Olanzapine + fluoxetine

Concomitant use with MAOIs, or within 14 days of discontinuing MAOIs, or within 5 weeks of discontinuing olanzapine + fluoxetine. Initiation of treatment in patients receiving linezolid or IV methylthioninium chloride. Concurrent use with thioridazine or within at least 5 weeks of discontinuing olanzapine + fluoxetine. Concomitant use with pimozide.

Patient with history of seizures and risk factors for seizures, including head trauma, brain damage, alcoholism, or conditions that may decrease the seizure threshold (e.g. Alzheimer's disease); severe cardiac disease, ischaemic heart disease, haemodynamic instability, hypercholesterolaemia or pre-existing dyslipidaemia; risk factors for QT prolongation (e.g. congenital long QT syndrome, history of prolonged QT, family history of prolonged QT or sudden cardiac death), other conditions predisposing to cardiac arrhythmias (e.g. hypokalaemia, hypomagnesaemia, bradyarrhythmias or other arrhythmias, uncompensated heart failure, recent MI); predisposition for orthostatic hypotension or those who would not tolerate transient hypotensive episodes (e.g. cerebrovascular disease, dehydration, hypovolaemia); pre-existing low WBC or history of drug-induced leucopenia or neutropenia; reduced gastrointestinal motility, history of paralytic ileus, urinary retention, benign prostatic hyperplasia, narrow-angle glaucoma; diabetes or other glucose regulation disorders; strenuous exercise or extreme heat exposure. Smokers and those at risk for aspiration pneumonia. Patients with combined factors for reduced metabolism (e.g. females, nonsmokers) or enhanced sensitivity to olanzapine. CYP2D6 poor metabolisers. Not approved for dementia-related psychosis. Avoid abrupt withdrawal. Concomitant use with NSAIDs, aspirin, and other anticoagulants. Hepatic impairment. Children and elderly. Pregnancy and lactation. Patient Counselling This drug may cause somnolence, if affected, do not drive or operate machinery. Monitoring Parameters Evaluate for history of metabolic syndrome annually. Monitor renal function, LFTs, TSH and serum electrolytes annually (check serum Na as needed in at-risk patients); vital signs at least weekly during the 1st 3-4 weeks of therapy and 4 weeks after dose changes; weight, height, or BMI 8-12 weeks after treatment initiation or dose changes and quarterly thereafter; CBC and ECG as clinically indicated. Obtain fasting plasma glucose, HbA_1C, and lipid panel 12 weeks after treatment initiation or dose changes and annually thereafter; prolactin level (if with symptoms). Closely monitor for signs of clinical worsening, depression, suicidal tendencies, unusual behavioural changes, and serotonin syndrome. Assess for fall risk, extrapyramidal symptoms (every visit, 4 weeks after starting treatment or dose changes and annually thereafter), and signs of hyperglycaemia.

Significant: Suicidal thinking and behaviour in children, adolescents and young adults; hypersensitivity reactions (e.g. lupus-like syndrome, vasculitis, laryngospasm, anaphylactoid reactions, pulmonary inflammatory disease); precipitation of mania or hypomania (in patients with bipolar disorder); extrapyramidal symptoms (e.g. dystonia, akathisia, tardive dyskinesia, pseudoparkinsonism); impaired platelet aggregation leading to increased risk of bleeding events (e.g. gastrointestinal bleeding, haematomas, epistaxis, postpartum bleeding [particularly when used in the month before delivery]); oesophageal dysmotility or aspiration, orthostatic hypotension, CNS depression, increased risk of fall due to somnolence and motor or sensory instability, consequently bone fractures; ocular effects (e.g. mild pupillary dilation which may result to an episode of narrow-angle glaucoma); impaired core body temperature regulation, anticholinergic effects (e.g. blurred vision, constipation, xerostomia, urinary retention); dose-related hyperprolactinaemia, SIADH (leading to hyponatraemia), metabolic changes (e.g. hyperglycaemia, dyslipidaemia, significant weight gain [≥7% of baseline weight]), transaminase elevations; sexual dysfunction; withdrawal syndrome. Cardiac disorders: Bradycardia. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, flatulence, dyspepsia, abdominal distention. General disorders and administration site conditions: Oedema, fatigue, fever. Investigations: Decreased serum bicarbonate, decreased serum bilirubin; increased BUN and uric acid levels. Metabolism and nutrition disorders: Increased appetite. Musculoskeletal and connective tissue disorders: Back pain, limb pain, arthralgia, musculoskeletal stiffness. Nervous system disorders: Disturbance in attention, hypersomnia, lethargy. Reproductive system and breast disorders: Dysmenorrhoea, erectile dysfunction. Respiratory, thoracic and mediastinal disorders: Sinusitis. Skin and subcutaneous tissue disorders: Photosensitivity reaction, alopecia, pruritus, dry skin, ecchymoses. Vascular disorders: Vasodilatation.
Potentially Fatal: Serotonin syndrome, neuroleptic malignant syndrome (NMS); altered cardiac conduction, QT prolongation, ventricular arrhythmia including torsades de pointes; drug reaction with eosinophilia and systemic symptoms (DRESS); severe hyperglycaemia associated with ketoacidosis or hyperosmolar coma; blood dyscrasias (e.g. leucopenia, neutropenia, agranulocytosis), haemorrhage; cerebrovascular effects (e.g. stroke, TIA).

Increased risk of bleeding with NSAIDs, aspirin, and warfarin. Increased risk of QT prolongation with antipsychotics (e.g. chlorpromazine, droperidol, iloperidone, mesoridazine), antibiotics (e.g. erythromycin, gatifloxacin, moxifloxacin, sparfloxacin), class Ia antiarrhythmics (e.g. procainamide, quinidine), class III antiarrhythmics (e.g. amiodarone, sotalol), pentamidine, methadone, halofantrine, mefloquine, dolasetron, or tacrolimus. Olanzapine: May antagonise the effects of levodopa and dopamine agonists. May enhance the effects of certain antihypertensives. May potentiate orthostatic hypotension with benzodiazepines (e.g. diazepam). Increased clearance with CYP1A2 inducers (e.g. carbamazepine). Decreased clearance with CYP1A2 inhibitors (e.g. fluvoxamine). Fluoxetine: May increase the serum levels of clozapine, alprazolam, and haloperidol. Increased serum concentration with CYP2D6 inhibitors. May increase serum levels and toxicity of phenytoin.

Antidepressants / Antipsychotics

N06AB03 - fluoxetine ; Belongs to the class of selective serotonin reuptake inhibitors. Used in the management of depression.
N05AH03 - olanzapine ; Belongs to the class of diazepines, oxazepines and thiazepines antipsychotics