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Teicoplanin is not for intraventricular use. The manufacturer strongly discourage injecting Teicoplanin into the brain.

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Symbyax (Olanzapine and Fluoxetine) - Uses, Dose, Side effects

Symbyax (Olanzapine and Fluoxetine) is a combination pill containing the atypical antipsychotic drug olanzapine and selective serotonin reuptake inhibitor, fluoxetine. It is used to treat bipolar depression and treatment-resistant depression.

Symbyax (Olanzapine and fluoxetine) Uses:

Acute Depression, (associated with bipolar I disorder):
- Associated with bipolar I disorder, treatment of acute depressive episodes.
Symbyax for treatment resistant Depression:
- Used for treatment-resistant depression treatment (eg, unresponsive to 2 trials of different antidepressants in the current episode)

Symbyax (Olanzapine and Fluoxetine) Dose in Adults

In patients predisposed to hypotension, with hepatic impairment, with combined factors for reduced metabolism (females, the elderly, nonsmokers), or enhanced sensitivity to olanzapine, lower doses (olanzapine 3-6 mg per fluoxetine 25 mg) should be used.
In this patient population, dose adjustments should be made cautiously.

Symbyax (Olanzapine and Fluoxetine) Dose in the treatment of depression associated with bipolar I disorder:

Initial:

In the evening, Olanzapine 6 mg per fluoxetine 25 mg once daily.
Adjust dose based on response & tolerability.

Usual dose:

Olanzapine 6-12 mg per fluoxetine 25-50 mg.
The safety of daily doses of olanzapine >18 mg per fluoxetine >75 mg have not been evaluated.

Symbyax (Olanzapine and Fluoxetine) Dose in treatment-resistant depression:

Initial:

In the evening, 6 mg per fluoxetine 25 mg once daily.
Adjust dose based on response & tolerability.

Usual dose:

Olanzapine 6-18 mg per fluoxetine 25-50 mg.
The safety of daily doses of olanzapine >18 mg per fluoxetine >75 mg have not been evaluated.

Note:

Rather than fixed-dose combination product (Symbyax), when using individual components of fluoxetine with olanzapine, approximate dosage correspondence is as follows:
- Olanzapine 2.5 mg + fluoxetine 20 mg = Symbyax 3/25
- Olanzapine 5 mg + fluoxetine 20 mg = Symbyax 6/25
- Olanzapine 12.5 mg + fluoxetine 20 mg = Symbyax 12/25
- Olanzapine 5 mg + fluoxetine 50 mg = Symbyax 6/50
- Olanzapine 12.5 mg + fluoxetine 50 mg = Symbyax 12/50

Discontinuation of therapy:
- Gradually taper the dose (eg, over 2 to 4 weeks) to withdrawal symptoms and detect reemerging symptoms, when discontinuing antidepressant treatment that has lasted for >3 weeks and acute antipsychotic treatment.
- Prior history of antidepressant withdrawal symptoms, or high doses of antidepressants, reasons for a slower antidepressant titration (eg, over 4 weeks) include the use of a drug with a half-life <24 hours (eg, paroxetine, venlafaxine).
- Resume the previously prescribed dose & decrease dose at a more gradual rate, if intolerable withdrawal symptoms occur.
- Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering from months to years with close monitoring to allow for the detection of prodromal symptoms of disease recurrence.
- Evidence supporting ideal taper rates is limited.

MAO inhibitor recommendations:

Switching to or from an MAO inhibitor intended to treat psychiatric disorders:
- Allow fourteen days to elapse between discontinuing an MAO inhibitor intended to treat psychiatric disorders and initiation of olanzapine/fluoxetine.
- Allow five weeks to elapse between discontinuing olanzapine/fluoxetine and initiation of an MAO inhibitor intended to treat psychiatric disorders.

Symbyax (Olanzapine and Fluoxetine) Dose in Children

Symbyax (Olanzapine and Fluoxetine) Dose in Children:

In patients predisposed to hypotension, with hepatic impairment, with combined factors for reduced metabolism (females, nonsmokers), or enhanced sensitivity to olanzapine, lower doses (olanzapine 3 to 6 mg/fluoxetine 25 mg) should be used.
In this patient population, dose adjustments should be made cautiously.

Symbyax (Olanzapine and Fluoxetine) Dose in the treatment of depression associated with bipolar I disorder:

Children and Adolescents 10 to 17 years:

P/O: Initial dose:

- In the evening, Olanzapine 3 mg /fluoxetine 25 mg.
- Adjust dose based on response & tolerability.

Usual dose:

- Olanzapine 6-12 mg/fluoxetine 25-50 mg.
- In pediatrics, the safety of fluoxetine doses >50 mg in combination with olanzapine doses >12 mg has not been studied.

Note:

Rather than fixed-dose combination product (Symbyax), when using individual components of fluoxetine with olanzapine, approximate dosage correspondence is as follows:
- - Olanzapine 2.5 mg + fluoxetine 20 mg = Symbyax 3/25
  - Olanzapine 5 mg + fluoxetine 20 mg = Symbyax 6/25
  - Olanzapine 12.5 mg + fluoxetine 20 mg = Symbyax 12/25
  - Olanzapine 5 mg + fluoxetine 50 mg = Symbyax 6/50
  - Olanzapine 12.5 mg + fluoxetine 50 mg = Symbyax 12/50

- Discontinuation of therapy:
  - Refer to adult dosing.
- MAO inhibitor recommendations:
  - Refer to adult dosing.

Pregnancy Risk Factor C

This combination was used in animal reproduction studies.
Contact individual agents for more information.

Use of fluoxetine and Olanzapine during breastfeeding

Olanzapine, fluoxetine and other drugs are secreted into breast milk.
Manufacturer recommends that a decision is made regarding whether to stop nursing or discontinue using the drug.
This consideration should be taken in light of the possibility of serious adverse reactions in the infant while nursing.
Contact individual agents for more information.

Symbyax (Olanzapine and Fluoxetine) Dose in Kidney Disease:

No dosage adjustment required.

