Olanzapine and fluoxetine

The following adverse reactions are discussed in more detail in other sections of the labeling:

• Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
• Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see WARNINGS AND PRECAUTIONS]
• Neuroleptic Malignant syndrome (NMS) [see WARNINGS AND PRECAUTIONS]
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) [see WARNINGS AND PRECAUTIONS]
• Hyperglycemia [see WARNINGS AND PRECAUTIONS]
• Dyslipidemia [see WARNINGS AND PRECAUTIONS]
• Weight Gain [see WARNINGS AND PRECAUTIONS]
• Serotonin Syndrome [see WARNINGS AND PRECAUTIONS]
• Angle-Closure Glaucoma [see WARNINGS AND PRECAUTIONS]
• Allergic Reactions and Rash [see WARNINGS AND PRECAUTIONS]
• Activation of Mania/Hypomania [see WARNINGS AND PRECAUTIONS]
• Tardive Dyskinesia [see WARNINGS AND PRECAUTIONS]
• Orthostatic Hypotension [see WARNINGS AND PRECAUTIONS]
• Leukopenia, Neutropenia, and Agranulocytosis [see WARNINGS AND PRECAUTIONS]
• Dysphagia [see WARNINGS AND PRECAUTIONS]
• Seizures [see WARNINGS AND PRECAUTIONS]
• Abnormal Bleeding [see WARNINGS AND PRECAUTIONS]
• Hyponatremia [see WARNINGS AND PRECAUTIONS]
• Potential for Cognitive and Motor Impairment [see WARNINGS AND PRECAUTIONS]
• Body Temperature Dysregulation [see WARNINGS AND PRECAUTIONS]
• QT Prolongation [see WARNINGS AND PRECAUTIONS]
• Hyperprolactinemia [see WARNINGS AND PRECAUTIONS]
• Discontinuation Adverse Reactions [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect or predict the rates observed in practice.

The data in the tables represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse reaction of the type listed. A reaction was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.

Adults - The information below is derived from a clinical study database for SYMBYAX consisting of 2547 patients with treatment resistant depression, depressive episodes associated with Bipolar I Disorder, Major Depressive Disorder with psychosis, or sexual dysfunction with approximately 1085 patient-years of exposure. The conditions and duration of treatment with SYMBYAX varied greatly and included (in overlapping categories) open-label and double-blind phases of studies, inpatients and outpatients, fixed-dose and dose-titration studies, and short-term or long-term exposure.

Adverse Reactions Associated with Discontinuation of Treatment in Short-Term, Controlled Studies Including Depressive Episodes Associated with Bipolar I Disorder and Treatment Resistant Depression - Overall, 11.3% of the 771 patients in the SYMBYAX group discontinued due to adverse reactions compared with 4.4% of the 477 patients for placebo. Adverse reactions leading to discontinuation associated with the use of SYMBYAX (incidence of at least 1% for SYMBYAX and greater than that for placebo) using MedDRA Dictionary coding were weight increased (2%) and sedation (1%) versus placebo patients which had 0% incidence of weight increased and sedation.

Commonly Observed Adverse Reactions in Controlled Studies Including Depressive Episodes Associated with Bipolar I Disorder and Treatment Resistant Depression - In short-term studies, the most commonly observed adverse reactions associated with the use of SYMBYAX (incidence ≥ 5% and at least twice that for placebo in the SYMBYAX-controlled database) using MedDRA Dictionary coding were: disturbance in attention, dry mouth, fatigue, hypersomnia, increased appetite, peripheral edema, sedation, somnolence, tremor, vision blurred, and weight increased. Adverse reactions reported in clinical trials of olanzapine and fluoxetine in combination are generally consistent with treatment-emergent adverse reactions during olanzapine or fluoxetine monotherapy.

In a 47-week maintenance study in adults with treatment resistant depression, adverse reactions associated with SYMBYAX use were generally similar to those seen in short-term studies. Weight gain, hyperlipidemia, and hyperglycemia were observed in SYMBYAX-treated patients throughout the study.

