ISOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ISOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN (ISOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN).
Isocaine hydrochloride (mepivacaine) is an amino amide local anesthetic that blocks sodium ion channels in nerve cell membranes, thereby inhibiting the initiation and conduction of nerve impulses. Levonordefrin is a vasoconstrictor that acts on alpha-adrenergic receptors to cause local vasoconstriction, prolonging the anesthetic effect.
| Metabolism | Isocaine hydrochloride (mepivacaine) is primarily metabolized in the liver by cytochrome P450 enzymes, mainly CYP1A2 and CYP3A4, to inactive metabolites. Levonordefrin is metabolized by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). |
| Excretion | Renal excretion of metabolites, primarily 4-hydroxy-2,6-dimethylaniline glucuronide and sulfate conjugates; less than 5% excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is approximately 2.1 hours; clinically, accumulation may occur with repeated doses in renal impairment. |
| Protein binding | Approximately 60% bound to plasma proteins, primarily alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd is approximately 1.0 L/kg; distribution is rapid and extensive, indicating high tissue uptake. |
| Bioavailability | Intravenous: 100%; Intramuscular: ~100%; Subcutaneous: ~100%; Oral: 10-30% due to first-pass metabolism. |
| Onset of Action | Infiltration: 2-5 minutes; Nerve block: 5-10 minutes; Topical: 2-5 minutes. |
| Duration of Action | Infiltration: 45-90 minutes (with epinephrine analog levonordefrin); Nerve block: 60-90 minutes; Pulpal anesthesia: 30-90 minutes. |
| Molecular Weight | 270.8 |
Adult dental infiltration or nerve block: 1-2 mL of 2% solution (20 mg/mL isocaine hydrochloride with levonordefrin 1:20,000) administered subcutaneously; maximum single dose 5 mL (100 mg isocaine hydrochloride); maximum total dose 7 mL per appointment.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dosing adjustment required for mild to moderate renal impairment; for severe impairment (GFR <30 mL/min), consider reducing dose by 25-50% due to risk of methemoglobinemia; monitor methemoglobin levels. |
| Liver impairment | Child-Pugh Class A: No adjustment. Class B: Reduce dose by 50%; maximum single dose 50 mg. Class C: Avoid use or use with extreme caution; alternative agent recommended. |
| Pediatric use | Weight-based dose: 1-2 mg/kg isocaine hydrochloride per injection, maximum 4.4 mg/kg total; not to exceed adult doses. For dental procedures, typical dose 0.5-1 mL per injection site depending on weight. |
| Geriatric use | Elderly patients (≥65 years): Reduced dose due to decreased hepatic metabolism; initial dose 50% of adult dose; maximum single dose 50 mg; monitor for CNS and cardiovascular side effects. |
| 1st trimester | Avoid use in first trimester due to potential teratogenic effects. Lidocaine is generally low risk, but levonordefrin may cause uterine vasoconstriction. |
| 2nd trimester | Use with caution. Levonordefrin may increase maternal heart rate and blood pressure; monitor fetal heart rate. Only when benefits outweigh risks. |
| 3rd trimester | Use with caution near term. Levonordefrin may reduce uterine blood flow; avoid in preeclampsia. May cross placenta; minimal risk of neonatal effects. |
Clinical note
Comprehensive clinical and safety monograph for ISOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN (ISOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN).
| Placental transfer | Lidocaine readily crosses the placenta; fetal/maternal ratio ~0.5-0.7. Levonordefrin undergoes placental metabolism, minimal transfer. |
| Breastfeeding | Lidocaine is excreted into breast milk in low amounts; likely compatible with breastfeeding. Levonordefrin levels are negligible. Monitor infant for drowsiness or irritability. Limit maternal doses. |
■ FDA Black Box Warning
Intravascular injection of local anesthetics can cause sudden cardiac arrest, especially in children. Resuscitative equipment and personnel trained in advanced cardiac life support must be immediately available.
| Serious Effects |
Hypersensitivity to amide-type anestheticsHypersensitivity to levonordefrin or sulfitesSevere hypertensionUncontrolled hyperthyroidismCardiac decompensationConcurrent MAO inhibitors or tricyclic antidepressants
| Precautions | Risk of systemic toxicity from inadvertent intravascular injection, Caution in patients with hepatic impairment due to reduced metabolism, Caution in patients with cardiovascular disease due to vasoconstrictor effects of levonordefrin, Avoid use in patients with severe hypertension or thyrotoxicosis, Use lowest effective dose to minimize risk of adverse effects |
| Food/Dietary | No significant food interactions. Avoid alcohol before and after dental procedure to reduce risk of bleeding and enhanced sedation. |
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| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | In the first trimester, no well-controlled studies in humans; animal studies insufficient. In second and third trimesters, lidocaine (component) crosses placenta with fetal serum levels ~50% maternal; no major teratogenic risk in typical doses. Levonordefrin is a vasoconstrictor; risk of uteroplacental insufficiency at high doses. Avoid during first trimester if possible. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate during administration; fetal heart rate monitoring if multiple injections or high doses used. Observe for signs of maternal or fetal bradycardia due to vasoconstrictor. |
| Fertility Effects | No known effects on human fertility; animal studies not conducted. |
| Clinical Pearls | ISOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN is a dental anesthetic combination. Levonordefrin is a vasoconstrictor that prolongs anesthetic action. Avoid intravascular injection to prevent systemic toxicity. Use caution in patients with cardiovascular disease, hypertension, or hyperthyroidism due to levonordefrin. Maximum dose: 5.4 mg/kg of isocaine base. Contraindicated in patients with sulfite allergy (contains sodium metabisulfite). |
| Patient Advice | You will receive an injection for dental numbness lasting about 1-3 hours. · Avoid chewing on the numbed area to prevent accidental injury. · Do not eat or drink hot liquids until sensation fully returns. · Report any signs of allergic reaction (rash, swelling, difficulty breathing) immediately. · Inform your dentist if you have heart disease, high blood pressure, or thyroid problems. |