Symbyax (Olanzapine and Fluoxetine) Dose in Liver Disease:

Initial:

In the evening, Olanzapine 3-6 mg/fluoxetine 25 mg once daily.
Use caution adjusting dose (metabolism may be decreased).

Common Side Effects of Symbyax (Olanzapine and fluoxetine):

Cardiovascular:
- Edema
Central Nervous System:
- Drowsiness
- Fatigue
Endocrine & Metabolic:
- Hyperprolactinemia
- Increased Serum Triglycerides
- Increased LDL Cholesterol
- Increased Serum Cholesterol
- Weight Gain
- Decreased HDL Cholesterol
- Decreased Serum Bicarbonate
Gastrointestinal:
- Increased Appetite
- Xerostomia
Hepatic:
- Increased Serum ALT
- Increased Serum AST
- Decreased Serum Bilirubin

Less Common Side Effects Of Symbyax (Olanzapine and fluoxetine):

Cardiovascular:
- Orthostatic Hypotension
- Prolonged Q-T Interval On ECG
- Vasodilation
Central Nervous System:
- Manic Reaction
- Disturbance In Attention
- Restlessness
- Anxiety
- Abnormality In Thinking
- Nervousness
- Pain
- Suicidal Ideation
- Amnesia
- Chills
Dermatologic:
- Ecchymoses
- Skin Photosensitivity
Endocrine & Metabolic:
- Glycosuria
- Hypoalbuminemia
- Increased Uric Acid
- Hypophosphatemia
- Hypermenorrhea
- Weight Loss
- Menstrual Disease
Gastrointestinal:
- Dyspepsia
- Flatulence
- Abdominal Distension
- Diarrhea
- Dysgeusia
Genitourinary:
- Dysmenorrhea
- Erectile Dysfunction
- Mastalgia
- Urinary Frequency
- Urinary Incontinence
Hematologic & Oncologic:
- Decreased Hemoglobin
- Lymphocytopenia
Hepatic:
- Increased Liver Enzymes
Neuromuscular & Skeletal:
- Tremor
- Arthralgia
- Limb Pain
- Weakness
- Back Pain
- Stiffness
- Neck Stiffness
Ophthalmic:
- Blurred Vision
Renal:
- Increased Blood Urea Nitrogen
Respiratory:
- Sinusitis
Miscellaneous:
- Fever

Rare side effects of Symbyax (Olanzapine and Fluoxetine):

Cardiovascular:
- Bradycardia
- Tachycardia
Central Nervous System:
- Anorgasmia
Endocrine & Metabolic:
- Decreased Libido
- Increased Gamma-Glutamyl Transferase
Genitourinary:
- Ejaculatory Disorder
Hepatic:
- Increased Serum Alkaline Phosphatase

Contraindications to Symbyax (Olanzapine and Fluoxetine):

MAO inhibitors are recommended for the treatment of psychiatric disorders. They should be used concurrently within 5 weeks after discontinuing olanzapine/fluoxetine or within 2 weeks.
Intravenous methyleneblue or linezolid is given to a patient who has received olanzapine/fluoxetine.
Use with pimozide and thioridazine

