Prescribing information For Healthcare Professionals Only

ACTIVE INGREDIENT(S):

700 mg, 1000 mg paliperidone

Please refer to Summary of Product Characteristics (SmPC) before prescribing.

INDICATION(S): 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.

DOSAGE & ADMINISTRATION: Gluteal intramuscular injection only. It should be injected slowly, deep into the upper-outer quadrant of the gluteal muscle. 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 Adults: Administer dose in gluteal muscle only. Use 1½ inch, 20 gauge (0.9 mm × 38 mm) needle, regardless of body weight. BYANNLI for patients adequately treated with 1-monthly paliperidone palmitate at doses of 100 mg or 150 mg:  Initiate BYANNLI in place of the next scheduled dose of 1-monthly paliperidone palmitate injectable (± 7 days). The BYANNLI dose should be based on the previous 1-monthly paliperidone palmitate injectable dose. Thereafter BYANNLI should be administered by gluteal intramuscular injection once every 6 months (± 14 days). BYANNLI for patients adequately treated with 3-monthly paliperidone palmitate injection at doses of 350 mg or 525 mg: 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. Thereafter BYANNLI should be administered by gluteal intramuscular injection once every 6 months (± 14 days).  Refer to the SmPC for full details of transitioning patients to BYANNLI. Dose adjustment of BYANNLI can be made every 6 months between the dose levels of 700 mg and 1000 mg. Alternate injections between left and right sides. Children: No safety or efficacy data available.  Elderly: No safety or efficacy data available for patients > 65 years.  Renal impairment: Mild (creatinine clearance ≥ 50 to < 80 ml/min): patients 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. 1000 mg dose of BYANNLI is not recommended for patients with mild renal impairment. Moderate or severe (creatinine clearance < 50 ml/min): Not recommended.  Hepatic impairment: Caution in severe hepatic impairment.

CONTRAINDICATIONS: Hypersensitivity to paliperidone, risperidone or any of the excipients.

SPECIAL WARNINGS & PRECAUTIONS: Do not use in acutely agitated or severely psychotic patients. Not recommended in elderly dementia patients. Caution in cardiovascular disease (including family history of QT prolongation), cerebrovascular disease, hypotension, prolactin-dependent tumours, seizures, Parkinson’s disease and in conjunction with medicines that prolong QT interval. May induce orthostatic hypotension. If tardive dyskinesia occurs, consider discontinuing all antipsychotics. Caution is warranted in patients receiving both, psychostimulants (e.g., methylphenidate) and paliperidone concomitantly, as extrapyramidal symptoms could emerge when adjusting one or both medications. Gradual withdrawal of stimulant treatment is recommended. Events of leucopenia, neutropenia, and agranulocytosis reported with antipsychotics, including BYANNLI, additional monitoring or cessation of treatment may be required. If Neuroleptic Malignant Syndrome (NMS) occurs discontinue all antipsychotics. Rarely, anaphylactic reactions reported in patients previously tolerating oral risperidone/paliperidone. If occur, discontinue BYANNLI, initiate general supportive measures, monitor until resolved. Appropriate clinical monitoring in diabetics and those with risk factors for diabetes advisable. Advise of potential for weight gain, monitor weight regularly. Priapism reported with oral paliperidone. Caution in patients experiencing conditions which may contribute to core body temperature elevation. Identify all possible risk factors for venous thromboembolism (VTE) before and during treatment and take preventive measures. Antiemetic effect (observed in paliperidone preclinical studies) may mask overdosage with certain

medicines, intestinal obstruction, Reye’s syndrome, brain tumour etc. Avoid inadvertent injection into a blood vessel. Intraoperative floppy iris syndrome (IFIS) observed during cataract surgery in patients treated with medicines with alpha 1a-adrenergic antagonist effect, such as BYANNLI.

