olanzapine (Zyprexa, Zydis, Zyprexa, Relprevv)
Jump to navigation
Jump to search
Introduction
Tradename: Zyprexa.
FDA-approved generic Oct 2011[14]
Indications
- psychotic disorders including schizophrenia
- psychosis & agitation in the elderly
- treatment of acute mania & depression in patients with bipolar disorder[4]
- used for anorexia nervosa[6]
Contraindications
(Caution)
- cardiovascular disease
- cerebrovascular disease
- hypovolemia
- dehydration
- seizures
- Alzheimer's disease
- hepatic insufficiency
- prostatic hypertrophy
- narrow-angle glaucoma
- history of paralytic ileus
- history of breast cancer
- elderly or nursing home patients
- adolescents[13]
Dosage
- start 5-10 mg PO QD
- increase by 5 mg/day at intervals >= 1 week
- average effective dose: 10-15 mg PO QD
- max dose: 20 mg PO QD
Tabs: 2.5, 5, 7.5, 10 mg. Injection (Zyprexa IM), extended release Zyprexa Relprevv
Tablets: oral disintegrating tablets (Zydis)
Pharmacokinetics
- oral doses are well absorbed (unaffected by food)
- peak plasma concentrations are reached 6 hours after oral dose
- eliminated extensively by 1st pass metabolism
- 93% bound to plasma proteins
- 1/2 life 21-54 hours
- metabolized in the liver by:
- metabolites excreted in urine (57%) & feces (30%)
- 10-N-glucuronide (44%) & 4'-N-desmethyl (31%) derivatives are the major metabolites
- 7% recovered unchanged in the urine
elimination via liver
1/2life = 21-54 hours
protein binding = 93 %
Monitor
- serum glucose, Lipid panel, weight
Adverse effects
- common (> 10%)
- less common (1-10%)
- dystonic reactions, parkinsonism, akathisia, anxiety, personality changes, fever, dry mouth, constipation, abdominal pain, weight gain, arthralgia, amblyopia, rhinitis, cough, pharyngitis
- uncommon (< 1%)
- other [2, 4]
- sedation
- headache
- nausea
- anticholinergic effects
- orthostatic hypotension
- tremor
- rhinitis
- weakness[4]
- falls in the elderly
- gait ataxia
- dyslipidemia:
- increased serum cholesterol non non-HDL cholesterol
- increased serum triglycerides[8][12]
- hyperglycemia[8]
- increased risk of diabetes mellitus[9] relative to risperidone & conventional antipsychotics odds ratio 4.2
- increased risk of diabetic ketoacidosis[20]
- does NOT appear to cause agranulocytosis
- lower risk of extrapyramidal effects than respiridone
- increased risk of stroke (2-3 fold) in patients with dementia[10]
- weight gain, substantial[12]; greatest among antipsychotics[21]
- olanzapine > quetiapine > risperidone > aripiprazole[12]
- in adolescents 8.5 kg after 11 weeks of therapy[12]
- melatonin 5 mg QD may attenuate weight gain[17]
- 2 unexplained deaths following IM injection[15]
- Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)[18]
- black box warning[16]
- increased risk of hyperglycemia
- increased risk of cerebrovascular events
- increased risk of mortality in patients with dementia
- drug adverse effects of antipsychotic agents
- drug adverse effects of atypical antipsychotic agents
- drug adverse effects of psychotropic agents
- drug adverse effects of dopaminergic receptor antagonists
- drug adverse effects of antihypertensive agents
Drug interactions
- similar to clozapine
- cyt P450 inhibitors may decrease metabolism of olanzapine
- decreased effect with:
- increased effect with:
- cyt P450 1A2 inhibitors such as fluvoxamine
- increased toxicity:
- increased sedation with alcohol or other CNS depressants, orthostatic hypotension with antihypertensive agents
- any drug which inhibits cyt P450 1A2 or cyt P450 2D6 can increase olanzapine levels
- any drug which induces cyt P450 1A2 or cyt P450 2D6 can diminish olanzapine levels
- drug interaction(s) of antipsychotics & dopamine receptor agonists
- drug interaction(s) of antipsycotics with benzodiazepines
- drug interaction(s) of NSAIDs & antihypertensives
Mechanism of action
- atypical antipsychotic (see clozapine)
- combined dopamine & serotonin receptor blockade
- affinity for several receptors
- reduces irritability, euphoria & psychosis[4]
More general terms
- atypical antipsychotic agent; second generation antipsychotic
- dopaminergic receptor antagonist
- serotonin antagonist
Additional terms
- clozapine (Clozaril)
- cytochrome p450 1A2 (cytochrome P3-450, phenacetin deethylase, cytochrome p450-4, CYP1A2)
- cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)
Component of
