Type I hypersensitivity reactions may include anaphylaxis (a life-threatening allergic reaction), angioedema (swelling of the deeper layers of the skin), low blood pressure, rapid heart rate, swollen tongue, difficulty breathing, wheezing, or rash. These signs and symptoms are consistent with the reactions reported in the 52 cases. Several cases reported multiple hypersensitivity reactions occurring at the same time, with some of these reactions occurring after the first dose of Saphris.
Healthcare professionals should be aware of the risk of hypersensitivity reactions with Saphris and counsel patients who are receiving the drug about how to recognize the signs and symptoms of a serious allergic reaction. Saphris should not be used in patients with a known hypersensitivity to the drug.
Patients should seek emergency medical attention immediately if they develop any signs and symptoms of a serious allergic reaction while taking Saphris.
Additional Information for Patients
- Serious allergic reactions have been reported in patients treated with Saphris.
- Patients should seek emergency medical attention immediately if they develop any signs and symptoms of a serious allergic reaction such as:
- Difficulty breathing
- Swelling of the face, tongue or throat
- Feeling lightheaded
- Serious side effects from the use of Saphris should be reported to the FDA MedWatch program, using the information in the "Contact Us" box at the bottom of this page.
- Type I hypersensitivity reactions, including anaphylaxis and angioedema, have been observed in patients treated with Saphris. In several cases, these reactions occurred after the first dose.
- The hypersensitivity reactions included: anaphylaxis, angioedema, hypotension, tachycardia, swollen tongue, dyspnea, wheezing, and rash.
- Saphris is contraindicated in patients with a known hypersensitivity to the product.
- Patients should be educated to recognize the signs and symptoms of a serious allergic reaction and advised to contact a healthcare professional immediately if they experience any of these symptoms while taking Saphris.
- Adverse events involving Saphris should be reported to the FDA MedWatch program using the information in the "Contact Us" box at the bottom of this page.
Saphris (asenapine maleate) was FDA-approved on August 13, 2009. A search of the AERS database from approval through September 7, 2010 identified 52 cases that reported Type I hypersensitivity reactions associated with Saphris use. 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 one hypersensitivity reaction following Saphris use. Eight cases reported hypersensitivity reactions after just one dose of Saphris. The reactions reported following one dose included possible angioedema, respiratory distress, and possible anaphylaxis.
Type I hypersensitivity reactions typically require a history of previous exposure to the drug. However, the absence of a known prior exposure does not exclude the reaction, because sensitization may have occurred to a cross-reactive compound in the past even if the patient showed no signs of allergy to the sensitizing product. To date, no specific drug has shown cross-reactivity with Saphris.
Of the 52 cases, 15 reported a resolution of symptoms following Saphris discontinuation, while two of these cases reported a reappearance of symptoms upon reintroduction of Saphris. Nineteen of the cases resulted in hospitalization or emergency room visits, and therapeutic interventions were reported in seven cases.
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.
Facts about Saphris (asenapine maleate)
- In a class of medications called atypical antipsychotics.
- Used to treat symptoms of schizophrenia and bipolar disorder.
- From approval in August 2009 to June 2011, approximately 235,000 prescriptions were dispensed for Saphris and approximately 87,000 patients received a dispensed prescription for Saphris from U.S. outpatient retail pharmacies.1,2
- SDI, Vector One®: National (VONA). August 2009-June 2011. Data extracted August 2011.
- SDI, Vector One®: Total Patient Tracker (TPT). August 2009-June 2011. Data extracted August 2011.
Source : FDA (Sept 2011)
Link to Source
FDA Drug Safety Communication: Children born to mothers who took Valproate products while pregnant may have impaired cognitive development
Valproate products include: valproate sodium (Depacon), divalproex sodium (Depakote, Depakote CP, and Depakote ER), valproic acid (Depakene and Stavzor), and their generics.
