Improving your health since 2000
n: oh-LAN-za-peen/floo-OX-e-teen HYE-droe-KLOR-ide Class: Antipsychotic/Antidepressant combination
- Capsules, oral olanzapine 3 mg/fluoxetine hydrochloride 25 mg
- Capsules, oral olanzapine 6 mg/fluoxetine hydrochloride 25 mg
- Capsules, oral olanzapine 6 mg/fluoxetine hydrochloride 50 mg
- Capsules, oral olanzapine 12 mg/fluoxetine hydrochloride 25 mg
- Capsules, oral olanzapine 12 mg/fluoxetine hydrochloride 50 mg
Unknown; however, it is suspected that activation of 3 monoaminergic neural systems (dopamine, norepinephrine, and serotonin) is responsible for an enhanced antidepressant effect.
Acute treatment of depressive episodes associated with bipolar I disorder in adults; acute treatment of treatment-resistant depression in adults who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode.
Coadministration with thioridazine (or within 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. Adjust the dosage as needed. Usual dose is olanzapine 6 to 12 mg/fluoxetine 15 to 50 mg.Treatment-Resistant Depression
PO Start with olanzapine 6 mg/fluoxetine 25 mg daily in the evening. Adjust the dosage as needed. Usual dose is olanzapine 6 to 18 mg/fluoxetine 25 to 50 mg.Special Populations
PO Start with olanzapine 3 mg/fluoxetine 25 mg to olanzapine 6 mg/fluoxetine 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, women), or patients who may be pharmacodynamically sensitive to olanzapine. If indicated, perform dose escalation with caution.
Store between 59° and 86°F. Protect from moisture.
Increased risk of serotonin syndrome (eg, hyperreflexia, incoordination, weakness) has been reported. Observe patients closely.Antiarrhythmics (eg, propafenone)
Metabolism may be inhibited by fluoxetine, resulting in elevated plasma concentrations and increasing the pharmacologic effects and risk of adverse reactions. Closely monitor the clinical response.Antihypertensives (eg, beta-blockers, calcium channel blockers)
Antihypertensive effects may be enhanced by olanzapine. Monitor BP and adjust the antihypertensive dose as needed.Antipsychotic agents (eg, aripiprazole, clozapine, haloperidol, pimozide, risperidone, thioridazine)
Elevated serum antipsychotic levels and/or QTc prolongation may occur. Pimozide and thioridazine are contraindicated with fluoxetine; do not administer thioridazine with fluoxetine or within a minimum of 5 wk of fluoxetine discontinuation. Monitor the clinical response and adjust the aripiprazole dose as needed.Atomoxetine
Atomoxetine plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Closely monitor the clinical response and adjust the atomoxetine dose as needed.Benzodiazepines (eg, alprazolam, diazepam)
Orthostatic hypotension of olanzapine may be potentiated by diazepam, half-life of diazepam may be prolonged by fluoxetine, and plasma concentrations of alprazolam may be increased. Monitor the clinical response and adjust the benzodiazepine dose as needed.Bupropion
Unexpected adverse effects, including serotonin syndrome, may occur. Closely monitor the patient.Buspirone
Effects of buspirone may be decreased. Paradoxical worsening of obsessive-compulsive disorder or serotonin syndrome has been reported. If coadministration cannot be avoided, closely monitor the patient for worsening clinical status as well as serotonin syndrome.Clopidogrel
Clopidogrel plasma concentrations and pharmacologic effects may be decreased. Avoid coadministration.CNS-active drugs (eg, alcohol)
Use with caution; titrate the dose and monitor the clinical status of the patient. Concurrent use of alcohol is not recommended.Cyclosporine, phenytoin, tricyclic antidepressants (eg, desipramine, imipramine)
Blood levels of these agents may be increased by fluoxetine. Monitor the clinical response of the patient and the concentrations of these agents when appropriate.Cyproheptadine
Pharmacologic effects of fluoxetine may be decreased. If coadministration cannot be avoided, closely monitor the clinical response. If an interaction is suspected, consider discontinuing cyproheptadine.Dextromethorphan
Dextromethorphan plasma concentrations and risk of toxicity may be increased. If coadministration cannot be avoided, closely monitor the clinical response and adjust the dextromethorphan dose as needed.Digoxin
Digoxin plasma concentrations may be elevated, increasing the pharmacologic effect and risk of toxicity. If coadministration cannot be avoided, closely monitor the clinical response and digoxin concentrations.Dopamine agonists, levodopa