Adverse Reactions Occurring at an Incidence of 2% or More in Short-Term Controlled Studies Including Depressive Episodes Associated with Bipolar I Disorder and Treatment Resistant Depression - Table 16 enumerates the treatment-emergent adverse reactions associated with the use of SYMBYAX (incidence of at least 2% for SYMBYAX and twice or more than for placebo). The SYMBYAX-controlled column includes patients with various diagnoses while the placebo column includes only patients with bipolar depression and major depression with psychotic features.

Table 16: Adverse Reactions: Incidence in the Short-Term Controlled Clinical Studies in Adults

Dystonia, Class Effect for Antipsychotics - Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, the frequency and severity are greater with high potency and at higher doses of first generation antipsychotic drugs. In general, an elevated risk of acute dystonia may be observed in males and younger age groups receiving antipsychotics; however, events of dystonia have been reported infrequently ( < 1%) with the olanzapine and fluoxetine combination.

Sexual Dysfunction - In the pool of controlled SYMBYAX studies in patients with bipolar depression, there were higher rates of the treatment-emergent adverse reactions decreased libido, anorgasmia, erectile dysfunction and abnormal ejaculation in the SYMBYAX group than in the placebo group. One case of decreased libido led to discontinuation in the SYMBYAX group. In the controlled studies that contained a fluoxetine arm, the rates of decreased libido and abnormal ejaculation in the SYMBYAX group were less than the rates in the fluoxetine group. None of the differences were statistically significant.

Sexual dysfunction, including priapism, has been reported with all SSRIs. While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects.

There are no adequate and well-controlled studies examining sexual dysfunction with SYMBYAX or fluoxetine treatment. Symptoms of sexual dysfunction occasionally persist after discontinuation of fluoxetine treatment.

In a single 8-week randomized, double-blind, fixed-dose study comparing 10 (N=199), 20 (N=200), and 40 (N=200) mg/day of olanzapine in patients with Schizophrenia or Schizoaffective Disorder, statistically significant differences among 3 dose groups were observed for the following safety outcomes: weight gain, prolactin elevation, fatigue, and dizziness. Mean baseline to endpoint increase in weight (10 mg/day: 1.9 kg; 20 mg/day: 2.3 kg; 40 mg/day: 3 kg) was observed with significant differences between 10 vs 40 mg/day. Incidence of treatment-emergent prolactin elevation > 24.2 ng/mL (female) or > 18.77 ng/mL (male) at any time during the trial (10 mg/day: 31.2%; 20 mg/day: 42.7%; 40 mg/day: 61.1%) with significant differences between 10 vs 40 mg/day and 20 vs 40 mg/day; fatigue (10 mg/day: 1.5%; 20 mg/day: 2.1%; 40 mg/day: 6.6%) with significant differences between 10 vs 40 and 20 vs 40 mg/day; and dizziness (10 mg/day: 2.6%; 20 mg/day: 1.6%; 40 mg/day: 6.6%) with significant differences between 20 vs 40 mg, was observed.

Following is a list of treatment-emergent adverse reactions reported by patients treated with SYMBYAX in clinical trials. This listing is not intended to include reactions (1) already listed in previous tables or elsewhere in labeling, (2) for which a drug cause was remote, (3) which were so general as to be uninformative, (4) which were not considered to have significant clinical implications, or (5) which occurred at a rate equal to or less than placebo.

Reactions are classified by body system using the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; and rare reactions are those occurring in fewer than 1/1000 patients.

Body as a Whole - Frequent: chills, neck rigidity, photosensitivity reaction; Rare: death1.

Cardiovascular System - Frequent: vasodilatation; Infrequent: QT-interval prolonged.

Digestive System - Frequent: diarrhea; Infrequent: gastritis, gastroenteritis, nausea and vomiting, peptic ulcer; Rare: gastrointestinal hemorrhage, intestinal obstruction, liver fatty deposit, pancreatitis.

