ZIPRASIDONE HYDROCHLORIDE

ZIPRASIDONE HYDROCHLORIDE
(zip-ra-si'done)
Geodon
Classifications: psychotherapeutic; antipsychotic, atypical;
Therapeutic: antipsychotic, atypical

Prototype: Clozapine
Pregnancy Category: C

Availability

20 mg, 40 mg, 60 mg, 80 mg capsules; 20 mg/mL injection; 10 mg/mL suspension

Action

Exerts antischizophrenic effects through dopamine (D2) and serotonin (5-HT2A) receptor antagonist. Exerts antidepressant effects through 5-HT1A agonism, 5-HT1D antagonism, and serotonin/norepinephrine reuptake inhibition.

Therapeutic Effect

Improves symptoms of schizophrenia, schizoaffective disorder, and psychotic depression.

Uses

Treatment of schizophrenia, acute bipolar mania.

Unlabeled Uses

Tourette's syndrome.

Contraindications

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 or adolescents are not established.

Cautious Use

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; schizophrenia; suicide potential; children >7 y for use in Tourette's syndrome only.

Route & Dosage

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

Administration

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).

Adverse Effects (≥1%)

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.

Interactions

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.

Pharmacokinetics

Absorption: Well absorbed with 60% reaching systemic circulation. Peak: 6–8 h. Metabolism: Extensively in the liver. Elimination: 20% of metabolites in urine, 66% of metabolites in bile. Half-Life: 7 h.

Nursing Implications

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 for signs and symptoms of suicidality.
  • 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.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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