Ziprasidone was administered for 24 months in the diet at doses of 2, 6, or 12 mg/kg/day to rats, and 50, 100, or 200 mg/kg/day to mice (0.1 to 0.6 and 1 to 5 times the maximum recommended human dose (MRHD) of 200 mg/day based on mg/mZiprasidone had no effect on serum prolactin in rats in a 5-week dietary study at the doses that were used in the carcinogenicity study. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. **Dizziness includes the adverse reaction terms dizziness and lightheadedness.An analysis for dose response in the schizophrenia 4-study pool revealed an apparent relation of adverse reaction to dose for the following reactions: asthenia, postural hypotension, anorexia, dry mouth, increased salivation, arthralgia, anxiety, dizziness, dystonia, hypertonia, somnolence, tremor, rhinitis, rash, and abnormal visionThe incidence of reported EPS (which included the adverse reaction terms extrapyramidal syndrome, hypertonia, dystonia, dyskinesia, hypokinesia, tremor, paralysis and twitching) for ziprasidone-treated patients in the short-term, placebo-controlled schizophrenia trials was 14% vs. 8% for placebo. It has a molecular weight of 412.94 (free base), with the following chemical name: 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2Ziprasidone capsules USP contain a monohydrochloride, monohydrate salt of Ziprasidone. The most common reactions associated with dropout in the Ziprasidone-treated patients were akathisia, anxiety, depression, dizziness, dystonia, rash and vomiting, with 2 dropouts for each of these reactions among Ziprasidone patients (1%) compared to one placebo patient each for dystonia and rash (1%) and no placebo patients for the remaining adverse reactions.Table 12 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse reactions that occurred during acute therapy (up to 3 weeks) in patients with bipolar mania, including only those reactions that occurred in 2% or more of patients treated with Ziprasidone and for which the incidence in patients treated with Ziprasidone was greater than the incidence in placebo-treated patients.Explorations for interactions on the basis of gender did not reveal any clinically meaningful differences in the adverse reaction occurrence on the basis of this demographic factor.The following adverse reactions have been identified during post-approval use of Ziprasidone hydrochloride. It is not known if this is a direct result of the illness or other comorbid factors.Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including Ziprasidone, during the third trimester of pregnancy. As Ziprasidone is cleared substantially by the liver, the presence of hepatic impairment would be expected to increase the AUC of Ziprasidone; a multiple-dose study at 20 mg twice daily for 5 days in subjects (n=13) with clinically significant (Childs-Pugh Class A and B) cirrhosis revealed an increase in AUC 0-12 of 13% and 34% in Childs-Pugh Class A and B, respectively, compared to a … Patients with a pre-existing low WBC or a history of drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and should discontinue ziprasidone at the first sign of decline in WBC in the absence of other causative factors.Patients with neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system (CNS) pathology.The management of NMS should include: (1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; (2) intensive symptomatic treatment and medical monitoring; and (3) treatment of any concomitant serious medical problems for which specific treatments are available. Ziprasidone use should be avoided in combination with other drugs that are known to prolong the QTc interval [see Contraindications and Drug Interactions ]. Appropriate care is advised when prescribing Ziprasidone for patients who will be experiencing conditions which may contribute to an elevation in core body temperature, e.g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration.The possibility of a suicide attempt is inherent in psychotic illness or bipolar disorder, and close supervision of high-risk patients should accompany drug therapy.