Hemic and Lymphatic System - Frequent: ecchymosis; Infrequent: anemia, thrombocytopenia; Rare: leukopenia, purpura.

Metabolic and Nutritional - Frequent: generalized edema, weight loss; Rare: bilirubinemia, creatinine increased, gout.

Musculoskeletal System - Rare: osteoporosis.

Nervous System - Frequent: amnesia; Infrequent: ataxia, buccoglossal syndrome, coma, depersonalization, dysarthria, emotional lability, euphoria, hypokinesia, movement disorder, myoclonus; Rare: hyperkinesia, libido increased, withdrawal syndrome.

Respiratory System - Infrequent: epistaxis, yawn; Rare: laryngismus.

Skin and Appendages - Infrequent: alopecia, dry skin, pruritus; Rare: exfoliative dermatitis.

Special Senses - Frequent: taste perversion; Infrequent: abnormality of accommodation, dry eyes.

Urogenital System - Frequent: breast pain, menorrhagia2, urinary frequency, urinary incontinence; Infrequent: amenorrhea2, female lactation2, hypomenorrhea2, metrorrhagia2, urinary retention, urinary urgency, urination impaired; Rare: breast engorgement2.

The following adverse reactions were not observed in SYMBYAX-treated patients during premarketing clinical studies but have been reported with olanzapine or fluoxetine monotherapy: aplastic anemia, bruxism, cholestatic jaundice, diabetic coma, dysuria, eosinophilic pneumonia3, erythema multiforme, esophageal ulcer, gynecological bleeding, headache, hypotension, jaundice, neutropenia, sudden unexpected death3, sweating, and violent behaviors3. Random triglyceride levels of ≥ 1000 mg/dL have been reported.

The information below is derived from a single, 8-week, randomized, placebo-controlled clinical trial investigating SYMBYAX for the treatment of bipolar I depression in patients 10 to 17 years of age.

Adverse Reactions Associated with Discontinuation of Treatment in the single pediatric study - Overall, 14.1% of the 170 patients in the SYMBYAX group discontinued due to adverse reactions compared with 5.9% of the 85 patients for placebo. Adverse reactions leading to discontinuation associated with the use of SYMBYAX (incidence of at least 1% for SYMBYAX and greater than that for placebo) using MedDRA Dictionary coding were weight increased (2.9%), suicidal ideation (1.8%), bipolar disorder (1.2%), and somnolence (1.2%) versus placebo patients which had 0% incidence of weight increased, bipolar disorder, and somnolence, and a 1.2% incidence of suicidal ideation.

Adverse Reactions Occurring at an Incidence of 2% or more and greater than placebo - Table 17 enumerates the treatment-emergent adverse reactions associated with the use of SYMBYAX (incidence of at least 2% for SYMBYAX and twice or more than for placebo).

Table 17: Treatment-Emergent Adverse Reactions: Incidence in a 8-week randomized, double-blind, placebo-controlled clinical trial in pediatric bipolar I depression.

Vital Signs And Laboratory Studies

Vital Signs - Tachycardia, bradycardia, and orthostatic hypotension have occurred in SYMBYAX-treated patients [see WARNINGS AND PRECAUTIONS]. The mean standing pulse rate of SYMBYAX-treated patients was reduced by 0.7 beats/min.

Laboratory Changes - In SYMBYAX clinical studies (including treatment resistant depression, depressive episodes associated with Bipolar I Disorder, Major Depressive Disorder with psychosis, or sexual dysfunction), SYMBYAX was associated with statistically significantly greater frequencies for the following treatment-emergent findings in laboratory analytes (normal at baseline to abnormal at any time during the trial) compared to placebo: elevated prolactin (28% vs 5%); elevated urea nitrogen (3% vs 0.8%); elevated uric acid (3% vs 0.5%); low albumin (3% vs 0.3%); low bicarbonate (14% vs 9%); low hemoglobin (3% vs 0%); low inorganic phosphorus (2% vs 0.3%); low lymphocytes (2% vs 0%); and low total bilirubin (15% vs 4%).

