ZIPRASIDONE HYDROCHLORIDE
(zip-ra-si'done)
Geodon
Classifications: central nervous system (cns) agent; psychotherapeutic agent; antipsychotic; atypical
Prototype: Clozapine
Pregnancy Category: C
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20 mg, 40 mg, 60 mg, 80 mg capsules; 20 mg/mL injection
Unrelated to phenothiazine or butrophenone antipsychotic agents. Exhibits high in vitro binding affinity for the following receptors: dopamine D2 and D3, serotonin 5HT2A, 5HT2C, 5HT1A, 5HT1D, and the alpha-1-adrenergic receptors, and moderate affinity for the histamine H1 receptor. Antagonist at the D2, 5HT2A and 5HT1D receptors, and an agonist at the 5HT1A receptor. Additionally, inhibits synaptic reuptake of serotonin and norepinephrine. Antagonism at other receptors may explain
some of the other therapeutic and adverse effects (e.g., orthostatic hypotension).
Mechanism of action is unknown; probably related to inhibition of synaptic reuptake of serotonin and norepinephrine through
antagonism of dopamine type 2 (D2) and serotonin type 2 (5HT2) antagonism.
Treatment of schizophrenia, acute bipolar mania.
Tourette's syndrome.
Hypersensitivity to ziprasidone; history of QT prolongation including congenital long QT syndrome or with other drugs known
to prolong the QT interval; AV block, bundle branch block, cardiac arrhythmias, congenital heart disease, recent MI or uncompensated
heart failure; bradycardia, hypokalemia or hypomagnesemia; intravenous administration; neuroleptic malignant syndrome and
tardive dyskinesia; dehydration or hypovolemia; UV exposure and tanning beds; pregnancy (category C), lactation. Safety and
efficacy in children are not established.
History of seizures, CVA, dementia, Parkinson's disease, or Alzheimer disease; known cardiovascular disease, conduction abnormalities,
treatment with antihypertensive drugs; cerebrovascular disease; hepatic impairment; seizure disorder, seizures; breast cancer;
risk factors for elevated core body temperature; esophageal motility disorders and risk of aspiration pneumonia; suicide potential;
children >7 y for use in Tourette's syndrome only.
Schizophrenia
Adult: PO Start with 20 mg b.i.d. with food, may increase q2d up to 80 mg b.i.d. if needed IM 10 mg q2h or 20 mg q4h up to max of 40 mg/d
Acute Mania
Adult: PO Start with 40 mg b.i.d. with food; may increase q2d up to 80 mg b.i.d. if needed
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Note:
CONTRAINDICATIONS for this drug. Do NOT administer to anyone with a history of cardiac arrhythmias or other cardiac disease, hypokalemia, hypomagnesemia, prolonged
QT/QTc interval, or to anyone on other drugs known to prolong the QTc interval. Withhold drug and consult physician if any
of the foregoing conditions are present.
Oral
- Give with food.
- Make dosage adjustments at intervals of
2 d.
Intramuscular
- Give deep IM into a large muscle.
- Store at 15°–30° C (59°–86° F).
Body as a Whole: Asthenia, myalgia, weight gain, flu-like syndrome, face edema, chills, hypothermia. CNS:
Somnolence, akathisia, dizziness, extrapyramidal effects, dystonia, hypertonia, agitation, tremor, dyskinesias, hostility, paresthesia,
confusion, vertigo, hypokinesia, hyperkinesias, abnormal gait, oculogyric crisis, hypesthesia, ataxia, amnesia, cogwheel rigidity,
delirium, hypotonia, akinesia, dysarthria, withdrawal syndrome, buccoglossal syndrome, choreoathetosis, diplopia, incoordination,
neuropathy. CV: Tachycardia, postural hypotension, prolonged QTc interval, hypertension. GI:
Nausea, constipation, dyspepsia, diarrhea, dry mouth, anorexia, abdominal pain, vomiting. Metabolic: Hyperglycemia, diabetes mellitus. Respiratory: Rhinitis, increased cough, dyspnea. Skin: Rash, fungal dermatitis, photosensitivity. Special Senses: Abnormal vision.
Drug:
Carbamazepine may decrease ziprasidone levels; ketoconazole may increase ziprasidone levels; may enhance hypotensive effects of antihypertensive agents; may antagonize effects of levodopa; increased risk of arrhythmias and heart block due to prolonged QTc interval with antiarrhythmic agents, amoxapine,
arsenic trioxide,
chlorpromazine,
clarithromycin,
daunorubicin,
diltiazem,
dolasetron,
doxorubicin,
droperidol,
erythromycin,
halofantrine,
indapamide,
levomethadyl,
local anesthetics, maprotiline,
mefloquine,
mesoridazine,
octreotide,
pentamidine,
pimozide,
probucol,
gatifloxacin,
grepafloxacin,
levofloxacin,
moxifloxacin,
sparfloxacin,
tricyclic antidepressants, tacrolimus,
thioridazine,
troleandomycin; additive CNS depression with sedative-hypnotics, anxiolytics, ethanol,
opiate agonists.
Absorption: Well absorbed with 60% reaching systemic circulation. Peak: 6–8 h. Metabolism: Extensively metabolized in the liver. Elimination: 20% of metabolites excreted in urine, 66% of metabolites excreted in bile. Half-Life: 7 h.
Assessment & Drug Effects
- Lab tests: Baseline and periodic ECG, serum potassium and serum magnesium, especially with concomitant diuretic therapy. Periodically
monitor blood glucose.
- Monitor diabetics for loss of glycemic control.
- Monitor for S&S of torsade de pointes (e.g., dizziness, palpitations, syncope), tardive dyskinesia (see Appendix F) especially
in older adult women and with prolonged therapy, and the appearance of an unexplained rash. Withhold drug and report to physician
immediately if any of these develop.
- Monitor I&O ratio and pattern: Notify physician if diarrhea, vomiting or any other conditions develops which may cause electrolyte
imbalance.
- Monitor BP lying, sitting, and standing. Report orthostatic hypotension to physician.
- Monitor cognitive status and take appropriate precautions.
- Monitor for loss of seizure control, especially with a history of seizures or dementia.
Patient & Family Education
- Carefully monitor blood glucose levels if diabetic.
- Be aware that therapeutic effect may not be evident for several weeks.
- Report any of the following to a health care provider immediately: Palpitations, faintness or loss of consciousness, rash,
abnormal muscle movements, vomiting or diarrhea.
- Do not drive or engage in potentially hazardous activities until response to drug is known.
- Make position changes slowly and in stages to prevent dizziness upon arising.
- Avoid strenuous exercise, exposure to extreme heat, or other activities that may cause dehydration.
- Do not breast feed while taking this drug.
Canadian drug name; 
Prototype drug