XEPLION Prolonged release suspension for injection Ref.[7473] Active ingredients: Paliperidone

Posology

Recommended initiation of Xeplion is with a dose of 150 mg on treatment day 1 and 100 mg one week later (day 8), both administered in the deltoid muscle in order to attain therapeutic concentrations rapidly (see section 5.2). The third dose should be administered one month after the second initiation dose. The recommended monthly maintenance dose is 75 mg; some patients may benefit from lower or higher doses within the recommended range of 25 to 150 mg based on individual patient tolerability and/or efficacy. Patients who are overweight or obese may require doses in the upper range (see section 5.2). Following the second initiation dose, monthly maintenance doses can be administered in either the deltoid or gluteal muscle.

Adjustment of the maintenance dose may be made monthly. When making dose adjustments, the prolonged release characteristics of Xeplion should be considered (see section 5.2), as the full effect of maintenance doses may not be evident for several months.

Switching from oral prolonged release paliperidone or oral risperidone to Xeplion

Xeplion should be initiated as described at the beginning of section 4.2 above. During monthly maintenance treatment with Xeplion, patients previously stabilised on different doses of paliperidone prolonged release tablets can attain similar paliperdone steady-state exposure by injection. The Xeplion maintenance doses needed to attain similar steady-state exposure are shown as follows:

Doses of paliperidone prolonged release tablets and Xeplion needed to attain similar steady-state paliperidone exposure during maintenance treatment:

Previous oral paliperidone or oral risperidone can be discontinued at the time of initiation of treatment with Xeplion. Some patients may benefit from gradual withdrawal. Some patients switching from higher paliperidone oral doses (e.g. 9-12 mg daily) to gluteal injections with Xeplion may have lower plasma exposure during the first 6 months after the switch. Therefore, alternatively, it could be considered to give deltoid injections for the first 6 months.

Switching from risperidone long acting injection to Xeplion

When switching patients from risperidone long acting injection, initiate Xeplion therapy in place of the next scheduled injection. Xeplion should then be continued at monthly intervals. The one-week initiation dosing regimen including the intramuscular injections (day 1 and 8, respectively) as described in section 4.2 above is not required. Patients previously stabilised on different doses of risperidone long acting injection can attain similar paliperidone steady-state exposure during maintenance treatment with Xeplion monthly doses according to the following:

Doses of risperidone long acting injection and Xeplion needed to attain similar paliperidone exposure at steady-state:

Discontinuation of antipsychotic medicinal products should be made in accordance with appropriate prescribing information. If Xeplion is discontinued, its prolonged release characteristics must be considered. The need for continuing existing extrapyramidal symptoms (EPS) medicine should be re-evaluated periodically.

Missed doses

Avoiding missed doses

It is recommended that the second initiation dose of Xeplion be given one week after the first dose. To avoid a missed dose, patients may be given the second dose 4 days before or after the one-week (day 8) time point. Similarly, the third and subsequent injections after the initiation regimen are recommended to be given monthly. To avoid a missed monthly dose, patients may be given the injection up to 7 days before or after the monthly time point.

If the target date for the second Xeplion injection (day 8 ± 4 days) is missed, the recommended reinitiation depends on the length of time which has elapsed since the patient’s first injection.

Missed second initiation dose (<4 weeks from first injection)

If less than 4 weeks have elapsed since the first injection, then the patient should be administered the second injection of 100 mg in the deltoid muscle as soon as possible. A third Xeplion injection of 75 mg in either the deltoid or gluteal muscles should be administered 5 weeks after the first injection (regardless of the timing of the second injection). The normal monthly cycle of injections in either the deltoid or gluteal muscle of 25 mg to 150 mg based on individual patient tolerability and/or efficacy should be followed thereafter.

Missed second initiation dose (4-7 weeks from first injection)

If 4 to 7 weeks have elapsed since the first injection of Xeplion, resume dosing with two injections of 100 mg in the following manner:

1. a deltoid injection as soon as possible
2. another deltoid injection one week later
3. resumption of the normal monthly cycle of injections in either the deltoid or gluteal muscle of 25 mg to 150 mg based on individual patient tolerability and/or efficacy.

Missed second initiation dose (>7 weeks from first injection)

If more than 7 weeks have elapsed since the first injection of Xeplion, initiate dosing as described for the initial recommended initiation of Xeplion above.

Missed monthly maintenance dose (1 month to 6 weeks)

After initiation, the recommended injection cycle of Xeplion is monthly. If less than 6 weeks have elapsed since the last injection, then the previously stabilised dose should be administered as soon as possible, followed by injections at monthly intervals.

Missed monthly maintenance dose (>6 weeks to 6 months)

If more than 6 weeks have elapsed since the last injection of Xeplion, the recommendation is as follows:

For patients stabilised with doses of 25 to 100 mg

1. a deltoid injection as soon as possible at the same dose the patient was previously stabilised on
2. another deltoid injection (same dose) one week later (day 8)
3. resumption of the normal monthly cycle of injections in either the deltoid or gluteal muscle of 25 mg to 150 mg based on individual patient tolerability and/or efficacy.

