Label Changes for:
Symbyax (olanzapine and fluoxetine hydrochloride) Capsules
Changes have been made to the WARNINGS and PRECAUTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
WARNINGS AND PRECAUTIONS
Post-marketing cases of QT interval prolongation and ventricular arrhythmia including Torsade de Pointes have been reported in patients treated with fluoxetine. Fluoxetine should be used with caution in patients with congenital long QT syndrome; a previous history of QT prolongation; a family history of long QT syndrome or sudden cardiac death; and other conditions that predispose to QT prolongation and ventricular arrhythmia. Such conditions include concomitant use of drugs that prolong the QT interval; hypokalemia or hypomagnesemia; recent myocardial infarction, uncompensated heart failure, bradyarrhythmias, and other significant arrhythmias; and conditions that predispose to increased fluoxetine exposure (overdose, hepatic impairment, use of CYP2D6 inhibitors, CYP2D6 poor metabolizer status, or use of other highly protein-bound drugs). Fluoxetine is primarily metabolized by CYP2D6 [see Contraindications (4.2), Adverse Reactions (6), Drug Interactions (7.7, 7.8), Overdose (10.1), and Clinical Pharmacology (12.3)].
Pimozide and thioridazine are contraindicated for use with fluoxetine. Avoid the concomitant use of drugs known to prolong the QT interval. These include specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol,; specific antibiotics (e.g.,erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or Tacrolimus…
4.1 Monoamine Oxidase Inhibitors (MAOIs)
- The use of MAOIs intended to treat psychiatric disorders with SYMBYAX or within 5 weeks of stopping treatment with SYMBYAX is contraindicated because of an increased risk of serotonin syndrome. The use of SYMBYAX within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated. [see Dosage and Administration (2.4) and Warnings and Precautions (5.7)].
- Starting SYMBYAX in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome. [see Dosage and Administration (2.5) and Warnings and Precautions (5.7)].
5 WARNINGS AND PRECAUTIONS
5.7 Serotonin Syndrome
- The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including SYMBYAX, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, ryptophan, buspirone, and St. John's Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
7 DRUG INTERACTIONS
7.1 Monoamine Oxidase Inhibitors (MAOIs)
- SYMBYAX should not be used in combination with an MAOI, or within a minimum of 14 days of discontinuing therapy with an MAOI. There have been reports of serious, sometimes...
7.3 Serotonergic Drugs
- Based on the mechanism of action of SNRIs and SSRIs, including SYMBYAX, and the potential for serotonin syndrome, caution is advised.....
8.0 USE IN SPECIFIC POPULATIONS
- Neonates exposed to fluoxetine, a component of SYMBYAX, and other SSRIs or serotonin and norepinephrine reuptake inhibitors (SNRIs), late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding.
- Physicians should also note the results of a prospective longitudinal study of 201 pregnant women with a history of major depression, who were euthymic at the beginning of either on antidepressants or had received antidepressants less than 12 weeks prior to their last menstrual period, and were in remission. Women who discontinue .....Several recent epidemiologic studies suggest a positive statistical association between SSRI (including fluoxetine) use in pregnancy and PPHN. Other studies do not show a significant statistical association.
- When treating a pregnant woman with SYMBYAX, the physician should carefully consider both the potential risks of taking an SSRI, along with the established benefits of treating depression with an antidepressant. This decision can only be made on a case by case basis [see Dosage and Administration (2.3)].
17 PATIENT COUNSELING INFORMATION
17.8 Serotonin Syndrome
- Patients should be cautioned about the risk of serotonin syndrome with the concomitant use of SYMBYAX and other serotonergic agents including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort [see Contraindications (4.1)and Warnings and Precautions (5.7), and Drug Interactions (7.3)]. Patients should be advised.....
Who should not take SYMBYAX?
- Do not take SYMBYAX if you take a Monoamine Oxidase Inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid
USE IN SPECIFIC POPULATIONS
- An elevation of early postnatal mortality (survival through postnatal day 4 was 69% per litter) and reduced bodyweight (approximately 8% in females) occurred among offspring at the highest dose; the no-effect dose was 0.5 (olanzapine) plus 1 (fluoxetine) mg/kg/day (0.25 and 0.13 times the MRHD on a mg/m2 body surface area)…
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
Additional Findings Observed in Clinical Studies
- Other Adverse Reactions Observed with Olanzapine or Fluoxetine Monotherapy multiple adverse reactions added
6.2 Vital Signs and Laboratory Studies
- Extensive changes to laboratory changes section
8 USE IN SPECIAL POPULATIONS
- ...Symbyax section added
- ...Fluoxetine section modified
17 PATIENT COUNSELING INFORMATION
17.18 Use in Specific Populations
- ...Symbyax should be...