Adult Dosing
Depressive episodes associated with bipolar I disorder
- Adults: Start fluoxetine/olanzapine 25 mg/6 mg PO qpm; consider dose adjustments according to tolerability and efficacy [Max: 75/18 mg (fluoxetine/olanzapine)/day]
- Elderly, female patients or patients predisposed to hypotension: Start fluoxetine/olanzapine 25 mg/3 mg PO qpm; titrate cautiously when indicated
Treatment-resistant depression
- Adults: Start fluoxetine/olanzapine 25 mg/6 mg PO qpm; consider dose adjustments according to tolerability and efficacy [Max: 75/18 mg (fluoxetine/olanzapine)/day]
- Elderly, female patients or patients predisposed to hypotension: Start fluoxetine/olanzapine 25 mg/3 mg PO qpm; titrate cautiously when indicated
Note:
- Taper dose gradually to discontinue
Pediatric Dosing
- Safety and effectiveness in pediatric patients have not been established
[Outline]
See Supplemental Patient Information
- Worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior may occur in patients with MDD; this risk may persist until significant remission occurs
- Younger patients are more prone to suicidality; suicidality risk did not increase in patients >24 yrs of age and the risk decreased in patients >65 yrs of age [US Black Box Warning]
- Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania have occurred in adults and pediatric patients receiving antidepressants; such symptoms may represent precursors to emerging suicidality
- Monitor and closely observe patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial few months of a course of drug therapy or at times of dose modifications
- Consider changing the therapeutic regimen or discontinuation of therapy on persistent worsening of depression, or on experiencing emergent suicidality, or on abrupt onset of symptoms suggesting worsening of depression or suicidality, especially if these symptoms are severe, abrupt in onset, and were not part of the patient’s presenting symptoms
- Considering discontinuation of treatment, taper medication as rapidly as feasible, but with due recognition that abrupt discontinuation can be associated with certain symptoms
- Alert families and caregivers of patients being treated with antidepressants for MDD or other indications, both psychiatric and nonpsychiatric, about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and also for the emergence of suicidality, and to report such symptoms immediately to health care providers
- Prescribe the smallest quantity of capsules consistent with good patient management to reduce the risk of overdose
- Therapy unapproved for use in treating any indications in the pediatric population
- Elderly patients with dementia-related psychosis are at an increased risk of death when treated with antipsychotic drugs. Fluoxetine/olanzapine is unapproved for the treatment of patients with dementia-related psychosis [US Black Box Warning]
- Cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, have occurred in patients in trials of olanzapine in geriatric patients with dementia-related psychosis
- Potentially fatal symptom complex sometimes referred to as neuroleptic malignant syndrome (NMS) has occurred in association with administration of olanzapine. Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability. Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure
- The diagnostic evaluation of patients with NMS is complicated. While making diagnosis, it is crucial to exclude cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms; other important considerations in the differential diagnosis include central anticholinergic toxicity, heart stroke, drug fever, and primary central nervous system pathology
- Immediately discontinue antipsychotic drugs and other drugs not essential for concomitant therapy, provide intensive symptomatic treatment and medical monitoring, and provide treatment for any concomitant serious medical problems for the management of NMS
- Carefully consider potential reintroduction of drug therapy in patients recovered from NMS as recurrences of NMS have been reported
- Consider the risks and benefits when prescribing fluoxetine/olanzapine to patients with an established diagnosis of diabetes mellitus, or having borderline increased blood glucose level (fasting 100-126 mg/dL, nonfasting 140-200 mg/dL)
- Regularly monitor patients treated with fluoxetine/olanzapine for worsening of glucose control; perform fasting blood glucose test at the beginning of treatment and periodically thereafter
- Monitor patients treated with atypical antipsychotics for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness
- Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has occurred in patients treated with fluoxetine/olanzapine
- Undesirable alterations in lipid have been reported during therapy. Clinically monitor lipids at baseline and periodically perform follow-up lipid evaluations in patients receiving fluoxetine/olanzapine
- Consider potential consequences of weight gain prior to initiation of therapy; regularly monitor weight in patients receiving this drug
- Potentially life-threatening serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions have occurred during therapy. Discontinue therapy and provide appropriate supportive symptomatic therapy. Monitor patients for the emergence of serotonin syndrome or NMS-like signs and symptoms
- Discontinue therapy on appearance of rash or of other possible allergic phenomena for which an alternative etiology cannot be identified
- A major depressive episode may be the initial presentation of bipolar disorder. Prior to initiating treatment with an antidepressant, adequately screen patients with depressive symptoms to determine if they are at risk for bipolar disorder. Consider a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. Closely monitor patients for the development of symptoms of mania/hypomania during therapy with fluoxetine/olanzapine
- Risk of developing irreversible tardive dyskinesia increases as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increases. Elderly women are more prone to the syndrome of potentially irreversible, involuntary, dyskinetic movements. Syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn
- Prescribe this drug in a manner that is most likely to minimize the risk of tardive dyskinesia. Discontinue therapy on occurrence of signs and symptoms of tardive dyskinesia; however, periodically reassess the need for continued treatment
- Orthostatic hypotension associated with dizziness, tachycardia, bradycardia and, in certain patients, syncope, may occur especially during initial dose-titration period
