ziprasidone (Zeldox, Geodon)
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Indications
- psychotic disorders, esp schizophrenia (FDA approved 2001)
- agitation
- psychosis & agitation in the elderly[8]
Contraindications
- recent myocardial infarction
- uncompensated heart failure
- long QT syndrome
- history of QT prolongation[7]
Dosage
- start 20 mg PO BID with food
- max 80 mg PO BID
- no additional benefit observed for doses > 20 mg BID
- IM dosing available
Tabs: 20, 40, 60 80 mg.
Injection: (Geodon IM)
Pharmacokinetics
- well-absorbed after oral administration
- absorption increased 2-fold when administered with food
- peak plasma levels reached 6-8 hours after oral dose
- absolute bioavailability of oral 20 mg dose is 60%
- effects due to parent compound
- volume of distribution 1.5 L/kg
- > 99% bound to plasma proteins, primarily albumin & alpha-1 acid glycoprotein
- metabolized in the liver by:
- cyt P450 3A4 & 1A2 (1/3)
- aldehyde oxidase (2/3) followed by thiolmethyl- transferase
- elimination 1/2 life of 7 hours
- steady-state levels reached after 3 days of dosing
elimination via liver
1/2life = 7 hours
protein binding = >99 %
Adverse effects
- less weight gain than other atypical antipsychotics
- prolongation of QT interval*
- adverse effects of antipsychotics in general
- orthostatic hypotension
- rash/urticaria (5%)
- seizures (0.4%)
- hyperprolactinemia
- potential for motor & cognitive impairment
- priapism (1 case)
- dysregulation of core temperature
- may increase risk of diabetes mellitus[6]
- black box warning[8]
- increased risk of hyperglycemia
- increased risk of cerebrovascular events
- increased risk of mortality in patients with dementia
- rare but serious skin reaction (DRESS)[9]
* higher risk of QT prolongation than other antipsychotics; little published data for use in elderly[8]
- supportive measures
- gastric lavage & activated charcoal
- drug adverse effects of antipsychotic agents
- drug adverse effects of atypical antipsychotic agents
- drug adverse effects of psychotropic agents
Drug interactions
- carbamazepine decreases levels of ziprasidone (35%)
- ketoconazole increases levels of ziprasidone
- do not use concurrently with other drugs that prolong the QT interval
- caution when used with antihypertensive agents
- drug interaction(s) of antipsychotics & dopamine receptor agonists
- drug interaction(s) of antipsycotics with benzodiazepines
- drug interaction(s) of gabapentinoid with psychotropic agent
Laboratory
Mechanism of action
- binds with high affinity to: (Ki's in nM)
- dopamine receptors
- dopamine D2 receptor (4.8)
- dopamine D3 receptor (7.2)
- serotonin receptors
- serotonin 5HT1a receptor (3.4)
- serotonin 5HT1d receptor (2)
- serotonin 5HT2a receptor (0.4)
- serotonin 5HT2c receptor (1.3)
- alpha-1 adrenergic receptor (10)
- dopamine receptors
- binds with moderate affinity to:
- antagonist activity at:
- agonist activity at
- inhibits synaptic re-uptake of serotonin & norepinephrine
Notes
Manufacturer: Pfizer
More general terms
Additional terms
- 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)
References
- ↑ Prescriber's Letter 7(8):45 2000
- ↑ Prescriber's Letter 8(3):14 2001
- ↑ Prescriber's Letter 9(1):S1 2002
- ↑ Physicians Desk Reference (PDR) 56th ed, 2002
- ↑ Prescriber's Letter 9(8):45 2002
- ↑ Jump up to: 6.0 6.1 Prescriber's Letter 10(11):62 2003
- ↑ Jump up to: 7.0 7.1 Espinosa RT & Eslami MS, Clinical Geriatrics 12(1):45. 2004
- ↑ Jump up to: 8.0 8.1 8.2 8.3 Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
- ↑ Jump up to: 9.0 9.1 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
- ↑ Department of Veterans Affairs, VA National Formulary
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=60853
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=60854
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=65685
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=154068
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=219099