Warnings and precautions

Allergies and rash
- Fluffy use has been linked to significant rash, allergic reactions, such as vasculitis and lupus-like syndrome, laryngospasm, anaphylactoid responses & pulmonary inflammation disease.
- Stop using the product if you are unable to identify the cause.
Modified cardiac conduction
- Olanzapine could alter cardiac conduction.
- Life-threatening arrhythmias can be caused by therapeutic doses antipsychotics.
Anticholinergic effects
- Olanzapine can cause constipation, xerostomia and blurred vision.
- Patients with reduced gastrointestinal motility, BPH, xerostomia, and/or visual problems (including narrow angle glaucoma) should be cautious.
- Comparatively to other neuroleptics olanzapine is a mild cholinergic antagonist.
Bleeding Risk:
- Fluoxetine can increase bleeding risk when taken with NSAIDs, Warfarin, aspirin or warfarin.
- Reports indicate that SSRI use can cause bleeding that ranges from minor bruising and epistaxis to serious hemorhage.
Blood dyscrasias
- Antipsychotic use has been linked to Leukopenia and Neutropenia in clinical trials and postmarketing reports.
- Periodic blood count assessments should be done if there are any risk factors, such as low WBC or a history of drug-induced neutropenia/ leukopenia.
- Stop treatment immediately if there are any signs of blood disorders or an absolute neutrophil count below 1000/mm3.
Effects on the cerebrovascular system:
- For the unapproved use of olanzapine in elderly patients with dementia-related psychosis, a placebo-controlled trial showed an increase in cerebrovascular effects (eg transient ischemic attacks, stroke) that was not reported.
Depression in the CNS:
- CNS depression can lead to mental or physical impairment.
- Patients should be cautious about driving or operating machinery that requires mental alertness.
- Olanzapine can be mildly to very sedating when compared to other antipsychotics.
- It has been shown that dose-related effects can be observed.
Dyslipidemia
- Dose-related increases in cholesterol and triglycerides were observed with olanzapine.
- Use olanzapine with caution in patients with abnormal lipid profiles.
Aspiration and Esophageal Dysmotility:
- Aspiration and esophageal dysmotility have been linked to antipsychotic use.
- Risk increases with age.
- Patients at high risk of aspiration pneumonia should be treated with caution, especially if they are older than 75 years.
Extrapyramidal symptoms
- Olanzapine can cause additionalpyramidal symptoms (EPS), which may include pseudo-parkinsonism and acute dystonic reactions. These reactions are generally less common than those of conventional antipsychotics. Frequency is similar to that of placebo.
- Higher doses can increase the risk of dystonia (and possibly other EPS), if conventional antipsychotics are used, especially in younger patients.
- Higher vulnerability to tardive dyskinesia is associated with older age, female gender, postmenopausal status and Parkinson disease symptoms.
- If you have tardive dyskinesia symptoms, discontinue therapy.
Falls
- May increase the chance of falls from somnolence, orthostatichypotension, motor or sensory instability, and may also lead to increased risk for falls.
- Fall risk assessments should be done for patients who are ill or taking medication.
Fractures
- Antidepressant treatment has been shown to reduce the risk of bone fractures.
- If an antidepressant-treated person presents with unresolved bone pain or tenderness, swelling, swelling, or bruising, there may be a fragility fracture.
Hyperglycemia
- Atypical antipsychotics were associated with hyperglycemia.
- Sometimes, extreme cases may be associated with hyperosmolar or ketoacidosis.
- Olanzapine might be more closely associated with hyperglycemia than other antipsychotics atypical.
- Patients with diabetes and other disorders of glucose regulation should be cautious.
- Assess for a worsening in glucose control.
- Patients at high risk for diabetes (eg obesity or family history), should have a baseline fasting glucose (FBS) and periodic assessment of their glucose regulation.
Hyperprolactinemia
- Olanzapine can cause dose-related rises in prolactin levels.
- Patients with breast cancer are not aware of the clinical significance or prolactin-dependent tumors such as hyperprolactinemia.
- Prolactin levels were increased in clinical manifestations such as breast-, sexual- and menstrual-related events.
Multiorgan hypersensitivity reactions (drug response with eosinophilia or systemic symptoms [DRESS]).
- There have been reports of potentially fatal and sometimes deadly multiorgan hypersensitivity reactions to olanzapine.
- You may experience a cutaneous reaction (rash, exfoliative dermatitis), fever & lymphadenopathy, as well as eosinophilia and fever with systemic complications (eg hepatitis.
- Stop using olanzapine if you suspect DRESS.
Neuroleptic malignant Syndrome (NMS).
- Olanzapine may be used in conjunction with NMS.
- You should examine your mental state for changes in mood, fever, rigidity, and autonomic instability.
Ocular effects
- This may cause mild pupillary dilation, which can in some cases lead to narrow-angle glaucoma.
- Patients who have not undergone an iridectomy to reduce the risk of narrow-angle glaucoma should be evaluated.
Orthostatic hypotension
- Orthostatic hypotension may occur.
- Patients at high risk for this effect should be supervised.
Extension of QT
- Fluoxetine can cause QT prolongation and ventricular arrhythmia, which may also include torsade des pointes.
- Patients at high risk for QT prolongation should be cautious.
  - congenital long QT syndrome, history or prolonged QT, sudden cardiac death or family history of prolongedQT
  - Other conditions that can lead to arrhythmias include:
    - Hypokalemia
    - Hypomagnesemia
    - Recent MI,
    - Uncompensated Heart Failure
    - Bradyarrhythmias and other arrhythmias
    - Concomitant use other agents that prolong the QT interval
    - Increased fluoxetine exposure due to hepatic impairment, overdose, hepatic dysfunction, use of CYP2D6 inhibits, poor CYP2D6 metabolizer status, concomitant usage of other high-protein-bound drugs
- ECG examination is recommended when initiating treatment for patients at risk of QT prolongation or ventricular arrhythmia.
- Consider quitting therapy if ventricular arrhythmia is suspected.
Serotonin syndrome
- Particularly when combined with:
  - Other serotonrgic agents include triptans and TCAs.
  - Agents that inhibit serotonin metabolism, such as MAO inhibitors, are used to treat mental disorders.
- Potentially life-threatening serotonin Syndrome (SS) has been linked to serotonergic drugs (eg, SSRIs and SNRIs).
- Pay attention to signs of SS, such as mental changes (eg, agitation and hallucinations), delirium, coma, and other symptoms.
- Autonomic instability (eg tachycardia or labile blood pressure, diaphoresis).
- Neuromuscular changes (eg tremors, rigidity, myoclonus).
- GI symptoms (eg nausea, vomiting, diarrhea, etc.) & seizures.
- Stop taking any serotonergic agents or treatment if you notice signs or symptoms.
Sexual dysfunction
- This may lead to or exacerbate sexual dysfunction.
SIADH and Hyponatremia
- SSRIs were and are now associated with SIADH.
- Hyponatremia is rare, with severe cases of serum sodium 110 mg/L. This condition is most common in the elderly.
- Concurrent use of diuretics and volume depletion 7 likely increases the risk.
- Consider discontinuing treatment if hyponatremia symptoms are present.
Temperature regulation
- It is possible to have impaired core body temperature regulation.
- Be careful with heat exposure, strenuous exercise, heat, dehydration, or concomitant anticholinergic medication.
Weight loss
- Significant weight gain (>=7%) has been seen with antipsychotic therapy.
- Product-specific incidences vary.
- Dose-related changes were observed with olanzapine.
- Take a look at your waist circumference and BMI.
Cardiovascular disease
- Patients with severe heart disease, hemodynamic instability and prior myocardial injury, hypercholesterolemia, or other serious conditions should be cautious.
Dementia[US Boxed Warning]
- Patients with dementia-related behavioral problems are more likely to die if they are treated with antipsychotics than those who receive placebo.
- Nature revealed that most deaths were either from cardiovascular disease (eg heart failure, sudden death) and infectious diseases (eg pneumonia).
- Olanzapine or fluoxetine are not approved for the treatment of dementia-related psychosis.
Hepatic impairment
- Patients with hepatic impairment or disease should be used with caution.
- It is recommended to start with the lowest dose.
- May increase transaminases, primarily ALT.
Hypomania and mania:
- This may lead to psychosis in some patients, or a shift towards mania or hypomania among patients with bipolar disorder.
- Patients with bipolar disorder should avoid monotherapy.
- Patients with depressive symptoms should be tested for bipolar disorder.
- FDA approval has been granted for this combination to treat depressive episodes related to bipolar disorder.
Renal impairment
- Use caution in patients suffering from renal disease.
- It may be necessary to reduce the dosage.
Seizure disorder
- Patients at high risk of seizures should be treated with caution, especially those who have had seizures in the past, suffered from brain damage or are receiving concurrent treatment with medications that could lower the seizure threshold.
- Elderly patients could be at greater risk for seizures due to the increased prevalence of predisposing conditions.

