Local Anesthetic, Injectable

Production of local or regional anesthesia for surgery and obstetrics, and for postoperative pain management

B

Local anesthetics rapidly cross the placenta and may cause varying degrees of maternal, fetal, and neonatal toxicity. Close maternal and fetal monitoring (heart rate and electronic fetal monitoring advised) are required during obstetrical use. Excretion in breast milk unknown. Use caution in breast-feeding mothers.

Known hypersensitivity to levobupivacaine, bupivacaine, or any local anesthetic of the amide type.

Unintended intravenous injection may result in cardiac arrest. Use caution when the higher concentration formulations of levobupivacaine are used. Volumes of the high concentration are more likely to produce cardiac toxicity. The 0.75% solution should not be used in obstetrical patients. Use with caution in patients with hypotension, hypovolemia, heart block, hepatic or cardiac impairment.

>10%:

Central nervous system: Pain (postoperative) (7% to 18%), fever (7% to 17%)

Cardiovascular: Hypotension (20% to 31%)

Gastrointestinal: Nausea (12% to 21%), vomiting (8% to 14%)

Hematologic: Anemia (10% to 12%)

1% to 10%:

Central nervous system: Pain (4% to 8%), headache (5% to 7%), dizziness (5% to 6%), hypoesthesia (3%), somnolence (1%), anxiety (1%), hypothermia (2%)

Cardiovascular: Abnormal EKG (3%), bradycardia (2%), tachycardia (2%), hypertension (1%)

Dermatologic: Pruritus (4% to 9%), purpura (1%)

Endocrine & metabolic: Breast pain - female (1%)

Gastrointestinal: Constipation (3% to 7%), enlarged abdomen (3%), flatulence (2%), abdominal pain (2%), dyspepsia (2%), diarrhea (1%)

Genitourinary: Urinary incontinence (1%), urine flow decreased (1%), urinary tract infection (1%)

Hematologic: Leukocytosis (1%)

Local: Anesthesia (1%)

Neuromuscular & skeletal: Back pain (6%), rigors (3%), paresthesia (2%)

Ocular: Diplopia (3%)

Renal: Albuminuria (3%), hematuria (2%)

Respiratory: Cough (1%)

Miscellaneous: Fetal distress (5% to 10%), delayed delivery (6%), hemorrhage in pregnancy (2%), uterine abnormality (2%), increased wound drainage (1%)

<1%: Asthenia, edema, postural hypotension, hypokinesia, involuntary muscle contraction, generalized spasm, tremor, syncope, arrhythmia, extrasystoles, atrial fibrillation, cardiac arrest, ileus, elevated bilirubin, confusion, apnea, bronchospasm, dyspnea, pulmonary edema, respiratory insufficiency, increased sweating, skin discoloration

Related to local concentration or due to unintended intrathecal or intravenous injection. Symptoms may include restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, respiratory arrest, twitching, depression or drowsiness. In addition, cardiac toxicity, including AV block, bradycardia, arrhythmia, and hypotension may occur. Treatment is symptomatic.

CYP3A4 and CYP1A2 substrate. Although not specifically studied, inducers and inhibitors of these enzymes are likely to alter the metabolism of levobupivacaine.

Store at room temperature (20°C to 25°C/68°F to 77°F). Disinfectants containing heavy metals should not be used for mucous membrane disinfection since they have been related to incidents of swelling and edema. Isopropyl or ethyl alcohol is recommended. Stability of solution in vial has been demonstrated following an autoclave cycle at 121°C for 15 minutes.

Not compatible with alkaline pH solutions (pH >8.5). Compatible with 0.9% Sodium Chloride Injection USP, and with saline solutions containing fentanyl, and clonidine. Stable for 24 hours in PVC bags at room temperature when diluted in normal saline. Use preservative free 0.9% sodium chloride in epidural infusion.

