Schizophrenia Daily News Blog

Eli Lilly Updates Label Warning for Zyprexa to Better Inform on Side-Effects

Eli Lilly, the maker of Zyprexa, said that new label changes were made as part of ongoing talks with the Food and Drug Administration (FDA). The company said that the new labels include warnings on weight gain and higher levels of triglycerides and cholesterol, while updating the information in the warning for elevated blood sugar. Eli Lilly added that it will continue to provide more information as required by the FDA.

Zyprexa’s label now acknowledges that the drug appears to cause high blood sugar (which can lead to diabetes) more than other atypical antipsychotic medicines for schizophrenia and bipolar disorder.

The New York Times reported that Lilly has previously argued that by those criteria Zyprexa was no worse in causing increased blood sugar than the competitors' products. Other drugs in this class include J&J’s Risperdal, AstraZeneca’s Seroquel, Bristol-Myers Squibb’s Abilify and Pfizer’s Geodon

The new Zyprexa label is also to indicate that patients who take Zyprexa continue to gain weight for as long as two years after starting therapy. The New York Times suggested that this label change "contradicts some earlier public statements by Lilly that weight gain on Zyprexa tends to plateau after a few months of use. One in six patients who take Zyprexa will gain more than 33 pounds after two years of use, the label says."

This new labeling information is available at www.Zyprexa.com.

The updates reflect recently completed pooled analyses of Lilly's clinical trial data in adults and adolescents, information from two large non-Lilly studies of atypical antipsychotics (CATIE and CAFÉ) and discussions with the FDA. Specifically, the changes include new warnings for weight gain and hyperlipidemia (elevation of triglycerides and cholesterol) and updated information in the warning for hyperglycemia (elevated blood sugar), including additional language on a greater association of increases in glucose levels with olanzapine than with some other atypical antipsychotics. Lilly continues to work with the FDA and will provide additional data and analyses as they become available.

"Lilly continues to recommend that clinicians consult expert guidelines for treating people with antipsychotics, particularly the monitoring of lipids and blood glucose, regardless of the medication prescribed," Dr. Corya said.

Read additional News Stories:

Lilly Adds Label Warnings for Mental Drug Zyprexa (New York Times)

Physicians, patients and caregivers who have additional questions may call the LillyAnswers Center at 1-800-LillyRx, or find additional information about the medications at www.zyprexa.com.

Zyprexa Background from Eli Lilly:

Zyprexa is indicated in the United States for the short- and long-term treatment of schizophrenia, acute mixed and manic episodes of bipolar I disorder, and maintenance treatment of bipolar disorder. Since Zyprexa was introduced in 1996, it has been prescribed to approximately 22 million people worldwide. Zyprexa is not approved for patients under 18 years of age.

Zyprexa is not approved for the treatment of patients with dementia-related psychosis. Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared with those patients taking a placebo.

In addition, compared to elderly patients with dementia-related psychosis taking a placebo, there was a significantly higher incidence of cerebrovascular adverse events in elderly patients with dementia-related psychosis treated with Zyprexa.

Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics, including Zyprexa.

While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose levels appears to fall on a continuum and olanzapine appears to have a greater association than some other atypical antipsychotics. Physicians should consider the risks and benefits when prescribing olanzapine to patients with an established diagnosis of diabetes mellitus, or who have borderline increased blood glucose level. Patients taking olanzapine should be monitored regularly for worsening of glucose control. Persons with risk factors for diabetes who are starting on atypical antipsychotics should undergo baseline and periodic fasting blood glucose testing. Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood glucose testing.

Undesirable alterations in lipids have been observed with olanzapine use. Clinical monitoring, including baseline and follow-up lipid evaluations in patients using olanzapine, is advised. Significant, and sometimes very high, elevations in triglyceride levels have been observed with olanzapine use. Modest mean increases in total cholesterol have also been seen with olanzapine use.

Potential consequences of weight gain should be considered prior to starting olanzapine. Patients receiving olanzapine should receive regular monitoring of weight.

As with all antipsychotic medications, a rare and potentially fatal condition known as NMS has been reported with Zyprexa. If signs and symptoms appear, immediate discontinuation is recommended. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.

Also, as with all antipsychotic treatment, prescribing should be consistent with the need to minimize Tardive Dyskinesia (TD). The risk of developing TD and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic increase. The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.

The most common treatment-emergent adverse event associated with Zyprexa in placebo-controlled, short-term schizophrenia and bipolar mania trials was somnolence. Other common events were dizziness, weight gain, personality disorder (COSTART term for nonaggressive objectionable behavior), constipation, akathisia, postural hypotension, dry mouth, asthenia, dyspepsia, increased appetite and tremor.

Full prescribing information, including a boxed warning, is available at www.zyprexa.com .

Symbyax Background

Symbyax is indicated in the United States for bipolar depression.

Antidepressants can increase suicidal thoughts and behaviors in children, teens and young adults. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for worsening depression symptoms, unusual changes in behavior or thoughts of suicide. Patients and caregivers should be especially observant within the first few months of treatment or after a change in dose. Symbyax is not approved for patients under 18 years of age.

Symbyax is not approved for the treatment of patients with dementia-related psychosis. Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared with those patients taking a placebo.

In addition, compared to elderly patients with dementia-related psychosis taking a placebo, there was a significantly higher incidence of cerebrovascular adverse events in elderly patients with dementia-related psychosis treated with olanzapine, a component of Symbyax.

Symbyax should not be used with an MAOI or within at least 14 days of discontinuing an MAOI. At least five weeks should be allowed after stopping Symbyax before starting an MAOI. Thioridazine should not be given with Symbyax or within at least five weeks after stopping Symbyax. Concomitant use of Symbyax in patients taking pimozide is contraindicated. Symbyax is contraindicated in patients with known hypersensitivity to the product or any component of the product.

Hyperglycemia, in some cases associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics, including olanzapine alone, as well as olanzapine taken concomitantly with fluoxetine. While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose levels appears to fall on a continuum and olanzapine appears to have a greater association than some other atypical antipsychotics. Physicians should consider the risks and benefits when prescribing Symbyax to patients with an established diagnosis of diabetes mellitus, or having borderline increased blood glucose level. Patients taking Symbyax should be monitored regularly for worsening of glucose control. Persons with diabetes who are started on atypicals should be monitored regularly for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood glucose testing. Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood glucose testing.

Undesirable alterations in lipids have been observed with Symbyax use. Clinical monitoring, including baseline and follow-up lipid evaluations in patients using Symbyax, is advised. Significant, and sometimes very high, elevations in triglyceride levels have been observed with Symbyax use. Significant increases in total cholesterol have also been seen with Symbyax use.

Potential consequences of weight gain should be considered prior to starting Symbyax. Patients receiving Symbyax should receive regular monitoring of weight.

Symbyax may induce orthostatic hypotension associated with dizziness, tachycardia, bradycardia, and in some patients, syncope, especially during the initial dose-titration period. Particular caution should be used in patients with known cardiovascular disease, cerebrovascular diseases, or those predisposed to hypotension.

If rash or other possibly allergic phenomena appear for which an alternative etiology cannot be determined, immediate discontinuation is recommended.

As with all antipsychotic medications, a rare and potentially fatal condition known as NMS has been reported with olanzapine. If signs and symptoms appear, immediate discontinuation is recommended. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.

Also, as with all antipsychotic treatment, prescribing should be consistent with the need to minimize Tardive Dyskinesia (TD). The risk of developing TD and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic increase. The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.