BUPIVACAINE LIPOSOME
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BUPIVACAINE LIPOSOME (BUPIVACAINE LIPOSOME).
Bupivacaine liposome is a long-acting local anesthetic that reversibly blocks nerve impulse propagation by inhibiting sodium ion influx through voltage-gated sodium channels in neuronal cell membranes. The liposomal formulation provides sustained release of bupivacaine, prolonging analgesic effect.
| Metabolism | Primarily metabolized in the liver via CYP1A2 and CYP3A4 mediated N-dealkylation and glucuronidation to inactive metabolites (e.g., desbutylbupivacaine, 4-hydroxybupivacaine). Excretion mainly in urine. |
| Excretion | Primarily hepatic metabolism to 3-hydroxybupivacaine and desbutylbupivacaine; renal excretion of metabolites accounts for ~95% of elimination, with <5% unchanged drug excreted in urine; biliary/fecal excretion minimal (<5%). |
| Half-life | Terminal elimination half-life is approximately 12-24 hours (mean 18 hours) due to prolonged release from liposomal depot; significantly longer than conventional bupivacaine (2-4 hours), reflecting slow absorption rate-limited elimination. |
| Protein binding | 85-95% bound primarily to alpha-1-acid glycoprotein (AAG), with binding being concentration-dependent; high AAG binding reduces free fraction. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 10-20 L (0.14-0.29 L/kg) for free bupivacaine, but apparent Vd is larger (~50 L) when considering total drug due to extensive tissue distribution; reflects limited distribution to highly perfused organs. |
| Bioavailability | Bioavailability after local infiltration is 100% (administered directly at site) because it is designed for local administration; systemic absorption occurs but with sustained release; not used orally or intravenously. |
| Onset of Action | Onset of sensory blockade occurs within 5-10 minutes after local infiltration, comparable to conventional bupivacaine; maximal analgesic effect develops over 1-2 hours. |
| Duration of Action | Duration of analgesia is 24-72 hours after single-dose infiltration, with some studies reporting up to 96 hours; prolonged due to sustained release from multivesicular liposomes, providing extended postoperative pain relief. |
Local infiltration: up to 266 mg (20 mL of 1.3% or 10 mL of 2.66%) single dose; interscalene brachial plexus block: up to 133 mg (10 mL of 1.3%) single dose; sciatic nerve block in the popliteal fossa: up to 133 mg (10 mL of 1.3%) single dose; adductor canal block: up to 133 mg (10 mL of 1.3%) single dose; max dose 266 mg per procedure.
| Dosage form | INJECTABLE, LIPOSOMAL |
| Renal impairment | No dose adjustment required for any degree of renal impairment including ESRD. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: consider reducing dose; Child-Pugh C: contraindicated or avoid use. |
| Pediatric use | Not approved for pediatric patients (<18 years); safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; may be more sensitive to effects; use with caution and consider lower doses. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BUPIVACAINE LIPOSOME (BUPIVACAINE LIPOSOME).
| Breastfeeding | Bupivacaine is excreted in human milk in small amounts; the milk-to-plasma ratio (M/P) is approximately 0.3-0.5 for conventional bupivacaine. No data on liposomal formulation. Consider the developmental and health benefits of breastfeeding, the mother's clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or underlying maternal condition. |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. Animal reproduction studies have not been conducted with liposomal bupivacaine. Bupivacaine HCl crosses the placenta. Use in early pregnancy may be associated with fetal bradycardia or acidosis; risk of teratogenicity is low based on clinical experience with bupivacaine. Avoid use in obstetrical paracervical block due to fetal bradycardia. |
■ FDA Black Box Warning
Not approved for use in children <18 years. Not for use in obstetric paracervical block anesthesia. Risk of chondrolysis with intra-articular infusions (especially in shoulder surgery).
| Serious Effects |
["Hypersensitivity to bupivacaine or any component of the liposomal formulation","Intra-articular use (risk of chondrolysis)","Obstetric paracervical block anesthesia","Severe hemorrhagic shock or severe hypotension","Use in children <18 years"]
| Precautions | ["Avoid intravascular injection; may cause cardiac arrest or arrhythmias","Risk of systemic toxicity (CNS excitation/depression) if administered in large doses","Avoid use in patients with known hypersensitivity to amide anesthetics","Use with caution in hepatic impairment, severe renal impairment, and elderly patients","Not for use in spinal or epidural anesthesia"] |
| Food/Dietary | No specific food interactions have been identified with bupivacaine liposome. However, patients should avoid alcohol for at least 24 hours after administration due to potential additive CNS depression. |
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| Fetal Monitoring | Monitor maternal vital signs (heart rate, blood pressure) and fetal heart rate during administration, especially if used near term or during labor. Observe for signs of systemic toxicity, including CNS and cardiovascular effects. Continuous fetal monitoring recommended if used for labor analgesia. |
| Fertility Effects | No specific studies on fertility with liposomal bupivacaine. Bupivacaine HCl did not impair fertility in animal studies at doses up to 30 mg/kg/day. However, high doses may affect reproductive organs (e.g., decreased sperm motility) at systemic toxic levels. |
| Clinical Pearls | Bupivacaine liposome (Exparel) is FDA-approved for single-dose infiltration into surgical sites and interscalene brachial plexus block. Do NOT use for epidural, intrathecal, or regional intravenous blocks. Onset is delayed (up to 30-60 min) due to slow release; consider adjunctive short-acting local anesthetic for immediate postoperative pain. Maximum dose is 266 mg (20 mL of 1.3% solution); do NOT exceed. Do NOT administer with other local anesthetics in the same syringe, as it may disrupt liposome integrity. Store at 2-8°C; do not freeze. Monitor for signs of local anesthetic systemic toxicity (LAST) including perioral numbness, tinnitus, and seizures. Liposomal bupivacaine is not interchangeable with non-liposomal formulations. |
| Patient Advice | This medication is a long-acting local anesthetic injected at the surgical site to provide pain relief for up to 72 hours. · Do not drive or operate heavy machinery for at least 24 hours after surgery until the effects are known. · Seek immediate medical attention if you experience numbness or tingling around the mouth, ringing in the ears, dizziness, blurred vision, or seizures. · Report any signs of infection at the injection site, such as redness, swelling, or warmth. · Avoid alcohol consumption for at least 24 hours after receiving the injection as it may increase side effects. · Follow your doctor's instructions for additional pain relief if needed; do not take extra doses of local anesthetics without consulting your doctor. |