Levobupivacaine is the S-enantiomer of bupivacaine. It blocks both the initiation and transmission of nerve impulses by decreasing the neuronal membrane's permeability to sodium ions, which results in inhibition of depolarization with resultant blockade of conduction. Local anesthetics reversibly prevent generation and conduction of electrical impulses in neurons by decreasing the transient increase in permeability to sodium. The differential sensitivity generally depends on the size of the fiber; small fibers are more sensitive than larger fibers and require a longer period for recovery. Sensory pain fibers are usually blocked first, followed by fibers that transmit sensations of temperature, touch, and deep pressure. High concentrations block sympathetic somatic sensory and somatic motor fibers. The spread of anesthesia depends upon the distribution of the solution. This is primarily dependent on the site of administration and volume of drug injected.

Onset: Epidural: 10-14 minutes

Duration (dose-dependent): 1-8 hours

Absorption: Dependent on route of administration and dose

Distribution: 67 L

Protein binding: >97% in plasma

Metabolism: Hepatic, extensive metabolism via CYP3A4 and CYP1A2

Half-life: 1.3 hours

Time to peak: 30 minutes after epidural dosing

Elimination: In urine (71%) and feces (24%), as metabolites

Adults: Note: Rapid injection of a large volume of local anesthetic solution should be avoided. Fractional (incremental) doses are recommended.

Surgical Anesthesia:

Epidural for surgery:

Concentration 0.5% to 0.75%; volume 10-20 mL; dose 50-150 mg; moderate to complete motor block

Epidural - C-section:

Concentration 0.5%; volume 20-30 mL; dose 100-150 mg; moderate to complete motor block

Peripheral nerve:

Concentration 0.25% to 0.5%; volume 0.4 mL/kg (30 mL); dose 1-2 mg/kg (75-150 mg); moderate to complete motor block

Ophthalmic:

Concentration 0.75%; volume 5-15 mL; dose 37.5-112.5 mg; moderate to complete motor block

Local infiltration:

Concentration 0.25%; volume 60 mL; dose 150 mg; motor block - not applicable

Pain Management:

Labor analgesia (epidural bolus):

Concentration 0.25%; volume 10-20 mL; dose 25-50 mg; minimal to moderate motor block

Postoperative pain (epidural infusion):

Concentration 0.125% to 0.25%; volume 4-10 mL/hour; dose 5-25 mg/hour; minimal to moderate motor block

Maximum dosage: Epidural doses up to 375 mg have been administered incrementally to patients during a surgical procedure.

Intraoperative block and postoperative pain: 695 mg in 24 hours

Postoperative epidural infusion over 24 hours: 570 mg

Single-fractionated injection for brachial plexus block: 300 mg

Isoporpyl or ethyl alcohol are recommended to disinfect the surface of the vial. Disinfectants containing heavy metals should not be used for mucous membrane disinfection since they have been related to incidents of swelling and edema. Prior to administration, it is essential that aspiration for blood or cerebrospinal fluid (where applicable) be performed prior to injecting any local anesthetic, both before the original dosage and at all subsequent doses (to avoid intravascular or intrathecal injection). A negative aspiration does not ensure against intrathecal or intravascular injection. Rapid injection of a large volume of local anesthetic solution should be avoided. Fractional (incremental) doses are recommended. Monitor patient during and after injection for symptoms of CNS or cardiac toxicity.

Monitor the patient during and after injection for symptoms of CNS or cardiac toxicity

No information available to require special precautions

No effects or complications noted

This medication is given to reduce sensation in the injected area. You will experience decreased sensation to pain, heat, or cold in the area and/or decreased muscle strength (depending on area of application) until the effects wear off; use necessary caution to reduce incidence of possible injury until full sensation returns. Immediately report chest pain or palpitations; increased restlessness, anxiety, or dizziness; skeletal or muscle weakness; difficulty breathing; ringing in ears; or changes in vision.

Injection: 2.5 mg/mL (10 mL, 30 mL); 5.0 mg/mL (10 mL, 30 mL); 7.5 mg/mL (10 mL, 30 mL)