Effects of levodopa and dopamine agonists may be antagonized by olanzapine. Use with caution.Drugs that induce CYP1A2 (eg, carbamazepine, omeprazole, rifampin)
May decrease olanzapine concentrations. In addition, carbamazepine levels may be increased. Monitor the clinical response and concentrations of the CYP1A2 inducer and olanzapine when coadministration of either agent is started or stopped.Drugs that inhibit CYP1A2 (eg, estrogens, fluvoxamine, fluoroquinolone antibiotics)
May elevate olanzapine plasma levels, increasing the risk of adverse reactions. Monitor the clinical response and adjust the olanzapine/fluoxetine dose as needed.Drugs that interfere with hemostasis (eg, aspirin, NSAIDs, warfarin)
Risk of bleeding may be increased. Caution patients about the increased risk of bleeding and the signs of GI bleeding.Fenfluramine
Serotonin syndrome may occur because of additive serotonergic effects. Concurrent use is not recommended.Galantamine
Pharmacologic effects and plasma concentrations of galantamine may be increased. Consider close clinical monitoring and galantamine dosage adjustment.Iloperidone
Iloperidone plasma concentrations and pharmacologic effects may be increased. A modification of the iloperidone dosage is recommended.Linezolid
Serotonin syndrome may occur. Allow at least 2 wk after stopping linezolid before administering fluoxetine.Lithium
Fluoxetine may increase or decrease lithium levels. Lithium toxicity and increased serotonergic effects have been reported. Monitor plasma lithium concentrations following initiation of therapy.Macrolide and related antibiotics (eg, clarithromycin)
Fluoxetine plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Serotonin syndrome may result. Closely monitor the clinical response.MAOIs (eg, isocarboxazid, phenelzine)
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.Methylene blue
The risk of CNS toxicity, including serotonin syndrome, may be increased. Use an alternative agent for methylene blue.Methylphenidate, nefazodone, opioid analgesics (eg, meperidine, tramadol), St. John's wort
Serotonin syndrome may occur because of additive serotonergic effects. Closely monitor the patient for adverse reactions.Metoclopramide
Metoclopramide plasma concentrations may be increased by fluoxetine. Serotonin syndrome may occur. Monitor for adverse reactions and adjust the metoclopramide dose as needed.Phosphodiesterase type 5 (PDE5) inhibitors (eg, sildenafil)
Fluoxetine may inhibit PDE5 inhibitor metabolism. If concurrent use cannot be avoided, coadminister with caution and reduce the initial dose of PDE5 inhibitor.Ritonavir
Plasma levels of ritonavir and fluoxetine may be elevated, increasing the pharmacologic effects and adverse reactions of both agents. Fluoxetine and ritonavir may inhibit the metabolism of each other. Ritonavir has also been reported to decrease olanzapine concentrations and pharmacologic effects. Monitor the clinical response and adjust the dose of one or both agents as needed.Sibutramine
Serotonin syndrome may occur. Concurrent use is not recommended.Smoking
Olanzapine clearance is approximately 40% higher in smokers than nonsmokers; however, no dosage adjustment is needed.SNRIs (eg, venlafaxine), SSRIs (eg, fluoxetine)
Serotonin syndrome has occurred. Concurrent use is not recommended.Sympathomimetics (eg, amphetamine)
Coadministration may cause increased sympathomimetic effects and an increased risk of serotonin syndrome. Monitor for increased CNS effects and adjust dose as needed.Tamoxifen
Clinical response to tamoxifen may be reduced. Avoid coadministration. If an antidepressant is needed, citalopram, escitalopram, or venlafaxine are less likely to interact.Terbinafine
Fluoxetine plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Monitor the clinical response and adjust the olanzapine/fluoxetine dose as needed.Tetrabenazine
Tetrabenazine plasma concentrations and pharmacologic effects may be increased. Use with caution.Trazodone
Serotonin syndrome may occur. Use with caution.Tryptophan
Risk of adverse reactions (eg, agitation, GI distress, restlessness) may be increased. Concomitant use is not recommended.Vinblastine
Vinblastine metabolism may be decreased; consider giving a reduced dose.Warfarin
Altered anticoagulant effects, including increased bleeding, may occur. Monitor PT.Zolpidem
Fluoxetine may shorten the onset of action and increase the effect of zolpidem. Monitor the clinical response and adjust the zolpidem dose as needed.
