Abbreviated prescribing information

EXPAREL LIPOSOMAL 133 MG/10 ML and  266 MG/20 ML PROLONGED-RELEASE DISPERSION FOR INJECTION  – (BUPIVACAINE) – ABBREVIATED PRESCRIBING INFORMATION (API)

Consult the summary of product characteristics before prescribing. Additional information is available on request.

 

Presentations: Each mL contains 13.3 mg bupivacaine in a multivesicular liposomal dispersion. Each 10 mL vial contains 133 mg bupivacaine; each 20 mL vial contains 266 mg bupivacaine. Indication: Brachial plexus block or femoral nerve block for treatment of post-operative pain in adults; field block for treatment of somatic post-operative pain from small- to medium-sized surgical wounds in adults and children aged 6 years or older. Posology and method of administration: Recommended dose: Recommended dose is based on the size of the surgical site, volume required to cover the area, and individual patient factors. In paediatric patients ³ 6 years, administer EXPAREL liposomal at a dose of 4 mg/kg. Do not exceed a maximum dose of 266 mg (20 mL of undiluted medicinal product).  Refer to full SmPC for dose examples for different procedures. Co-administration with other local anaesthetics: Use EXPAREL liposomal with caution including monitoring for neurologic and cardiovascular effects related to local anaesthetic systemic toxicity. It should not be used interchangeably with other formulations of bupivacaine. Bupivacaine hydrochloride (immediate release formulations) and EXPAREL liposomal may be administered simultaneously in the same syringe as long as the ratio of the mg dose of bupivacaine solution to EXPAREL liposomal does not exceed 1:2. If preparing admixture, the total amount of bupivacaine used (EXPAREL liposomal + bupivacaine HCl) should not exceed 400 mg equivalents of bupivacaine HCl in adults. Elderly patients: Use care in dose selection as bupivacaine is substantially excreted by the kidney and there may be an increased risk of toxic reactions in patients with impaired renal function. No dose adjustment is required; however, greater sensitivity of some older individuals cannot be excluded. The risk of falls may increase for elderly patients. Hepatic/renal impairment: Risk of toxic reactions may be greater in patients with impaired renal function, therefore use care when selecting dose. No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh score 5-6) or moderate hepatic impairment (Child-Pugh score 7-9). Insufficient data to recommend use in patients with severe (Child-Pugh score ≥10) hepatic impairment. Paediatrics: Safety and efficacy not established for administration as a field block in children aged 1 to < 6 years old, nor as a nerve block in children aged 1 to < 18 years old. Do not use in children aged < 1 year old as neonates and infants have a decreased ability to metabolize anaesthetics due to an immature hepatic system. Method of administration: Infiltration or perineural use only. Intended for single-dose administration only. Inject slowly (1-2 ml per injection) with frequent aspiration to minimize the risk of inadvertent intravascular injection. Administer with a 25 gauge or larger bore needle to maintain the structural integrity of the liposomal bupivacaine particles. Contraindications: Hypersensitivity to the active substance or to any of the excipients; Hypersensitivity to local anaesthetic medicinal products of the amide type; Obstetrical paracervical block anaesthesia due to risk of foetal bradycardia or death; Intravascular administration; Intra-articular administration. Special warnings and precautions for use: Local anaesthetic systemic toxicity: Due to potential risk of severe life-threatening adverse reactions associated with the administration of bupivacaine, EXPAREL liposomal should be administered in a setting where trained personnel and equipment are available to promptly treat patients who show evidence of neurological or cardiac toxicity. Perform careful, constant monitoring of cardiovascular and respiratory vital signs and state of consciousness after injection of bupivacaine. Toxic local anaesthetic blood concentrations depress cardiac conductivity and excitability, which may lead to atrioventricular block, ventricular arrhythmia, and cardiac arrest, which can be fatal. In addition, toxic local anaesthetic blood concentrations depress myocardial contractility and cause peripheral vasodilation, leading to decreased cardiac output and arterial blood pressure. No correlation of cases of potential local anaesthetic systemic toxicity with surgical procedure or route of administration has been found with EXPAREL liposomal, but redosing of EXPAREL liposomal, overdose, or concomitant use with other local anaesthetics may increase the risk. Neurologic effects: Central nervous system reactions are characterized by excitation and/or depression. Restlessness, anxiety, dizziness, tinnitus, blurred vision, or tremors may occur, possibly proceeding to convulsions. However, excitation may be transient or absent, with depression being the first manifestation of an adverse reaction. This may quickly be followed by drowsiness merging into unconsciousness and respiratory arrest. Other central nervous system effects may include nausea, vomiting, chills, and constriction of the pupils. Neurologic effects following field block may include persistent anaesthesia, paraesthesias, weakness, and paralysis, all of which may have slow, incomplete, or no recovery. Cardiovascular function impairment: Use with caution in patients with impaired cardiovascular function as they may be less able to compensate for functional changes associated with the prolongation of atrioventricular conduction produced by these medicinal products. Hepatic impairment: Use cautiously in patients with hepatic disease. Patients with severe hepatic disease are at a greater risk of developing toxic plasma concentrations. Consider increased monitoring for local anaesthetic systemic toxicity in subjects with moderate to severe hepatic disease. Renal impairment: Bupivacaine metabolites are extensively excreted by the kidney. Thus, the risk of toxic reactions to this medicinal product may be greater in patients with impaired renal function. Allergic reactions: May rarely occur as a result of hypersensitivity to the local anaesthetic or to other ingredients. Chondrolysis: Intra-articular infusions of local anaesthetics, including EXPAREL liposomal, following arthroscopic and other surgical procedures are contraindicated. There have been post-marketing reports of chondrolysis in patients receiving such infusions. Methaemoglobinaemia: Patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methaemoglobinaemia, cardiac or pulmonary compromise, or concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition. If local anaesthetics must be used in these patients, perform close monitoring for symptoms and signs of methaemoglobinaemia. Warnings and precautions specific to EXPAREL liposomal: It is not possible to convert dosing from any other formulations of bupivacaine to EXPAREL liposomal and vice versa, and no substitution with other bupivacaine containing products should be made. Use caution when co-administering EXPAREL liposomal and bupivacaine HCl, particularly to highly vascular areas where higher systemic absorption is expected. No data on admixing of EXPAREL with other local anaesthetics in children – not recommended. No data on using EXPAREL liposomal followed by other bupivacaine formulations. EXPAREL liposomal has not been evaluated and is not recommended for epidural or intrathecal use. Also not recommended as a femoral nerve block if early mobilization/ambulation is part of the patient’s recovery plan due to potential for temporary sensory and/or motor loss which may last for up to 5 days. Interactions:  Use of EXPAREL liposomal with other local anaesthetics: Use with caution in patients receiving other local anaesthetics or active substances structurally related to amide-type local anaesthetics, e.g. certain anti-arrhythmics, such as lidocaine, mexiletine, as systemic toxic effects are additive.The addition of local anaesthetics administered within 96 hours following administration of EXPAREL liposomal should take into account the total bupivacaine exposure. EXPAREL liposomal should only be admixed with bupivacaine. If lidocaine is administered, ensure EXPAREL liposomal is administered at least 20 minutes later. Oxidizing medicinal products: Patients administered local anaesthetics may be at increased risk of methaemoglobinamia when concurrently exposed to the following oxidizing medicinal products: Nitrates/Nitrites – nitroglycerin, nitroprusside, nitric oxide, nitrous oxide; Local anaesthetics – benzocaine, lidocaine, bupivacaine, mepivacaine, tetracaine, prilocaine, procaine, articaine, ropivacaine; Antineoplastic medicinal products – cyclophosphamide, flutamide, rasburicase, isofamide, hydroxyurea; Antibiotics – dapsone, sulfonamides, nitrofurantoin, para-aminosalicylic acid; Antimalarials – chloroquine, primaquine; Anticonvulsants – phenytoin, sodium valproate, phenobarbital; Other medicinal products – acetaminophen, metoclopramide, sulfa medicines (e.g., sulfasalazine), quinine. Other medicinal products: When a topical antiseptic is applied, allow the site to dry before EXPAREL liposomal is administered into the site. Do not allow EXPAREL liposomal to come into contact with antiseptics such as povidone iodine in solution. Pregnancy and lactation: Pregnancy: Not recommended during pregnancy and in women of childbearing potential not using contraception; Breastfeeding: A decision must be made whether to discontinue breast-feeding or to discontinue EXPAREL liposomal therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. Ability to drive and use machines:

