Trade Names:Symbyax- Capsules olanzapine 3 mg/fluoxetine hydrochloride 25 mg- Capsules olanzapine 6 mg/fluoxetine hydrochloride 25 mg- Capsules olanzapine 6 mg/fluoxetine hydrochloride 50 mg- Capsules olanzapine 12 mg/fluoxetine hydrochloride 25 mg- Capsules olanzapine 12 mg/fluoxetine hydrochloride 50 mg
Unknown; however, it is suspected that activation of 3 monoaminergic neural systems (dopamine, norepinephrine, serotonin) is responsible for an enhanced antidepressant effect.
Treatment of depressive episodes associated with bipolar I disorder; treatment of treatment-resistant depression.
Coadministration with thioridazine (or within at least 5 wk of stopping olanzapine/fluoxetine), an MAOI (or within 14 days of discontinuing an MAOI and at least 5 wk after stopping olanzapine/fluoxetine), or pimozide.
PO Start with olanzapine 6 mg/fluoxetine 25 mg daily in the evening. If indicated, dosage adjustments can be made based on efficacy and tolerability. Antidepressant efficacy has been demonstrated up to 12 mg/50 mg. Safety of doses above 18 mg/75 mg has not been evaluated.Treatment Resistant DepressionAdults
PO Start with olanzapine 6 mg/fluoxetine 25 mg. If indicated, dosage adjustments can be made according to efficacy and tolerability. Antidepressant efficacy has been demonstrated up to 18 mg/50 mg. Safety of doses above 18 mg/75 mg has not been evaluated.Special PopulationsAdults
PO Start with 3mg/25 mg to 6 mg/25 mg for patients with a predisposition to hypotensive reactions, patients with hepatic impairment, patients who exhibit a combination of factors that may slow metabolism (eg, elderly patients, nonsmoking status, female gender), or those patients who may be pharmacodynamically sensitive to olanzapine. If indicated, perform dose escalation with caution.
Store capsules at 59° to 86°F. Protect from moisture.
Increased risk of serotonin syndrome (eg, incoordination, hyperreflexia, weakness) has been reported rarely.Antiarrhythmics (eg, propafenone), risperidone
Inhibition of metabolism by fluoxetine, resulting in elevated plasma concentrations and increasing the pharmacologic effects and risk of adverse reactions.Antihypertensives
Antihypertensive effects may be enhanced by olanzapine.Benzodiazepines (eg, alprazolam, diazepam)
The orthostatic hypotension of olanzapine may be potentiated by diazepam; the half-life of diazepam may be prolonged by fluoxetine; plasma concentrations of alprazolam may be increased.Buspirone
Effects of buspirone may be decreased.Carbamazepine
Plasma concentrations of olanzapine may be decreased by carbamazepine, and plasma levels of carbamazepine may be increased by fluoxetine.Charcoal
Absorption of fluoxetine and olanzapine may be decreased.Clozapine, cyclosporine, haloperidol, phenytoin, tricyclic antidepressants (eg, desipramine, imipramine)
Blood levels of these agents may be increased by fluoxetine.CNS active drugs (eg, alcohol)
Use with caution; titrate the dose and monitor the clinical status of the patient.Cyproheptadine
Pharmacologic effects of fluoxetine may be decreased.Digoxin, warfarin
May be displaced from protein binding site by fluoxetine, increasing the risk of adverse effects.Drugs metabolized by CYP2D6 (eg, amitriptyline, flecainide, vinblastine)
Fluoxetine inhibits CYP2D6 activity and makes patients with normal CYP2D6 metabolic activity resemble poor metabolizers. Coadminister fluoxetine with agents metabolized by this enzyme with caution.Drugs that induce CYP1A2 (eg, omeprazole, rifampin)
May decrease olanzapine concentrations.Drugs that inhibit CYP1A2 (eg, mexiletine)
May elevate olanzapine plasma levels, increasing the risk of adverse reactions.Drugs that interfere with hemostasis (eg, aspirin, NSAIDs, warfarin)
Risk of bleeding may be increased.Levodopa, dopamine agonists
Effects of levodopa and dopamine agonist may be antagonized by olanzapine.Linezolid
Serotonin syndrome may occur.Lithium
Fluoxetine may increase or decrease lithium levels. Lithium toxicity and increased serotonergic effects have been reported.MAOIs (eg, isocarboxazid)
Administration with olanzapine/fluoxetine (or administration within 14 days of discontinuing an MAOI and at least 5 wk after stopping olanzapine/fluoxetine) is contraindicated; death has been reported with coadministration of MAOIs and fluoxetine.Metoclopramide
Serotonin syndrome may occur.PDE5 inhibitors (eg, sildenafil)
Fluoxetine may inhibit PDE5 inhibitor metabolism.Pimozide