For patients stabilised with 150 mg

1. a deltoid injection as soon as possible at the 100 mg dose
2. another deltoid injection one week later (day 8) at the 100 mg dose
3. resumption of the normal monthly cycle of injections in either the deltoid or gluteal muscle of 25 mg to 150 mg based on individual patient tolerability and/or efficacy.

Missed monthly maintenance dose (>6 months)

If more than 6 months have elapsed since the last injection of Xeplion, initiate dosing as described for the initial recommended initiation of Xeplion above.

Special populations

Elderly

Efficacy and safety in elderly > 65 years have not been established.

In general, recommended dosing of Xeplion for elderly patients with normal renal function is the same as for younger adult patients with normal renal function. However, because elderly patients may have diminished renal function, dose adjustment may be necessary (see Renal impairment below for dosing recommendations in patients with renal impairment).

Renal impairment

Xeplion has not been systematically studied in patients with renal impairment (see section 5.2). For patients with mild renal impairment (creatinine clearance ≥50 to <80 mL/min), recommended initiation of Xeplion is with a dose of 100 mg on treatment day 1 and 75 mg one week later, both administered in the deltoid muscle. The recommended monthly maintenance dose is 50 mg with a range of 25 to 100 mg based on patient tolerability and/or efficacy.

Xeplion is not recommended in patients with moderate or severe renal impairment (creatinine clearance <50 mL/min) (see section 4.4).

Hepatic impairment

Based on experience with oral paliperidone, no dose adjustment is required in patients with mild or moderate hepatic impairment. As paliperidone has not been studied in patients with severe hepatic impairment, caution is recommended in such patients (see section 5.2).

Paediatric population

The safety and efficacy of Xeplion in children and adolescents <18 years of age have not been established. No data are available.

Method of administration

Xeplion is intended for intramuscular use only. It must not be administered by any other route. It should be injected slowly, deep into the deltoid or gluteal muscle. Each injection should be administered by a health care professional. Administration should be in a single injection. The dose should not be given in divided injections.

The day 1 and day 8 initiation doses must each be administered in the deltoid muscle in order to attain therapeutic concentrations rapidly (see section 5.2). Following the second initiation dose, monthly maintenance doses can be administered in either the deltoid or gluteal muscle. A switch from gluteal to deltoid (and vice versa) should be considered in the event of injection site pain if the injection site discomfort is not well tolerated (see section 4.8). It is also recommended to alternate between left and right sides (see below).

For instructions for use and handling of Xeplion, see package leaflet (information intended for medical or healthcare professionals).

Deltoid muscle administration

The recommended needle size for initial and maintenance administration of Xeplion into the deltoid muscle is determined by the patient’s weight. For those ≥90 kg, the 1 1⁄2 inch, 22 gauge needle (38.1 mm x 0.72 mm) is recommended. For those <90 kg, the 1-inch, 23 gauge needle (25.4 mm x 0.64 mm) is recommended. Deltoid injections should be alternated between the two deltoid muscles.

Gluteal muscle administration

The recommended needle size for maintenance administration of Xeplion into the gluteal muscle is the 11⁄2-inch, 22 gauge needle (38.1 mm x 0.72 mm). Administration should be made into the upper-outer quadrant of the gluteal area. Gluteal injections should be alternated between the two gluteal muscles.

Symptoms

In general, expected signs and symptoms are those resulting from an exaggeration of paliperidone’s known pharmacological effects, i.e. drowsiness and sedation, tachycardia and hypotension, QT prolongation, and extrapyramidal symptoms. Torsade de pointes and ventricular fibrillation have been reported in a patient in the setting of overdose with oral paliperidone. In the case of acute overdose, the possibility of multiple drug involvement should be considered.

Management

Consideration should be given to the prolonged release nature of the medicinal product and the long elimination half-life of paliperidone when assessing treatment needs and recovery. There is no specific antidote to paliperidone. General supportive measures should be employed. Establish and maintain a clear airway and ensure adequate oxygenation and ventilation.

Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring for possible arrhythmias. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluid and/or sympathomimetic agents. In case of severe extrapyramidal symptoms, anticholinergic agents should be administered. Close supervision and monitoring should continue until the patient recovers.

2 years.

Do not store above 30°C.

Pre-filled syringe (cyclic-olefin-copolymer) with a plunger stopper, backstop, and tip cap (bromobutyl rubber) with a 22G 1 1⁄2-inch safety needle (0.72 mm x 38.1 mm) and a 23G 1-inch safety needle (0.64 mm x 25.4 mm).

Pack sizes: Pack contains 1 pre-filled syringe and 2 needles.

Any unused product or waste material should be disposed of in accordance with local requirements.