Vasodilatation (at least 1%); bradycardia; orthostatic hypotension; QT interval prolongation; tachycardia; venous thromboembolic events, including deep venous thrombosis and pulmonary embolism (postmarketing).
Somnolence (14%); fatigue (12%); tremor (9%); sedation (8%); disturbances in attention, hypersomnia (5%); restlessness (4%); asthenia, lethargy (3%); abnormal thinking, nervousness (2%); amnesia (at least 1%); decreased libido; dystonic symptoms; extrapyramidal symptoms.
Blurred vision (5%).
Increased appetite (20%); dry mouth (15%); flatulence (3%); abdominal distention (2%); diarrhea, taste perversion (at least 1%).
Glycosuria (4%); erectile dysfunction (2%); breast pain, menorrhagia, urinary frequency, urinary incontinence (at least 1%); abnormal ejaculation, anorgasmia.
Ecchymosis (at least 1%).
Elevated hepatic transaminases (ALT, AST, GGT) and alkaline phosphatase; cholestatic or mixed liver injury, hepatitis (postmarketing).
Elevated prolactin (28%); low total bilirubin (15%); low bicarbonate (14%); elevated ALT (5%); elevated urea nitrogen, elevated uric acid, low albumin, low Hgb (3%); low inorganic phosphorus, low lymphocytes (2%).
Increased triglycerides (68%); elevated glucose levels (37%); increased cholesterol (36%); 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, pyrexia (2%); chills, photosensitivity reaction (at least 1%); rhabdomyolysis (postmarketing).
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death compared with those taking placebo. Although the causes of death were varied, most of the deaths appeared to be CV (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Olanzapine/fluoxetine is not approved for the treatment of dementia-related psychosis.Suicidality
Compared with placebo, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorder and other psychiatric disorders. Appropriately monitor and closely observe patients of all ages who are started on antidepressant therapy for clinical worsening, suicidality, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the health care provider.
Monitor for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of therapy, or at times of dose increases or decreases. Monitor patients for development of mania/hypomania symptoms. Regularly monitor patient's weight. Monitor fasting blood glucose and lipid profile at the beginning of and periodically during treatment. Monitor patients for worsening of glucose control and for symptoms of hyperglycemia, including polydipsia, polyuria, polyphagia, and weakness. Frequently monitor CBC in patients with a history of clinically significant low WBC or drug-induced leukopenia/neutropenia during the first few months of therapy. Monitor patients with clinically significant neutropenia for fever or other signs or symptoms of infection. Monitor patients for the emergence of serotonin syndrome or NMS-like signs and symptoms.
Category C . Neonates exposed to fluoxetine late in the third trimester have developed persistent pulmonary hypertension of the newborn and other complications requiring prolonged hospitalization, respiratory support, and tube feeding. Consider potential risks and benefits of treatment when treating women during the third trimester. Consider tapering fluoxetine in the third trimester.
Fluoxetine and olanzapine are excreted in breast milk. The manufacturer recommends that women receiving olanzapine/fluoxetine do not breast-feed.
Not approved for use in children.
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 of concomitant diseases or other drug therapy.
Anaphylactoid reactions, including bronchospasm, angioedema, and urticaria, have been reported. Rarely, pulmonary reactions, including inflammatory processes of varying histopathology and/or fibrosis, have been reported.
Use with caution.
Use with caution in patients with clinically significant prostatic hypertrophy, narrow-angle glaucoma, a history of paralytic ileus, or related conditions, or with diseases or conditions that could affect hemodynamic responses.
SSRIs, including fluoxetine, may increase the risk of bleeding.
Antipsychotics may 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 their ability.
Withdrawal symptoms have been reported after rapid discontinuation of therapy. If discontinuing treatment or reducing the dose, gradually taper the dose and monitor the patient for withdrawal symptoms. If significant withdrawal symptoms develop, reinstitute previous dosing schedule and attempt a less-rapid tapering regimen after the patient has stabilized.