As with olanzapine, asymptomatic elevations of hepatic aminotransferases [ALT, AST, and GGT] and alkaline phosphatase have been observed with SYMBYAX. In the SYMBYAX-controlled database, clinically significant ALT elevations (change from < 3 times the upper limit of normal [ULN] at baseline to ≥ 3 times ULN) were observed in 5% (38/698) of patients exposed to SYMBYAX compared with 0.5% (2/378) of placebo-treated patients and 4% (33/751) of olanzapine-treated patients. ALT elevations ≥ 5 times ULN were observed in 2% (11/701) of SYMBYAX-treated patients, compared to 0.3% (1/379) of placebo-treated patients and 1% (11/760) of olanzapine-treated patients. No patient with elevated ALT values experienced jaundice or liver failure, or met the criteria for Hy's Rule. ALT values returned to normal, or were decreasing, at last follow-up in the majority of patients who either continued treatment with SYMBYAX or discontinued SYMBYAX.

Rare postmarketing reports of hepatitis have been received in patients treated with olanzapine. Very rare cases of cholestatic or mixed liver injury have also been reported in the postmarketing period in patients treated with olanzapine.

Caution should be exercised in patients with signs and symptoms of hepatic impairment, in patients with preexisting conditions associated with limited hepatic functional reserve, and in patients who are being treated with potentially hepatotoxic drugs.

An increase in creatine phosphokinase has been reported very rarely in SYMBYAX-treated patients and infrequently in clinical trials of olanzapine-treated patients.

QT Interval Prolongation - The mean increase in QTc interval for SYMBYAX-treated patients (4.4 msec) in clinical studies was significantly greater than that for placebo-treated (-0.8 msec), olanzapine-treated (-0.3 msec) patients, and fluoxetine-treated (1.7 msec) patients. There were no significant differences between patients treated with SYMBYAX, placebo, olanzapine, or fluoxetine in the incidence of QTc outliers ( > 500 msec).

In a single 8-week randomized, placebo-controlled clinical trial investigating SYMBYAX for treatment of bipolar I depression in patients 10 to 17 years of age, the following was observed:

Vital Signs - In the SYMBYAX-treated patients compared with placebo-treated patients, the mean orthostatic blood pressure and standing pulse rate were not significantly different between treatment groups.

Body Weight: An increase in weight greater than or equal to 7% occurred in 52.4% of the SYMBYAX group and 3.6% of the placebo group. Weight gain greater than or equal to 15% occurred in 14.1% of the SYMBYAX group and none of the placebo group.

Laboratory Changes - SYMBYAX was associated with statistically significantly greater frequencies for the following treatment-emergent findings in laboratory analytes (normal or low at baseline to abnormal at any time during the trial) compared to placebo: elevated ALT (45.9% vs 2.5%); elevated AST (33.7% vs 7.6%); high fasting total cholesterol (28.9% vs 8.2%); high fasting LDL cholesterol (19.7% vs 6.5%); high fasting triglycerides (52.3% vs 27.3%), and elevated prolactin (85% vs 36%). No patient with elevated hepatic enzyme values experienced jaundice or liver failure, or met the criteria for Hy's Rule. Five patients experienced an adverse event potentially associated with elevated prolactin; these events included dysmenorrhoea, galactorrhoea, and ovulation disorder.

QT Interval Prolongation - SYMBYAX was associated with a statistically significantly greater mean increase in QTcF interval (8.2 msec [95% CI 6.2, 10.2]) compared with placebo. No patients developed QTc increases ≥ 60 msec or QTc ≥ 480 msec [see WARNINGS AND PRECAUTIONS].

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of SYMBYAX. Because these reactions are reported voluntarily from a population of uncertain size, it is difficult to reliably estimate their frequency or evaluate a causal relationship to drug exposure.

Adverse reactions reported since market introduction that were temporally (but not necessarily causally) related to SYMBYAX therapy include the following: rhabdomyolysis and venous thromboembolic events (including pulmonary embolism and deep venous thrombosis).