Olanzapine and fluoxetine: Drug Interaction

Risk Factor C (Monitor therapy)
Acetylcholinesterase Inhibitors	May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors.
Acetylcholinesterase Inhibitors (Central)	May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients.
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.)	May enhance the antiplatelet effect of other Agents with Antiplatelet Properties.
Alizapride	May enhance the CNS depressant effect of CNS Depressants.
Alpelisib	May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers).
Amifampridine	Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine.
Amphetamines	Antipsychotic Agents may diminish the stimulatory effect of Amphetamines.
Amphetamines	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Amphetamines.
Anticholinergic Agents	May enhance the adverse/toxic effect of other Anticholinergic Agents.
Anticoagulants	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Exceptions: Bemiparin; Enoxaparin; Heparin.
Antidiabetic Agents	Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Antiemetics (5HT3 Antagonists)	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Antihepaciviral Combination Products	May decrease the serum concentration of OLANZapine.
Antipsychotic Agents	Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Apixaban	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely.
Aspirin	Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin.
Beta-Blockers	Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Beta-Blockers. Exceptions: Acebutolol; Atenolol; Betaxolol (Ophthalmic); Betaxolol (Systemic); Bisoprolol; Carteolol (Ophthalmic); Esmolol; Labetalol; Levobunolol; Metipranolol; Nadolol; Sotalol.
Blood Glucose Lowering Agents	Selective Serotonin Reuptake Inhibitors may enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
Blood Pressure Lowering Agents	May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).
Botulinum Toxin-Containing Products	May enhance the anticholinergic effect of Anticholinergic Agents.
Brexanolone	CNS Depressants may enhance the CNS depressant effect of Brexanolone.
Brexanolone	Selective Serotonin Reuptake Inhibitors may enhance the CNS depressant effect of Brexanolone.
Brimonidine (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Broccoli	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
BuPROPion	FLUoxetine may enhance the neuroexcitatory and/or seizure-potentiating effect of BuPROPion. BuPROPion may increase the serum concentration of FLUoxetine.
Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Cannabidiol	CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Cannabidiol.
Cannabis	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
Cannabis	May enhance the CNS depressant effect of CNS Depressants.
CarBAMazepine	FLUoxetine may increase the serum concentration of CarBAMazepine.
CarBAMazepine	May decrease the serum concentration of OLANZapine.
Cephalothin	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased.
Chloral Betaine	May enhance the adverse/toxic effect of Anticholinergic Agents.
Chlorphenesin Carbamate	May enhance the adverse/toxic effect of CNS Depressants.
Cimetidine	May increase the serum concentration of FLUoxetine.
Clarithromycin	FLUoxetine may enhance the QTc-prolonging effect of Clarithromycin. Clarithromycin may increase the serum concentration of FLUoxetine.
CloZAPine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of CloZAPine.
CloZAPine	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
CNS Depressants	May enhance the adverse/toxic effect of other CNS Depressants.
CNS Depressants	May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced.
Cobicistat	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Collagenase (Systemic)	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased.
CYP1A2 Inducers (Moderate)	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
CYP1A2 Inhibitors (Moderate)	May decrease the metabolism of CYP1A2 Substrates (High risk with Inhibitors).
CYP2C19 Substrates (High risk with Inhibitors)	CYP2C19 Inhibitors (Moderate) may decrease the metabolism of CYP2C19 Substrates (High risk with Inhibitors).
CYP2C9 Inhibitors (Moderate)	May decrease the metabolism of CYP2C9 Substrates (High risk with Inhibitors).
CYP2D6 Inhibitors (Moderate)	May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors).
Cyproheptadine	May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors.
Cyproterone	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
Dabigatran Etexilate	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor.
Darunavir	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Dasatinib	May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Deferasirox	May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors).
Deoxycholic Acid	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased.
Desmopressin	Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Desmopressin.
Dimethindene (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Doxylamine	May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended.
Dronabinol	May enhance the CNS depressant effect of CNS Depressants.
Droperidol	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Droperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
DULoxetine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of DULoxetine.
Edoxaban	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased.
Esketamine	May enhance the CNS depressant effect of CNS Depressants.
Fat Emulsion (Fish Oil Based)	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties.
Fesoterodine	CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine.
Flibanserin	CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Flibanserin.
Flupentixol	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Flupentixol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Galantamine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Galantamine.
Gastrointestinal Agents (Prokinetic)	Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).
Glucagon	Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased.
Glucosamine	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Guanethidine	Antipsychotic Agents may diminish the therapeutic effect of Guanethidine.
Haloperidol	FLUoxetine may enhance the QTc-prolonging effect of Haloperidol. FLUoxetine may increase the serum concentration of Haloperidol.
HydrOXYzine	May enhance the CNS depressant effect of CNS Depressants.
Ibritumomab Tiuxetan	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding.
Ibrutinib	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties.
Imatinib	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Indoramin	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Indoramin.
Inotersen	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Ioflupane I 123	Selective Serotonin Reuptake Inhibitors may diminish the diagnostic effect of Ioflupane I 123.
Itopride	Anticholinergic Agents may diminish the therapeutic effect of Itopride.
Kava Kava	May enhance the adverse/toxic effect of CNS Depressants.
LamoTRIgine	May enhance the sedative effect of OLANZapine.
Limaprost	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Lofexidine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Lofexidine.
Lumacaftor	May decrease the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor may increase the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers).
Lumefantrine	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Magnesium Sulfate	May enhance the CNS depressant effect of CNS Depressants.
Metaxalone	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Methylphenidate	Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents.
Methylphenidate	May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased.
Metoprolol	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Metoprolol.
MetyroSINE	CNS Depressants may enhance the sedative effect of MetyroSINE.
MetyroSINE	May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors.
MetyroSINE	May enhance the adverse/toxic effect of Antipsychotic Agents.
Mianserin	May enhance the anticholinergic effect of Anticholinergic Agents.
Minocycline	May enhance the CNS depressant effect of CNS Depressants.
