Posology : מינונים

4.2    Posology and method of administration

Posology
Patients who are adequately treated with 1-monthly paliperidone palmitate injectable (preferably for four months or more) and do not require dose adjustment may be switched to 3-monthly paliperidone injection.

TREVICTA should be initiated in place of the next scheduled dose of 1-monthly paliperidone palmitate injectable (± 7 days). The TREVICTA dose should be based on the previous 1-monthly paliperidone palmitate injectable dose using a 3.5-fold higher dose shown in the following table: 
TREVICTA doses for patients adequately treated with 1-monthly paliperidone palmitate injectable
If the last dose of 1-monthly paliperidone       Initiate TREVICTA at the following dose palmitate injectable is
50 mg                                       175 mg
75 mg                                       263 mg
100 mg                                       350 mg
150 mg                                       525 mg

There is no equivalent dose of TREVICTA for the 25 mg dose of 1-monthly paliperidone palmitate injectable which was not studied.

Following the initial TREVICTA dose, TREVICTA should be administered by intramuscular injection once every 3 months (± 2 weeks, see also Missed dose section).

If needed, dose adjustment of TREVICTA can be made every 3 months in increments within the range of 175 mg to 525 mg based on individual patient tolerability and/or efficacy. Due to the long-acting nature of TREVICTA, the patient’s response to an adjusted dose may not be apparent for several months (see section 5.2). If the patient remains symptomatic, they should be managed according to clinical practice.

Switching from other antipsychotic medicinal products
TREVICTA is to be used only after the patient has been adequately treated with 1-monthly paliperidone palmitate injectable preferably for four months or more.

Switching from TREVICTA to other antipsychotic medicinal products
If TREVICTA is discontinued, its extended release characteristics must be considered.

Switching from TREVICTA to 1-monthly paliperidone palmitate injectable For switching from TREVICTA to 1-monthly paliperidone palmitate injectable, 1-monthly paliperidone palmitate injectable should be administered at the time the next TREVICTA dose was to be administered using a 3.5-fold lower dose shown in the following table. The initiation dosing as described in the prescribing information for 1-monthly paliperidone palmitate injectable is not required. The 1-monthly paliperidone palmitate injectable should then continue to be dosed at monthly intervals as described within its prescribing information.

Doses of 1-monthly paliperidone palmitate injectable for patients switching from TREVICTA If the last dose of TREVICTA is            Initiate 1-monthly paliperidone palmitate injectable 3 months later at the following dose
175 mg                                           50 mg
263 mg                                           75 mg
350 mg                                          100 mg
525 mg                                          150 mg

Switching from TREVICTA to oral daily paliperidone extended release tablets For switching from TREVICTA to paliperidone extended release tablets, the daily dosing of paliperidone extended release tablets should be started 3 months after the last TREVICTA dose and treatment continued with paliperidone extended release tablets as described in the table below. The following table provides recommended dose conversion regimens to allow patients previously stabilised on different doses of TREVICTA to attain similar paliperidone exposure with paliperidone extended release tablets.


Doses of paliperidone extended release tablets for patients switching from TREVICTA* Week number after last TREVICTA dose
Last TREVICTA dose Week 12 to Week 18, Week 19 to Week 24,                                        From Week 25 (Week 0)                        inclusive                      inclusive                       onwards Daily dose of paliperidone extended release tablets
175 mg                            3 mg                           3 mg                            3 mg 263 mg                            3 mg                           3 mg                            6 mg
350 mg                            3 mg                           6 mg                            9 mg 525 mg                            6 mg                           9 mg                           12 mg * All doses of once daily paliperidone extended release tablets should be individualised to the specific patient, taking into consideration variables such as reasons for switching, response to previous paliperidone treatment, severity of psychotic symptoms, and/or propensity for side effects.

Missed dose

Dosing window
TREVICTA should be injected once every 3 months. To avoid a missed dose of TREVICTA patients may be given the injection up to 2 weeks before or after the 3-month time point.