Bupivacaine could have a major influence on the ability to drive and use machines. Inform patients in advance that bupivacaine liposomal dispersion can cause temporary loss of sensation and/or  motor function that may last for up to 5 days. Undesirable effects:  For full list of side effects, consult SmPC. ‘Common’ and ‘serious’ side effects are included in this prescribing information. Adult Population: Common side effects (≥1/100 to <1/10): dysgeusia, vomiting, constipation, hypoaesthesia oral, nausea. Serious uncommon (≥1/1000 to <1/100): motor dysfunction, bradycardia, tachycardia, blood creatinine increased, alanine aminotransferase increased, aspartate aminotransferase increased; Serious Rare (≥1/10,000 to <1/1000): monoplegia, atrial fibrillation, tachyarrhythmia, sinus tachycardia, apnoea, hypoxia, atelectasis, dyspnoea, haematochezia, drug eruption, electrocardiogram ST segment elevation, hepatic enzyme increased, white blood cell count increased; Serious Frequency unknown (cannot be estimated from the available data): hypersensitivity, seizure, palsy, cardiac arrest, local anaesthetic systemic toxicity (LAST). Paediatric population: Very common side effects (≥1/10): anaemia, tachycardia, hypotension, vomiting, constipation, nausea, pruritus, muscle twitching. Common side effects (≥1/100 to <1/10): Hypersensitivity, anxiety, hypoaesthesia, paraesthesia, burning sensation, dizziness, dysgeusia, syncope, visual impairment, vision blurred, hypoacusis,  bradycardia, hypertension, dyspnoea, tachypnoea, abdominal pain, diarrhoea, hypoaesthesia oral, dyspepsia, rash, musculoskeletal chest pain, pain in extremity, muscular weakness, muscle spasms, chest pain, pyrexia, delayed recovery from anaesthesia, seroma, fall. Frequency not known: somnolence, LAST. Legal Category: Prescription only medicine. Cost: Available in packs of 10 vials of 10ml or 20ml. EXPAREL 10ml x 10 Vials: £1,349.00; EXPAREL 20ml x 10 Vials: £2,418.00. Marketing Authorisation Holder: Ireland: Pacira Ireland Ltd, Unit 13, Classon House, Dundrum Business Park, Dundrum, Dublin 14, D14W9Y3, Ireland; UK: Pacira Ltd, Wessex House, Marlow Road, Bourne End, Buckinghamshire, SL8 5SP, United Kingdom. Marketing Authorisation Number:

EU/1/20/1489/001-004 (Ireland); PLGB 34175/0003 (UK), PLGB 34175/0004 (UK). Date of last revision of the API text: February 2023

 

 

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in Google play or Apple App store for the UK and at hpra.ie/homepage/about-us/report-an-issue for Ireland. Adverse events should also be reported via drugsafety@pacira.com
PP-EX-GB-0036 3rd February 2023