REFERENCES

1 This term represents a serious adverse event but does not meet the definition for adverse drug reactions. It is included here because of its seriousness.

2 Adjusted for gender.

3 These terms represent serious adverse events but do not meet the definition for adverse drug reactions. They are included here because of their seriousness

Fluoxetine is an antidepressant in a group of drugs called selective serotonin reuptake inhibitors (SSRIs).

Olanzapine is an antipsychotic medication. These drugs affect chemicals in the brain.

The combination of fluoxetine and olanzapine is used to treat depression caused by bipolar disorder (manic depression). Fluoxetine and olanzapine is also used to treat depression after at least 2 other medications have been tried without successful treatment of symptoms.

Fluoxetine and olanzapine may also be used for other purposes not listed in this medication guide.

Drinking alcohol can increase certain side effects of fluoxetine and olanzapine.

Fluoxetine and olanzapine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

• Store olanzapine/fluoxetine at room temperature.
• Keep this and all medicine out of the reach of children.
• Keep away from moisture. Do not store in the bathroom or other areas where the medication may be exposed to moisture.
• Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your body's response to olanzapine/fluoxetine.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For olanzapine and fluoxetine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to olanzapine and fluoxetine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of olanzapine and fluoxetine combination to treat bipolar I depression in children younger than 10 years of age, and in children with treatment resistant depression. Safety and efficacy have not been established in these groups.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of olanzapine and fluoxetine combination in the elderly. However, elderly patients are more likely to have dementia or age-related liver, kidney, or heart problems, which may require caution or an adjustment in the dose for patients receiving olanzapine and fluoxetine combination.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking olanzapine and fluoxetine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using olanzapine and fluoxetine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Amisulpride
• Bepridil
• Bromopride
• Cisapride
• Clorgyline
• Dronedarone
• Furazolidone
• Iproniazid
• Isocarboxazid
• Levomethadyl
• Linezolid
• Mesoridazine
• Methylene Blue
• Metoclopramide
• Moclobemide
• Nialamide
• Pargyline
• Phenelzine
• Pimozide
• Piperaquine
• Procarbazine
• Rasagiline
• Saquinavir
• Selegiline
• Sparfloxacin
• Terfenadine
• Thioridazine
• Toloxatone
• Tranylcypromine
• Ziprasidone