Coadministration of pimozide and fluoxetine is contraindicated because of the potential risk of increased QTc prolongation, which could result in life-threatening arrhythmias. Bradycardia has been reported during coadministration with fluoxetine.Protein-bound drugs
Because fluoxetine is tightly bound to plasma protein, the risk of adverse reactions may be increased if fluoxetine is displaced from protein-binding sites by other tightly bound drugs.Ritonavir
Plasma levels of ritonavir and fluoxetine may be elevated, increasing the pharmacologic effects and adverse reactions of both agents; risk of serotonin syndrome may be increased.Sibutramine
Serotonin syndrome may occur.SNRIs (eg, venlafaxine), SSRIs (eg, fluoxetine)
Serotonin syndrome has occurred.St. John's wort
Serotonin syndrome may occur.Sumatriptan
Hyperreflexia, incoordination, and weakness have been reported with coadministration of sumatriptan and an SSRI (eg, fluoxetine).Sympathomimetics (eg, amphetamine)
Increased sympathomimetic effects and increased risk of serotonin syndrome.Tamoxifen
Clinical response to tamoxifen may be reducedThioridazine
Administration with olanzapine/fluoxetine or within a minimum of 5 wk after discontinuing olanzapine/fluoxetine is contraindicated.Tramadol, trazodone
Serotonin syndrome may occur.Tryptophan
Risk of adverse reactions (eg, agitation, GI distress, restlessness) may be increased.Zolpidem
Plasma concentrations of zolpidem may be increased.
None well documented.
Vasodilatation (at least 1%); venous thromboembolic events including pulmonary embolism and deep venous thrombosis (postmarketing).
Increased appetite (20%); somnolence (14%); fatigue (12%); tremor (9%); sedation (8%); disturbances in attention, hypersomnia (5%); restlessness (4%); asthenia, lethargy (3%); abnormal thinking, nervousness, pyrexia (2%); amnesia (at least 1%).
Blurred vision (5%).
Dry mouth (15%); flatulence (3%); abdominal distention (2%); diarrhea, taste perversion (at least 1%).
Erectile dysfunction (2%); breast pain, menorrhagia, urinary frequency, urinary incontinence (at least 1%).
Ecchymosis (at least 1%).
Increased weight (25%); generalized edema, weight loss (at least 1%).
Arthralgia (4%); pain in extremity (3%); musculoskeletal stiffness (2%); neck rigidity (at least 1%).
Peripheral edema (9%); edema (3%); pain (2%); chills, photosensitivity (at least 1%); rhabdomyolysis (postmarketing).
Compared with placebo, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorders and other psychiatric disorders. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber.Increased mortality
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death compared with those taking placebo. Over a course of a 10-wk controlled trial, the rate of death in drug-treated patients was about 4.5% compared with 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either CV (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Olanzapine/fluoxetine is not approved for the treatment of dementia-related psychosis.
Monitor children and adults for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of therapy, or at times of dose changes, either increases or decreases. Evaluate children at least weekly with face-to-face contact with the patient or their family members or caregiver during the first 4 wk of therapy, then every other week for the next 4 wk, then at 12 wk, and as clinically indicated thereafter. Regularly monitor patient's weight. Periodic assessment of LFTs is recommended. Monitor fasting blood glucose and lipid profile at the beginning of, and periodically during, treatment.Suicidality
The following symptoms may represent precursors to suicidality and should be reported to health care provider immediately if noted or suspected: aggressiveness, agitation, anxiety, hostility, hypomania, impulsivity, insomnia, irritability, mania, panic attacks, and psychomotor restlessness. Frequently assess patient for response to treatment. Ensure therapy is periodically reviewed to determine if therapy needs to be continued without change or if a dose change (eg, increase, decrease, discontinuation) is indicated.
Category C .
Undetermined; however, fluoxetine and olanzapine are excreted in breast milk.
Safety and efficacy not established.
Use with caution, usually starting at the lower end of the dosing range, because of the greater frequency of decreased hepatic, renal, or cardiac function and concomitant diseases or other drug therapy.
Anaphylactoid reactions, including bronchospasm, angioedema, and urticaria, have been reported.