Valproate products are FDA-approved drugs to treat seizures, and manic or mixed episodes associated with bipolar disorder (manic-depressive disorder), and to prevent migraine headaches. They are also used off-label (for unapproved uses) for other conditions, particularly for other psychiatric condition
[6-30-2011] The U.S. Food and Drug Administration (FDA) is informing the public that children born to mothers who take the anti-seizure medication valproate sodium or related products (valproic acid and divalproex sodium) during pregnancy have an increased risk of lower cognitive test scores than children exposed to other anti-seizure medications during pregnancy. This conclusion is based on the results of epidemiologic studies that show that children born to mothers who took valproate sodium or related products throughout their pregnancy tend to score lower on cognitive tests (IQ and other tests) than children born to mothers who took other anti-seizure medications during pregnancy.
In the primary epidemiologic study upon which FDA’s conclusion is based, cognitive tests were performed at age three. In supportive studies, cognitive tests were performed at ages five to 16. Cognitive tests are commonly used to assess development in a variety of areas, including intelligence, abstract reasoning, and problem solving.
The long-term effects on cognitive development from exposure to valproate sodium or related products during pregnancy are unknown. It is also not known whether these effects occur when fetal exposure is limited to less than the full duration of pregnancy, such as the first trimester.
FDA has evaluated all available evidence to date, and will be adding information about the risk of lower cognitive test scores to the valproate product labels in the Warnings and Precautions section, the Use in Specific Populations: Pregnancy section, and to the Medication Guides that are being developed for the valproate drug products.
FDA previously warned pregnant women and women of childbearing age about valproate use during pregnancy due to the known risk of birth defects (teratogenic effects) of these products. A teratogen is anything known to cause birth defects during development of an embryo or fetus. Valproate products are assigned to Pregnancy Category D. FDA released an Information for Healthcare Professionals communication in December 2009 on the risk of neural tube birth defects following exposure to valproate products during pregnancy.
The benefits and the risks of valproate sodium and related products should be carefully weighed when prescribing these drugs to women of childbearing age, particularly for conditions not usually associated with permanent injury or death. If the use of valproate is not essential, alternative medications that have a lower risk to the fetus of birth defects and adverse cognitive effects should be considered in pregnant women and women of childbearing age. If the decision is made to use valproate in women of childbearing age, effective birth control should be used.(See Data Summary).
Additional Information for Patients
- Valproate should not be stopped without talking to a healthcare professional, even in pregnant women. Stopping valproate suddenly can cause serious problems. Not treating epilepsy or bipolar disorder (manic-depressive disorder) during pregnancy can be harmful to women and their developing babies.
- If you take valproate during pregnancy, know that there is a higher risk that your child may have birth defects or may score lower on cognitive tests (tests that measure mental ability and capacity, such as IQ tests) in childhood than if you use another anti-seizure medicine during pregnancy.
- Women of childbearing age who decide to take valproate should use effective birth control (contraception) while taking the drug. Women should talk to their healthcare professionals about the best kind of birth control to use while taking valproate.
- Before you start valproate, you should tell your healthcare professional if you are pregnant or are planning to become pregnant. Healthcare professionals may discuss other treatment options with you.
- You should tell your healthcare professional right away if you become pregnant while taking valproate. You and your healthcare provider should decide if you should continue to take valproate while you are pregnant.
- If you become pregnant while taking valproate, you should talk to your healthcare professional about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect additional information about the safety of antiepileptic drugs during pregnancy. Information about the North American Drug Pregnancy Registry can be found at http://www.massgeneral.org/aed/.
- If you took valproate while pregnant, let your child’s pediatrician know.
- Valproate passes into breast milk, but its effects on developing babies remain unknown. You should talk to your healthcare professional about the best way to feed your baby if you take valproate.
- You should report any side effects you experience to the FDA MedWatch program using the information in the “Contact Us” box at the bottom of the page.
Additional Information for Healthcare Professionals
- Inform women of childbearing age of the increased risk for adverse effects on cognitive development with prenatal valproate exposure.
- Continue to counsel women of childbearing potential taking valproate about the increased risk of major malformations, including neural tube defects, when valproate is used during pregnancy.
- Weigh the benefits and risks of valproate when prescribing this drug to women of childbearing age, particularly when treating a condition not usually associated with permanent injury or death. Alternative medications that have a lower risk of adverse birth outcomes should be considered. Healthcare professionals should discuss the relative risks and benefits of appropriate alternative therapies.
