ZIPRASIDONE MESYLATE injection, powder, lyophilized, for solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Summary of Product characteristics (SPC)

30-01-2024

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Active ingredient:

ZIPRASIDONE MESYLATE (UNII: 3X6SAX83JZ) (ZIPRASIDONE - UNII:6UKA5VEJ6X)

Available from:

HF Acquisition Co LLC, DBA HealthFirst

Administration route:

INTRAMUSCULAR

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Ziprasidone mesylate for injection, intramuscular is indicated for acute agitation in schizophrenic patients. When deciding among the alternative treatments available for the condition needing treatment, the prescriber should consider the finding of ziprasidone’s greater capacity to prolong the QT/QTc interval compared to several other antipsychotic drugs [see WARNINGS AND PRECAUTIONS (5.3)]. Prolongation of the QTc interval is associated in some other drugs with the ability to cause torsade de pointes-type arrhythmia, a potentially fatal polymorphic ventricular tachycardia, and sudden death. In many cases this would lead to the conclusion that other drugs should be tried first. Whether ziprasidone will cause torsade de pointes or increase the rate of sudden death is not yet known [see WARNINGS AND PRECAUTIONS ( 5.3)] Acute Treatment of Agitation in Schizophrenia Ziprasidone mesylate for injection intramuscular is indicated for the treatment of acute agitation in schizophrenic adult patients for whom treatment with ziprasidone is appropriate and who need intramuscular antipsychotic medication for rapid control of agitation. [see Clinical Trials (14.1)]. Since there is no experience regarding the safety of administering ziprasidone intramuscular to schizophrenic patients already taking oral ziprasidone, the practice of co-administration is not recommended. 4.1 QT Prolongation Because of ziprasidone’s dose-related prolongation of the QT interval and the known association of fatal arrhythmias with QT prolongation by some other drugs, ziprasidone is contraindicated: in patients with a known history of QT prolongation (including congenital long QT syndrome) in patients with recent acute myocardial infarction in patients with uncompensated heart failure Pharmacokinetic/pharmacodynamic studies between ziprasidone and other drugs that prolong the QT interval have not been performed. An additive effect of ziprasidone and other drugs that prolong the QT interval cannot be excluded. Therefore, ziprasidone should not be given with: dofetilide, sotalol, quinidine, other Class Ia and III anti-arrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, halofantrine, mefloquine, pentamidine, arsenic trioxide, levomethadyl acetate, dolasetron mesylate, probucol or tacrolimus. other drugs that have demonstrated QT prolongation as one of their pharmacodynamic effects and have this effect described in the full prescribing information as a contraindication or a boxed or bolded warning [see WARNINGS AND PRECAUTIONS ( 5.3)]. 4.2 Hypersensitivity Ziprasidone is contraindicated in individuals with a known hypersensitivity to the product. 8.1 Pregnancy Pregnancy Category C In animal studies ziprasidone demonstrated developmental toxicity, including possible teratogenic effects at doses similar to human therapeutic doses. When ziprasidone was administered to pregnant rabbits during the period of organogenesis, an increased incidence of fetal structural abnormalities (ventricular septal defects and other cardiovascular malformations and kidney alterations) was observed at a dose of 30 mg/kg/day (3 times the MRHD of 200 mg/day on a mg/m2 basis). There was no evidence to suggest that these developmental effects were secondary to maternal toxicity. The developmental no-effect dose was 10 mg/kg/day (equivalent to the MRHD on a mg/m2 basis). In rats, embryofetal toxicity (decreased fetal weights, delayed skeletal ossification) was observed following administration of 10 to 160 mg/kg/day (0.5 to 8 times the MRHD on a mg/m2 basis) during organogenesis or throughout gestation, but there was no evidence of teratogenicity. Doses of 40 and 160 mg/kg/day (2 and 8 times the MRHD on a mg/m2 basis) were associated with maternal toxicity. The developmental no-effect dose was 5 mg/kg/day (0.2 times the MRHD on a mg/m2 basis). There was an increase in the number of pups born dead and a decrease in postnatal survival through the first 4 days of lactation among the offspring of female rats treated during gestation and lactation with doses of 10 mg/kg/day (0.5 times the MRHD on a mg/m2 basis) or greater. Offspring developmental delays and neurobehavioral functional impairment were observed at doses of 5 mg/kg/day (0.2 times the MRHD on a mg/m2 basis) or greater. A no-effect level was not established for these effects. There are no adequate and well-controlled studies in pregnant women. Ziprasidone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Non-teratogenic Effects Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. Ziprasidone mesylate for injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 8.2 Labor and Delivery The effect of ziprasidone on labor and delivery in humans is unknown. 