MARCAINE HYDROCHLORIDE PRESERVATIVE FREE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MARCAINE HYDROCHLORIDE PRESERVATIVE FREE (MARCAINE HYDROCHLORIDE PRESERVATIVE FREE).
Bupivacaine blocks sodium ion channels in nerve cell membranes, preventing the generation and conduction of nerve impulses, resulting in local anesthesia.
| Metabolism | Metabolized primarily in the liver via N-dealkylation and conjugation with glucuronic acid; enzyme CYP3A4 involved. |
| Excretion | Primarily hepatic metabolism to 2,6-pipecoloxylidide (PPX) and subsequent renal excretion. Renal excretion of unchanged bupivacaine accounts for approximately 5-10% of the dose. The remainder is eliminated as metabolites (PPX and others) in urine. Fecal excretion is negligible. |
| Half-life | Terminal elimination half-life in adults: 2.7 ± 1.2 hours (range 1.5-5.5 hours). In neonates, half-life is prolonged to approximately 8.1 ± 8.2 hours due to immature hepatic and renal function. |
| Protein binding | Approximately 95% bound to plasma proteins, primarily to alpha-1-acid glycoprotein (AAG). Binding is concentration-dependent, with lower binding at high concentrations due to saturation of AAG. Also binds to albumin to a lesser extent. |
| Volume of Distribution | Apparent volume of distribution (Vd_ss): approximately 1.0 L/kg (range 0.6-1.5 L/kg). This large Vd indicates extensive tissue distribution, particularly into well-perfused organs and adipose tissue. |
| Bioavailability | Intravenous: 100%. Epidural: near 100% after absorption into systemic circulation. Peripheral nerve blocks: systemic bioavailability is near 100% after absorption. Oral: negligible (<10%) due to extensive first-pass hepatic metabolism. |
| Onset of Action | Epidural: 5-10 minutes for initial sensory blockade. Caudal: 5-10 minutes. Peripheral nerve block: 10-20 minutes depending on site and concentration. Local infiltration: 1-5 minutes. |
| Duration of Action | Epidural analgesia: 60-120 minutes (with epinephrine, up to 150-200 minutes). Peripheral nerve block: 2-4 hours (with epinephrine, up to 6-8 hours). Local infiltration: 1-3 hours. Duration is dose- and concentration-dependent. |
| Molecular Weight | 288.43 |
Local infiltration: up to 30 mL of 0.5% (150 mg) per dose. Peripheral nerve block: 30-40 mL of 0.5% (150-200 mg). Epidural: 15-20 mL of 0.5% (75-100 mg). Maximum single dose: 2.5 mg/kg (225 mg for 90 kg). Repeat doses after 3 hours, max 400 mg/24h.
| Dosage form | INJECTABLE |
| Renal impairment | No dosage adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, consider reduced doses and extended intervals due to potential accumulation; monitor for toxicity. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50% and monitor. Child-Pugh Class C: Avoid use or use with extreme caution; consider alternative agent. |
| Pediatric use | Weight-based: 0.5-2.5 mg/kg for infiltration and nerve blocks. Maximum single dose: 2.5 mg/kg. Do not exceed concentrations of 0.25% for children under 12. For epidural: 1-2 mg/kg bolus followed by 0.1-0.25 mg/kg/h infusion, not to exceed 1 mg/kg in 4 hours. |
| Geriatric use | Reduce initial doses by 20-30% due to decreased hepatic clearance and increased sensitivity. Use lower concentrations (0.25%) and smallest effective volume. Monitor for hypotension and bradycardia. Maximum single dose: 2 mg/kg. |
| 1st trimester | Bupivacaine crosses the placenta. Epidural use is considered safe, but high doses or intravascular injection may cause maternal toxicity and fetal bradycardia. Risk of teratogenicity is low based on animal data and human experience. |
| 2nd trimester | Similar to first trimester; epidural use is safe. Monitoring for maternal hypotension and fetal heart rate changes is recommended. |
| 3rd trimester | Epidural bupivacaine is commonly used for labor analgesia. Risk of fetal bradycardia and neonatal depression is low with appropriate dosing. Paracervical block is contraindicated due to risk of fetal bradycardia. |
Clinical note
Comprehensive clinical and safety monograph for MARCAINE HYDROCHLORIDE PRESERVATIVE FREE (MARCAINE HYDROCHLORIDE PRESERVATIVE FREE).