Mirabegron	Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron.
Multivitamins/Fluoride (with ADE)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Multivitamins/Minerals (with ADEK, Folate, Iron)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Multivitamins/Minerals (with AE, No Iron)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Nabilone	May enhance the CNS depressant effect of CNS Depressants.
Nebivolol	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Nebivolol.
Nicergoline	CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MMDL metabolite may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MDL metabolite may be decreased.
NIFEdipine	FLUoxetine may enhance the adverse/toxic effect of NIFEdipine.
NiMODipine	FLUoxetine may increase the serum concentration of NiMODipine.
Nitroglycerin	Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption.
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective)	Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors.
Nonsteroidal Anti-Inflammatory Agents (Topical)	May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors.
Obeticholic Acid	May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors).
Obinutuzumab	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.
Omega-3 Fatty Acids	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Ondansetron	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Panobinostat	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Peginterferon Alfa-2b	May decrease the serum concentration of FLUoxetine.
Pentamidine (Systemic)	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Pentosan Polysulfate Sodium	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents.
Pentoxifylline	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Phenytoin	FLUoxetine may increase the serum concentration of Phenytoin.
Propafenone	May enhance the QTc-prolonging effect of FLUoxetine. FLUoxetine may increase the serum concentration of Propafenone.
Prostacyclin Analogues	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
QT-prolonging Antidepressants (Moderate Risk)	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Antipsychotics (Moderate Risk)	May enhance the QTc-prolonging effect of OLANZapine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Amisulpride; CloZAPine; Droperidol; Flupentixol; OLANZapine; Pimozide.
QT-prolonging Class IC Antiarrhythmics (Moderate Risk)	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Kinase Inhibitors (Moderate Risk)	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Miscellaneous Agents (Moderate Risk)	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Domperidone.
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk)	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Quinolone Antibiotics (Moderate Risk)	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Quinagolide	Antipsychotic Agents may diminish the therapeutic effect of Quinagolide.
Ramosetron	Anticholinergic Agents may enhance the constipating effect of Ramosetron.
RifAMPin	May decrease the serum concentration of OLANZapine.
Rifapentine	May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers).
Ritonavir	May decrease the serum concentration of OLANZapine.
Rivaroxaban	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor.
Rufinamide	May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.
Salicylates	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result.
Saquinavir	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Saquinavir. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Selective Serotonin Reuptake Inhibitors	CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced.
Serotonin Modulators	May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid.
Serotonin Modulators	May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline.
Tamsulosin	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tamsulosin.
Tedizolid	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Teriflunomide	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
Tetrahydrocannabinol	May enhance the CNS depressant effect of CNS Depressants.
Tetrahydrocannabinol and Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Thiazide and Thiazide-Like Diuretics	Selective Serotonin Reuptake Inhibitors may enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics.
Thiazide and Thiazide-Like Diuretics	Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics.
Thrombolytic Agents	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents.
Thyroid Products	Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Thyroid Products. Thyroid product dose requirements may be increased.
Timolol (Ophthalmic)	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Timolol (Ophthalmic).
Tobacco (Smoked)	May diminish the therapeutic effect of OLANZapine. Tobacco (Smoked) may decrease the serum concentration of OLANZapine.
Topiramate	Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate.
Tricyclic Antidepressants	FLUoxetine may enhance the serotonergic effect of Tricyclic Antidepressants. FLUoxetine may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined.
Trimeprazine	May enhance the CNS depressant effect of CNS Depressants.
Tropisetron	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tropisetron.
Valbenazine	CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Valbenazine.
Valproate Products	May decrease the serum concentration of OLANZapine.
Vitamin E (Systemic)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Vitamin K Antagonists (eg, warfarin)	Selective Serotonin Reuptake Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists.
Voriconazole	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Risk Factor D (Consider therapy modification)
Abiraterone Acetate	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity.
Alcohol (Ethyl)	May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Management: Patients receiving selective serotonin reuptake inhibitors should be advised to avoid alcohol. Monitor for increased psychomotor impairment in patients who consume alcohol during treatment with selective serotonin reuptake inhibitors.
Anti-Parkinson Agents (Dopamine Agonist)	Antipsychotic Agents (Second Generation [Atypical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider using an alternative antipsychotic agent when possible in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine or quetiapine, which may convey the lowest interaction risk.
ARIPiprazole	FLUoxetine may enhance the adverse/toxic effect of ARIPiprazole. Specifically, the risk of neuroleptic malignant syndrome may be increased. ARIPiprazole may enhance the serotonergic effect of FLUoxetine. This could result in serotonin syndrome. FLUoxetine may increase the serum concentration of ARIPiprazole. Management: Aripiprazole dose should be reduced by at least half, except when used adjunctively for depression. Consult full interaction monograph or aripiprazole prescribing information for complete details.
ARIPiprazole Lauroxil	CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Please refer to the full interaction monograph for details concerning the recommended dose adjustments.
Asunaprevir	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
AtoMOXetine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of AtoMOXetine. Management: Initiate atomoxetine at a reduced dose (adult doses -- patients up to 70kg: 0.5mg/kg/day; patients 70kg or more: 40mg/day) in patients receiving a strong CYP2D6 inhibitor.
Bemiparin	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding.
Blonanserin	CNS Depressants may enhance the CNS depressant effect of Blonanserin.
Brexpiprazole	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual with a strong CYP2D6 inhibitor, reduce to 25% of usual if used with both a strong CYP2D6 inhibitor and a CYP3A4 inhibitor; these recommendations do not apply if treating major depressive disorder.
Buprenorphine	CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants.
BusPIRone	May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Selective Serotonin Reuptake Inhibitors may decrease the metabolism of BusPIRone. Management: The combination of a selective serotonin reuptake inhibitor and buspirone should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome.