Esophageal dysmotility and aspiration have been associated with antipsychotic drug use.
Prolonged seizures have been rarely reported in patients receiving concurrent electroconvulsive therapy treatment.
Leukopenia/neutropenia has been reported temporally related to antipsychotic agents, including olanzapine. Agranulocytosis has also been reported.
Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma, or death, has occurred.
Undesirable alterations in lipids have been observed. Very high (eg, more than 500 mg/dL) triglyceride elevations have occurred.
Elevated prolactin levels may occur; the elevation persists during administration.
Hyponatremia has occurred during SSRI treatment and is often the result of SIADH. Use with caution in patients who are elderly or volume-depleted, or who are taking diuretics.
May be precipitated by fluoxetine in patients at risk of bipolar disorder.
Has occurred in association with olanzapine and is potentially fatal.
Orthostatic hypotension, associated with bradycardia, dizziness, tachycardia, and, in some patients, syncope, may occur. Use caution in patients with CV disease, cerebrovascular disease, or conditions predisposing to hypotension (eg, concurrent treatment with antihypertensives, dehydration, hypovolemia).
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 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 (eg, Alzheimer dementia).
Development of a potentially life-threatening serotonin syndrome or NMS-like reactions may occur with SSRIs, including fluoxetine, but particularly with coadministration of serotonergic drugs (eg, triptans), drugs that impair metabolism of serotonin (eg, MAOIs), or antipsychotics or other dopamine antagonists.
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 highest among elderly patients, especially women.
There is a potential for weight gain with treatment.
Acute psychosis, aggression, agitation, arrhythmias, essential tremor, hypertension, hypotension, impaired consciousness (coma), impaired neurologic function (ataxia, confusion, convulsions, dysarthria), lethargy, somnolence (sedation).
Copyright © 2009 Wolters Kluwer Health.
Not all side effects for fluoxetine / olanzapine may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.
Applies to fluoxetine / olanzapine: oral capsule
In addition to its needed effects, some unwanted effects may be caused by fluoxetine / olanzapine. In the event that any of these side effects do occur, they may require medical attention.
You should check with your doctor immediately if any of these side effects occur when taking fluoxetine / olanzapine:More common
Some of the side effects that can occur with fluoxetine / olanzapine may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:More common
Applies to fluoxetine / olanzapine: oral capsule
Commonly reported side effects associated with fluoxetine-olanzapine treatment in short-term controlled studies at an incidence of at least 5% and double that of placebo were disturbance in attention, dry mouth, fatigue, hypersomnia, increased appetite, peripheral edema, sedation, somnolence, tremor, blurred vision, and increased weight.
Statistically significant differences in the incidence of weight gain, prolactin elevation, fatigue, and dizziness have been observed in a single 8-week randomized, double-blind, fixed dose study comparing 10 mg, 20 mg, and 40 mg olanzapine in patients with schizophrenia or schizoaffective disorder. Side effects associated with treatment discontinuation were increased weight and sedation.
In a single, 8-week, randomized, placebo-controlled clinical trial of fluoxetine-olanzapine for the treatment of bipolar I depression in patients aged 10 to 17 years, the side effects that lead to discontinuation that occurred at an incidence of at least 1% and greater than that of the placebo group were increased weight, suicidal ideation, bipolar disorder, and somnolence.[Ref]
Antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. An increased risk of suicidal thinking and behavior in children, adolescents, and young adults (aged 18 to 24 years) with major depressive disorder (MDD) and other psychiatric disorders has been reported with short-term use of antidepressant drugs.
Adult and pediatric patients receiving antidepressants for MDD, as well as for psychiatric and nonpsychiatric indications, have reported symptoms that may be precursors to emerging suicidality, including anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania. Causality has not been established.
Placebo-controlled clinical trials in elderly patients with dementia-related psychosis showed a significantly increased risk of death in olanzapine-treated patients (3.5%) compared to placebo-treated patients (1.5%).
