FDA Safety Changes: Symbyax, Zoladex, INOmax

Yael Waknine

October 14, 2009

October 14, 2009 — The US Food and Drug Administration (FDA) has approved safety labeling revisions to warn of the risk for leukopenia/neutropenia in patients receiving antipsychotics, including olanzapine; the potential for hyperglycemia in patients receiving treatment with gonadotropin-releasing hormone agonists, including goserelin acetate; and the potential for heart failure in patients with left ventricular dysfunction receiving treatment with inhaled nitric oxide.

Antipsychotic Agents May Be Linked to Risk for Leukopenia/Neutropenia

The FDA approved class labeling revisions for the atypical antipsychotic agent olanzapine to warn of a temporal relationship with the development of leukopenia/neutropenia; agranulocytosis has also been reported. On August 31, the label for Symbyax (marketed in combination with fluoxetine HCl; Eli Lilly & Co) was updated.

Patients with risk factors for leukopenia/neutropenia, such as preexisting low white blood cell count (WBC) or a history of drug-induced leukopenia/neutropenia, should have frequent monitoring of complete blood count (CBC) during the first few months of treatment. Antipsychotic therapy should be discontinued at the first sign of a clinically significant decline in WBC that cannot be attributed to other causes.

Patients with clinically significant neutropenia should be carefully monitored for fever or other signs of infection and treated promptly if symptoms occur. Antipsychotic therapy should be discontinued for severe neutropenia (absolute neutrophil counts < 1000 mm3) and WBC monitored until recovery.

Olanzapine/fluoxetine is indicated for the acute treatment of depressive episodes associated with bipolar I disorder in adults, and treatment-resistant major depressive disorder that does not respond to 2 separate trials of different antidepressants.

Gonadotropin-Releasing Hormone Agonists Linked to Risk for Hyperglycemia

The FDA approved class labeling revisions for goserelin acetate implants to warn of the potential for hyperglycemia in patients receiving treatment with gonadotropin-releasing hormone agonists. On August 31, the label for Zoladex (AstraZeneca) was updated.

Hyperglycemia can manifest as new-onset diabetes mellitus or the worsening of glycemic control in established cases, the FDA said. Regular monitoring of blood glucose levels is recommended for patients receiving goserelin therapy.

Goserelin is indicated with flutamide for the management of locally confined prostate cancer and the palliative treatment of advanced prostate cancer.

Use of Inhaled Nitric Oxide (INOmax) May Worsen Left Ventricular Dysfunction

On August 26, the FDA approved safety labeling revisions for inhaled nitric oxide (INOmax; INO Therapeutics, Inc) to warn of the potential for heart failure in patients with preexisting left ventricular dysfunction.

Use of inhaled nitric oxide in this setting, even for short durations, may increase pulmonary capillary wedge pressure, leading to pulmonary edema and other serious adverse events.

Nitric oxide is used to promote capillary and pulmonary dilatation in term and near-term (> 34 weeks' gestation) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension. Use of nitric oxide in these neonates has been shown to improve oxygenation and reduce the need for extracorporeal membrane oxygenation.

Symbyax Prescribing Information

Zoladex Prescribing Information

INOmax Prescribing Information

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