ZELDOX Capsule Ref.[27776] Active ingredients: Ziprasidone

Dosing Considerations

The absorption of ziprasidone is increased up to two-fold in the presence of a meal. ZELDOX (ziprasidone hydrochloride) should be administered with a meal. See also: WARNINGS and PRECAUTIONS, QT Prolongation, Recommendations regarding Risk Factors for QTc Prolongation.

Recommended Dose and Dosage Adjustment

Schizophrenia

Initial Treatment:

ZELDOX may be administered at an initial daily dose of 40 mg BID with a meal. However, individual patients may benefit from an initial dose of 20 mg BID. Daily dosage may subsequently be adjusted on the basis of clinical status up to 80 mg BID. Dosage adjustments, if indicated, should generally occur at intervals of not less than 2 days, since steady-state is achieved within 1 to 3 days.

Efficacy in schizophrenia was studied in a dose range of 20 to 100 mg BID in short-term, placebocontrolled clinical trials. There were trends toward dose response within the range of 20 to 80 mg BID, but results were not consistent. An increase to a dose greater than 80 mg BID is not generally recommended. The safety of doses above 100 mg BID has not been systematically evaluated in clinical trials.

Maintenance Treatment

It is recommended that responding patients with schizophrenia be continued on ZELDOX at the lowest dose needed to maintain remission. The efficacy of ZELDOX 20, 40, or 80 mg BID in maintenance treatment has been established over a 12-month treatment period.

Patients should be periodically reassessed to determine the need for maintenance treatment. While there is no body of evidence available to answer the question of how long the patient should be treated with ZELDOX, the effectiveness of maintenance treatment is well established for many other antipsychotic drugs.

Bipolar Disorder

Bipolar Mania

Initial Treatment:

Oral ziprasidone should be administered at an initial daily dose of 40 mg BID with a meal. The dose should then be increased to 60 mg or 80 mg BID on the second day of treatment and subsequently adjusted on the basis of toleration and efficacy within the range 40-80 mg BID. In the flexible-dose clinical trials, the mean daily dose administered was approximately 120 mg.

Maintenance Treatment:

There is no body of evidence available from controlled trials to guide a clinician in the longer-term management of a patient who improves during treatment of mania with ziprasidone. While it is generally agreed that pharmacological treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no systematically obtained data to support the use of ziprasidone in such longer-term treatment (i.e., beyond 3 weeks).

Dosage in Special Populations

Dosage adjustments are generally not required on the basis of age, gender, race, or renal impairment.

Geriatrics (>65 years old)

Given the greater sensitivity of this population, a lower starting dose, slower titration, and careful monitoring during the initial dosing period may be considered for elderly patients when clinical factors warrant (see WARNINGS AND PRECAUTIONS-Special Populations, Geriatrics).

ZELDOX is not indicated for treatment of elderly patients with dementia (see WARNINGS AND PRECAUTIONS – Serious Warnings and Precautions).

Hepatic Impairment

Lower doses should be considered for hepatic insufficiency, considering that <1% of ziprasidone is cleared renally, and there is a lack of experience with ziprasidone in patients with severe hepatic impairment.

Missed Dose

The missed dose should be taken at the next scheduled dose. Doses should not be doubled.

Symptoms

In premarketing trials, accidental or intentional overdosage of ziprasidone was documented in 10 patients. All of these patients survived without sequelae. In the patient taking the largest confirmed amount, 3240 mg, the only symptoms reported were minimal sedation, slurring of speech, and transitory hypertension (200/95).

In post-marketing use, the most common adverse events reported in association with ziprasidone overdose generally included extrapyramidal symptoms, somnolence, tremor, and anxiety. Hypertension, hypotension, diarrhea, tachycardia, and prolongation of the QTc and QRS intervals have also been reported.

Treatment

There is no specific antidote to ziprasidone, and it is not dialyzable. The possibility of multiple drug involvement should be considered.

In case of acute overdosage, establish and maintain an airway and ensure adequate oxygenation and ventilation. Intravenous access should be established and gastric lavage (after intubation, if patient is unconscious) and administration of activated charcoal together with a laxative should be considered. The possibility of obtundation, seizure, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis.

Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias. If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry a theoretical hazard of additive QTprolonging effects that might be additive to those of ziprasidone.

Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids. If sympathomimetic agents are used for vascular support, epinephrine and dopamine should not be used, since beta stimulation combined with α1-antagonism associated with ziprasidone may worsen hypotension. Similarly, it is reasonable to expect that the alpha-adrenergic-blocking properties of bretylium might be additive to those of ziprasidone, resulting in problematic hypotension.

In cases of severe extrapyramidal symptoms, anticholinergic medication should be administered.

Close medical supervision and monitoring should continue until the patient recovers.

For management of a suspected drug overdose, contact your regional Poison Control Centre.

Store at controlled room temperature between 15-30°C.