Anxiety, restlessness, and suicidal ideation were reported as a treatment-emergent side effect in an 8-week randomized, double-blind, placebo-controlled clinical trial in pediatric bipolar I depression in patients aged 10 to 17 years.[Ref]
Common (1% to 10%): Nervousness, restlessness, thinking abnormal
Uncommon (0.1% to 1%): Depersonalization, emotional lability, euphoria
Rare (less than 0.1%): Withdrawal syndrome
Frequency not reported: Bruxism, violent behaviors[Ref]
Very common (10% or more): Somnolence
Common (1% to 10%): Disturbance in attention, taste perversion, tremor
Uncommon (0.1% to 1%): Ataxia, coma, dysarthria, hypokinesia, movement disorder, myoclonus
Rare (less than 0.1%): Hyperkinesia
Frequency not reported: Dystonias, headache[Ref]
Dystonias may occur in the first few days of treatment; males and younger age groups appear to be at a greater risk for acute dystonia. The frequency and severity of symptoms appear greater with high potency and at higher doses of first generation antipsychotic drugs, but may occur at low doses.
One retrospective study of 23 outpatients with Parkinson's disease treated with 40 mg of fluoxetine a day reported that three patients experienced worsening of parkinsonism, two patients experienced improvement of parkinsonism, and 18 patients experienced no change. Another small study reported a series of four patients who experienced worsening of parkinsonism during treatment with fluoxetine.
Potentially life-threatening serotonin syndrome has been reported with SSRIs and SNRIs as monotherapy, but particularly with concomitant use of other serotonergic drugs and drugs that impair the metabolism of serotonin.
Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex, has been reported in connection to treatment with antipsychotic drugs, including olanzapine.
A number of case reports have implicated fluoxetine in causing seizures. Twelve of 6000 patients experienced convulsions during pre-marketing testing.
A case of dose-dependent exacerbation of preexisting, mild restless legs syndrome (which ultimately required discontinuation of fluoxetine) has been reported.
Somnolence and tremor were reported as a treatment-emergent side effect in an 8-week randomized, double-blind, placebo-controlled clinical trial in pediatric bipolar I depression in patients aged 10 to 17 years.[Ref]
Numerous cases of hyponatremia have been reported following treatment with an SSRI. Risk factors for the development of SSRI- associated hyponatremia including advanced age, female gender, concomitant use of diuretics, low body weight, and lower baseline serum sodium levels have been identified. Hyponatremia tends to develop within the first few weeks of treatment (range 3 to 120 days) and typically resolves within 2 weeks (range 48 hours to 6 weeks) after therapy has been discontinued with some patients requiring treatment. The proposed mechanism for the development of hyponatremia involves SIADH via release of antidiuretic hormone.
Hyperglycemia has been reported with olanzapine alone as well as in combination with fluoxetine. In an analysis of 7 controlled clinical studies, 2 of which were placebo controlled, with treatment duration up to 12 weeks, fluoxetine-olanzapine was associated with a greater mean change in random glucose compared to placebo (+8.65 mg/dL versus -3.86 mg/dL). The difference in mean changes was greater in patients with evidence of glucose dysregulation at baseline. Epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia in patients treated with atypical antipsychotics. The association between atypical antipsychotic therapy and increases in glucose levels appears greater with olanzapine than some other atypical antipsychotic agents.
Elevated uric acid, low albumin, low bicarbonate, and low inorganic phosphorus were observed at a statistically significant greater frequency in the fluoxetine-olanzapine group compared to the placebo group in adult clinical studies. Clinically meaningful increases in total cholesterol and triglyceride levels, sometimes greater than 500 mg/dL have also been observed in adults.
Clinically significant weight gain across all baseline BMI categories has been reported in clinical trials with fluoxetine-olanzapine. An analysis of 7 controlled clinical studies (2 of which were placebo-controlled) reported that, after a median exposure of eight weeks, 22% of patients treated with fluoxetine-olanzapine had gained at least 7% of their baseline weight. Long-term studies with fluoxetine-olanzapine (n=431), where patients were treated with this combination for at least 48 weeks, showed a mean weight gain of 6.7 kg.
