Geodon (ziprasidone mesylate)

Dosage of ziprasidone hydrochloride is expressed in terms of the hydrochloride monohydrate. Dosage of ziprasidone mesylate is expressed in terms of ziprasidone.

Ziprasidone hydrochloride is available as capsules and is administered orally twice daily with food for optimal absorption. Absorption of ziprasidone is increased up to 2-fold in the presence of food. Swallow ziprasidone capsules whole; do not open, crush, or chew the capsules.

Store ziprasidone hydrochloride capsules at 25degreesC (excursions permitted between 15-30degreesC).

Ziprasidone mesylate is available in a single-dose vial as lyophilized powder for IM injection. Ziprasidone mesylate is administered only by IM injection and should not be administered IV.

The lyophilized powder for injection must be reconstituted prior to administration by adding 1.2 mL of sterile water for injection to single-dose vials of ziprasidone to provide a solution containing 20 mg/mL. Other solutions should not be used to reconstitute ziprasidone mesylate injection, and the drug should not be admixed with other drugs. The vials should be shaken vigorously to ensure complete dissolution. Strict aseptic technique must be observed since the drug contains no preservative or bacteriostatic agent. Ziprasidone mesylate injection should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

To administer a 10 mg dose, draw up 0.5 mL of the reconstituted solution. To administer a 20 mg dose, draw up 1 mL of the reconstituted solution. Discard any unused portion. Refer to the full prescribing information for additional details on preparation and administration.

Store ziprasidone mesylate for injection at 25degreesC (excursions permitted between 15-30degreesC) in dry form; protect from light. Following reconstitution, ziprasidone mesylate for injection is stable, when protected from light, for 24 hours at 15-30degreesC or for up to 7 days when refrigerated at 2-8degreesC.

No dosing information is available for this tab.

No dosing information is available for this tab.

Less than one-third of ziprasidone's metabolic clearance is mediated by cytochrome P-450 (CYP)-catalyzed oxidation, mainly by CYP3A4 and possibly by CYP1A2 to a much lesser extent. Ziprasidone did not substantially inhibit CYP 1A2, 2C9, 2C19, 2D6, or 3A4 isoenzymes in vitro.

Approximately two-thirds of ziprasidone is metabolized via a combination of chemical reduction by glutathione and enzymatic reduction by aldehyde oxidase. There are no known clinically important inhibitors or inducers of aldehyde oxidase.

All interaction studies described below have been conducted with oral ziprasidone.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Known history of QT-interval prolongation (including congenital long QT syndrome), recent acute myocardial infarction, or uncompensated heart failure.

*Concomitant therapy with drugs that prolong the QT interval.

*Known hypersensitivity to ziprasidone.

*Concomitant use with monoamine oxidase inhibitors (MAOIs; including linezolid and IV methylene blue), or use within 14 days of stopping MAOIs.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Adverse effects occurring in 5% or more of patients with schizophrenia receiving oral ziprasidone and at a frequency at least twice that reported with placebo include somnolence and respiratory tract infection.

Adverse effects occurring in 5% or more of patients with bipolar mania receiving oral ziprasidone and at a frequency at least twice that reported with placebo include somnolence, extrapyramidal symptoms, dizziness, akathisia, abnormal vision, asthenia, and vomiting.

Adverse effects occurring in 5% or more of patients with schizophrenia receiving IM ziprasidone 10 or 20 mg and at a frequency at least twice that reported among those receiving IM ziprasidone 2 mg include somnolence, headache, and nausea.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

Safety and efficacy of ziprasidone have not been established in pediatric patients.

A pregnancy exposure registry is available that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including ziprasidone, during pregnancy. Clinicians are encouraged to enroll patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 866-961-2388 or online at https://womensmentalhealth.org/research/pregnancyregistry/.

Currently available data from published epidemiologic studies of pregnant women exposed to ziprasidone have not established a drug-associated risk of major birth defects, miscarriage, or adverse outcomes in the mother or fetus. However, there are risks to the mother (e.g., risk of relapse, hospitalization, suicide) associated with untreated schizophrenia or bipolar I disorder and with exposure to antipsychotics, including ziprasidone, during pregnancy. Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth.

In animals, administration of ziprasidone to pregnant rats and rabbits during the period of organogenesis caused developmental toxicity at dosages similar to human therapeutic dosages. Ziprasidone was teratogenic in rabbits at 3 times the maximum recommended human dose. In rats exposed to ziprasidone during gestation and lactation, increased perinatal pup mortality and delayed neurobehavioral and functional development of offspring were observed at doses less than or similar to human therapeutic dosages.

Neonates exposed to antipsychotic agents, including ziprasidone, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Symptoms reported have included agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder. The complications have varied in severity; some neonates recovered within hours to days without specific treatment while others have required prolonged hospitalization. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately.

Limited data indicate that ziprasidone distributes into human milk. There are no reports of adverse effects on breast-fed infants exposed to ziprasidone through breast milk; however, excess sedation, irritability, poor feeding, and extrapyramidal symptoms (tremors and abnormal muscle movements) have been reported in infants exposed to other atypical antipsychotics through breast milk. There are no data on the effects of ziprasidone on milk production.

Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for ziprasidone and any potential adverse effects on the breast-fed child from the drug or from the mother's underlying condition.

Monitor infants exposed to ziprasidone for excess sedation, irritability, poor feeding, and extrapyramidal symptoms (tremors and abnormal muscle movements).

Although dosage adjustment of oral ziprasidone is generally not necessary in geriatric patients, the manufacturer states that use of lower initial dosages, slower titration, and careful monitoring during the initial dosing period may be considered in some geriatric patients.

IM ziprasidone has not been systematically evaluated in geriatric patients (>=65 years of age).

In clinical studies evaluating oral ziprasidone hydrochloride, 2.4% of patients were 65 years of age and older. Although no overall differences in safety or efficacy of oral ziprasidone were observed between geriatric and younger adults and other reported clinical experience has not identified differences in responses between geriatric and younger patients receiving the drug, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out. Because multiple factors may increase the pharmacodynamic response to ziprasidone or cause poorer tolerance or orthostasis, lower initial dosages, slower titration, and careful monitoring during the initial dosing period should be considered in some geriatric patients.

Ziprasidone mesylate IM injection has not been systematically evaluated in geriatric patients.

In a multiple-dose study and a population pharmacokinetic evaluation of oral ziprasidone, no clinically important differences in pharmacokinetics were observed between geriatric and younger adults.

Geriatric patients with dementia-related psychosis treated with ziprasidone are at an increased risk of cerebrovascular adverse reactions (including stroke) and death compared with those treated with placebo. The manufacturer states that ziprasidone is not approved for the treatment of patients with dementia-related psychosis.