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Olanzapine / fluoxetine

Class
Antipsychotics / antidepressants
Subclass
Atypical antipsychotic / selective serotonin reuptake inhibitor combination
Generic name
OLANZapine / fLUoxetine
Brand names
Symbyax®
Contains
Fluoxetine
Olanzapine
Common formulations
Capsule
See also
Olanzapine pamoate ER (Zyprexa Relprevv®)
Fluoxetine DR
Dosage and administration
Adults patients
Depressive episodes in patients with bipolar disorder
•
Start at: 6/25 mg PO qHS
•
Maintenance: 6-12/25-50 mg PO qHS
•
Maximum: 18/75 mg per day
Start at 3-6/25 mg in patients with hepatic impairment, risk factors for hypotension, or a combination of factors reducing the metabolism of olanzapine or fluoxetine in combination (female gender, elderly, nonsmoking status), or those patients who may be pharmacodynamically sensitive to olanzapine.
Major depressive disorder • Treatment-resistant
•
Start at: 6/25 mg PO qHS
•
Maintenance: 6-18/25-50 mg PO qHS
•
Maximum: 18/75 mg per day
Start at 3-6/25 mg in patients with hepatic impairment, risk factors for hypotension, or a combination of factors reducing the metabolism of olanzapine or fluoxetine in combination (female gender, elderly, nonsmoking status), or those patients who may be pharmacodynamically sensitive to olanzapine.
Indications for use
Labeled indications
Adults
•
Treatment of depressive episodes in patients with bipolar disorder
•
Treatment of major depressive disorder (treatment-resistant)
Safety risks
Boxed warnings
Increased risk of mortality
•
Do not use olanzapine for the management of dementia-related psychosis in elderly patients because of the increased risk of fatal cerebrovascular accidents.
Suicidal ideation
•
Use extreme caution in patients with major depressive disorder or other psychiatric disorders, particularly in children, adolescents, and young adults. Monitor closely for suicidality and unusual changes in behavior.
Contraindications
Hypersensitivity to olanzapine/fluoxetine or its component
Concomitant use of MAOIs
•
Do not use fluoxetine with or within 14 days of stopping MAOIs. Do not use MAOIs within 5 weeks of stopping fluoxetine.
Concomitant use of pimozide or thioridazine
•
Do not use fluoxetine with pimozide or pimozide because of the risk of QT prolongation. Do not initiate thioridazine until 5 weeks after fluoxetine has been discontinued.
Warnings and precautions
Acute angle-closure glaucoma
•
Use caution in patients with untreated anatomically narrow angles.
Allergic skin reaction, anaphylactoid reactions
•
Maintain a high level of suspicion, as fluoxetine may cause allergic and anaphylactoid reactions such as bronchospasm, angioedema, and urticaria.
Antidepressant discontinuation syndrome
•
Do not discontinue abruptly in any patient.
Anxiety, nervousness, insomnia
•
Maintain a high level of suspicion, as fluoxetine has been associated with these adverse events.
Bleeding
•
Use caution in patients taking aspirin, NSAIDs, antiplatelet or anticoagulant therapy.
Cognitive difficulties, motor impairment
•
Use extreme caution in patients performing activities requiring mental alertness, such as driving or operating machinery.
Decreased gastrointestinal motility
•
Use caution in patients with constipation or a history of paralytic ileus or related conditions.
Decreased WBC count, decreased blood neutrophil count, agranulocytosis
•
Maintain a high level of suspicion, as olanzapine has been associated with an increased risk of leukopenia, neutropenia, and agranulocytosis. Monitor CBC frequently during the first few months in patients with a history of a clinically significant low WBC or drug-induced leukopenia/neutropenia. Monitor patients with clinically significant neutropenia for fever and other symptoms or signs of infection.
DRESS syndrome
•
Maintain a high level of suspicion, as olanzapine has been associated with an increased risk of DRESS syndrome.
Dysphagia
•
Maintain a high level of suspicion, as olanzapine has been associated with an increased risk of esophageal dysmotility and aspiration.
Exacerbation of urinary retention
•
Use caution in patients with a current diagnosis or prior history of urinary retention or clinically significant prostatic hypertrophy.
Falls
•
Maintain a high level of suspicion, as olanzapine can cause somnolence, postural hypotension, and motor and sensory instability, which may result in falls and fractures.
Hyperprolactinemia
•
Maintain a high level of suspicion, as long-term use of olanzapine may increase prolactin levels.
Hyponatremia, SIADH
•
Use caution in all patients, especially in the elderly and in patients with volume depletion or taking diuretics.
Impaired thermoregulation
•
Maintain a high level of suspicion, as antipsychotic agents have been associated with an increased risk of impaired thermoregulation, resulting in a reduced ability to lower core body temperature.
Loss of appetite, weight loss
•
Use caution in patients with underweight or bulimia.
Mania
•
Use caution in patients with bipolar disorder. Screen patients for any personal or family history of bipolar disorder before initiating fluoxetine.