Increased weight, appetite, blood triglycerides, and cholesterol were reported as treatment-emergent side effects in an 8 week randomized, double-blind, placebo-controlled clinical trial in pediatric bipolar I depression in patients aged 10 to 17 years. High fasting total cholesterol, high fasting LDL cholesterol, and high fasting triglycerides were observed at statistically significant greater frequencies in the fluoxetine-olanzapine group compared to the placebo group.[Ref]
Very common (10% or more): High fasting LDL cholesterol, high fasting triglycerides, high fasting total cholesterol, low bicarbonate, increased appetite, increased weight
Common (1% to 10%): Elevated uric acid, low albumin, low inorganic phosphorus, weight loss
Rare (less than 0.1%): Gout
Frequency not reported: Hyperglycemia, increased creatine phosphokinase, random triglyceride levels of 1000 mg/dL or more[Ref]
The mean standing pulse rate in patients treated with fluoxetine-olanzapine was reduced by 0.7 beats/minute.
QTcF interval prolongation of 450 milliseconds or more for males and 470 milliseconds for females was reported at an incidence of at least 1% in clinical trials. The mean increase in QTc interval was reported as significantly greater in fluoxetine-olanzapine treated patients than placebo-treated patients, olanzapine-treated, and fluoxetine-treated patients.
Mean increases in QTcF interval of 8.2 milliseconds was observed at a statistically significant greater frequency in the fluoxetine-olanzapine group compared to the placebo group in a single 8-week randomized, placebo-controlled clinical trial for bipolar I depression in children and adolescents aged 10 to 17 years.
One placebo-controlled study has suggested that fluoxetine has no effects on intraventricular conduction. Other case reports have suggested that fluoxetine may rarely provoke dysrhythmias. Other conflicting case reports have suggested that fluoxetine may have a propensity to provoke and alleviate vasoconstriction. Several cases of unexpected death occurring shortly after initiation of fluoxetine therapy have been reported in elderly patients with multiple medical problems.
In one case report, QTc prolongation and torsades de pointes developed in an elderly woman 6 months after starting therapy with fluoxetine 20 mg daily. The QTc interval returned to normal following discontinuation of fluoxetine. Four additional cases suggesting fluoxetine-associated QTc prolongation or torsades de pointes have been reported.[Ref]
Very common (10% or more): Edema
Common (1% to 10%): Generalized edema, vasodilatation
Frequency not reported: Bradycardia, hypotension, orthostatic hypotension, tachycardia
Postmarketing reports: Deep vein thrombosis[Ref]
Accidental overdose was reported as a treatment-emergent side effect in an 8-week randomized, double-blind, placebo-controlled clinical trial in pediatric bipolar I depression in patients aged 10 to 17 years.[Ref]
Very common (10% or more): Fatigue
Common (1% to 10%): Asthenia, chills, neck rigidity, pain, pyrexia
Rare (less than 0.1%): Death
Frequency not reported: Body temperature dysregulation[Ref]
Common (1% to 10%): Breast pain, erectile dysfunction, menorrhagia, urinary frequency, urinary incontinence
Uncommon (0.1% to 1%): Amenorrhea, female lactation, hypomenorrhea, metrorrhagia, urinary retention, urinary urgency, impaired urination
Rare (less than 0.1%): Breast engorgement, increased libido
Frequency not reported: Abnormal ejaculation, anorgasmia, decreased libido, dysuria, gynecological bleeding[Ref]
Urinary retention and galactorrhea have been reported with other SSRIs.
The estimates of the incidence of untoward sexual experience and performance may underestimate their actual incidence, partly because patients and physicians may be reluctant to discuss this issue. In placebo-controlled clinical trials ejaculation disorder (primarily ejaculation delay) was reported as a treatment-emergent side effect at an incidence of 6% and at least twice the incidence in placebo-treated male patients.
