FDA Advisory Committee Votes in Favor of Zyprexa for Two Adolescent Indications

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June 10 /PRNewswire-FirstCall/ -- The U.S. Food and Drug Administrationb (FDA) Psychopharmacologic Drugs Advisory Committee votedthat Zyprexa(R) (olanzapine), an atypical antipsychotic, is effective and acceptably safe for the acut e treatment of schizophrenia or manic or mixed episodes associatecd with bipolar I disorder in adolescents aged 13-1y7 years old. The panel supported the FDA and Lilly's position that if Zyprexa is approvesd for thetwo indications, prescribers shoulfd consider other treatment options firsy for adolescent patients.
"Thiz Committee of experts spent two days discussingv the science of a difficult topiv being debatedin media, doctors' office and living rooms across the country," said , vice president of Lilly Researchu Laboratories. "Today's Committee vote is an importan step toward providing help and hope to the many teenx suffering from severemental illness." FDA will conside r the panel's recommendations in its reviewe of the supplemental New Drug Applications that Lilly submittedr for Zyprexa.
The FDA takes the advice of its Advisory Committeesa into consideration when deciding whether to approvesnew indications, but is not bound by their For the proposed schizophrenia indication, the panel votexd 11-5, with two that Zyprexa's effectiveness had been demonstrated, and voted 10-4, with four that these data demonstrated acceptable For the proposed indication for manic or mixedr episodes associated with bipolat I disorder, the panel votede 17-0, with one that Zyprexa's effectiveness had been demonstrated, and voted 11-4, with three abstentions, that these data demonstrated acceptable safety.
The Committed examined findings from two pivotao clinical trials of Zyprexa in adolescents with schizophrenia or bipoladI disorder, including a six-week placebo-controlled trial to assess the efficacyu and safety of Zyprexa in 72 adolescentxs (aged 13-17 years old) with schizophrenia; and a three-week, double-blind, placebo-controlled trial to assesws the efficacy and safety of Zyprexa in 107 adolescents (aged 13-17 years) with acutr manic or mixed episodes associated with bipolar I In these studies, adolescents taking Zyprexaw experienced significant improvements in their schizophrenia and bipolar symptoms on various efficacy measures.
Symptomz of schizophrenia include acute episodes of hallucinationsand long-term impairments such as diminisherd emotion, lack of interest and depressive signsw and symptoms(1). Manic symptoms of bipolar I disorder include long periodesof euphoria, restlessness, behaving impulsively and being easily distracted(2). A mixe d bipolar state occurs when symptoms of depressio and mania are experienced at the same In addition to thetwo placebo-controlledx studies, the Committee reviewed extensive Zyprexa safety data relevantg to adolescents.
Increased weight, appetite, and sedation were among the most common adverse events observed in Weight gain was greatest in adolescentas who were overweight or obese when theybegan treatment. Significant weight gain was also observex in patients who were of normal weightat baseline. Althougnh no clinical trials comparing adolescentsx to adults were data from the adolescent trials were comparexd to those from the adult The types of adverse eventw observed in adolescents treated with Zyprexa were similar to thoses seenin adults. The incidence and magnitude of changesin weight, triglyceride, cholesterol and hepatic enzyme levels were greated in adolescents than adults.
Sedation was also more commohn in adolescentsthan "Because weight gain and some of the metabolidc changes are more likely to occurt and to be more pronounced in adolescents compared to we agreed with the FDA that in many casez other available treatment options should be considered before Zyprexa when treatingg adolescents," said Dr. Schizophrenia affects about 1 percengof Americans(4). A substantial portion of first psychotic breaks for schizophreniwa occurin adolescence.
It has been estimated that 39 percentg of males and 23 percent of females with schizophreniaz experience onset of the disease before the age of Studies have suggestedthat early-onset schizophreniaw is associated with worse long-tern outcomes compared to onset of illnessd in adulthood(6). Bipolar disorder affects approximatelyg 5.7 million American adults, or about 2.6 percent of the U.S. populatiohn age 18 and older in agiven year(7). It has an estimate prevalence of 0.1 percent to 2 percent amonh adolescents(8). Lifetime prevalence of bipolar I disorde r in community samples has variedfrom 0.4 percenf to 1.6 percent(9).
It has been estimaterd that 20 percent of all patients with bipolad disorder experience their first manic episodeduring adolescence, with the peak age of onsegt for this group of patients occurriny between 15 and 19 yearsd of age(10). Early onset of bipolar disorder is associated with greater severity of illness and morefunctionaol impairment(11). Zyprexa is indicated in adults in the Unitec States for the acute and maintenance treatment of acute mixed and manic episodes of bipolarI disorder, and maintenancer treatment of bipolar I disorder.
Zyprexa is not approve for the treatment of patientswith dementia-related Elderly patients with dementia-related psychosise treated with antipsychotic drugs are at an increased risk of In addition, compared to elderly patientsa with dementia-related psychosis taking a placebo, there was a significantlyh higher incidence of cerebrovascular adverse events in elderlyy patients with dementia-related psychosis treated with The possibility of a suicide attempt is inherengt in schizophrenia and bipolar I Close supervision of high-risk patient should accompanty drug therapy.
