ZELDOX

What it is

ZELDOX IM is ziprasidone mesilate powder for injection. It is presented as a sterile lyophilised powder in a single dose vial. When reconstituted with 1.2 mL Water for Injections, each vial contains 20 mg ziprasidone and 294 mg of the inactive ingredient, sulfobutyl betadex sodium (SBECD) per mL.

Approved indications

— Acute treatment and short term management of agitation and disturbed behaviour in patients with schizophrenia and related psychoses when oral therapy is not appropriate.

Dosing overview

The recommended dose is 10 to 20 mg administered as required up to a maximum dose of 40 mg per day. Doses of 10 mg may be administered every 2 hours, doses of 20 mg may be administered every 4 hours up to a maximum of 40 mg per day. Intramuscular administration of ziprasidone for more than three consecutive days has not been studied. If therapy is indicated, oral ziprasidone hydrochloride capsules, up to 80 mg twice daily, should replace the intramuscular administration as soon as possible.

Key safety warnings

Ziprasidone causes a mild to moderate prolongation of the QT interval. Some drugs that prolong the QT/QTc interval have been associated with the occurrence of torsade de pointes and with sudden unexplained death. There have been rare post-marketing reports of torsade de pointes in patients with multiple confounding risk factors taking ziprasidone. Certain circumstances may increase the risk of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including bradycardia, electrolyte imbalances (especially hypokalaemia or hypomagnesaemia), concomitant use of other drugs that prolong the QTc interval, and presence of congenital prolongation of the QT interval. Ziprasidone should be discontinued in patients who are found to have persistent QTc measurements greater than 500 msec. Neuroleptic malignant syndrome, a potentially fatal complex, has been reported in association with antipsychotic drugs, including ziprasidone. The clinical manifestations are hyperthermia, muscle rigidity, altered mental status and signs of autonomic instability such as irregular pulse and blood pressure, tachycardia, cardiac arrhythmias and diaphoresis. If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all antipsychotic drugs, including ziprasidone, should be discontinued. Drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported with ziprasidone exposure. DRESS consists of a combination of three or more of the following: cutaneous reaction such as rash or exfoliative dermatitis, eosinophilia, fever, lymphadenopathy, and one or more systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and pericarditis. Other severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome, have also been reported with ziprasidone exposure. SCARs are sometimes fatal and ziprasidone should be discontinued if SCARS occur. Dizziness, tachycardia and postural hypotension are not unusual in patients following intramuscular administration of ziprasidone. Single cases of hypertension have also been reported. Caution should be exercised, particularly in ambulatory patients. Fatalities with the use of ziprasidone IM, generally in patients with multiple confounding risk factors, have been reported. Although a causal relationship has not been established, ziprasidone IM should be used with caution.

Contraindications

Known hypersensitivity to any ingredient of the product. Recent acute myocardial infarction. Uncompensated heart failure. Conditions with a potential to increase QT interval, including QT-interval prolongation or history of QT prolongation, congenital long QT syndrome, use with other drugs known to increase the QT interval, and arrhythmias treated with Class IA and III antiarrhythmic drugs.

Regulatory history

ZELDOX IM (ziprasidone as mesilate) 20 mg powder for injection vial was first listed on the ARTG on 24 August 2023.