EXPAREL LIPOSOMAL

EXPAREL liposomal should be administered in a setting where trained personnel and appropriate resuscitation equipment are available to promptly treat patients who show evidence of neurological or cardiac toxicity. Posology The recommended dose of EXPAREL liposomal in adults and children aged 6 years or older is based on the following factors: • Size of the surgical site • Volume required to cover the area • Individual patient factors A maximum dosage of 266 mg (20 mL of undiluted medicinal product) must not be exceeded.

Field block (infiltration around small- to medium-sized surgical wounds) • In patients undergoing bunionectomy, a total of 106 mg (8 mL) of EXPAREL liposomal was administered, with 7 mL infiltrated into the tissues surrounding the osteotomy and 1 mL infiltrated into the subcutaneous tissue.

• In patients undergoing haemorrhoidectomy, a total of 266 mg (20 mL) of EXPAREL liposomal was diluted with 10 mL of normal saline, for a total of 30 mL, divided into six 5 mL aliquots, injected by visualizing the anal sphincter as a clock face and slowly infiltrating one aliquot to each of the even numbers to produce a field block.

• In paediatric patients aged 6 years and older, EXPAREL liposomal should be administered at a dose of 4 mg/kg (maximum not to exceed 266 mg). , 1:14 dilution by volume). The total volume of expansion will be dependent on the incision length.

6. Peripheral nerve block (femoral and brachial plexus) • In patients undergoing total knee arthroplasty (TKA), a total of 266 mg (20 mL) of EXPAREL liposomal was administered as a femoral nerve block. • In patients undergoing total shoulder arthroplasty or rotator cuff repair, a total of 133 mg (10 mL) of EXPAREL liposomal was diluted with 10 mL of normal saline, for a total volume of 20 mL, was administered as a brachial plexus nerve block.

Co-administration with other local anaesthetics The toxic effects of local anaesthetics are additive and their co-administration, taking into account the dose of local anaesthetic and the extended pharmacokinetic profile of EXPAREL liposomal, should be used with caution including monitoring for neurologic and cardiovascular effects related to local anaesthetic systemic toxicity.

5. EXPAREL liposomal is a liposomal preparation and should not be used interchangeably with any 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 milligram dose of bupivacaine solution to EXPAREL liposomal does not exceed 1:2.

5%). The most important serious adverse reactions associated with EXPAREL liposomal were systemic toxic reactions. Systemic toxic reactions usually present shortly after administration of bupivacaine but may be delayed in some cases.

001% from post-marketing data). 001% from post-marketing data). Tabulated list of adverse reactions in adults The adverse reactions associated with EXPAREL liposomal in adults from clinical trials and post-marketing surveillance are presented below in Table 1 according to the MedDRA System Organ Classification and by frequency.

Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000) and very rare (< 1/10 000) and frequency not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 1 Table of adverse drug reactions (ADRs) in adults System organ class Frequency Adverse drug reactions Immune system disorders Not known Hypersensitivity Psychiatric disorders Rare Confusional state, anxiety Common Dysgeusia Uncommon Motor dysfunction, sensory loss, dizziness, somnolence, hypoaesthesia, burning sensation, headache Rare Syncope, monoplegia, presyncope, lethargy Nervous system disorders Not known Seizure, palsy Eye disorders Rare Visual impairment, vision blurred Ear and labyrinth disorders Rare Diplacusis Uncommon Bradycardia, tachycardia Rare Atrial fibrillation, tachyarrhythmia, sinus tachycardia Cardiac disorders Not known Cardiac arrest Uncommon HypotensionVascular disorders Rare Hypertension, flushing Respiratory, thoracic, and mediastinal disorders Rare Apnoea, hypoxia, atelectasis, dyspnoea, oropharyngeal pain Common Vomiting, constipation, hypoaesthesia oral, nausea Gastrointestinal disorders Rare Haematochezia, dysphagia, abdominal distension, abdominal discomfort, abdominal pain upper, diarrhoea, salivary hypersecretion, dry mouth, dyspepsia, oral pruritus, paraesthesia oral Uncommon Urticaria, pruritus generalised, pruritus, skin irritation Skin and subcutaneous tissue disorders Rare Drug eruption, hyperhidrosis, erythema, rash, nail discolouration Uncommon Mobility decreased, muscular weakness, muscle spasms, muscle twitching, arthralgia Musculoskeletal and connective tissue disorders Rare Joint swelling, groin pain, joint stiffness, musculoskeletal chest pain, pain in extremity Renal and urinary disorders Not known Urinary retention Uncommon PyrexiaGeneral disorders and administration site conditions Rare Peripheral swelling, non-cardiac chest pain, chills, feeling hot, injection site pain, pain System organ class Frequency Adverse drug reactions Not known Lack of efficacy Uncommon Blood creatinine increased, alanine aminotransferase increased, aspartate aminotransferase increased Investigations Rare Electrocardiogram ST segment elevation, hepatic enzyme increased, white blood cell count increased Uncommon Contusion, post procedural oedema, fall Rare Muscle injury, seroma, wound complication, incision site erythema, procedural pain Injury, poisoning, and procedural complications Not known Local anaesthetic systemic toxicity (LAST) Tabulated list of adverse reactions in the paediatric population Adverse reactions associated with EXPAREL liposomal in paediatrics from clinical trials and post-marketing surveillance are presented below in Table 2 according to the MedDRA System Organ Classification and by frequency.

4. Special populations Elderly patients (65 years of age or older) Care should be taken in dose selection of EXPAREL liposomal in elderly patients because bupivacaine is known to be substantially excreted by the kidney, and the risk of toxic reactions to bupivacaine may be greater in patients with impaired renal function.

2). The risk of falls may increase for the elderly patients. Renal impairment Bupivacaine or its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions may be greater in patients with impaired renal function.

2). Hepatic impairment Bupivacaine is metabolized by the liver. No dosage adjustment is required in patients with mild hepatic impairment (Child-Pugh score 5-6) or moderate hepatic impairment (Child Pugh score 7-9). 2). Paediatric population The safety and efficacy of EXPAREL liposomal have not yet been established for administration as a field block in children aged 1 to less than 6 years of age, nor as a nerve block in children aged 1 to less than 18 years of age.

No data are available. EXPAREL liposomal should not be used in children aged less than 1 year of age because neonates and infants have a decreased ability to metabolize anaesthetics due to an immature hepatic system. Method of administration EXPAREL liposomal is for administration by infiltration or perineural use only.

EXPAREL liposomal is intended for single-dose administration only. EXPAREL liposomal should be injected slowly (generally 1 to 2 mL per injection) with frequent aspiration, when clinically appropriate, to check for blood and minimize the risk of inadvertent intravascular injection.

EXPAREL liposomal is to be administered with a 25 gauge or larger bore needle to maintain the structural integrity of the liposomal bupivacaine particles. 6. 1. • Hypersensitivity to local anaesthetic medicinal products of the amide type.

1. • Hypersensitivity to local anaesthetic medicinal products of the amide type. • Obstetrical paracervical block anaesthesia due to risk of foetal bradycardia or death. • Intravascular administration. 4).