Contents

Search

ziprasidone (Zeldox, Geodon)

Indications: - psychotic disorders, esp schizophrenia (FDA approved 2001) - agitation - psychosis & agitation in the elderly [8] Contraindications: 1) recent myocardial infarction 2) uncompensated heart failure 3) long QT syndrome 4) history of QT prolongation [7] Dosage: 1) start 20 mg PO BID with food 2) max 80 mg PO BID 3) no additional benefit observed for doses > 20 mg BID 4) IM dosing available Tabs: 20, 40, 60 80 mg. Injection: (Geodon IM) Pharmacokinetics: 1) well-absorbed after oral administration 2) absorption increased 2-fold when administered with food 3) peak plasma levels reached 6-8 hours after oral dose 4) absolute bioavailability of oral 20 mg dose is 60% 5) effects due to parent compound 6) volume of distribution 1.5 L/kg 7) > 99% bound to plasma proteins, primarily albumin & alpha-1 acid glycoprotein 8) metabolized in the liver by: a) cyt P450 3A4 & 1A2 (1/3) d) aldehyde oxidase (2/3) followed by thiolmethyl- transferase 9) elimination 1/2 life of 7 hours 10) steady-state levels reached after 3 days of dosing Adverse effects: 1) less weight gain than other atypical antipsychotics 2) prolongation of QT interval* 3) adverse effects of antipsychotics in general a) neuroleptic malignant syndrome b) tardive dyskinesia c) dysphagia 4) orthostatic hypotension 5) rash/urticaria (5%) 6) seizures (0.4%) 7) hyperprolactinemia 8) potential for motor & cognitive impairment 9) priapism (1 case) 10) dysregulation of core temperature 11) may increase risk of diabetes mellitus [6] 12) black box warning [8] a) increased risk of hyperglycemia b) increased risk of cerebrovascular events c) increased risk of mortality in patients with dementia 13) rare but serious skin reaction (DRESS) [9] * higher risk of QT prolongation than other antipsychotics; little published data for use in elderly [8] Overdose: 1) supportive measures 2) gastric lavage & activated charcoal Drug interactions: 1) carbamazepine decreases levels of ziprasidone (35%) 2) ketoconazole increases levels of ziprasidone 3) do not use concurrently with other drugs that prolong the QT interval 4) caution when used with antihypertensive agents Laboratory: - ziprasidone in blood - ziprasidone in serum/plasma - ziprasidone in urine Mechanism of action: 1) binds with high affinity to: (Ki's in nM) a) dopamine receptors 1] dopamine D2 receptor (4.8) 2] dopamine D3 receptor (7.2) b) serotonin receptors 1] serotonin 5HT1a receptor (3.4) 2] serotonin 5HT1d receptor (2) 3] serotonin 5HT2a receptor (0.4) 4] serotonin 5HT2c receptor (1.3) c) alpha-1 adrenergic receptor (10) 2) binds with moderate affinity to: -> histamine H1 receptor (47) 3) antagonist activity at: a) dopamine D2 receptor b) serotonin 5HT1d receptor & serotonin 5HT2a receptor c) histamine H1 receptor d) alpha-1 adrenergic receptors (10) 4) agonist activity at - serotonin 5HT1a receptor 5) inhibits synaptic re-uptake of serotonin & norepinephrine Notes: Manufacturer: Pfizer

Interactions

drug interactions drug adverse effects (more general classes) monitor with atypical antipsychotic agents

Related

cytochrome p450 1A2 (cytochrome P3-450, phenacetin deethylase, cytochrome p450-4, CYP1A2) cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

General

atypical antipsychotic agent; second generation antipsychotic

Properties

SIZE: MW = 377 GRAMS/MOLE MISC-INFO: elimination route LIVER 1/2life 7 HOURS protein-binding >99%

Database Correlations

PUBCHEM correlations

References

  1. Prescriber's Letter 7(8):45 2000
  2. Prescriber's Letter 8(3):14 2001
  3. Prescriber's Letter 9(1):S1 2002
  4. Physicians Desk Reference (PDR) 56th ed, 2002
  5. Prescriber's Letter 9(8):45 2002
  6. Prescriber's Letter 10(11):62 2003
  7. Espinosa RT & Eslami MS, Clinical Geriatrics 12(1):45. 2004
  8. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
  9. FDA MedWatch. Dec 11, 2014 Ziprasidone (Marketed as Geodon and Generics): Drug Safety Communication - Rare But Potentially Fatal Skin Reactions. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm426624.htm
  10. Department of Veterans Affairs, VA National Formulary