Using olanzapine and fluoxetine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abciximab
• Abiraterone
• Acecainide
• Aceclofenac
• Acemetacin
• Acenocoumarol
• Ajmaline
• Alfentanil
• Alfuzosin
• Almotriptan
• Amineptine
• Amiodarone
• Amisulpride
• Amitriptyline
• Amitriptylinoxide
• Amoxapine
• Amphetamine
• Amtolmetin Guacil
• Anagrelide
• Ancrod
• Anisindione
• Antithrombin III Human
• Apixaban
• Apomorphine
• Aprindine
• Ardeparin
• Argatroban
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Asenapine
• Aspirin
• Astemizole
• Atazanavir
• Azimilide
• Azithromycin
• Bedaquiline
• Bemiparin
• Benzphetamine
• Bivalirudin
• Bretylium
• Brexpiprazole
• Bromazepam
• Bromfenac
• Brompheniramine
• Bufexamac
• Buprenorphine
• Bupropion
• Buserelin
• Butorphanol
• Cangrelor
• Carbamazepine
• Celecoxib
• Certoparin
• Chloral Hydrate
• Chloroquine
• Chlorpheniramine
• Chlorpromazine
• Choline Salicylate
• Cilostazol
• Cinacalcet
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clomipramine
• Clonixin
• Clopidogrel
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Crizotinib
• Cyclobenzaprine
• Dabigatran Etexilate
• Dabrafenib
• Dalteparin
• Danaparoid
• Dasatinib
• Defibrotide
• Degarelix
• Delamanid
• Dermatan Sulfate
• Desipramine
• Desirudin
• Deslorelin
• Desmopressin
• Desvenlafaxine
• Deutetrabenazine
• Dexfenfluramine
• Dexibuprofen
• Dexketoprofen
• Dextroamphetamine
• Dextromethorphan
• Dibenzepin
• Diclofenac
• Dicumarol
• Diflunisal
• Dihydrocodeine
• Dipyridamole
• Dipyrone
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxepin
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Doxylamine
• Droperidol
• Drotrecogin Alfa
• Droxicam
• Duloxetine
• Ebastine
• Edoxaban
• Efavirenz
• Eletriptan
• Eliglustat
• Enflurane
• Enoxaparin
• Epoprostenol
• Eptifibatide
• Eribulin
• Erythromycin
• Escitalopram
• Etodolac
• Etofenamate
• Etoricoxib
• Famotidine
• Felbamate
• Felbinac
• Fenfluramine
• Fenoprofen
• Fentanyl
• Fepradinol
• Feprazone
• Fingolimod
• Flecainide
• Flibanserin
• Floctafenine
• Fluconazole
• Flufenamic Acid
• Fluoxetine
• Fluphenazine
• Flurbiprofen
• Fluvoxamine
• Fondaparinux
• Formoterol
• Foscarnet
• Fosphenytoin
• Frovatriptan
• Galantamine
• Gatifloxacin
• Gemifloxacin
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Halothane
• Heparin
• Histrelin
• Hydrocodone
• Hydromorphone
• Hydroquinidine
• Hydroxychloroquine
• Hydroxytryptophan
• Hydroxyzine
• Ibuprofen
• Ibutilide
• Iloperidone
• Iloprost
• Imipramine
• Indomethacin
• Iobenguane I 123
• Isoflurane
• Isradipine
• Itraconazole
• Ivabradine
• Ketoconazole
• Ketoprofen
• Ketorolac
• Lapatinib
• Lepirudin
• Leuprolide
• Levofloxacin
• Levomilnacipran
• Levorphanol
• Lidoflazine
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lorcaserin
• Lornoxicam
• Loxoprofen
• Lumefantrine
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Mefloquine
• Melitracen
• Meloxicam
• Meperidine
• Methadone
• Methamphetamine
• Metronidazole
• Mifepristone
• Milnacipran
• Mirtazapine
• Mizolastine
• Morniflumate
• Morphine
• Morphine Sulfate Liposome
• Moxifloxacin
• Nabumetone
• Nadroparin
• Nafarelin
• Nalbuphine
• Naproxen
• Naratriptan
• Nebivolol
• Nefazodone
• Nepafenac
• Niflumic Acid
• Nilotinib
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Norfloxacin
• Nortriptyline
• Octreotide
• Olanzapine
• Ondansetron
• Opipramol
• Oxaprozin
• Oxycodone
• Oxymorphone
• Oxyphenbutazone
• Paliperidone
• Palonosetron
• Panobinostat
• Parecoxib
• Parnaparin
• Paroxetine
• Pasireotide
• Pazopanib
• Pentamidine
• Pentazocine
• Pentosan Polysulfate Sodium
• Periciazine
• Perphenazine
• Phenindione
• Phenprocoumon
• Phenylbutazone
• Piketoprofen
• Pimavanserin
• Pirmenol
• Piroxicam
• Pitolisant
• Pixantrone
• Posaconazole
• Prajmaline
• Pranoprofen
• Prasugrel
• Probucol
• Procainamide
• Prochlorperazine
• Proglumetacin
• Promethazine
• Propafenone
• Propranolol
• Propyphenazone
• Proquazone
• Protein C
• Protriptyline
• Quetiapine
• Quinine
• Ranolazine
• Remifentanil
• Reviparin
• Ribociclib
• Rilpivirine
• Risperidone
• Ritonavir
• Rivaroxaban
• Rizatriptan
• Rofecoxib
• Safinamide
• Salicylic Acid
• Salsalate
• Selexipag
• Sematilide
• Sertindole
• Sertraline
• Sevoflurane
• Sibutramine
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Sodium Salicylate
• Solifenacin
• Sorafenib
• Sotalol
• Spiramycin
• St John's Wort
• Sufentanil
• Sulfamethoxazole
• Sulfinpyrazone
• Sulindac
• Sulpiride
• Sultopride
• Sumatriptan
• Sunitinib
• Tacrolimus
• Tamoxifen
• Tapentadol
• Tedisamil
• Telavancin
• Telithromycin
• Tenoxicam
• Terbinafine
• Tetrabenazine
• Tianeptine
• Tiaprofenic Acid
• Ticagrelor
• Ticlopidine
• Tinzaparin
• Tiotropium
• Tirofiban
• Tizanidine
• Tolfenamic Acid
• Tolmetin
• Tolterodine
• Toremifene
• Tramadol
• Trazodone
• Treprostinil
• Trifluoperazine
• Trimethoprim
• Trimipramine
• Triptorelin
• Tryptophan
• Valbenazine
• Valdecoxib
• Vandetanib
• Vardenafil
• Vasopressin
• Vemurafenib
• Venlafaxine
• Vilazodone
• Vinflunine
• Vorapaxar
• Voriconazole
• Vorinostat
• Vortioxetine
• Warfarin
• Zolmitriptan
• Zotepine
• Zuclopenthixol