- Leukopenia, neutropenia, and agranulocytosis have occurred with the use of antipsychotics. Frequently monitor complete blood count (CBC) during the first few months of therapy in patients with a history of a clinically significant low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia. Consider discontinuation of therapy at the first sign of a clinically significant decline in WBC in the absence of other causative factors
- Esophageal dysmotility and aspiration have been reported in patients receiving antipsychotic agents. Fluoxetine/olanzapine is unapproved for the treatment of patients with Alzheimer’s disease
- Avoid concomitant use with drugs that potentially lower the seizure threshold
- Fluoxetine component of this combination drug may increase the risk of bleeding reactions. Co-administration with NSAIDs, aspirin, warfarin, or drugs that affect coagulation may potentiate the risk of GI or other bleeding
- Hyponatremia may occur during therapy. Geriatric patients and those taking diuretics or who are volume depleted may be more prone to the risk of developing hyponatremia due to the result of the syndrome of inappropriate antidiuretic hormone secretion. Discontinue therapy and initiate appropriate medical therapy
- Patients receiving this combination drug should be warned of the risks involved in performing hazardous tasks such as operating machinery or driving a car because the drug may impair the mental and/or physical abilities necessary for performing such tasks
- Therapy may disrupt the body’s ability to reduce core body temperature. Take utmost care while prescribing this medication for patients who will be experiencing conditions which may contribute to an elevation in core body temperature
- Fluoxetine/olanzapine may elevate prolactin levels, which may persist during administration. Hyperprolactinemia may inhibit reproductive function by impairing gonadal steroidogenesis in both male and female patients
- Fluoxetine exhibits long elimination half-life; hence, changes in dose will not be fully reflected in plasma for several weeks, affecting both strategies for titration to final dose and withdrawal from treatment
- Monitor fasting blood glucose and lipid profiles at the beginning of therapy and periodically thereafter
- Consider a gradual reduction in the dose rather than abrupt cessation whenever possible
- Therapy should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
- Caution patients about the combined effects with alcohol or other CNS depressants because of the sedative effects of fluoxetine/olanzapine therapy
- Post-marketing cases of QT interval prolongation and ventricular arrhythmia including Torsade de Pointes have been reported in patients treated with fluoxetine
Cautions: Use cautiously in
- Severe renal impairment
- Hepatic impairment
- Risk of diabetes mellitus
- History of cardiovascular disease
- History of conduction abnormalities
- Dehydration
- Hypovolemia
- Treatment with antihypertensive medications
- Hypotension
- Cerebrovascular disease
- Dementia
- Elderly patients with dementia
- History or risk of seizure disorder
- Concomitant use with drugs that lowers seizure threshold
- History of neuroleptic malignant syndrome
- Hyponatremia
- Risk of aspiration pneumonia
- Suicidal ideation
- Prostatic hypertrophy
- Angle-closure glaucoma
- Paralytic ileus
- Leukopenia
- Poor CYP2D6 metabolizer
- History of drug-induced leukopenia or neutropenia
- Changes in smoking habit
- Concomitant use of olanzapine- and fluoxetine-containing products
- Pregnancy >20 wks gestation
- High environmental temperature
Supplemental Patient Information
- Inform the patients, families and caregivers to be alert for the unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and during dose adjustments and instruct them to immediately report such symptoms to the health professional
- Advise patients to refrain from hazardous activities requiring mental alertness such as operating machinery or driving an automobile
- Patients should be advised to avoid excessive use of alcohol during therapy
- Advise patients to communicate with their physicians if they become pregnant during course of therapy or intend to become pregnant
Pregnancy Category:C
Breastfeeding: Average amount of drug in breastmilk is higher with fluoxetine than with most other SSRIs. The active metabolite, norfluoxetine, is detectable in the serum of most breastfed infants during the first 2 months postpartum and in a few thereafter. If fluoxetine is required by the mother, it is not a reason to discontinue breastfeeding. Most experts recommend against changing medications during breastfeeding if the mother was taking fluoxetine during pregnancy or if other antidepressants have been ineffective. However, agents with lower excretion into breastmilk may be preferred while nursing a newborn or preterm infant. Monitor breastfed infant for behavioral side effects such as colic, fussiness or sedation and for adequate weight gain. Limited available literature indicates that maternal doses of olanzapine up to 20 mg/day produce low levels in milk and undetectable levels in the serum of breastfed infants. Short-term side effects have not been reported, but sedation has occurred. Very limited prolonged follow-up of infants exposed to olanzapine indicates that infants generally developed normally, but combinations of antipsychotic agents can negatively affect development. Monitor the infant for drowsiness and developmental milestones, especially if other antipsychotics are used concurrently. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 18 January 2011). Manufacturer advises nursing women not to breastfeed their infants when receiving fluoxetine/olanzapine.
US Trade Name(s)
US Availability
fluoxetine/olanzapine (generic)
- CAPS:
- 25 mg/3 mg
- 25 mg/6 mg
- 25 mg/12 mg
- 50 mg/6 mg
- 50 mg/12 mg
Symbyax (fluoxetine/olanzapine)
- CAPS:
- 25 mg/3 mg
- 25 mg/6 mg
- 25 mg/12 mg
- 50 mg/6 mg
- 50 mg/12 mg
Canadian Trade Name(s)
Canadian Availability
UK Trade Name(s)
UK Availability
Australian Trade Name(s)
Australian Availability
[Outline]
Pricing data from www.DrugStore.com in U.S.A.
- Symbyax 12-50 MG CAPS [Bottle] (LILLY)
30 mg = $651.97
90 mg = $1864.88 - Symbyax 6-25 MG CAPS [Bottle] (LILLY)
30 mg = $453.99
90 mg = $1342.99 - Symbyax 3-25 MG CAPS [Bottle] (LILLY)
30 mg = $345.99
90 mg = $1003.96 - Symbyax 6-50 MG CAPS [Bottle] (LILLY)
30 mg = $480.97
90 mg = $1390.93 - Symbyax 12-25 MG CAPS [Bottle] (LILLY)
30 mg = $719.99
90 mg = $2110
Warning: This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit drugstore.com.