Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium
BYANNLI, a 6-monthly injection, is indicated for the maintenance treatment of schizophrenia in adult patients who are clinically stable on 1-monthly or 3-monthly paliperidone palmitate injectable products (see section 5.1).
Patients who are adequately treated with 1-monthly paliperidone palmitate injection at doses of 100 mg or 150 mg (preferably for four months or more) or 3-monthly paliperidone palmitate injection at doses of 350 mg or 525 mg (for at least one injection cycle) and do not require dose adjustment may be transitioned to 6-monthly paliperidone palmitate injection.
BYANNLI should be initiated in place of the next scheduled dose of 1-monthly paliperidone palmitate injection (± 7 days). To establish a consistent maintenance dose, it is recommended that the last two doses of 1-monthly paliperidone palmitate injection be the same dose strength before starting BYANNLI. The BYANNLI dose should be based on the previous 1-monthly paliperidone palmitate injectable dose shown in the following table:
Transitioning to BYANNLI for patients adequately treated with 1-monthly paliperidone palmitate injection:
| If the last dose of 1-monthly paliperidone injection is | Initiate BYANNLI at the following dose* |
| 100 mg | 700 mg |
| 150 mg | 1 000 mg |
* There are no equivalent doses of BYANNLI for the 25 mg, 50 mg or 75 mg doses of 1-monthly paliperidone palmitate injection, which were not studied.
BYANNLI should be initiated in place of the next scheduled dose of 3-monthly paliperidone palmitate injection (± 14 days). The BYANNLI dose should be based on the previous 3-monthly paliperidone palmitate injectable dose shown in the following table:
Transitioning to BYANNLI for patients adequately treated with 3-monthly paliperidone palmitate injection:
| If the last dose of 3-monthly paliperidone injection is | Initiate BYANNLI at the following dose* |
| 350 mg | 700 mg |
| 525 mg | 1 000 mg |
* There are no equivalent doses of BYANNLI for the 175 mg or 263 mg doses of 3-monthly paliperidone palmitate injection, which were not studied.
Following the initial BYANNLI dose, BYANNLI should be administered once every 6 months. If necessary, patients may be given the injection up to 2 weeks before or up to 3 weeks after the 6-month scheduled timepoint (see also Missed dose section).
If needed, dose adjustment of BYANNLI can be made every 6 months between the dose levels of 700 mg and 1 000 mg based on individual patient tolerability and/or efficacy. Due to the long-acting nature of BYANNLI 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.
Patients should not be switched directly from other antipsychotics as BYANNLI should only be initiated after the patient is stabilised on 3-monthly or 1-monthly paliperidone palmitate injectable products.
If BYANNLI is discontinued, its prolonged-release characteristics must be considered. Transitioning from BYANNLI to 1-monthly paliperidone palmitate injection When transitioning from BYANNLI to 1-monthly paliperidone palmitate injection, the 1-monthly injection should be administered at the time of the next scheduled BYANNLI dose as shown in the following table. The initiation dosing as described in the prescribing information for 1-monthly paliperidone palmitate injection is not required. The 1-monthly paliperidone palmitate injection should then be dosed at monthly intervals as described within the prescribing information for that product.
Doses of 1-monthly paliperidone palmitate injectable for patients transitioning from BYANNLI:
| If the last dose of BYANNLI is | Initiate 1-monthly paliperidone injection 6 months later at the following dose |
| 700 mg | 100 mg |
| 1 000 mg | 150 mg |
When transitioning patients from BYANNLI to 3-monthly paliperidone palmitate injection, the 3-monthly injection should be administered at the time of the next scheduled BYANNLI dose as shown in the following table. The initiation dosing regimen described in the prescribing information for 3-monthly paliperidone palmitate injection is not required. The 3-monthly paliperidone palmitate injection should then be dosed at 3-monthly intervals as described within the prescribing information for that product.
Doses of 3-monthly paliperidone palmitate injectable for patients transitioning from BYANNLI:
| If the last dose of BYANNLI is | Initiate 3-monthly paliperidone injectable 6 months later at the following dose |
| 700 mg | 350 mg |
| 1 000 mg | 525 mg |
When transitioning patients from BYANNLI to paliperidone prolonged-release tablets, the daily dosing of paliperidone prolonged-release tablets should be started 6 months after the last BYANNLI dose and treatment should be continued with paliperidone prolonged-release tablets as described in the table below. Patients previously stabilised on different doses of BYANNLI can attain similar paliperidone exposure with paliperidone prolonged-release tablets according to the following conversion regimens:
Doses of paliperidone prolonged-release tablets for patients transitioning from BYANNLI*:
| If the last dose of BYANNLI is | Months after last BYANNLI dose | ||
| 6 months to | 9 months More than 9 months to 12 months | More than 12 months | |
| Daily dose of paliperidone prolonged-release tablets | |||
| 700 mg | 3 mg | 6 mg | 9 mg |
| 1 000 mg | 6 mg | 9 mg | 12 mg |
* All doses of once daily paliperidone prolonged-release tablets should be individualised to the specific patient, taking into consideration variables such as reasons for transitioning, response to previous paliperidone treatment, severity of psychotic symptoms, and/or propensity for side effects.
BYANNLI should be injected once every 6 months. To avoid a missed dose of BYANNLI, patients may be given the injection up to 2 weeks before or up to 3 weeks after the scheduled 6-month time point.