Chlormethiazole	May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.
Cilostazol	CYP2C19 Inhibitors may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in patients who are also receiving inhibitors of CYP2C19.
Citalopram	CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with a moderate CYP2C19 inhibitor. Patients using this combination should be monitored closely for evidence of citalopram toxicity (e.g., serotonin syndrome, QT prolongation, etc.).
Clopidogrel	CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Due to a risk for impaired clopidogrel effectiveness with such a combination, carefully consider the need for a moderate CYP2C19 inhibitor in patients receiving clopidogrel. Monitor patients closely for evidence of a diminished response to clopidogrel.
Codeine	CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine.
CYP2D6 Inhibitors (Strong)	May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors).
CYP2D6 Substrates (High risk with Inhibitors)	CYP2D6 Inhibitors (Strong) may decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Exceptions: Ajmaline; Dapoxetine; Indoramin; Metoprolol; Tamoxifen; Timolol (Ophthalmic); Tropisetron.
Dabrafenib	May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C9 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
Dacomitinib	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index.
Deutetrabenazine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Deutetrabenazine. Management: The total daily dose of deutetrabenazine should not exceed 36 mg, and the maximum single dose of deutetrabenazine should not exceed 18 mg with concurrent use of a strong CYP2D6 inhibitor.
Dextromethorphan	Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Dextromethorphan. Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dextromethorphan. Management: Avoid the concurrent use of dextromethorphan and SSRIs, particularly fluoxetine and paroxetine, when possible. The risk for this interaction may persist for several weeks following discontinuation of fluoxetine or paroxetine.
Domperidone	QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
DOXOrubicin (Conventional)	CYP2D6 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP2D6 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided.
Eliglustat	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Management: Reduce the eliglustat dose to 84 mg daily. Avoid use of eliglustat in combination with a strong CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor.
Enoxaparin	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding.
Enzalutamide	May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP2C9 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C9 substrate should be performed with caution and close monitoring.
Fosphenytoin	May enhance the QTc-prolonging effect of FLUoxetine. FLUoxetine may increase the serum concentration of Fosphenytoin.
Gilteritinib	May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Avoid use of this combination if possible. If the combination cannot be avoided, monitor closely for evidence of reduced response to the selective serotonin reuptake inhibitor.
Heparin	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required.
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry)	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Management: Avoid combination when possible. If used, monitor more closely for evidence of bleeding. Discontinue herbal products with anticoagulant or antiplatelet actions 2 weeks prior to surgical, dental, or invasive procedures.
HYDROcodone	CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Iloperidone	CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP2D6 inhibitor.
Iohexol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.
Iomeprol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.
Iopamidol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.
Linezolid	May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Consider alternatives to this combination whenever possible. If clinically acceptable, wait at least 2 weeks (5 weeks for fluoxetine) after SSRI discontinuation to initiate linezolid.
Linezolid	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Due to a risk of serotonin syndrome/serotonin toxicity, discontinue serotonin modulators 2 weeks prior to the administration of linezolid. If urgent initiation of linezolid is needed, discontinue serotonin modulators immediately and monitor closely.
Lithium	May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could increase the risk of serotonin toxicity/serotonin syndrome. Management: This combination should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome.
Methotrimeprazine	CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established.
MiFEPRIStone	May increase the serum concentration of CYP2C9 Substrates (High risk with Inhibitors). Management: Use CYP2C9 substrates at the lowest recommended dose, and monitor closely for adverse effects, during and in the 2 weeks following mifepristone treatment.
Nonsteroidal Anti-Inflammatory Agents (Nonselective)	Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2selective NSAIDs reduce risk. Exceptions: Diclofenac (Topical); Ibuprofen (Topical); Piroxicam (Topical).
Opioid Agonists	CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
OxyCODONE	CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Perampanel	May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination.
Perhexiline	CYP2D6 Inhibitors may increase the serum concentration of Perhexiline. Management: Consider alternatives to this combination if possible. If combined, monitor for increased perhexiline serum concentrations and toxicities (eg, hypoglycemia, neuropathy, liver dysfunction). Perhexiline dose reductions will likely be required.
Pitolisant	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pitolisant. Management: Reduce the pitolisant dose by 50% if a strong CYP2D6 inhibitor is initiated. For patients receiving strong CYP2D6 inhibitors, initiate pitolisant at 8.9 mg once daily and increase after 7 days to a maximum of 17.8 mg once daily.
Pramlintide	May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract.
Primaquine	CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Primaquine. Management: Monitor for signs and symptoms of possible treatment failure with primaquine in patients who are taking strong CYP2D6 inhibitors. If efficacy of primaquine is compromised, may consider adjusting therapies.
QT-prolonging Agents (Highest Risk)	May enhance the QTc-prolonging effect of OLANZapine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Secretin	Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin.
Serotonin Reuptake Inhibitor/Antagonists	Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonin Reuptake Inhibitor/Antagonists. This may cause serotonin syndrome. Management: Consider alternatives, and use conservative initial dosing. Monitor patients receiving these combinations for signs/symptoms of serotonin toxicity.
Sodium Oxybate	May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated.
Suvorexant	CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended.
Tapentadol	May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Tetrabenazine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Tetrabenazine adult dose should be reduced by 50% when starting a strong CYP2D6 inhibitor. Maximum tetrabenazine adult dose is 50 mg/day when used with a strong CYP2D6 inhibitor.
Vortioxetine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Vortioxetine. Management: The vortioxetine dose should be reduced by 50% when used together with a strong CYP2D6 inhibitor. Following cessation of the strong CYP2D6 inhibitor, the vortioxetine dose should be returned to the normal level.
Zolpidem	CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol.
Risk Factor X (Avoid combination)
Aclidinium	May enhance the anticholinergic effect of Anticholinergic Agents.
Amisulpride	Antipsychotic Agents may enhance the adverse/toxic effect of Amisulpride. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Amisulpride	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk).
Azelastine (Nasal)	CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).