Missed doses
If scheduled dose is missed and the time since                        Action last injection is
> 3½ months up to 4 months                      The injection should be administered as soon as possible and then resume the 3-monthly injection schedule.
4 months to 9 months                            Use the recommended re-initiation regimen shown in the table below.
> 9 months                                      Re-initiate treatment with 1-monthly paliperidone palmitate injectable as described in the prescribing information for that product.
TREVICTA can then be resumed after the patient has been adequately treated with
1-monthly paliperidone palmitate injectable preferably for four months or more.

Recommended re-initiation regimen after missing 4 months to 9 months of TREVICTA Administer 1-monthly paliperidone palmitate      Then administer injectable, two doses one week apart (into     TREVICTA (into
If the last dose of deltoid muscle)                  deltoida or gluteal
TREVICTA was muscle)
Day 1                   Day 8          1 month after day 8
175 mg                50 mg                   50 mg                 175 mg 263 mg                75 mg                   75 mg                 263 mg
350 mg               100 mg                  100 mg                 350 mg 525 mg               100 mg                  100 mg                 525 mg a
See also Information intended for medical or healthcare professionals for deltoid injection needle selection based on body weight.

Special populations

Elderly
Efficacy and safety in elderly > 65 years have not been established.
In general, recommended dosing of TREVICTA for elderly patients with normal renal function is the same as for younger adult patients with normal renal function. As elderly patients may have reduced renal function, see Renal impairment below for dosing recommendations in patients with renal impairment.
Renal impairment
TREVICTA 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), dose should be adjusted and the patient stabilised using 1-monthly paliperidone palmitate injectable, and then transitioned to TREVICTA.

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

Hepatic impairment
TREVICTA has not been studied in patients with 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 TREVICTA in children and adolescents < 18 years of age have not been established. No data are available.

Method of administration

TREVICTA is intended for intramuscular use only. It must not be administered by any other route.
Each injection must be administered only by a healthcare professional giving the full dose in a single injection. It should be injected slowly, deep into the deltoid or gluteal muscle. A switch from gluteal to deltoid (and vice versa) should be considered for future injection in the event of injection site discomfort (see section 4.8).

TREVICTA must be administered using only the thin wall needles that are provided in the TREVICTA pack. Needles from the 1-monthly paliperidone palmitate injectable pack or other commercially available needles must not be used when administering TREVICTA (see Information intended for medical or healthcare professionals).

The contents of the pre-filled syringe should be inspected visually for foreign matter and discolouration prior to administration. It is important to shake the syringe vigorously with the tip up and a loose wrist for at least 15 seconds to ensure a homogeneous suspension. TREVICTA should be administered within 5 minutes after shaking. If more than 5 minutes pass before injection, shake vigorously again for at least 15 seconds to re-suspend the medicinal product. (See Information intended for medical or health care professionals).

Deltoid muscle administration
The specified needle for administration of TREVICTA into the deltoid muscle is determined by the patient’s weight.
•     For those ≥ 90 kg, the thin wall 1½ inch, 22 gauge (0.72 mm x 38.1 mm) needle should be used.
•     For those < 90 kg, the thin wall 1 inch, 22 gauge (0.72 mm x 25.4 mm) needle should be used.

It should be administered into the centre of the deltoid muscle. Deltoid injections should be alternated between the two deltoid muscles.

Gluteal muscle administration
The needle to be used for administration of TREVICTA into the gluteal muscle is the thin wall 1½ inch, 22 gauge (0.72 mm x 38.1 mm) needle regardless of body weight. It should be administered into the upper-outer quadrant of the gluteal muscle. Gluteal injections should be alternated between the two gluteal muscles.


Incomplete administration
To avoid incomplete administration of TREVICTA, the pre-filled syringe must be shaken vigorously for at least 15 seconds within 5 minutes prior to administration to ensure a homogeneous suspension (see Information intended for medical or health care professionals).

However, in the event of an incompletely injected dose, the dose remaining in the syringe should not be re-injected and another dose should not be given since it is difficult to estimate the proportion of the dose actually administered. The patient should be closely monitored and managed as clinically appropriate until the next scheduled 3-monthly injection of TREVICTA.