Table 3 Ziprasidone dosing recommendations* [9, 109, 163]

Schizophrenia (adults)

20-40 mg twice daily

60-80 mg twice daily

100 mg twice daily

↑ every 1–3 days

Bipolar mania (adults)

40 mg twice daily

60-80 mg twice daily

80 mg twice daily

↑ every 1–2 days

Elderly

No differences in the pharmacokinetics of ziprasidone were observed in a small study involving healthy elderly patients. A limited number of elderly with schizophrenia were exposed to ziprasidone in clinical trials who demonstrated similar tolerability as adults. These findings suggest that reduced dosing may not be necessary unless other considerations are present. Ziprasidone, like other atypical antipsychotics, is not indicated for elderly patients with dementia due the elevated risk of death.

Children

There is limited experience with ziprasidone in children under clinical trial conditions, as such data to support its safety and efficacy at any dose is insufficient. Mean dose is one small RCT in children (11.5 y) with tics was ~30 mg/day. In a larger RCT of older children & adolescents (13.6 y) with bipolar disorder, the mean dose was 120 mg/day in those weighing >45 kg.

Special populations

Dosage adjustments are generally not required on the basis of gender, race, or renal function. Dose reduction of 40-50% is recommended in the presence of severe hepatic insufficiency and of 20-30% in adolescents, first episode psychosis, organic brain syndrome, bipolar maintenance, underweight, and Asian ethnicity.

Potent inhibitors and inducers of CYP3A4

Dose modification of ziprasidone may be warranted. Pharmacokinetic studies demonstrate the potential for an estimated 30-40% change in systemic exposure to ziprasidone when co-administered with potent CYP3A4 inhibitors (e.g., clarithromycin, protease inhibitors, ketoconazole) and inducers (e.g., carbamazepine, St John’s wort).