Benzodiazepines	OLANZapine may enhance the adverse/toxic effect of Benzodiazepines. Management: Avoid concomitant use of parenteral benzodiazepines and IM olanzapine due to risks of additive adverse events (e.g., cardiorespiratory depression). Olanzapine prescribing information provides no specific recommendations regarding oral administration.
Bromopride	May enhance the adverse/toxic effect of Antipsychotic Agents.
Bromopride	May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors.
Bromperidol	May enhance the CNS depressant effect of CNS Depressants.
Cimetropium	Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium.
Dapoxetine	May enhance the adverse/toxic effect of Serotonin Modulators.
Dothiepin	Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dothiepin.
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.)	May enhance the antiplatelet effect of other Agents with Antiplatelet Properties.
Alizapride	May enhance the CNS depressant effect of CNS Depressants.
Alpelisib	May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers).
Amifampridine	Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine.
Amphetamines	Antipsychotic Agents may diminish the stimulatory effect of Amphetamines.
Amphetamines	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Amphetamines.
Anticholinergic Agents	May enhance the adverse/toxic effect of other Anticholinergic Agents.
Anticoagulants	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Exceptions: Bemiparin; Enoxaparin; Heparin.
Antidiabetic Agents	Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Antiemetics (5HT3 Antagonists)	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Antihepaciviral Combination Products	May decrease the serum concentration of OLANZapine.
Antipsychotic Agents	Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Apixaban	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely.
Aspirin	Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin.
Beta-Blockers	Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Beta-Blockers. Exceptions: Acebutolol; Atenolol; Betaxolol (Ophthalmic); Betaxolol (Systemic); Bisoprolol; Carteolol (Ophthalmic); Esmolol; Labetalol; Levobunolol; Metipranolol; Nadolol; Sotalol.
Blood Glucose Lowering Agents	Selective Serotonin Reuptake Inhibitors may enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
Blood Pressure Lowering Agents	May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).
Botulinum Toxin-Containing Products	May enhance the anticholinergic effect of Anticholinergic Agents.
Brexanolone	CNS Depressants may enhance the CNS depressant effect of Brexanolone.
Brexanolone	Selective Serotonin Reuptake Inhibitors may enhance the CNS depressant effect of Brexanolone.
Brimonidine (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Broccoli	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
BuPROPion	FLUoxetine may enhance the neuroexcitatory and/or seizure-potentiating effect of BuPROPion. BuPROPion may increase the serum concentration of FLUoxetine.
Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Cannabidiol	CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Cannabidiol.
Cannabis	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
Cannabis	May enhance the CNS depressant effect of CNS Depressants.
CarBAMazepine	FLUoxetine may increase the serum concentration of CarBAMazepine.
CarBAMazepine	May decrease the serum concentration of OLANZapine.
Cephalothin	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased.
Chloral Betaine	May enhance the adverse/toxic effect of Anticholinergic Agents.
Chlorphenesin Carbamate	May enhance the adverse/toxic effect of CNS Depressants.
Cimetidine	May increase the serum concentration of FLUoxetine.
Clarithromycin	FLUoxetine may enhance the QTc-prolonging effect of Clarithromycin. Clarithromycin may increase the serum concentration of FLUoxetine.
CloZAPine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of CloZAPine.
CloZAPine	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
CNS Depressants	May enhance the adverse/toxic effect of other CNS Depressants.
CNS Depressants	May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced.
Cobicistat	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Collagenase (Systemic)	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased.
CYP1A2 Inducers (Moderate)	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
CYP1A2 Inhibitors (Moderate)	May decrease the metabolism of CYP1A2 Substrates (High risk with Inhibitors).
CYP2C19 Substrates (High risk with Inhibitors)	CYP2C19 Inhibitors (Moderate) may decrease the metabolism of CYP2C19 Substrates (High risk with Inhibitors).
CYP2C9 Inhibitors (Moderate)	May decrease the metabolism of CYP2C9 Substrates (High risk with Inhibitors).
CYP2D6 Inhibitors (Moderate)	May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors).
Cyproheptadine	May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors.
Cyproterone	May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers).
Dabigatran Etexilate	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor.
Darunavir	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Dasatinib	May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Deferasirox	May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors).
Deoxycholic Acid	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased.
Desmopressin	Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Desmopressin.
Dimethindene (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Doxylamine	May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended.
Dronabinol	May enhance the CNS depressant effect of CNS Depressants.
Droperidol	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Droperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
DULoxetine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of DULoxetine.
Edoxaban	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased.
Eluxadoline	Anticholinergic Agents may enhance the constipating effect of Eluxadoline.
Glycopyrrolate (Oral Inhalation)	Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation).
Glycopyrronium (Topical)	May enhance the anticholinergic effect of Anticholinergic Agents.
Ipratropium (Oral Inhalation)	May enhance the anticholinergic effect of Anticholinergic Agents.
Levosulpiride	Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride.
Mequitazine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Mequitazine.
Methylene Blue	Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome.
Methylene Blue	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Metoclopramide	May enhance the adverse/toxic effect of Antipsychotic Agents.
Monoamine Oxidase Inhibitors	May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Methylene Blue; Tedizolid.
Orphenadrine	CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
Oxatomide	May enhance the anticholinergic effect of Anticholinergic Agents.
Oxomemazine	May enhance the CNS depressant effect of CNS Depressants.
Paraldehyde	CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
Pimozide	FLUoxetine may enhance the QTc-prolonging effect of Pimozide. FLUoxetine may increase the serum concentration of Pimozide.
Piribedil	Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Piribedil may diminish the therapeutic effect of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended.
Potassium Chloride	Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride.
Potassium Citrate	Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate.
Revefenacin	Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin.
Sulpiride	Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride.
Tamoxifen	CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites.
Thalidomide	CNS Depressants may enhance the CNS depressant effect of Thalidomide.
Thioridazine	FLUoxetine may enhance the QTc-prolonging effect of Thioridazine. FLUoxetine may increase the serum concentration of Thioridazine.
Tiotropium	Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium.
Tryptophan	May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome.
Umeclidinium	May enhance the anticholinergic effect of Anticholinergic Agents.
Urokinase	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase.