Use lower dose or less frequent dosing of fluoxetine in patients with cirrhosis.
Use lower starting dose (eg, olanzapine 6 mg/fluoxetine 25 mg) and slower dose escalation in patients with hepatic impairment, predisposition to hypotensive reactions, or combination of factors that may slow metabolism of medication (eg, nonsmoker, elderly patient, female gender).
SSRIs, including fluoxetine, may increase the risk of bleeding; coadministration of aspirin, NSAIDs, and warfarin may add to this risk.
Antipsychotics disrupt the ability to reduce core body temperature. Use with caution in patients who will experience conditions that may contribute to an elevation in core body temperature (eg, concomitant anticholinergic therapy, exposure to extreme heat, strenuous exercise, subject to dehydration).
Caution patients about operating potentially hazardous machinery (eg, driving) until it is known if the drug impairs ability. Avoid use of alcohol.
Use with caution in cardiac patients and in patients with diseases or conditions that could affect hemodynamic responses.
Withdrawal symptoms have been reported after rapid discontinuation of therapy. If treatment is to be discontinued, or the dose reduced, gradually taper the dose and monitor patient for withdrawal symptoms (eg, abnormal skin sensations, agitation, anxiety, confusion, dizziness, dysphoric mood, emotional lability, headaches, hypomania, insomnia, irritability, lethargy). If significant withdrawal symptoms develop, reinstitute previous dosing schedule and attempt a less rapid tapering regimen after patient has stabilized.
Because of the long elimination half-life of fluoxetine, changes in dose will not be fully reflected in plasma for several weeks, affecting titration to final dose and withdrawal from treatment.
Use with caution in patients at risk for aspiration pneumonia.
Prolonged seizures have been reported in patients receiving concurrent electroconvulsive therapy treatment and fluoxetine.
Undesirable alterations in lipids have been observed. Very high (eg, more than 500 mg/dL) triglyceride elevations have occurred.
Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma, or death, may occur. Monitor blood sugar in patients with diabetes when drug is started or dose is changed. Ensure fasting blood glucose is evaluated before starting therapy and periodically thereafter during therapy in patients with risk factors for diabetes mellitus (eg, family history of diabetes, obesity).
Olanzapine-treated patients often have elevation in prolactin levels. Associated clinical manifestations (eg, breast enlargement, galactorrhea) occur infrequently; however, there is no evidence of increased breast cancer risk.
Hyponatremia may occur as a result of SSRI treatment, often the hyponatremia appears to be the result of SIADH.
May be precipitated by fluoxetine in susceptible patients.
Has occurred and is potentially fatal. Monitor patient for symptoms of NMS (eg, altered mental status, diaphoresis, hyperpyrexia, irregular pulse and BP, muscle rigidity, tachycardia).
Orthostatic hypotension, associated with bradycardia, diaphoresis, dizziness, and tachycardia, may occur. Monitor patients with CV disease, cerebrovascular disease, or conditions predisposing to hypotension (eg, concurrent treatment with antihypertensives, dehydration, hypovolemia) during initiation of therapy, and following dose increases, for orthostatic hypotension; implement safety precautions if noted.
A major depressive episode may be the initial presentation of bipolar disorder, and treating such an episode with an antidepressant alone may increase the likelihood of precipitating a mixed/manic episode in patients at risk for bipolar disorder. Screen patients with depression for risk of bipolar disorder prior to initiating therapy with an antidepressant.
May occur; use with caution in patients with a history of seizures or with conditions that potentially lower the seizure threshold.
Development of a potentially life-threatening serotonin syndrome may occur with SSRIs, including fluoxetine, particularly with coadministration of serotonergic drugs (eg, triptans) and with drugs that impair metabolism of serotonin (eg, MAOIs).
Supervise depressed patients at risk during initial therapy. Prescribe the smallest quantity consistent with good patient management in order to reduce the risk of overdose.
Syndrome of potentially irreversible, involuntary dyskinetic movements may develop. Prevalence is higher among elderly patients, especially women. Use smallest effective dose for shortest period of time needed.
Asymptomatic elevations may occur.
May occur; document patient weight prior to and periodically during prolonged treatment.
Important overdose adverse reactions with single or multiple drugs include acute psychosis, aggression, agitation, arrhythmias, essential tremor, hypertension, hypokinesia, impaired consciousness (coma), impaired neurologic function (ataxia, confusion, convulsions, dysarthria), lethargy, and somnolence (sedation).
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