Missed doses:
| If scheduled dose is missed and the time since last injection is | Action |
|---|---|
| up to 6 months and 3 weeks | The injection of BYANNLI should be administered as soon as possible and then resume the 6-monthly injection schedule. |
| >6 months and 3 weeks up to <8 months | The injection of BYANNLI should not be administered. Use the recommended re-initiation regimen with 1-monthly paliperidone palmitate injectable as shown in the table below. |
| ≥8 months to ≤11 months | The injection of BYANNLI should not be administered. Use the recommended re-initiation regimen with 1-monthly paliperidone palmitate injectable as shown in the table below. |
| >11 months | The injection of BYANNLI should not be administered. Re-initiate treatment with 1-monthly paliperidone palmitate injectable as described in the prescribing information for that product. BYANNLI 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 > 6 months and 3 weeks up to <8 months of BYANNLI | ||
|---|---|---|
| If the last dose of BYANNLI was | Administer 1-monthly paliperidone palmitate injectable (into deltoida muscle) | Then administer BYANNLI (into gluteal muscle) |
| Day 1 | 1 month after Day 1 | |
| 700 mg | 100 mg | 700 mg |
| 1 000 mg | 150 mg | 1 000 mg |
| Recommended re-initiation regimen after missing ≥8 months to ≤11 months of BYANNLI | |||
|---|---|---|---|
| If the last dose of BYANNLI was | Administer 1-monthly paliperidone palmitate injectable (into deltoida muscle) | Then administer BYANNLI (into gluteal muscle) | |
| Day 1 | Day 8 | 1 month after Day 8 | |
| 700 mg | 100 mg | 100 mg | 700 mg |
| 1 000 mg | 100 mg | 100 mg | 1 000 mg |
a See Information intended for healthcare professionals for the 1-monthly paliperidone palmitate injectable product for deltoid injection needle selection based on body weight.
Efficacy and safety in elderly > 65 years have not been established.
In general, recommended dosing of BYANNLI 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.
While BYANNLI has not been systematically studied in patients with renal impairment, the plasma concentrations of orally administered paliperidone are increased in these patients (see sections 4.4 and 5.2).
Patients with mild renal impairment (creatinine clearance ≥50 to ≤80 mL/min) who are stabilised on either 100 mg 1-monthly paliperidone palmitate injectable or 350 mg 3-monthly paliperidone palmitate injectable can be transitioned to BYANNLI at the 700 mg dose only. The 1 000 mg dose of BYANNLI is not recommended for patients with mild renal impairment.
BYANNLI is not recommended in patients with moderate or severe renal impairment (creatinine clearance <50 mL/min).
BYANNLI 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).
The safety and efficacy of BYANNLI in children and adolescents < 18 years of age have not been established. No data are available.
BYANNLI is for gluteal 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 upper-outer quadrant of the gluteal muscle. A switch between the two gluteal muscles should be considered for future injections in the event of injection site discomfort (see section 4.8).
The needle for administration of BYANNLI is a thin wall 1½ inch, 20 gauge (0.9 mm × 38 mm) needle, regardless of body weight. BYANNLI must be administered using only the thin wall needle that is provided in the BYANNLI pack. Needles from the 3-monthly or 1-monthly paliperidone palmitate injectable pack or other commercially available needles must not be used when administering BYANNLI (see Information intended for healthcare professionals).
The contents of the pre-filled syringe should be inspected visually for foreign matter and discolouration prior to administration. This highly concentrated product requires specific steps to ensure complete resuspension.
It is important to shake the syringe with the syringe tip cap pointing up using a very fast up and down motion with a loose wrist for at least 15 seconds. Rest briefly, then shake again in the same way, using a very fast up and down motion with a loose wrist for a further 15 seconds to resuspend the medicinal product. Proceed immediately to inject BYANNLI. If more than five minutes passes before the injection is administered, shake the syringe again, as above to resuspend the medicinal product (see Information intended for healthcare professionals).
BYANNLI is a highly concentrated product that requires specific steps to ensure complete resuspension and prevent clogging of the needle during injection. Proper shaking can reduce the likelihood of an incomplete injection. Shipping and storing the carton in a horizontal orientation improves the ability to resuspend this highly concentrated product. Follow the details in the Information intended for healthcare professionals to avoid an incomplete injection.
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 6-monthly injection of BYANNLI.
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.
Consideration should be given to the long-acting 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.
This medicinal product does not require any special temperature storage conditions.
Ship and store in a horizontal position. See arrows on product carton for proper orientation.
Pre-filled syringe (cyclic-olefin-copolymer) with a plunger stopper, plunger rod, backstop, and tip cap (bromobutyl rubber) with a thin wall 20G 1½ inch (0.9 mm × 38 mm) safety needle.
Pack sizes: Pack contains 1 pre-filled syringe and 1 needle.
Ship and store this product in a horizontal orientation to improve the ability to resuspend this highly concentrated product and prevent clogging of the needle.
Shake the syringe very fast for at least 15 seconds, rest briefly, then shake again for 15 seconds. The suspension should be visually inspected before injection. When mixed well the product is uniform, thick and milky white. Full instructions for use and handling of BYANNLI are provided in the package leaflet (See Information intended for healthcare professionals).
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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