- Untreated or inadequately treated epilepsy or bipolar disorder during pregnancy increases the risk of complications in both the pregnant mother and her developing baby.
- If the decision is made to prescribe valproate to women of childbearing age, healthcare professionals should recommend use of effective contraception for women who are not planning a pregnancy.
- Inform patients of the North American Antiepileptic Drug (NAAED) Pregnancy Registry and encourage patients who become pregnant to enroll by calling 1-888-233-2334.
- Report adverse events involving valproate to the FDA MedWatch program, using the information in the “Contact Us” box at the bottom of the page.
Several published epidemiological studies have indicated that children exposed to valproate in utero have lower cognitive test scores than children exposed to either another antiepileptic drug in utero or to no antiepileptic drugs in utero. The largest of these studies is a prospective cohort study conducted in the United States and United Kingdom that found children with prenatal exposure to valproate throughout pregnancy had lower Differential Ability Scale (D.A.S) scores at age 3 (92 [95% confidence interval 88 to 97]) than children with prenatal exposure to the other evaluated antiepileptic drug monotherapy treatments: lamotrigine (101 [95% confidence interval 98 to 104]), carbamazepine (98 [95% confidence interval 95 to 102]) and phenytoin (99 [95% confidence interval 94 to 104]).1 The D.A.S., which has a mean score of 100 (SD = 15), is a battery of cognitive tests designed for children 2.5 to 17 years of age. The D.A.S. is a measure of cognitive development performed in children who are too young to undergo IQ testing, and generally correlates with IQ scores later in childhood. Although all of the available studies have methodological limitations, the weight of the evidence supports the conclusion that valproate exposure in utero causes subsequent adverse effects on cognitive development in offspring.
- Meador KJ, Baker GA, Browning N, et al. Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. N Engl J Med 2009;360:1597-605.
- Gaily E, Kantola-Sorsa E, Hiilesmaa V, et al. Normal intelligence in children with prenatal exposure to carbamazepine. Neurology 2004;62:28-32.
- Adab N, Jacoby AD, Chadwick D. Additional educational needs of children born to mothers with epilepsy. J Neuro Neurosurg Psychiatry 2001;70:15-21.
- Adab N, Kini U, Vinten J, et al. The longer term outcome of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry 2004;75:1575–83.
Link to Source
FDA Warns Pfizer Over Geodon Trial Overdosing
By Ed Silverman
The drugmaker was cited for failing to properly monitor pediatric clinical trials in which at least 13 children with bipolar disorder experienced overdosing that led to restless legs, tremors, involuntary facial movements and skin petechiae, which results from bleeding under the skin. The FDA cited Pfizer in an April 9 warning letter that noted the problem was originally found during FDA reviews in 2005.
The FDA wrote that "Pfizer failed to properly ensure monitoring of the study referenced above. As a result of inadequate monitoring, widespread overdosing of study subjects at multiple study sites was neither detected nor corrected in a timely manner," according to the letter.
For instance, the FDA cited an internal Pfizer document dated Oct. 3, 2007 and entitled "Safety Information on Affected Subjects," whicd noted that an additional six pediatric subjects in the study at two different sites experienced overdosing. And these occurred in June, July and August 2007 - several months after Pfizer supposedly retrained study monitors on correct dosing procedures.
This is the sort of episode that bolsters criticism of the deal in which drugmakers were awarded patent extensions for agreeing to run pediatric trials. Moreover, this is also the same drugmaker that was fined $301 million for improperly marketing Geodon for unapproved uses; unapproved patients, including children, and for higher doses than approved by the FDA (see here). The unfortunate take-away message suggests a disregard for children, although Pfizer says it takes the situation seriously and maintains it has instituted new procedures to prevent a recurrence.
In its letter, the agency noted the inspection is part of its Bioresearch Monitoring Program, which includes inspections designed "to evaluate the conduct of research and to ensure that the rights, safety, and welfare of the human subjects of those studies have been protected." The Pfizer inspection was performed due to "significant violations found during inspections of several clinical investigators" involved in the trial.
LINK TO SOURCE