ZYPADHERA* 210 mg, 300 mg, and 405 mg, powder and solvent for prolonged release suspension for injection.

Each 210 mg vial contains olanzapine pamoate monohydrate equivalent to 210 mg olanzapine. After reconstitution each ml of suspension contains 150 mg olanzapine.

Each 300 mg vial contains olanzapine pamoate monohydrate equivalent to 300 mg olanzapine. After reconstitution each ml of suspension contains 150 mg olanzapine.

Each 405 mg vial contains olanzapine pamoate monohydrate equivalent to 405 mg olanzapine. After reconstitution each ml of suspension contains 150 mg olanzapine.

For the full list of excipients see section 6.1.

Powder and solvent for prolonged release suspension for injection.

Powder: yellow solid

Solvent: clear, colourless to slightly yellow solution.

Maintenance treatment of adult patients with schizophrenia sufficiently stabilised during acute treatment with oral olanzapine.

ZYPADHERA 210 mg, 300 mg, and 405 mg, powder and solvent for prolonged release suspension for injection must not be confused with olanzapine 10 mg powder for solution for injection.

Posology

Patients should be treated initially with oral olanzapine before administering ZYPADHERA, to establish tolerability and response.

In order to identify the first ZYPADHERA dose for all patients, the scheme in Table 1 should be considered.

Table 1 Recommended dose scheme between oral olanzapine and ZYPADHERA

Dose adjustment

Patients should be monitored carefully for signs of relapse during the first one to two months of treatment. During antipsychotic treatment, improvement in the patient's clinical condition may take several days to some weeks. Patients should be closely monitored during this period. During treatment, dose may subsequently be adjusted on the basis of individual clinical status. After clinical reassessment, dose may be adjusted within the range 150 mg to 300 mg every 2 weeks or 300 to 405 mg every 4 weeks. (Table 1)

Supplementation

Supplementation with oral olanzapine was not authorised in double-blind clinical studies. If oral olanzapine supplementation is clinically indicated, then the combined total dose of olanzapine from both formulations should not exceed the corresponding maximum oral olanzapine dose of 20 mg/day.

Switching to other antipsychotic medicinal products

There are no systematically collected data to specifically address switching patients from ZYPADHERA to other antipsychotic medicinal products. Due to the slow dissolution of the olanzapine pamoate salt which provides a slow continuous release of olanzapine that is complete approximately six to eight months after the last injection, supervision by a clinician, especially during the first 2 months after discontinuation of ZYPADHERA, is needed when switching to another antipsychotic product, and is considered medically appropriate.

Special populations

Elderly patients

ZYPADHERA has not been systematically studied in elderly patients (> 65 years). ZYPADHERA is not recommended for treatment in the elderly population unless a well-tolerated and effective dose regimen using oral olanzapine has been established. A lower starting dose (150 mg/4 weeks) is not routinely indicated, but should be considered for those 65 and over when clinical factors warrant. ZYPADHERA is not recommended to be started in patients >75 years (see section 4.4).

Patients with renal and/or hepatic impairment

Unless a well-tolerated and effective dose regimen using oral olanzapine has been established in such patients, ZYPADHERA should not be used. A lower starting dose (150 mg every 4 weeks) should be considered for such patients. In cases of moderate hepatic insufficiency (cirrhosis, Child-Pugh class A or B), the starting dose should be 150 mg every 4 weeks and only increased with caution.

Smokers

The starting dose and dose range need not be routinely altered for non-smokers relative to smokers. The metabolism of olanzapine may be induced by smoking. Clinical monitoring is recommended and an increase of olanzapine dose may be considered if necessary (see section 4.5).

When more than one factor is present which might result in slower metabolism (female gender, geriatric age, non-smoking status), consideration should be given to decreasing the dose. When indicated, dose escalation should be performed with caution in these patients.

Paediatric population

The safety and efficacy of ZYPADHERA in children and adolescents below 18 years has not been established. Currently available data are described in sections 4.8 and 5.1 but no recommendation on a posology can be made.

Method of administration

FOR INTRAMUSCULAR USE ONLY. DO NOT ADMINISTER INTRAVENOUSLY OR SUBCUTANEOUSLY (See section 4.4)

ZYPADHERA should only be administered by deep intramuscular gluteal injection by a healthcare professional trained in the appropriate injection technique and in locations where post-injection observation and access to appropriate medical care in the case of overdose can be assured.

After each injection, patients should be observed in a healthcare facility by appropriately qualified personnel for at least 3 hours for signs and symptoms consistent with olanzapine overdose. Immediately prior to leaving the healthcare facility, it should be confirmed that the patient is alert, oriented, and absent of any signs and symptoms of overdose. If an overdose is suspected, close medical supervision and monitoring should continue until examination indicates that signs and symptoms have resolved (see section 4.4). The 3-hour observation period should be extended as clinically appropriate for patients who exhibit any signs or symptoms consistent with olanzapine overdose.

For instructions for use, see section 6.6.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Patients with known risk of narrow-angle glaucoma.