Using olanzapine and fluoxetine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alprazolam
• Amprenavir
• Betel Nut
• Buspirone
• Ciprofloxacin
• Cyproheptadine
• Delavirdine
• Digoxin
• Fluvoxamine
• Fosamprenavir
• Ginkgo
• Haloperidol
• Lithium
• Phenytoin
• Ritonavir
• Valproic Acid

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using olanzapine and fluoxetine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use olanzapine and fluoxetine, or give you special instructions about the use of food, alcohol, or tobacco.

• Tobacco

Other Medical Problems

The presence of other medical problems may affect the use of olanzapine and fluoxetine. Make sure you tell your doctor if you have any other medical problems, especially:

• Bipolar disorder (mood disorder with mania and depression), or risk of or
• Bleeding problems or
• Breast cancer, prolactin-dependent or
• Diabetes or
• Enlarged prostate or
• Glaucoma (angle-closure type) or
• Hyperglycemia (high blood sugar) or
• Hyperlipidemia (increased blood cholesterol or fats) or
• Hyperprolactinemia (increased prolactin in the blood) or
• Hyponatremia (low sodium in the blood) or
• Mania, history of or
• Paralytic ileus (bowels stop moving), history of or
• Seizures, history of or
• Trouble swallowing—Use with caution. May make these conditions worse.

• Blood vessel or circulation problems or
• Dehydration or
• Heart attack or stroke, history of or
• Heart disease or
• Heart failure or
• Heart rhythm problems (eg, QT prolongation), or history of or
• Hypokalemia (low potassium in the blood) or
• Hypomagnesemia (low magnesium in the blood) or
• Hypovolemia (low blood volume)—May cause side effects to become worse.

• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

(oh LAN za peen & floo OKS e teen)

• Antidepressant, Selective Serotonin Reuptake Inhibitor
• Second Generation (Atypical) Antipsychotic

Depression, acute (associated with bipolar I disorder): Treatment of acute depressive episodes associated with bipolar I disorder

Depression, treatment-resistant: Treatment of treatment-resistant depression (eg, unresponsive to 2 trials of different antidepressants in the current episode)

Use of MAO inhibitors intended to treat psychiatric disorders (concurrently, within 5 weeks of discontinuing olanzapine/fluoxetine, or within 2 weeks of discontinuing the MAO inhibitor); initiation of olanzapine/fluoxetine in a patient receiving linezolid or intravenous methylene blue; use with pimozide or thioridazine (Note: Thioridazine should not be initiated until 5 weeks after the discontinuation of fluoxetine.)

Initial: Olanzapine 3 to 6 mg/fluoxetine 25 mg once daily in the evening; use caution adjusting dose (metabolism may be decreased).

May be taken without regard to meals.