ARESTOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ARESTOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN (ARESTOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN).
Articaine hydrochloride is a local anesthetic of the amide type that blocks voltage-gated sodium channels in nerve cell membranes, inhibiting the generation and conduction of nerve impulses. Levonordefrin is a sympathomimetic vasoconstrictor that acts on alpha-adrenergic receptors to produce local vasoconstriction, reducing absorption of the anesthetic and prolonging its effect.
| Metabolism | Articaine is metabolized primarily by plasma esterases (butyrylcholinesterase) to its inactive metabolite articainic acid; levonordefrin is metabolized by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). |
| Excretion | Renal: primarily as metabolites (hydroxy derivatives) and unchanged drug; approximately 90% eliminated in urine as metabolites, <5% unchanged. Biliary/fecal: minor, <10%. |
| Half-life | Articaine: approximately 1-2 hours (terminal half-life). Levonordefrin: not separately reported; vasoconstrictor effect duration supports anesthetic action. Clinical context: half-life is short, reflecting rapid metabolism by plasma esterases; clinical duration of anesthesia is prolonged by levonordefrin. |
| Protein binding | Articaine: approximately 70-80% bound, primarily to albumin. Levonordefrin: not reported. |
| Volume of Distribution | Articaine: Vd ~1.0 L/kg. Clinical meaning: moderate distribution into total body water, consistent with local anesthetic profile. |
| Bioavailability | Not applicable for local anesthetic; administered parenterally (infiltration/block). By submucosal injection:100% systemically available (though redistributes locally). |
| Onset of Action | Local infiltration (dental): 1-3 minutes; nerve block: 2-4 minutes. |
| Duration of Action | Local infiltration: approximately 60-75 minutes (pulpal anesthesia), up to 180 minutes (soft tissue). Nerve block: 90-180 minutes (pulpal), up to 5 hours (soft tissue). Clinical notes: duration extended by levonordefrin; varies with injection site and dose. |
| Molecular Weight | 270.8 |
For local anesthesia: 1-5 mL of 2% solution (20 mg/mL) with levonordefrin 1:20,000, infiltrated locally; maximum single dose: 3.5 mg/kg (not to exceed 200 mg total).
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended; use with caution in severe renal impairment (CrCl <30 mL/min) due to potential accumulation of metabolites. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Consider 50% dose reduction. Child-Pugh C: Avoid use or reduce dose by 75%; monitor for systemic toxicity. |
| Pediatric use | Weight-based: 0.5-1.0 mg/kg per injection site, not to exceed 3.5 mg/kg total; maximum single dose 200 mg. Adjust for age and body weight; use lower concentrations (1:100,000 epinephrine equivalent). |
| Geriatric use | Reduce dose by 20-50% due to increased risk of cardiovascular and central nervous system effects; consider lower concentration and slower administration. |
| 1st trimester | Avoid unless clearly needed. Lidocaine crosses placenta. Levonordefrin may cause uterine vasoconstriction. Use lowest effective dose. |
| 2nd trimester | Use with caution. Fetal risk cannot be ruled out. Avoid near cervix/placenta to minimize fetal exposure. |
| 3rd trimester | Use with caution. Levonordefrin may reduce uterine blood flow. Consider alternative without vasoconstrictor. |
Clinical note
Comprehensive clinical and safety monograph for ARESTOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN (ARESTOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN).
| Placental transfer | Lidocaine crosses placenta by passive diffusion. Fetal/maternal ratio ~0.5-0.7. Levonordefrin likely crosses to a lesser extent due to polarity and metabolism. |
| Breastfeeding | Lidocaine excreted in breast milk in small amounts; unlikely to cause adverse effects in infant. Levonordefrin has minimal oral bioavailability. Use with caution; monitor infant for irritability or sedation. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to lidocaine or amide-type anestheticsHypersensitivity to levonordefrin or any sulfitesSevere bradycardia or heart blockUncontrolled hypertensionSevere hypotensionShockKnown methemoglobinemia
| Precautions | Risk of methemoglobinemia, especially with higher doses, in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency or exposure to oxidizing agents, Cardiovascular effects due to levonordefrin, including hypertension, hypotension, tachycardia, and cardiac arrhythmias; use caution in patients with cardiovascular disease, hypertension, or hyperthyroidism, Allergic reactions including anaphylaxis have been reported, Systemic toxicity due to inadvertent intravascular injection; observe proper injection technique, Use caution in patients with impaired liver function or severe renal impairment |
| Food/Dietary | No significant food interactions. Avoid alcohol consumption for at least 24 hours after the procedure as it may increase the risk of bleeding at the injection site. |
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| Lactation Rating | L2 |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Limited human data, animal studies suggest risk of fetal cardiovascular abnormalities at high doses. Second/third trimesters: May cause uteroplacental vasoconstriction and fetal hypoxia; avoid use during labor due to risk of maternal hypertension and fetal bradycardia. |
| Fetal Monitoring | Monitor maternal heart rate, blood pressure, and signs of systemic toxicity. Fetal heart rate monitoring recommended if used near term or in high doses. Observe for uterine hypertonus if administered during labor. |
| Fertility Effects | No evidence of direct effects on fertility. In animal studies, high doses caused implantation failure, but relevance to human fertility is unknown. |
| Clinical Pearls | ARESTOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN is a dental anesthetic containing articaine HCl 4% with epinephrine 1:100,000. Levonordefrin is a vasoconstrictor added to prolong local anesthesia. Avoid use in patients with sulfite sensitivity (articaine contains sodium metabisulfite). Maximum dose: 7 mg/kg (articaine) and not to exceed 0.5 mg levonordefrin per appointment. Do not inject into inflamed or infected tissues due to increased absorption. Aspirate before injection to prevent intravascular administration. |
| Patient Advice | You may experience numbness in your mouth, lips, and tongue for several hours after the injection; avoid eating or drinking hot liquids until sensation returns to prevent burns. · Do not chew on the numb area to avoid accidental injury. · If you have a history of sulfite allergy, inform your dentist before the procedure. · Contact your dentist immediately if you experience severe headache, rapid heartbeat, or difficulty breathing after the injection. · This medication can cause temporary dizziness or lightheadedness; avoid driving until the effects have worn off. |