MARCAINE HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MARCAINE HYDROCHLORIDE (MARCAINE HYDROCHLORIDE).
Bupivacaine is an amide-type local anesthetic that blocks voltage-gated sodium channels in nerve cell membranes, reversibly inhibiting nerve impulse propagation, particularly in sensory fibers.
| Metabolism | Primarily hepatic via CYP1A2 and CYP3A4; major metabolite is pipecolylxylidine (PPX). |
| Excretion | Primarily hepatic metabolism; less than 5% excreted unchanged in urine. Metabolites are excreted renally, with a small amount in feces via biliary elimination. |
| Half-life | Terminal elimination half-life is approximately 2.5 to 3.5 hours in adults; may be prolonged in neonates (8-12 hours) or patients with hepatic impairment. |
| Protein binding | Approximately 95% bound primarily to alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | 1.3 L/kg; indicates extensive tissue distribution, characteristic of lipophilic amide local anesthetics. |
| Bioavailability | Not applicable for injection; negligible oral bioavailability due to extensive first-pass metabolism. For infiltration or nerve block, bioavailability is 100% at the site of administration. |
| Onset of Action | Epidural: 5-15 minutes; Caudal: 5-15 minutes; Peripheral nerve block: 5-15 minutes; Infiltration: 1-5 minutes; Intrathecal: rapid onset within 1-5 minutes. |
| Duration of Action | Epidural: 1.5-3 hours; Peripheral nerve block: 2-8 hours depending on dose and site; Infiltration: 1-3 hours; Intrathecal: 1-2 hours. Duration may be prolonged with epinephrine. |
| Molecular Weight | 342.9 Da (as hydrochloride salt, anhydrous) |
Adults: 0.5% solution infiltrated up to 175 mg (35 mL) for minor procedures; for major procedures, up to 225 mg (45 mL) with epinephrine. Repeat doses at 3-hour intervals. Maximum dose 400 mg with epinephrine.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended for GFR > 30 mL/min. For GFR < 30 mL/min, reduce dose by 25-50% and monitor for toxicity. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 40%. Child-Pugh C: Contraindicated or use with extreme caution and 50% dose reduction. |
| Pediatric use | Weight-based: 0.5% solution, maximum 2 mg/kg for infiltration; for regional blocks, 1.5 mg/kg. With epinephrine, up to 3 mg/kg. Use lowest effective dose. |
| Geriatric use | Elderly: Reduce dose by 20-30% due to age-related decreases in clearance; use lower concentrations (0.25%) and minimal volumes. Monitor for CNS and cardiac effects. |
| 1st trimester | Bupivacaine hydrochloride is Pregnancy Category C. Animal studies have shown an embryocidal effect. There are no adequate and well-controlled studies in pregnant women. Use only if potential benefit justifies potential risk to the fetus. |
| 2nd trimester | Bupivacaine crosses the placenta. Use caution during labor and delivery; may cause fetal bradycardia and neonatal depression. Use lowest effective dose. |
| 3rd trimester | Same as T2. Avoid use in paracervical block obstetrics due to risk of fetal bradycardia and acidosis. |
Clinical note
Comprehensive clinical and safety monograph for MARCAINE HYDROCHLORIDE (MARCAINE HYDROCHLORIDE).
| Placental transfer | Bupivacaine crosses the placenta by passive diffusion. The fetal/maternal ratio is approximately 0.2-0.4. Highly protein-bound (95%) limits fetal exposure. |
| Breastfeeding | Bupivacaine is excreted into breast milk in small amounts. The relative infant dose is estimated to be <4% of the maternal weight-adjusted dose. Compatible with breastfeeding; however, monitor infant for signs of local anesthetic toxicity, especially if high doses are used. |
■ FDA Black Box Warning
Risk of cardiac arrest and seizures following unintentional intravascular injection; use with extreme caution when administering large doses. Avoid rapid injection. Resuscitative equipment and personnel trained in advanced cardiac life support must be immediately available.
| Serious Effects |
Hypersensitivity to bupivacaine or other amide-type local anestheticsObstetric paracervical block anesthesiaIntravenous regional anesthesia (Bier block)Severe hypotensionShockInfection at the injection site
| Precautions | Risk of systemic toxicity (CNS and cardiovascular), particularly with high doses or accidental intravascular injection. Use with caution in patients with hepatic impairment, cardiac disease, or myasthenia gravis. Monitor for signs of methemoglobinemia (rare). Avoid use in patients with severe hypotension or shock. |
| Food/Dietary | No known food interactions. |
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| Lactation Rating | L2 (Probably Compatible) |
| Teratogenic Risk | Bupivacaine hydrochloride is classified as FDA Pregnancy Category C. In the first trimester, there is a potential risk of teratogenicity based on animal studies showing adverse effects at high doses, but no well-controlled human studies exist. During the second and third trimesters, use may cause fetal bradycardia, acidosis, and central nervous system depression due to placental transfer. Risk of fetal hypoxia and bradycardia increases with higher doses or inadvertent intravascular injection. Paracervical block in early pregnancy is associated with fetal bradycardia. |
| Fetal Monitoring | Continuous maternal heart rate and blood pressure monitoring, fetal heart rate monitoring (especially after paracervical or epidural block), assessment for signs of local anesthetic systemic toxicity (LAST) including perioral numbness, metallic taste, tinnitus, seizures; fetal assessment for bradycardia and acidosis via electronic fetal monitoring if indicated. |
| Fertility Effects | No specific studies on human fertility effects. Animal studies at high doses showed no significant reproductive impairment. Local anesthetics are not known to affect fertility at clinically used doses. However, use during assisted reproductive procedures (e.g., oocyte retrieval) may transiently affect implantation if high doses are used locally. |
| Clinical Pearls | Bupivacaine is highly protein-bound and has a slow dissociation from sodium channels, resulting in prolonged duration of action. Use with caution in hepatic impairment due to extensive liver metabolism. Avoid intravenous regional anesthesia (Bier block) as it can cause severe cardiac toxicity. Maximum single dose for infiltration is 175 mg (without epinephrine) or 225 mg (with epinephrine). |
| Patient Advice | Report any numbness or weakness that persists longer than expected. · Seek immediate medical attention if you experience ringing in ears, metallic taste, or dizziness. · Avoid driving or operating machinery until full sensation and motor function return. · Inform your doctor if you have liver disease or are taking antiarrhythmic drugs. |