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 Department of Veterans Affairs, VA National Formulary
restricted to monotherapy for the treatment of acute agitation associated with schizophrenia or bipolar I mania. - ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 4.0 4.1 4.2 4.3 Prescriber's Letter 7(7):41 2000
- ↑ PDR 2000
- ↑ 6.0 6.1 Prescriber's Letter 8(9):52 2001
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 8.0 8.1 8.2 Prescriber's Letter 9(3):17 2002
- ↑ 9.0 9.1 Journal Watch 22(19):149-50, 2002 Koro CE et al, BMJ 325:243, 2002 http://bmj.com/cgi/content/full/325/7358/243
- ↑ 10.0 10.1 Safety Data on Zyprexa (Olanzapine) and Symbyax (Olanzapine and Fluoxetine): Elderly Patients with Dementia-Related Psychosis Prescriber's Letter 11(4):20 2004 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200406&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 11.0 11.1 Prescriber's Letter 11(6):34 2004 Olanzapine for Nausea Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200609&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 12.0 12.1 12.2 12.3 12.4 Correll CU et al Cardiometabolic Risk of Second-Generation Antipsychotic Medications During First-Time Use in Children and Adolescents JAMA. 2009;302(16):1765-1773 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19861668 <Internet> http://jama.ama-assn.org/cgi/content/short/302/16/1765
Varley CK & McClellan J Implications of Marked Weight Gain Associated With Atypical Antipsychotic Medications in Children and Adolescents JAMA. 2009;302(16):1811-1812 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19861677 <Internet> http://jama.ama-assn.org/cgi/content/short/302/16/1811 - ↑ 13.0 13.1 FDA MedWatch Zyprexa (olanzapine): Use in Adolescents http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm198402.htm
- ↑ 14.0 14.1 FDA NEWS RELEASE: Oct. 24, 2011 FDA approves first generic olanzapine to treat schizophrenia, bipolar disorder http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm277022.htm
- ↑ 15.0 15.1 FDA MedWatch. June 18, 2013 Zyprexa Relprevv (Olanzapine Pamoate): Drug Safety Communication - FDA Investigating Two Deaths Following Injection. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm357601.htm
FDA Medwatch. March 23, 2015 Zyprexa Relprevv (olanzapine pamoate): Drug Safety Communication - FDA Review of Study Sheds Light on Two Deaths Associated with the Injectable Schizophrenia Drug. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm439472.htm
FDA Safety Alert: March 23, 2015 FDA Drug Safety Communication: FDA review of study sheds light on two deaths associated with the injectable schizophrenia drug Zyprexa Relprevv (olanzapine pamoate). http://www.fda.gov/Drugs/DrugSafety/ucm439147.htm - ↑ 16.0 16.1 Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
- ↑ 17.0 17.1 Romo-Nava F et al. Melatonin attenuates antipsychotic metabolic effects: An eight-week randomized, double-blind, parallel-group, placebo- controlled trial. Bipolar Disord 2014 Mar 17 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24636483 <Internet> http://onlinelibrary.wiley.com/doi/10.1111/bdi.12196/abstract
- ↑ 18.0 18.1 FDA Safety Alert. May 10, 2016 Olanzapine: Drug Safety Communication - FDA Warns About Rare But Serious Skin Reactions. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm500123.htm
- ↑ Medical Knowledge Self Assessment Program (MKSAP) 19. American College of Physicians, Philadelphia 2021
- ↑ 20.0 20.1 NEJM Knowledge+ Endocrinology
- ↑ 21.0 21.1 Sabe M, Pallis K, Solmi M et al Comparative Effects of 11 Antipsychotics on Weight Gain and Metabolic Function in Patients With Acute Schizophrenia: A Dose-Response Meta-Analysis. J Clin Psychiatry. 2023 Feb 8;84(2):22r14490. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36752753
- ↑ Sandhya L et al. Randomized double-blind placebo-controlled study of olanzapine for chemotherapy- related anorexia in patients with locally advanced or metastatic gastric, hepatopancreaticobiliary, and lung cancer. J Clin Oncol 2023 May 10; 41:2617 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36977285 Clinical Trial. https://ascopubs.org/doi/10.1200/JCO.22.01997
Roeland EJ, Bohlke K, Baracos VE et al Cancer Cachexia: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2023 Sep 1;41(25):4178-4179. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37467399