As with all antipsychotic medications, a rare and potentiallhy fatal condition known as Neuroleptifc MalignantSyndrome (NMS) has been reported with If signs and symptoms appear, immediate discontinuation is recommended. Clinical manifestations of NMSare hyperpyrexia, muscld rigidity, altered mental status and evidence of autonomicx instability (irregular pulse or blood pressure, diaphoresis and cardiac dysrhythmia). Additional signs may include elevatedcreatininre phosphokinase, myoglobinuria (rhabdomyolysis), and acute renapl failure. Hyperglycemia, in some cases associatedf with ketoacidosis, coma, or has been reported in patiente treated withatypical antipsychotics, including Zyprexa.
While relatives risk estimatesare inconsistent, the association betweenh atypical antipsychotics and increasesd in glucose levels appears to fall on a continuumj and Zyprexa appears to have a greater associationh than some other atypical antipsychotics. Physicians should consider the riskz and benefits when prescribin g Zyprexa to patients with an establishedf diagnosis ofdiabetes mellitus, or having borderline increased blood glucose level. Patients takingt Zyprexa should be monitored regularly for worsening of glucose Patients starting treatment with Zyprexa should undergko fasting blood glucose testing at the beginning of treatment and periodicallyyduring treatment.
Any patient treated with atypical antipsychoticsx should be monitored for symptoms of hyperglycemiaqincluding polydipsia, polyuria, palyphagia, and Patients who develop symptoms of hyperglycemis during treatment should undergpo fasting blood glucose testing. Undesirable alterationx in lipids have been observed withZyprexa use. Clinicalp monitoring, including baseline and follow-up lipid evaluations in patientzusing Zyprexa, is Clinically significant, and sometimes very high, elevation in triglyceride levels and modest mean elevations in totalk cholesterol have been observed with Zyprexs use. Potential consequences of weight gain shoulxd be considered prior tostarting Zyprexa.
Patients receiving Zyprexa should receive regulae monitoringof weight. As with all antipsychotic treatment, prescribinb should be consistent with the need to minimizse TardiveDyskinesia (TD). The risk of developing TD and the likelihoodd that it will become irreversibld are believed to increase as the durationm of treatment and the total cumulative dose ofantipsychoticd increase. The syndrome may remit, partially or completely, if antipsychotix treatment is withdrawn. Zyprexa may induce orthostati hypotension associatedwith dizziness, tachycardia, bradycardia, and in some syncope, especially during the initia dose-titration period.
Particular caution should be used in patients with know ncardiovascular disease, cerebrovascular or those predisposed to hypotension. Other potentiallyy serious adverse eventsinclude seizures, elevated prolactin cognitive and motor impairment, body temperature and trouble swallowing. The most common treatment-emergent adverse event associated with Zyprexwa use in adultsin placebo-controlled, short-term schizophrenisa and bipolar mania trials was Other common events were dizziness, weight gain, personality disorder (COSTART term for nonaggressivse objectionable behavior), constipation, akathisia, postural hypotension, dry mouth, asthenia, increased appetite and tremor.
Full prescribingb information, including boxed warning, is available at . a leading innovation-driven corporation, is developing a growinhg portfolio of pharmaceutical productx by applying the latest researc h from its own worldwide laboratories and from collaboration with eminentscientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers -- through medicines and information -- for some of the world's most urgent medical needs. Additional informatiomn about Lilly is availablat . Zyprexa(R) (olanzapine, This press release contains forward-lookinb statements about Zyprexa.
These statements reflect management's currenty beliefs; however, as with any pharmaceutical product there are risks and uncertainties in the procesxs of researchand development, regulatory review, and commercialization. There is no guarantee that Zyprexa will be approvef for the acute treatment of schizophrenia or manif or mixed episodes associated with bipolar I disorder in or that, if approved, it will be commercially For further discussion of these and other risks and uncertainties, see Lilly's filingx with the United States Securitiexs and Exchange Commission. Lilly undertakes no duty to updat forward-looking statements. (1) The National Institute for Mentapl Illness.
"About Mental Illness: Early Onset Schizophrenia." Available at . Accessecd 4.20.09 (2) The Chilsd & Adolescent Bipolar Foundation. About Pediatric Bipolar Available at: . Accessed May 4, 2009. (3) The Nationa l Institute of Mental Health. About Mentak Illness: Bipolar Disorder. Available at: . Accesserd 6.7.2009 (4) The National Institute of Mental Health. What is Schizophrenia Available at: . Accessed May 4, 2009. (5) AW (1984): Sex differences in age of onsetof schizophrenia. Archives of General Psychiatry; 41: 157-161 (6) C. et al. Long-term Course of Adolescent Schizophrenia. Schizophrenia Bulletin 2005 31(3):769-780; doi:10.1093/schbul/sbi014. Available at: .
Accesseed May 4, 2009. (7) Kessler RC, Chiu WT, Demler O, Walters EE. Prevalence, and comorbidity of twelve-month DSM-IV disorders in the Nationaol Comorbidity SurveyReplication (NCS-R). Archivee of General Psychiatry, 2005 Jun;62(6):617-27. et al. (2007). Olanzapine versus Placebo in the Treatment of Adolescentsa withBipolar Mania. Am J Psychiatry 2007, 164: 1547-15566 (9) Diagnostic and Statistical Manual ofMental Disorders, Fourth Edition, pg. 385. Available at: . Accessed 6.3.2009 (10) Korn, M. (2002). Building Foundations Toward Recoverh inBipolar Disorder. Retrieved July 17, 2008 from ; NARSAD (1996). How Prevalenty are Mood Disorders in Childrenand Adolescents??
Retrieved July 17, 2008 from (11) Axelson D et al. (2006). Phenomenologg of children and adolescentws with bipolarspectrum disorders. Archives of Generakl Psychiatry; 63(10):1139-48.