SIDE EFFECTS: Very Common: insomnia. Common: upper respiratory tract infection, urinary tract infection, influenza, hyperprolactinaemia, hyperglycaemia, weight increased, weight decreased, decreased appetite, agitation, depression, anxiety, parkinsonism, akathisia, sedation/ somnolence, dystonia, dizziness, dyskinesia, tremor, headache, tachycardia, hypertension, cough, nasal congestion, abdominal pain, vomiting, nausea, constipation, diarrhoea, dyspepsia, toothache, transaminases increased, musculoskeletal pain, back pain, arthralgia, amenorrhoea, pyrexia, asthenia, fatigue, injection site reaction. Other side effects reported with paliperidone include: pneumonia, respiratory tract infection, cellulitis, thrombocytopenia, diabetes mellitus, electrocardiogram QT prolonged, bradycardia, subcutaneous abscess, neutropenia, inappropriate antidiuretic hormone secretion, diabetic ketoacidosis, NMS, cerebral ischaemia, unresponsive to stimuli, loss of consciousness, depressed level of consciousness, glaucoma, atrial fibrillation, pulmonary congestion, pancreatitis, faecaloma, urinary retention, hypothermia, agranulocytosis, anaphylactic reaction, water intoxication, diabetic coma, pulmonary embolism, pneumonia aspiration, intestinal obstruction, ileus, Stevens-Johnson syndrome/toxic epidermal necrolysis, angioedema, rhabdomyolysis, injection site necrosis. Other side effects reported with risperidone (paliperidone is the active metabolite of risperidone): Weight gain: 10.6% of BYANNLI-treated subjects experienced weight gain of ≥ 7%. Laboratory tests: Serum prolactin: increases in serum prolactin observed. Class effects: QT prolongation, ventricular arrhythmias, sudden unexplained death, cardiac arrest, and Torsade de pointes may occur with antipsychotics. Cases of venous thromboembolism, including pulmonary embolism and deep vein thrombosis, also reported.  

Refer to SmPC for other side effects.

PREGNANCY: Plasma exposure to paliperidone after a single dose of BYANNLI is expected to remain for up to 4 years. BYANNLI should only be used in women planning to become pregnant if clearly necessary. BYANNLI should not be used during pregnancy unless clearly necessary.

LACTATION: Breast-fed infants may be at risk even from BYANNLI administration long before breast-feeding. Patients currently under treatment or who have been treated in the past 4 years with BYANNLI should not breast feed.

INTERACTIONS: Caution with medicines that prolong QT interval e.g., class IA and class III antiarrhythmics, some antihistaminics, some antibiotics, some other antipsychotics, some antimalarials. Potential for BYANNLI to affect other medicines: Caution in conjunction with: other centrally acting medicines e.g., anxiolytics, antipsychotics, hypnotics, opiates, alcohol; medicines known to lower seizure threshold i.e., phenothiazines, butyrophenones, tricyclics, SSRI’s, tramadol, mefloquine; medicines capable of inducing orthostatic hypotension (an additive effect may be observed when BYANNLI is co-administered); levodopa and other dopamine agonists (paliperidone may antagonize their effect- use lowest effective dose of each treatment if this combination necessary e.g., end-stage Parkinson’s disease). Interaction of BYANNLI with lithium unlikely. Potential for other medicines to affect BYANNLI: Administration of oral paliperidone and paroxetine (a potent CYP2D6 inhibitor) showed no clinically significant effect on paliperidone pharmacokinetics. Co-administration of oral paliperidone once daily with carbamazepine 200 mg twice daily decreases plasma concentration of paliperidone by 37%. Re-evaluate/increase BYANNLI dose at carbamazepine initiation. No clinically significant interaction expected between valproate and BYANNLI. Caution when BYANNLI is co administered with risperidone or with oral paliperidone for extended periods of time. Limited safety data for concomitant use of BYANNLI with other antipsychotics. The combined use of psychostimulants (e.g. methylphenidate) with paliperidone can lead to extrapyramidal symptoms upon change of either/both treatments

Refer to SmPC for full details of interactions.

LEGAL CATEGORY: Prescription Only Medicine

MARKETING AUTHORISATION HOLDER:
Great Britain: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG, UK.
Northern Ireland: Janssen Cilag International NV, Turnhoutseweg 30, B 2340 Beerse, Belgium.

FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG, UK. 

Prescribing information last revised: March 2022