Symbyax

FDA label

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Renal Undefined

Hepatic Hepatic impairment: start 3/25–6/25 mg; use lower or less frequent dose in cirrhosis.

MAOI washout: ≥14 days after stopping an MAOI before starting; ≥5 weeks after stopping this drug before starting an MAOI (or thioridazine). TRD evidence note (not a max): efficacy studied at olanzapine 6–18 mg / fluoxetine 25–50 mg; safety above 18/75 mg not evaluated.

Instructions

• Once daily in the evening; food effect on the combination not studied (components unaffected)
• Start 3/25–6/25 mg and escalate cautiously if: predisposed to hypotension, hepatic impairment, slowed metabolism (female + geriatric + nonsmoker), or olanzapine-sensitive
• Taper on discontinuation — fluoxetine/SSRI discontinuation symptoms reported
• Fluoxetine's long half-life: dose changes not fully reflected in plasma for several weeks
• Periodically reexamine need for continued treatment

Available strengths

• cap 3/25, 6/25, 6/50, 12/25, 12/50 mg

Contraindications

• MAOIs for psychiatric disorders — serotonin syndrome risk; not within 5 weeks after stopping olanzapine/fluoxetine, not within 14 days after stopping the MAOI; do not start in patients on linezolid or IV methylene blue
• Pimozide — QT prolongation (CYP2D6 inhibition raises pimozide levels)
• Thioridazine — QT prolongation; do not use within 5 weeks of stopping olanzapine/fluoxetine

Cautions

• Neuroleptic malignant syndrome — discontinue immediately
• DRESS — discontinue if suspected
• Metabolic changes: hyperglycemia (rarely ketoacidosis/coma/death), dyslipidemia, weight gain — baseline + periodic fasting glucose/lipids, monitor weight
• Serotonin syndrome, especially with other serotonergic agents
• Activation of mania/hypomania — screen for bipolar disorder
• Tardive dyskinesia
• Orthostatic hypotension (bradycardia/syncope; worst during titration)
• Leukopenia/neutropenia/agranulocytosis — monitor CBC if prior low WBC
• Seizures — caution with seizure history/lowered threshold
• Increased bleeding risk with NSAIDs, aspirin, warfarin
• Hyponatremia/SIADH
• QT prolongation incl. torsade (fluoxetine)
• Anticholinergic effects; angle-closure glaucoma; cognitive/motor impairment; hyperprolactinemia; sexual dysfunction

Adverse reactions

• Adults: sedation/somnolence, weight increased, increased appetite, dry mouth, fatigue, edema, tremor, disturbance in attention, blurred vision
• 10–17 y: sedation, weight increased, increased appetite, tremor, triglycerides increased, hepatic enzymes increased

Pregnancy Third-trimester antipsychotic exposure → neonatal EPS/withdrawal; late-pregnancy SSRI → PPHN risk and poor neonatal adaptation; <2-fold increased postpartum hemorrhage risk with SSRI in month before delivery.

Lactation Olanzapine, fluoxetine, norfluoxetine present in milk; reports of infant sedation, irritability, poor feeding, EPS (olanzapine) and agitation, poor weight gain (fluoxetine).