Dysmenorrhea was reported as a treatment-emergent side effect in an 8-week randomized, double-blind, placebo-controlled clinical trial in pediatric bipolar I depression in patients aged 10 to 17 years.[Ref]
Common (1% to 10%): Ecchymosis
Uncommon (0.1% to 1%): Alopecia, dry skin, pruritus
Rare (less than 0.1%): Exfoliative dermatitis, purpura
Frequency not reported: Erythema multiforme, sweating[Ref]
Approximately 3% of fluoxetine-treated patients have been reported to develop a skin reaction.[Ref]
Very common (10% or more): Elevated prolactin
Frequency not reported: Diabetic coma[Ref]
Elevated prolactin levels were observed at a statistically significant greater frequency in the fluoxetine-olanzapine group compared to the placebo group in adult clinical studies and also in a single 8-week randomized, placebo-controlled clinical trial for bipolar I depression in children and adolescents aged 10 to 17 years.[Ref]
A study of 26,005 antidepressant users has reported 3.6 times more upper GI bleeding episodes with the use of SSRIs relative to the population who did not receive antidepressant medications. Upper gastrointestinal tract bleeding was observed in 3.9 times more frequently in patients receiving fluoxetine.
Dyspepsia was reported as a treatment-emergent side effect in an 8-week randomized, double-blind, placebo-controlled clinical trial in pediatric bipolar I depression in patients aged 10 to 17 years.[Ref]
Very common (10% or more): Dry mouth
Common (1% to 10%): Abdominal distension, diarrhea, flatulence
Uncommon (0.1% to 1%): Buccoglossal syndrome, gastritis, gastroenteritis, nausea and vomiting, peptic ulcer
Rare (less than 0.1%): Gastrointestinal hemorrhage, intestinal obstruction, pancreatitis
Frequency not reported: Esophageal ulcer[Ref]
Common (1% to 10%): Low hemoglobin, low lymphocytes
Uncommon (0.1% to 1%): Anemia, thrombocytopenia
Rare (less than 0.1%): Leukopenia
Frequency not reported: Aplastic anemia, neutropenia[Ref]
Low lymphocytes and low hemoglobin were observed at a statistically significant greater frequency in the fluoxetine-olanzapine group compared to the placebo group in adult clinical studies[Ref]
ALT levels reported to return to normal, or were decreasing, at last follow-up in the majority of patients who either continued or discontinued treatment with fluoxetine-olanzapine.
Low total bilirubin levels were observed at a statistically significant greater frequency in the fluoxetine-olanzapine group compared to the placebo group in adult clinical studies. Elevated ALT and AST levels were observed at statistically significant greater frequencies in the fluoxetine-olanzapine group compared to the placebo group in a single 8-week randomized, placebo-controlled clinical trial for bipolar I depression in children and adolescents aged 10 to 17 years.[Ref]
Very common (10% or more): Elevated ALT and AST, low total bilirubin
Common (1% to 10%): Clinically significant ALT elevation less than 3 times the upper limit of normal (ULN), ALT elevations 5 times the ULN or more.
Rare (less than 0.1%): Bilirubinemia , liver fatty deposit
Frequency not reported: Cholestatic jaundice, increased alkaline phosphatase, jaundice
Postmarketing reports: Cholestatic or mixed liver injury, hepatitis[Ref]
Common (1% to 10%): Photosensitivity reaction[Ref]
Common (1% to 10%): Arthralgia, musculoskeletal stiffness, pain in extremity
Rare (less than 0.1%): Osteoporosis
Postmarketing reports: Rhabdomyolysis[Ref]
Epidemiological studies, primarily in patients aged 50 years or older, have shown an increased risk of bone fractures in patients receiving SSRIs or TCAs.
Back pain was reported as a treatment-emergent side effect in an 8-week randomized, double-blind, placebo-controlled clinical trial in pediatric bipolar I depression in patients aged 10 to 17 years.[Ref]
Common (1% to 10%): Eye disorders
Uncommon (0.1% to 1%): Abnormality of accommodation, dry eyes[Ref]
Elevated urea nitrogen levels were observed at a statistically significant greater frequency in the fluoxetine-olanzapine group compared to the placebo group in adult clinical studies.
Glycosuria was reported at an incidence of 4.4% of patients treated with fluoxetine-olanzapine in an analysis of 6 controlled clinical studies, compared to 1.4% in the placebo group.[Ref]
Common (1% to 10%): Elevated urea nitrogen, glycosuria
Rare (less than 0.1%): Increased creatinine[Ref]
Common (1% to 10%): Sinusitis
Uncommon (0.1% to 1%): Epistaxis, yawn
Rare (less than 0.1%): Laryngismus
Frequency not reported: Eosinophilic pneumonia
Postmarketing reports: Pulmonary embolism[Ref]
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