| Placental transfer | Bupivacaine readily crosses the placenta via passive diffusion. Fetal/maternal ratio ranges from 0.2 to 0.4 depending on protein binding and pH gradient. Protein binding is high (95%), limiting free drug transfer. |
| Breastfeeding |
■ FDA Black Box Warning
Risk of cardiac arrest and death with use as an epidural anesthetic for obstetrical paracervical block. Bupivacaine should not be injected rapidly or in large doses due to risk of systemic toxicity and cardiac arrest.
| Serious Effects |
Hypersensitivity to bupivacaine or any amide-type local anestheticSevere hypotension or shockInfection at the injection siteBacteremiaCoagulopathy or anticoagulant therapy (for epidural/regional blocks)Severe aortic stenosis or other severe cardiac outflow obstruction (for epidural anesthesia)Myasthenia gravis (relative, but considered absolute for some formulations)Obstetric paracervical block (contraindicated due to risk of fetal bradycardia)
| Precautions | Risk of systemic toxicity (CNS and cardiac) if injected intravascularly, Use with caution in patients with hepatic impairment, Avoid use in patients with hypovolemia or shock, May cause methemoglobinemia |
| Food/Dietary | No significant food interactions known. Avoid alcohol consumption for at least 24 hours after administration, as it may increase the risk of central nervous system depression or additive effects. |
Loading safety data…
| Bupivacaine is excreted into breast milk in low concentrations (estimated infant dose <1% of maternal weight-adjusted dose). Oral bioavailability is low due to first-pass metabolism, making systemic effects in the infant unlikely. Epidural use is considered compatible with breastfeeding. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | FDA Pregnancy Category C. No adequate well-controlled studies in pregnant women. Bupivacaine crosses placenta. First trimester: No evidence of teratogenicity in animal studies, but risk cannot be excluded. Second/third trimester: Potential for fetal bradycardia, acidosis, and central nervous system depression if high doses or accidental intravascular injection occurs. Use only if clearly needed. |
| Fetal Monitoring | Continuous fetal heart rate monitoring during obstetrical use. Maternal vital signs (heart rate, blood pressure, ECG) and oxygen saturation. Assess for signs of local anesthetic systemic toxicity (LAST): perioral numbness, metallic taste, tinnitus, seizures, arrhythmias. After epidural or spinal administration, monitor for motor block progression and recovery. |
| Fertility Effects | No specific human data on fertility impairment. Animal studies have not shown adverse effects on fertility. However, local anesthetics may interfere with sperm motility in vitro at high concentrations; clinical significance unclear. |
| Clinical Pearls | Marca ine Hydrochloride Preservative Free (bupivacaine) is a long-acting amide local anesthetic with a slow onset. It is contraindicated for intravenous regional anesthesia (Bier block) due to risk of cardiotoxicity. For epidural use, a test dose of 2-3 mL with epinephrine helps detect intravascular injection (increased heart rate). Maximum safe dose: 2 mg/kg alone, 3 mg/kg with epinephrine. Use with caution in patients with hepatic impairment or pseudocholinesterase deficiency. For obstetrics, avoid paracervical block in pregnancy due to fetal bradycardia. |
| Patient Advice | Inform your doctor if you have liver disease, low blood pressure, or a history of allergic reactions to local anesthetics. · You may experience temporary numbness or loss of sensation and motor function in the treated area; avoid activities that require alertness until sensation returns. · Do not drive or operate machinery for at least 24 hours after receiving this medication. · Contact your healthcare provider immediately if you experience difficulty breathing, chest tightness, irregular heartbeat, seizures, or severe headache after injection. · If you are pregnant, planning to become pregnant, or breastfeeding, discuss risks and benefits with your doctor. · Store this medication at room temperature away from light and moisture; do not freeze. |