8.3 Nursing Mothers It is not known whether ziprasidone or its metabolites are excreted in human milk. It is recommended that women receiving ziprasidone should not breastfeed. 8.4 Pediatric Use The safety and effectiveness of ziprasidone in pediatric patients have not been established. 8.5 Geriatric Use Of the total number of subjects in clinical studies of ziprasidone, 2.4 percent were 65 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Nevertheless, the presence of multiple factors that might increase the pharmacodynamic response to ziprasidone, or cause poorer tolerance or orthostasis, should lead to consideration of a lower starting dose, slower titration, and careful monitoring during the initial dosing period for some elderly patients. Ziprasidone intramuscular has not been systematically evaluated in elderly patients (65 years and over). 8.6 Renal Impairment Because ziprasidone is highly metabolized, with less than 1% of the drug excreted unchanged, renal impairment alone is unlikely to have a major impact on the pharmacokinetics of ziprasidone. The pharmacokinetics of ziprasidone following 8 days of 20 mg twice daily dosing were similar among subjects with varying degrees of renal impairment (n=27), and subjects with normal renal function, indicating that dosage adjustment based upon the degree of renal impairment is not required. Ziprasidone is not removed by hemodialysis. Intramuscular ziprasidone has not been systematically evaluated in elderly patients or in patients with hepatic or renal impairment. As the cyclodextrin excipient is cleared by renal filtration, ziprasidone intramuscular should be administered with caution to patients with impaired renal function [see CLINICAL PHARMACOLOGY (12)]. 8.7 Hepatic Impairment 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 matched control group (n=14). A half-life of 7.1 hours was observed in subjects with cirrhosis compared to 4.8 hours in the control group. 8.8 Age and Gender Effects In a multiple-dose (8 days of treatment) study involving 32 subjects, there was no difference in the pharmacokinetics of ziprasidone between men and women or between elderly (>65 years) and young (18 to 45 years) subjects. Additionally, population pharmacokinetic evaluation of patients in controlled trials has revealed no evidence of clinically significant age or gender-related differences in the pharmacokinetics of ziprasidone. Dosage modifications for age or gender are, therefore, not recommended. 8.9 Smoking Based on in vitro studies utilizing human liver enzymes, ziprasidone is not a substrate for CYP1A2; smoking should therefore not have an effect on the pharmacokinetics of ziprasidone. Consistent with these in vitro results, population pharmacokinetic evaluation has not revealed any significant pharmacokinetic differences between smokers and nonsmokers. 9.3 Dependence Ziprasidone has not been systematically studied, in animals or humans, for its potential for abuse, tolerance, or physical dependence. While the clinical trials did not reveal any tendency for drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which ziprasidone will be misused, diverted, and/or abused once marketed. Consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of ziprasidone misuse or abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior).

Product summary:

Ziprasidone mesylate for injection is available in a single-dose vial as ziprasidone mesylate (20 mg ziprasidone/mL when reconstituted according to label instructions) [see DOSAGE AND ADMINISTRATION (2.3)]. Each mL of ziprasidone mesylate for injection (when reconstituted) affords a colorless to pale pink solution that contains 20 mg of ziprasidone and 4.7 mg of methanesulfonic acid solubilized by 294 mg of sulfobutylether β-cyclodextrin sodium (SBECD). Ziprasidone mesylate for injection should be stored at 20° to 25°C (68° to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] in dry form. Protect from light. Following reconstitution, Ziprasidone mesylate for injection can be stored, when protected from light, for up to 24 hours at 15°C to 30°C (59°F to 86°F) or up to 7 days refrigerated, 2°C to 8°C (36°F to 46°F).

Authorization status:

Abbreviated New Drug Application

ZIPRASIDONE MESYLATE injection, powder, lyophilized, for solution

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Summary of Product characteristics

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