EXPAREL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EXPAREL (EXPAREL).
Liposomal bupivacaine is a local anesthetic that blocks sodium channels in nerve cell membranes, inhibiting nerve impulse conduction and providing prolonged analgesia.
| Metabolism | Hepatic metabolism primarily via conjugation with glucuronic acid; minor metabolism by CYP450 enzymes (CYP3A4, CYP1A2, CYP2D6). |
| Excretion | Renal (approximately 96% as metabolites, <10% unchanged). Biliary/fecal excretion is negligible. |
| Half-life | Terminal elimination half-life is 12-48 hours (mean ~24 hours), reflecting prolonged release from the multivesicular liposome depot. |
| Protein binding | Approximately 96% bound to alpha-1-acid glycoprotein (AAG) and albumin, with binding dependent on drug concentration and AAG levels. |
| Volume of Distribution | After IV administration of free bupivacaine: ~0.6-0.8 L/kg. For Exparel, Vd is not directly applicable due to local administration; systemic Vd reflects released bupivacaine. |
| Bioavailability | Not applicable for IV route; after local infiltration, systemic bioavailability is essentially 100% due to complete absorption from the depot over time. |
| Onset of Action | Within 3-10 minutes after infiltration or regional block (due to burst release of free bupivacaine). |
| Duration of Action | Up to 72-96 hours in soft tissue (e.g., hemorroidectomy) and up to 48-60 hours in surgical wounds (e.g., bunionectomy). |
| Molecular Weight | 342.48 |
Local infiltration: up to 266 mg (20 mL) as a single dose; interscalene brachial plexus block: up to 133 mg (10 mL); femoral nerve block: up to 133 mg (10 mL). Maximum dose 266 mg. Administer via slow injection with frequent aspiration.
| Dosage form | INJECTABLE, LIPOSOMAL |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (eGFR <30 mL/min/1.73 m²); use with caution. |
| Liver impairment | No dosage adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate to severe impairment (Child-Pugh B or C); use with caution due to potential for increased systemic exposure. |
| Pediatric use | Not recommended for use in pediatric patients <18 years of age due to lack of safety and efficacy data. |
| Geriatric use | No specific dosage adjustment required. Monitor for prolonged duration of sensory and motor block; consider reduced doses based on clinical status (e.g., frailty, comorbidities). |
| 1st trimester | Liposomal bupivacaine has not been adequately studied in first trimester. Animal studies show no teratogenicity at clinically relevant doses; however, use only if clearly needed. |
| 2nd trimester | Limited data; no known fetal harm from bupivacaine. Use caution, especially during organogenesis. |
| 3rd trimester | Bupivacaine crosses placenta; may cause fetal bradycardia and CNS depression if high systemic levels occur. Use lowest effective dose. |
Clinical note
Comprehensive clinical and safety monograph for EXPAREL (EXPAREL).
| Placental transfer | Bupivacaine readily crosses the placenta by passive diffusion (maternal:fetal ratio ~0.2-0.4). Liposomal encapsulation may reduce free fraction and transfer, but limited data. |
| Breastfeeding | Bupivacaine is excreted into breast milk in low amounts. EXPAREL's liposomal formulation may alter kinetics; however, due to low oral bioavailability, risk to infant is minimal. Monitor for sedation. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to bupivacaine or any amide local anestheticObstetric paracervical block anesthesiaIntravenous regional anesthesia (Bier block)Severe hypotensionComplete heart block
| Precautions | Avoid intravascular injection; may result in cardiac arrest or severe systemic toxicity., Not recommended for use in children under 18 years., Use with caution in patients with hepatic impairment, severe renal impairment, or cardiovascular disease., Risk of chondrolysis when used for intra-articular infusions., Do not use in epidural, intrathecal, or intravenous routes. |
| Food/Dietary | No known food interactions. Avoid alcohol consumption as it may increase the risk of central nervous system depression. |
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| Lactation Rating | L2 - Safer |
| Teratogenic Risk | EXPAREL (liposomal bupivacaine) has not been studied in pregnant women. Animal reproduction studies have not been conducted with EXPAREL. Bupivacaine HCl, the active moiety, crosses the placenta. In pregnant women, bupivacaine can cause fetal bradycardia and neonatal depression when used for labor analgesia. Use during first trimester: Limited data; risk cannot be excluded. Use during second trimester: Consider risk-benefit. Use during third trimester: Avoid high doses near term due to potential fetal and neonatal adverse effects. |
| Fetal Monitoring | Monitor maternal vital signs (blood pressure, heart rate, oxygen saturation) continuously during administration and for at least 30 minutes after. Fetal heart rate monitoring is recommended when used during labor. Assess for signs of local anesthetic systemic toxicity (LAST): perioral numbness, metallic taste, tinnitus, dizziness, seizures, cardiac arrhythmias. Monitor for motor block and sensory level if used for neuraxial anesthesia. |
| Fertility Effects | No formal fertility studies have been conducted with EXPAREL. Bupivacaine did not impair fertility in animal studies at doses up to 4 times the maximum recommended human dose (MRHD) based on body surface area. Clinical relevance: Limited data; no known adverse effects on human fertility. |
| Clinical Pearls | Exparel (liposomal bupivacaine) is a long-acting local anesthetic formulation. It should not be used in place of traditional local anesthetics for immediate postoperative pain control; a short-acting agent may be co-administered. Avoid concurrent use with other local anesthetics as it may alter liposomal release. Do not use with non-bupivacaine local anesthetics. Exparel is contraindicated in patients with hypersensitivity to bupivacaine or amide anesthetics. Do not administer intravascularly; monitor for CNS and cardiac toxicity. Use with caution in hepatic impairment. Maximum dose is 266 mg (20 mL of 1.3% solution) in adults. |
| Patient Advice | Exparel is a long-acting numbing medicine that provides pain relief for up to 72 hours after surgery. · It is injected into the surgical site by your doctor before or during surgery. · You may still feel some sensation, but pain should be significantly reduced. · Do not apply heat or cold packs directly over the injection area for 24 hours. · Avoid strenuous activity or heavy lifting until your doctor advises it is safe. · Seek medical help if you experience symptoms like severe headache, confusion, ringing in ears, vision changes, or metallic taste. |