Metabolic changes
•
Maintain a high level of suspicion, as olanzapine has been associated with an increased risk of metabolic changes, including hyperglycemia, dyslipidemia, and weight gain. Obtain fasting blood glucose testing and a lipid profile before initiation and periodically during treatment.
Neuroleptic malignant syndrome
•
Maintain a high level of suspicion, as olanzapine has been associated with an increased risk of neuroleptic malignant syndrome.
Orthostatic hypotension
•
Use caution in patients with known CVD, cerebrovascular disease, conditions predisposing to hypotension, or taking other drugs increasing the risk of hypotension, bradycardia, respiratory or CNS depression.
Seizure
•
Use caution in patients with a history of seizure disorder.
Serotonin syndrome
•
Use caution in patients taking other serotonergic drugs (including triptans, TCAs, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St. John's Wort).
Sexual dysfunction
•
Maintain a high level of suspicion, as SSRIs have been associated with decreased libido, erectile dysfunction, and ejaculatory delay or failure in males, and decreased libido and delayed or absent orgasm in females.
Tardive dyskinesia
•
Maintain a high level of suspicion, as olanzapine has been associated with an increased risk of tardive dyskinesia, especially in the elderly.
Torsades de pointes, ventricular arrhythmias
•
Use extreme caution in patients with congenital long QT syndrome, bradycardia, hypokalemia, hypomagnesemia, recent acute myocardial infarction, uncompensated HF, or taking other QT-prolonging drugs.
Specific populations
Renal impairment
eGFR 0-90 mL/min/1.73 m²
•
Use acceptable. No dose adjustment required.
Renal replacement therapy
Any modality
•
Use acceptable. No dose adjustment required.
Hepatic impairment
Any severity
•
Use with caution. Start at dose of 3-6/25 mg.
Pregnancy and breastfeeding
Pregnancy
First and second trimesters • Australia Category: C
•
Use only if benefits outweigh potential risks. Enroll patients in a dedicated pregnancy outcome monitoring registry.
Third trimester • Australia Category: C
•
Consider safer alternatives. Enroll patients in a dedicated pregnancy outcome monitoring registry. Monitor neonates for extrapyramidal and/or withdrawal symptoms, direct toxic effects of the drug, serotonin syndrome and discontinuation syndrome. The use of SSRIs in late pregnancy is associated with an increased risk of postpartum hemorrhage, persistent pulmonary hypertension of the newborn, and symptoms of poor adaptation in the neonate.
Breastfeeding
Use only if benefits outweigh potential risks.
•
Monitor breastfed infants exposed to olanzapine/fluoxetine for excessive sedation, irritability, agitation, extrapyramidal symptoms, poor feeding, and poor weight gain.
Low excretion in breastmilk (5-25%).
Low levels in breastfed infants (5-25%).
May potentially cause adverse effects in breastfed infants.
Some adverse effects on lactation reported.
Adverse reactions
Very common > 10%
•
↓ serum bicarbonate, ↑ serum prolactin, dry mouth, peripheral edema, fatigue, ↑ appetite, somnolence, weight gain
Common 1-10%
•
Abdominal distension, fever, pain, stiffness, ↓ serum phosphate, ↓ blood lymphocyte count, extrapyramidal signs, ↑ serum triglycerides, ↑QT interval, arthralgia, ↑ serum cholesterol, asthenia, pain in extremity, dyspepsia, anxiety, ↑ BUN, ↑ serum uric acid, ↓ serum albumin, flatulence, anemia, blurred vision, inattention, ↑ serum ALT, nervousness, erectile dysfunction, suicidal ideation, back pain, dysmenorrhea, restlessness, sinusitis, tremor, ↑ liver enzymes
Unknown frequency
•
Anaphylactoid reactions, diabetic ketoacidosis, cholestasis, DRESS syndrome, neuroleptic malignant syndrome, hepatitis, acute pancreatitis, rhabdomyolysis, restless legs syndrome, deep venous thrombosis, pulmonary embolism, angioedema, urticaria, itching, jaundice, priapism, ↓ WBC count, ↓ blood neutrophil count, hypersalivation, ↑ serum cholesterol, ↑ serum triglycerides, tachycardia, bradycardia, orthostatic hypotension, ↑ serum ALP, ↑ serum AST, ↑ serum gamma-glutamyltransferase, aplastic anemia, atrial fibrillation, stroke, cataract, toxic epidermal necrolysis, eosinophilic pneumonia, erythema multiforme, erythema nodosum, exfoliative dermatitis, heart failure, cardiac arrest, hemolytic anemia, renal failure, optic neuritis, Stevens-Johnson syndrome, pulmonary hypertension, ventricular tachycardia, torsades de pointes, serotonin syndrome, acute angle-closure glaucoma, antipsychotic withdrawal, anosmia, dyskinesia, galactorrhea, gynecomastia, ↓ blood glucose, memory impairment, pancytopenia, ↓ platelet count, hostility, seizure, motor impairment, sexual dysfunction, priapism
Interactions
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