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 paliperidone or oral risperidone

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. Xeplion should be initiated as described at the beginning of section 4.2 above.

Switching from risperidone long acting injection

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-eva luated 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