Dosing and uses of Geodon (ziprasidone)
Adult dosage forms and strengths
capsule
- 20mg
- 40mg
- 60mg
- 80mg
powder for injection
- 20mg
Schizophrenia
20 mg PO q12hr with food initially; may be increased every other day PRN; not to exceed 80 mg q12hr
Periodically assess need for maintenance; clinical trials have documented no added benefit with doses above 20 mg q12hr
Acute Agitation With Schizophrenia
IM: 10 mg q2hr or 20 mg q4hr; not to exceed 40 mg/day; use IM for up to 3 days, and switch to PO if continuing past this time
Bipolar I Disorder
Acute treatment of manic or mixed episodes; maintenance therapy as adjunct to lithium or valproate
Acute treatment: 40 mg PO q12hr with food initially; on day 2, may be increased if necessary to 60-80 mg PO q12hr; adjust dose according to tolerance and efficacy within range of 40-80 mg q12hr
Maintenance: Continue at same dose at which patient was initially stabilized; periodically reassess need for maintenance therapy
Dosing Modifications
Renal impairment: Dose adjustment not necessary with PO administration; caution required with IM administration
Hepatic impairment: Use caution; drug undergoes extensive hepatic metabolism, which can increase systemic exposure
Pediatric dosage forms and strengths
capsule
- 20mg
- 40mg
- 60mg
- 80mg
powder for injection
- 20mg
Tourette Syndrome (Off-label)
Days 1-3: 5 mg/day
Days 4-28: Titrate to 40 mg/day divided q12hr
Geodon (ziprasidone) adverse (side) effects
>10%
Somnolence (11-15%)
Headache (11%)
Nausea (4-12%)
Extrapyramidal symptoms (2-31%)
Dizziness (3-16%)
1-10%
Respiratory disorders (1-8%)
Constipation (2-9%)
Dyspepsia (1-8%)
Rash (4-5%)
Tachycardia (2%)
Hypoesthesia (2%)
Priapism (1%)
Orthostatic hypotension (5%)
Xerostomia (1-5%)
Anorexia (2%)
Myalgia (2%)
Rhinitis (1-4%)
Cough (3%)
<1%
Syncope
Seizures
Frequency not defined
Prolongation of QT intervaL
Neuroleptic malignant syndrome (NMS)
Hyperprolactinemia
Drug reaction with eosinophilia and systemic syntoms
Postmarketing reports
Stevens-Johnson syndrome
Warnings
Black box warnings
Not approved for dementia-related psychosis; patients with dementia-related psychosis who are treated with antipsychotic drugs are at increased risk of death, as shown in short-term controlled trials; deaths in these trials appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature
Contraindications
Documented hypersensitivity
Any drugs or conditions that prolong QT intervaL
Recent acute myocardial infarction
Uncompensated heart failure
Cautions
Seizure disorders; may cause hypotension, EPS, and somnolence
Atypical antipsychotics have been associated with metabolic changes (eg, hyperglycemia, dyslipidemia, and body weight gain) that may increase cardiovascular/cerebrovascular risk
Hyperglycemia may occur and in some cases may be extreme, resulting in ketoacidosis, hyperosmolar coma, or death; monitor blood glucose of high-risk patients
Neuroleptic malignant syndrome reported with antipsychotic drugs
Tardive dyskinesia, acute dystonic reactions, pseudoparkinsonism, or akathisia may develop acutely or chronically
Discontinue if rash develops without an identified cause
Drug reaction with eosinophilia and systemic symptoms (DRESS) reported; DRESS consists of combination of three or more of the following: cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, lymphadenopathy and one or more systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and pericarditis; DRESS is sometimes fatal; discontinue therapy if DRESS suspected
Cutaneous adverse reactions, such as Stevens-Johnson syndrome, reported; severe cutaneous adverse reactions are sometimes fatal; discontinue therapy if suspected
Rare cases of priapism reported
FDA warning regarding off-label use for dementia in elderly (see Black box warnings)
May cause orthostatic hypotension
Suicide attempt is inherent in psychotic illness or bipolar disorder, close supervision of high-risk patients should accompany drug therapy
Dopamine2 antagonists may elevate prolactin levels; long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density
Leukopenia/neutropenia and agranulocytosis reported; possible risk factors for leukopenia/neutropenia include preexisting low white blood cell (WBC) count and history of drug-induced leukopenia/neutropenia
If patient has history of clinically significant low WBC count or drug-induced leukopenia/neutropenia, monitor complete blood count (CBC) frequently during first few months of therapy; discontinue drug at first sign of clinically significant WBC decline <1000/μL in absence of other causative factors, and continue monitoring WBC count until recovery
Antipsychotic agents have been associated with esophageal dysmotility and aspiration; use caution in patients at risk of pneumonia
May cause QTc prolongation, which has been associated with development of malignant ventricular arrhythmias (torsade de pointes) and sudden death; discontinue therapy in patients with persistent QTc intervals >500 msec; avoid hypokalemia or hypomagnesemia
Moderate to highly sedative; use caution when required to operate heavy machinery
May cause core body temperature regulation impairment; use caution with heat exposure, strenuous exercise, dehydration, or taking medications with anticholinergic effects
Make electrolyte imbalance corrections, especially hypomagnesemia or hypokalemia before and throughout therapy
Use with caution in hepatic impairment
Pregnancy and lactation
Pregnancy category: C
Neonates exposed to antipsychotic drugs during 3rd trimester of pregnancy are at risk for EPS or withdrawal symptoms after delivery; these complications vary in severity, with some being self-limited and others requiring ICU support and prolonged hospitalization
Lactation: Unknown if excreted in breast milk; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Geodon (ziprasidone)
Mechanism of action
Acts as antagonist at dopamine D2 and serotonin type 1 and 2 (5HT1D, 5HT2A) receptors; acts as agonist at serotonin 5HT1A receptor; moderately inhibits reuptake of norepinephrine and serotonin; has alpha-blocking and antihistaminic activity
Absorption
Bioavailability: 60% (PO); 100% (IM)
Peak plasma time: 6-8 hr (PO); ≤60 min (IM)
Distribution
Protein bound: 99%
Vd: 1.5 L/kg
Metabolism
Metabolized in liver by CYP3A4 (major) and CYP1A2 (minor)
Elimination
Half-life: 7 hr (PO); 2-5 hr (IM)
Total body clearance: 7.5 mL/min/kg
Excretion: Feces (66%), urine (20%)
