Symbyax Generic Name & Formulations
Olanzapine, fluoxetine (as HCl); 3mg/25mg, 6mg/25mg, 6mg/50mg, 12mg/50mg; caps.
Thienobenzodiazepine + SSRI.
Acute depressive episodes in bipolar I disorder. Treatment-resistant depression (TRD).
Symbyax Dosage and Administration
≥18yrs: Take once daily in the PM. Bipolar depression: initially one 6mg/25mg cap; range: 6–12mg/25–50mg. TRD: initially one 6mg/25mg cap; range: 6–18mg/25–50mg. Both: doses > olanzapine 18mg + fluoxetine 75mg: not studied. Risk of hypotension, hepatic impairment, slow metabolizers, or sensitive to olanzapine: initially 3mg/25mg to 6mg/25mg; titrate slowly and adjust as needed. Switching to or from MAOIs: see full labeling.
Bipolar depression: <10yrs: not established. Take once daily in the PM. 10–17yrs: initially one 3mg/25mg cap; range: 6–12mg/25–50mg. Doses > olanzapine 12mg + fluoxetine 50mg: not studied. TRD: <18yrs: not established.
Concomitant MAOIs during or within 5 weeks of discontinuing olanzapine/fluoxetine. Within 14 days of discontinuing an MAOI. Concomitant linezolid or IV methylene blue. Concomitant pimozide or thioridazine (may cause QTc prolongation).
Symbyax Boxed Warnings
Suicidal thoughts and behaviors. Increased mortality in elderly patients with dementia-related psychosis.
Increased risk of suicidal thinking and behavior in children, adolescents, and young adults; monitor for clinical worsening or unusual changes. Elderly with dementia-related psychosis (not approved use); increased risk of death or cerebrovascular events (eg, stroke, TIA). Monitor for serotonin syndrome or neuroleptic malignant syndrome-like signs/symptoms; discontinue if occurs. Discontinue if Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is suspected. Congenital or history of long QT syndrome and other conditions (eg, hypokalemia, hypomagnesemia, recent MI, uncompensated heart failure, bradyarrhythmias, other significant arrhythmias); monitor ECG periodically. Hepatic impairment. Pre-existing low WBCs or history of leukopenia/neutropenia; monitor CBCs during 1st few months of treatment; discontinue if WBCs decline. Cardio- or cerebrovascular disease. Hypovolemia. Dehydration. History of seizures or mania/hypomania. Tardive dyskinesia. Conditions that affect metabolism or hemodynamic response. Diabetes. Monitor for hyperglycemia, hyperlipidemia; do fasting blood glucose and lipids testing at beginning, and during therapy. Monitor for weight gain. Angle-closure glaucoma. Urinary retention. Significant prostatic hypertrophy. Constipation. History of paralytic ileus or related conditions. Breast cancer. Perform fall risk assessments when initiating and recurrently on long-term therapy. Hyponatremia (esp. in elderly). Hyperprolactinemia. Exposure to extreme heat. Dysphagia. Sexual dysfunction. Reevaluate periodically. Write ℞ for smallest practical amount. Avoid abrupt cessation. Hepatic impairment. Neonates: risk of extrapyramidal and/or withdrawal symptoms post delivery (due to SSRIs or SNRIs exposure during 3rd-trimester pregnancy). Labor & delivery. Pregnancy. Nursing mothers: not recommended.
Olanzapine: renal, fecal.
See Contraindications. Do not start with concomitant linezolid or IV methylene blue; if treatment is necessary, discontinue olanzapine/fluoxetine before starting; monitor for serotonin syndrome for 5 weeks or until 24hrs after last dose of linezolid or IV methylene blue, whichever comes first. Do not start thioridazine within at least 5 weeks of discontinuing olanzapine/fluoxetine. Concomitant SSRIs, SNRIs: not recommended. Increased risk of serotonin syndrome with other serotonergic drugs (eg, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, St. John's Wort) or with drugs that impair serotonin metabolism (eg, MAOIs, linezolid, IV methylene blue). Avoid concomitant drugs known to prolong the QT interval (eg, ziprasidone, iloperidone, chlorpromazine, erythromycin, moxifloxacin, Class IA & III antiarrhythmics, pentamidine, methadone, and others. May potentiate phenytoin, carbamazepine, haloperidol, clozapine, imipramine, desipramine, benzodiazepines, other protein bound drugs. May antagonize levodopa, dopamine agonists. May be potentiated by CYP1A2 inhibitors (eg, fluvoxamine). May be antagonized by CYP1A2 inducers (eg, carbamazepine), glucuronyl transferase enzyme inducers (rifampin, omeprazole). Increased risk of bleeding with NSAIDs, aspirin, warfarin, or others that affect coagulation; monitor. Orthostatic hypotension with antihypertensives, benzodiazepines, alcohol (avoid). Hyponatremia with diuretics. Caution with other drugs metabolized by CYP2D6 (eg, tricyclic antidepressants, antipsychotics, antiarrhythmics), drugs that lower seizure threshold, other CNS drugs, hepatotoxic agents, anticholinergics, other forms of olanzapine or fluoxetine. Smokers may have increased metabolism.
Symbyax Adverse Reactions
Sedation, increased weight or appetite, dry mouth, fatigue, edema, tremor, disturbance in attention, blurred vision, hypersomnia, somnolence; neuroleptic malignant syndrome, serotonin syndrome, rash or anaphylactoid reactions (discontinue if occurs), orthostatic hypotension, neutropenia, mania/hypomania, elevated liver enzymes. Children/adolescents: also elevated triglycerides.
Symbyax Clinical Trials
Symbyax Patient Counseling