Monitoring Parameters:

Vital signs (as indicated by a doctor).
Blood pressure (at baseline, repeat 3 months after antipsychotic initiation and then annually).
Fasting lipid panel (baseline); repeat 3 months after antipsychotics are started; if LDL levels are normal, repeat every 2-5 years or more if clinically necessary.
Fasting blood glucose/HbA
Weight
Height
BMI.
Waist circumference (baseline); repeat at 4, 8, and 12 weeks after initiating, changing or switching therapy, then quarterly. Switch to another antipsychotic if you experience a weight gain greater than 5 percent from your initial weight.
Obesity, diabetes, dyslipidemia and hypertension (baseline; repeated annually).
Mental state
CBC (as indicated by the doctor; patients who have a history of drug-induced leukopenia/neutropenia or low WBC will need to be monitored frequently in the first few months.
Changes in menstruation, fertility, and development of galactorrhea (at each visit for 12 weeks after antipsychotics are initiated, or until the dose becomes stable, then annually).
Abnormal involuntary movement or parkinsonian signs (baseline); repeat weekly until dose stabilization is achieved for at least 2 weeks after introduction, and for at most 2 weeks following any significant dose increases.
Tardive dyskinesia (every 12 Months; high-risk patients, every 6 Months).
Ocular examination: Annually for patients over 40 years old; once every two years for younger patients
Signs and symptoms of depression, anxiety or suicidal thoughts (especially when therapy is just beginning or when the doses are changed or increased), as well as sleep.
Serotonin syndrome symptoms and signs
Annually, and as indicated by a physician, electrolytes and liver function.
Clinically indicated serum sodium for at-risk populations (ADA 2004; Lehman 2004,; Marder 2004).

How to administer Symbyax (Olanzapine and Fluoxetine)?

In the evening, administer capsules once daily.
May be taken without regard to meals.

Mechanism of action of Olanzapine and fluoxetine:

Olanzapine, a 2nd-generation antipsychotic, is a powerful antagonist of serotonin 5HT-2A and 5HT-2C, dopamine 1-4, histamine h-1, alpha - 1, adrenergic receptor.
It exhibits moderate antagonism to 5-HT-3 and muscarinic m 1-5 receptors and weak binding of GABA-A, benzodiazepines, and beta-adrenergic receivers.
Fluoxetine blocks the neuronal reuptakes of serotonin.
It has minimal to no effect on the absorption of norepinephrine or dopamine.
It doesn't significantly bind to alpha-adrenergic or histamine receptors.
Combination pills of fluoxetine and olanzapine have an enhanced antidepressant effect. This could be due to synergistic increases on serotonin, norepinephrine and dopamine.

See individual agents.

International Brands of Olanzapine and fluoxetine:

Symbyax
Flunzapine
Fluzapine
Olanaprine

Olanzapine and fluoxetine Brand Names in Pakistan:

Olanzapine and fluoxetine Capsules 6 mg
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Symbyax (Olanzapine and Fluoxetine) - Uses, Dose, Side effects

Symbyax (Olanzapine and fluoxetine) Uses:

Acute Depression, (associated with bipolar I disorder):

Symbyax for treatment resistant Depression:

Symbyax (Olanzapine and Fluoxetine) Dose in Adults

Symbyax (Olanzapine and Fluoxetine) Dose in the treatment of depression associated with bipolar I disorder:

Initial:

Usual dose:

Symbyax (Olanzapine and Fluoxetine) Dose in treatment-resistant depression:

Initial:

Usual dose:

Note:

Discontinuation of therapy:

MAO inhibitor recommendations:

Symbyax (Olanzapine and Fluoxetine) Dose in Children

Symbyax (Olanzapine and Fluoxetine) Dose in Children:

Symbyax (Olanzapine and Fluoxetine) Dose in the treatment of depression associated with bipolar I disorder:

Children and Adolescents 10 to 17 years:

Note:

Pregnancy Risk Factor C

Use of fluoxetine and Olanzapine during breastfeeding

Symbyax (Olanzapine and Fluoxetine) Dose in Kidney Disease:

Symbyax (Olanzapine and Fluoxetine) Dose in Liver Disease:

Common Side Effects of Symbyax (Olanzapine and fluoxetine):

Cardiovascular:

Central Nervous System:

Endocrine & Metabolic:

Gastrointestinal:

Hepatic:

Less Common Side Effects Of Symbyax (Olanzapine and fluoxetine):

Cardiovascular:

Central Nervous System:

Dermatologic:

Endocrine & Metabolic:

Gastrointestinal:

Genitourinary:

Hematologic & Oncologic:

Hepatic:

Neuromuscular & Skeletal:

Ophthalmic:

Renal:

Respiratory:

Miscellaneous:

Rare side effects of Symbyax (Olanzapine and Fluoxetine):

Cardiovascular:

Central Nervous System:

Endocrine & Metabolic:

Genitourinary:

Hepatic:

Contraindications to Symbyax (Olanzapine and Fluoxetine):

Warnings and precautions

Allergies and rash

Modified cardiac conduction

Anticholinergic effects

Bleeding Risk:

Blood dyscrasias

Effects on the cerebrovascular system:

Depression in the CNS:

Dyslipidemia

Aspiration and Esophageal Dysmotility:

Extrapyramidal symptoms

Falls

Fractures

Hyperglycemia

Hyperprolactinemia

Multiorgan hypersensitivity reactions (drug response with eosinophilia or systemic symptoms [DRESS]).

Neuroleptic malignant Syndrome (NMS).

Ocular effects

Orthostatic hypotension

Extension of QT

Serotonin syndrome

Sexual dysfunction

SIADH and Hyponatremia

Temperature regulation

Weight loss

Cardiovascular disease

Dementia[US Boxed Warning]