50 mg, 75 mg, 100 mg & 150 mg prolonged release suspension for injectionPRESCRIBING INFORMATION
ACTIVE INGREDIENT(S): 50 mg, 75 mg, 100 mg or 150 mg paliperidone.
Please refer to Summary of Product Characteristics (SmPC) before prescribing.
INDICATION(S): XEPLION is indicated for maintenance treatment of schizophrenia in adult patients stabilised with paliperidone or risperidone. In selected adult patients with schizophrenia and previous responsiveness to oral paliperidone or risperidone, XEPLION may be used without prior stabilisation with oral treatment if psychotic symptoms are mild to moderate and a long-acting injectable treatment is needed.
DOSAGE & ADMINISTRATION: Intramuscular use only. Initiation doses (days 1 and 8) must be administered in deltoid muscle for therapeutic concentrations to be rapidly attained. Adults: 150 mg on treatment day 1 and 100 mg one week later (day 8 ± 4), both doses administered in deltoid muscle, using 1½ inch, 22 gauge needle (38.1 mm x 0.72 mm) for patients ³ 90 kg, or 1-inch, 23 gauge needle (25.4 mm x 0.64 mm) for those < 90 kg. The third dose should be administered one month after the second initiation dose. Recommended monthly maintenance dose is 75 mg (range 50 mg-150 mg) in either deltoid or gluteal muscle. Recommended needle size for maintenance administration of XEPLION into deltoid muscle is as for initiation doses, and for the gluteal muscle is the 1½-inch, 22 gauge needle (38.1 mm x 0.72 mm). To avoid a missed monthly maintenance dose patients may be given injection up to 7 days before or after the monthly time point. Consider maintenance doses in upper range for overweight/obese patients. Adjust maintenance dose at monthly intervals as necessary. Alternate injections between left and right sides. Discontinue previous oral paliperidone or risperidone at time of initiation of XEPLION treatment (gradual withdrawal may benefit some patients). When switching patients from RISPERDAL® CONSTATM, initiate XEPLION in place of next scheduled injection, continue at monthly intervals. 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): Initiate with 100 mg on treatment day 1 and 75 mg one week later (day 8). Recommended monthly maintenance dose 50 mg. 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. Caution in cardiovascular disease (including family history of QT prolongation), cerebrovascular disease (especially elderly patients with dementia and risk factors for stroke), hypotension/ hypotensive states, prolactin-dependent tumours, seizures (or conditions that lower seizure threshold), Parkinson’s disease and dementia with Lewy bodies. Discontinue all antipsychotics if neuroleptic malignant syndrome occurs. Consider discontinuation of all antipsychotics if tardive dyskinesia occurs. 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. Monitoring of white cell count (WCC) may be required. Discontinue XEPLION at first sign of clinically significant WCC in absence of other causes or if severe neutropenia (absolute neutrophil count <1 X 109/L). Rarely, anaphylactic reactions reported in patients previously tolerating oral risperidone/paliperidone. If occur, discontinue XEPLION, initiate general supportive measures and monitor until resolved. Appropriate clinical monitoring advised in patient with or at risk of diabetes. Advise of potential for weight gain, monitor weight regularly. Advise male patients to seek urgent medical care if priapism not resolved within 4 hours. Appropriate care advised for patients who will experience conditions that elevate core body temperature. 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 other conditions including overdose with certain medicines. Avoid inadvertent injection into a blood vessel. Intraoperative floppy iris syndrome (IFIS) has been observed during cataract surgery in patients treated with medicines with alpha1a-adrenergic antagonist effect, such as XEPLION.
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, galactorrhoea, pyrexia, asthenia, fatigue and injection site reaction. Other side effects reported with paliperidone include: pneumonia, respiratory tract infection, cellulitis, subcutaneous abscess, thrombocytopenia, neutropenia, agranulocytosis, hypersensitivity, anaphylactic reaction, inappropriate antidiuretic hormone secretion, diabetic ketoacidosis, diabetes mellitus, hypoglycaemia, water intoxication, neuroleptic malignant syndrome, tardive dyskinesia, cerebral ischaemia, loss of consciousness, convulsion, diabetic coma, glaucoma, atrial fibrillation, atrioventricular block, bradycardia, pulmonary embolism, venous thrombosis, pulmonary congestion, pneumonia aspiration, pancreatitis, faecaloma, intestinal obstruction, ileus, jaundice, Stevens-Johnson syndrome/toxic epidermal necrolysis, angioedema, rhabdomyolysis, urinary retention, hypothermia, body temperature increased, drug withdrawal syndrome (including neonatal), injection site necrosis. Injection site reactions: mild to moderate pain most commonly reported (tended to lessen in frequency and intensity over time). Weight gain: 12 % of XEPLION-treated subjects experienced weight gain of ³ 7% (from double-blind phase to endpoint) during 33-week open-label phase of long-term recurrence prevention study. Laboratory tests: Serum prolactin: increases in serum prolactin observed in clinical trial subjects (both genders) with XEPLION. Adverse reactions suggesting increase in prolactin levels reported overall in <1% of subjects. Class effects: 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: Should not be used during pregnancy unless clearly necessary.
LACTATION: Should not be used while breast-feeding.
INTERACTIONS: Caution with medicines that prolong QT interval e.g., class IA and class III antiarrhythmics, some antihistaminics, some other antipsychotics, some antimalarials. Potential for XEPLION 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, clozapine, tricyclics, SSRIs, tramadol, mefloquine etc; medicines capable of inducing orthostatic hypotension (an additive effect may be observed when XEPLION 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 XEPLION with lithium unlikely. Potential for other medicines to affect XEPLION: Concomitant 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 XEPLION dose at carbamazepine initiation. No clinically significant interaction expected between valproate and XEPLION. Caution when XEPLION is co- administered with risperidone or with oral paliperidone for extended periods of time. Limited safety data for concomitant use of XEPLION 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.
PRESENTATIONS, PACK SIZES, MARKETING AUTHORISATION NUMBER(S) & BASIC NHS COSTS
|PRESENTATIONS||PACK SIZES||MARKETING AUTHORISATION NUMBER||BASIC NHS COSTS|
|50 mg pre-filled syringe||1 dose||
|75 mg pre-filled syringe||
|100 mg pre-filled syringe||
|150 mg pre-filled syringe||
MARKETING AUTHORISATION HOLDER:
Great-Britain (PLGB): Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK.
Northern Ireland (EU); 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: April 2021