BUPIVACAINE HYDROCHLORIDE PRESERVATIVE FREE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BUPIVACAINE HYDROCHLORIDE PRESERVATIVE FREE (BUPIVACAINE HYDROCHLORIDE PRESERVATIVE FREE).
Bupivacaine blocks voltage-gated sodium channels on neuronal membranes, inhibiting the propagation of action potentials and resulting in local anesthesia.
| Metabolism | Hepatic metabolism primarily via CYP1A2 and CYP3A4. Major metabolite is pipecoloxylidine, which is renally excreted. |
| Excretion | Renal excretion accounts for approximately 95% of the dose, with about 50% excreted unchanged. The remainder is primarily hepatic metabolism followed by renal elimination of metabolites. Biliary/fecal excretion is minimal (<5%). |
| Half-life | Terminal elimination half-life is 2.7 hours (range 1.5-5.5 hours). Prolonged up to 8-10 hours in neonates and 24-48 hours in severe hepatic impairment. |
| Protein binding | 95-96% bound primarily to alpha-1-acid glycoprotein, with minor binding to albumin. |
| Volume of Distribution | Vd is 0.73-1.0 L/kg (range 50-70 L in adults). High tissue uptake indicates extensive distribution into well-perfused organs. |
| Bioavailability | Not applicable for local anesthetics; systemic absorption after regional administration is nearly complete (100%) but intended local effect. |
| Onset of Action | Epidural: 15-30 minutes. Peripheral nerve block: 15-40 minutes. Intrathecal: 5-10 minutes. Local infiltration: 2-10 minutes. |
| Duration of Action | Epidural: 2-4 hours (with epinephrine 3-6 hours). Peripheral nerve block: 4-12 hours (with epinephrine up to 24 hours). Intrathecal: 1-2.5 hours. Factors: dose, concentration, site, and addition of vasoconstrictors. |
0.25-0.5% solution, up to 2 mg/kg (max 150 mg) per dose via infiltration, peripheral nerve block, or epidural; may repeat every 3-6 hours as needed. For epidural: 0.5% solution, 15-20 mL for surgical anesthesia.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for GFR >30 mL/min; for GFR 10-30 mL/min, use with caution and reduce dose by 25%; for GFR <10 mL/min, avoid or use at 50% dose with monitoring for toxicity. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use due to delayed metabolism and increased risk of toxicity. |
| Pediatric use | Maximum dose 2 mg/kg, not to exceed 2.5 mg/kg with epinephrine; typical dose for local infiltration: 0.25-0.5%, 0.5-1 mL/kg; for caudal epidural: 0.25% solution, 1 mL/kg. |
| Geriatric use | Reduce dose by 20-30% due to decreased clearance; use lower concentrations (0.25%) and smaller volumes; monitor for prolonged effects and toxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BUPIVACAINE HYDROCHLORIDE PRESERVATIVE FREE (BUPIVACAINE HYDROCHLORIDE PRESERVATIVE FREE).
| Breastfeeding | Minimal excretion into breast milk; M/P ratio approximately 0.2-0.3. Considered compatible with breastfeeding due to low oral bioavailability. Monitor infant for drowsiness or feeding difficulties. |
| Teratogenic Risk | FDA Pregnancy Category C. In first trimester, risk to fetus is low but not eliminated; no adequate human studies. In second and third trimesters, bupivacaine can cross placenta; fetal acidosis may increase drug accumulation. No specific teratogenic effects reported at typical doses, but high doses or prolonged exposure may cause neonatal CNS depression. |
■ FDA Black Box Warning
Intravenous regional anesthesia (Bier block) is contraindicated. Use for obstetrical paracervical block may cause fetal bradycardia. Avoid rapid injection and excessive doses to prevent cardiac arrest.
| Serious Effects |
Hypersensitivity to bupivacaine or any amide anesthetic, intravenous regional anesthesia (Bier block), obstetrical paracervical block, severe hypotension, myasthenia gravis, known or suspected hypersensitivity to parabens (if multidose vial).
| Precautions | Risk of cardiac toxicity (arrhythmias, arrest) especially with high doses; use lowest effective dose. Caution in hepatic impairment, elderly, and debilitated patients. Monitor for CNS toxicity (seizures, confusion). Avoid intravascular injection; aspirate before injection. |
| Food/Dietary | No significant food interactions. Avoid grapefruit juice if bupivacaine is combined with CYP3A4 inhibitors. |
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| Fetal Monitoring | Monitor maternal vital signs (heart rate, blood pressure, oxygen saturation) and fetal heart rate continuously during administration. Assess for signs of local anesthetic systemic toxicity (LAST) and fetal bradycardia. Monitor uterine activity and labor progress. |
| Fertility Effects | No direct effects on human fertility reported. Animal studies at high doses showed no major reproductive impairment. Use for labor analgesia does not affect long-term fertility. |
| Clinical Pearls | Bupivacaine is highly protein-bound and cardiotoxic; use lower doses in elderly or hepatic impairment. Preservative-free formulation is mandatory for spinal/epidural use. Addition of epinephrine prolongs action but increases risk of cardiac toxicity. Monitor for CNS toxicity (perioral numbness, tinnitus) before cardiac signs. Use test dose with epinephrine to detect intravascular injection. Avoid in obstetrics for paracervical block due to fetal bradycardia. Maximum dose: 2 mg/kg without epinephrine, 3 mg/kg with epinephrine. |
| Patient Advice | Report any numbness of the tongue or lips, ringing in the ears, or dizziness immediately. · You may experience temporary loss of sensation and movement in the area injected. · Do not drive or operate machinery until full sensation and motor function return. · Avoid alcohol or sedatives for 24 hours after the procedure. · Contact your doctor if you develop severe headache, stiff neck, or fever after spinal anesthesia. |