Usual Adult Dose for Schizophrenia

Oral:
Initial dose: 20 mg orally twice a day
Maintenance dose: Adjust as clinically indicated at intervals of not less than 2 days
Maximum dose: 100 mg twice a day

Comments: A dose greater than 80 mg twice a day is generally not recommended.

Intramuscular:
Recommended dose: 10 to 20 mg IM; may repeat 10 mg IM every 2 hours or 20 mg IM every 4 hours up to maximum daily dose
Maximum dose: 40 mg IM per day
Duration of therapy: Use beyond 3 consecutive days has not been studied

Comments:

• Coadministration of IM ziprasidone to patient's already taking oral ziprasidone has not been studied and is not recommended.
• If long-term therapy is indicated, oral capsules should replace IM administration as soon as possible.

• Treatment of schizophrenia (oral)
• Acute treatment of agitation in schizophrenia (IM)

Usual Adult Dose for Bipolar Disorder

Acute Treatment of Manic or Mixed Episodes:

• Initial dose: 40 mg orally twice daily
• Increase dose to 60 mg or 80 mg twice daily on the second day; subsequently adjust dose based on tolerance and efficacy within the dose range of 40 to 80 mg orally twice a day

• Once stabilized, continue on same dose within the range of 40 to 80 mg orally twice daily.

• The mean ziprasidone dose administered in flexible-dose clinical trials was approximately 120 mg per day.
• Monotherapy has not been systematically evaluated for maintenance treatment of bipolar I disorder.

• As monotherapy for the acute management of manic or mixed episodes associated with bipolar I disorder
• As adjunct to lithium or valproate for the maintenance treatment of bipolar I disorder.

Renal Dose Adjustments

Oral: No adjustment recommended
IM: Use cautiously as the cyclodextrin excipient is cleared by renal filtration; IM formulation has not been systematically studied in patients with renal impairment.

Liver Dose Adjustments

Oral: No adjustment recommended.
IM: Use with caution; IM formulation has not been systematically studied in patients with hepatic impairment.

Dose Adjustments

Therapy with oral ziprasidone should replace IM administration as soon as possible.

No dosage adjustment is required in elderly patients, however, consider a lower oral starting dose and slower dose titration with careful monitoring during initial dosing period. .

In maintenance therapy, patients should be administered the lowest effective dose; to ensure the use of the lowest effective dose for the treatment of schizophrenia, patients should be observed for signs of improvement over a period of several weeks prior to upward dosage adjustment.

Precautions

US BOXED WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS:

• Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal-duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo-group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. This drug is not approved for the treatment of patients with dementia-related psychosis.

Dialysis

No data available; this drug is not removed by hemodialysis.

Other Comments

Administration advice:

• Take oral capsules with food
• Parenteral product is for IM administration only; do not give IV

• Reconstitute with 1.2 mL of sterile water for injection; shake vial vigorously until all drug is dissolved; final concentration is 20 mg/mL
• Single-use vials, unused portion should be discarded
• Following reconstitution, stable for up to 24 hours at 15 to 30C (59 to 86F) or up to 7 days refrigerated (2 to 8C or 36 to 46F)

• Consider potential for prolonging the QT interval when prescribing this drug.

• Cardiovascular: Obtain baseline electrolyte (potassium and magnesium) measurements, especially in patients at risk for significant electrolyte disturbances
• Cardiovascular: Orthostatic vital signs in at-risk patients
• Hematologic: CBC frequently during the first few months in patients with preexisting low WBC and/or a prior history of drug-induced leukopenia or neutropenia.
• Metabolic: Monitor for increases in blood sugar, weight, and lipids

• Patients should be instructed to report at the earliest onset any signs or symptoms that may be associated with Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
• Patients should be instructed to report conditions that may put them at risk for significant electrolyte disturbances, such as prolonged diarrhea; they should also be instructed to report any symptoms such as dizziness, palpitations, or syncope.
• Inform patient that this drug may cause dizziness upon arising; it is best to get up slowly from a seated or lying position.
• This drug may impair judgment, thinking, or motor skills; have patient avoid driving or operating machinery until adverse effects are determined.
• Advise patient to speak to physician or health care professional if pregnant, intend to become pregnant, or are breastfeeding.
• Advise patient that this drug may cause metabolic changes such as increases in blood sugar, body weight and lipids.
• Patients should avoid overheating and dehydration.