ISOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ISOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN (ISOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ISOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN (ISOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN).

Breastfeeding	Lidocaine excreted into breast milk in small amounts (<1% maternal dose); M/P ratio ~0.3-0.6. Levonordefrin likely minimal excretion. Compatible with breastfeeding with caution; avoid large doses.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to mepivacaine, levonordefrin, or other amide-type local anesthetics","Severe hypotension or cardiogenic shock","Thromboembolic disease","Use of MAO inhibitors or tricyclic antidepressants within 14 days","Severe hypertension or thyrotoxicosis"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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ISOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ISOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN (ISOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ISOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN (ISOCAINE HYDROCHLORIDE W/ LEVONORDEFRIN).

Breastfeeding	Lidocaine excreted into breast milk in small amounts (<1% maternal dose); M/P ratio ~0.3-0.6. Levonordefrin likely minimal excretion. Compatible with breastfeeding with caution; avoid large doses.
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.