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). |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EXPAREL (EXPAREL).
| Breastfeeding | Bupivacaine is excreted in human milk in small amounts. The milk-to-plasma (M/P) ratio for bupivacaine is approximately 0.3 to 0.5. After epidural administration, the relative infant dose is estimated to be <4% of the maternal weight-adjusted dose. EXPAREL has not been studied in lactating women. Clinical implications: Caution is advised; monitor the infant for signs of local anesthetic toxicity (e.g., irritability, feeding difficulties). |
| 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. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to bupivacaine or any amide-type local anesthetics","Obstetrical paracervical block anesthesia"]
| 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."] |
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| 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. |