Version July 2025
Note: Dosage varies with the anesthetic procedure, degree of anesthesia needed, vascularity of tissue, duration of anesthesia required, and physical condition of patient. Always use the lowest effective dose along with careful aspiration.
Dental anesthesia, infiltration, or conduction block: Usual dose: Mepivacaine 34 mg (1.7 mL) per site or mepivacaine 180 mg (9 mL) for entire oral cavity; maximum cumulative mepivacaine dose: 6.6 mg/kg or 400 mg (whichever is less) during any single dental sitting.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations.
Refer to adult dosing; reduce dose consistent with age and physical status.
Note: Dosage varies with the anesthetic procedure, degree of anesthesia needed, vascularity of tissue, duration of anesthesia required, and physical condition of patient. Always use the lowest effective dose along with careful aspiration.
Dental anesthesia, infiltration, or conduction block: Children and Adolescents: Maximum dosage must be carefully calculated on the basis of patient's weight. Manufacturer recommends a maximum mepivacaine dose of 6.6 mg/kg, but must not exceed 180 mg as a 2% solution. The American Academy of Pediatric Dentistry (AAPD) recommends a maximum mepivacaine dose of 4.4 mg/kg or a maximum total dose of 300 mg in any single dental sitting (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations.
The following adverse drug reactions are derived from product labeling unless otherwise specified. Reactions listed may be based on reports for other agents in the same pharmacologic class and may not be specifically reported for mepivacaine or levonordefrin. Also see Mepivacaine.
Frequency not defined:
Cardiovascular: Cardiovascular depression
Gastrointestinal: Oral paresthesia
Hypersensitivity: Hypersensitivity reaction (including nonimmune anaphylaxis)
Nervous system: Disorientation, dizziness, drowsiness, excitement, loss of consciousness, nervousness, seizure, tremor
Ophthalmic: Blurred vision
Hypersensitivity to mepivacaine, levonordefrin, local anesthetics of the amide-type, or any component of the formulation
Concerns related to adverse effects:
• CNS toxicity: Careful and constant monitoring of the patient's state of consciousness should be done following each local anesthetic injection; at such times, restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, depression, or drowsiness may be early warning signs of CNS toxicity. Treatment is primarily symptomatic and supportive.
• Methemoglobinemia: Has been reported with local anesthetics; clinically significant methemoglobinemia requires immediate treatment along with discontinuation of the anesthetic and other oxidizing agents. Onset may be immediate or delayed (hours) after anesthetic exposure. Patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, exposure to oxidizing agents or their metabolites, or infants <6 months of age are more susceptible and should be closely monitored for signs and symptoms of methemoglobinemia (eg, cyanosis, headache, rapid pulse, shortness of breath, light-headedness, fatigue).
• Respiratory arrest: Local anesthetics have been associated with rare occurrences of sudden respiratory arrest.
• Seizures: Convulsions due to systemic toxicity leading to cardiac arrest have also been reported, presumably following unintentional intravascular injection.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with arteriosclerotic heart disease, cerebral vascular insufficiency, heart block, hypertension, and ischemic heart disease; minimal amounts of vasoconstrictor should be used in this patient population.
• Diabetes: Use with caution in patients with diabetes.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Hyperthyroidism: Use with caution in patients with hyperthyroidism.
• Renal impairment: Use with caution in patients with renal impairment.
Special populations:
• Acutely ill patients: Use with caution in acutely ill patients; reduce dose consistent with age and physical status.
• Debilitated patients: Use with caution in debilitated patients; reduce dose consistent with age and physical status.
• Older adult: Use with caution in the elderly; reduce dose consistent with age and physical status.
• Pediatric: Use with caution in children; reduce dose consistent with age and physical status.
Dosage form specific issues:
• Potassium metabisulfite: Some preparations may contain potassium metabisulfite which may cause severe hypersensitivity reactions (anaphylaxis) in some individuals; use caution in patients with asthma.
Other warnings/precautions:
• Administration: Intravascular injections should be avoided; aspiration should be performed prior to administration; the needle must be repositioned until no return of blood can be elicited by aspiration; however, absence of blood in the syringe does not guarantee that intravascular injection has been avoided. Use with caution when there is inflammation and/or sepsis in the region of the proposed injection.
• Appropriate dosing: To avoid serious adverse effects and high plasma levels, the lowest dosage resulting in effective anesthesia should be administered. Repeated doses may cause significant increases in blood levels with each repeated dose due to the possibility of accumulation of the drug or its metabolites. Tolerance to elevated blood levels varies with patient status.
• Trained personnel: Dental practitioners using local anesthetic agents should be well trained in diagnosis and management of emergencies that may arise from the use of these agents. Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, solution [for dental use]:
Carbocaine 2% with Neo-Cobefrin: Mepivacaine hydrochloride 2% and levonordefrin 1:20,000 (1.7 mL) [contains edetate disodium, potassium metabisulfite]
Scandonest 2% L: Mepivacaine hydrochloride 2% and levonordefrin 1:20,000 (1.7 mL) [contains edetate disodium, potassium metabisulfite]
No
Administer slowly, with frequent aspirations before and during the injection to avoid intravascular injection. Use with caution when there is inflammation and/or sepsis in the region of the proposed injection.
Dental injection: Administer slowly, with frequent aspirations before and during the injection to avoid intravascular injection. Use with caution when there is inflammation and/or sepsis in the region of the proposed injection.
Dental anesthesia: Production of local anesthesia for dental procedures by infiltration or nerve block in adult and pediatric patients
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Alpha1-Blockers: May decrease therapeutic effects of Alpha-/Beta-Agonists. Risk C: Monitor
Articaine: May increase adverse/toxic effects of Local Anesthetics. Risk C: Monitor
Atomoxetine: May increase hypertensive effects of Sympathomimetics. Atomoxetine may increase tachycardic effects of Sympathomimetics. Risk C: Monitor
Benzylpenicilloyl Polylysine: Coadministration of Alpha-/Beta-Agonists and Benzylpenicilloyl Polylysine may alter diagnostic results. Management: Consider use of a histamine skin test as a positive control to assess a patient's ability to mount a wheal and flare response. Risk D: Consider Therapy Modification
Bornaprine: Sympathomimetics may increase anticholinergic effects of Bornaprine. Risk C: Monitor
Bromocriptine: May increase hypertensive effects of Alpha-/Beta-Agonists. Management: Consider alternatives to this combination when possible. If combined, monitor for hypertension and tachycardia, and do not coadminister these agents for more than 10 days. Risk D: Consider Therapy Modification
BUPivacaine (Liposomal): Local Anesthetics may increase adverse/toxic effects of BUPivacaine (Liposomal). Management: Liposomal bupivacaine should not be administered with local anesthetics, but may be administered 20 minutes or more after lidocaine. Avoid all local anesthetics within 96 hours after administration of liposomal bupivacaine. Risk X: Avoid
BUPivacaine: Local Anesthetics may increase adverse/toxic effects of BUPivacaine. Management: Avoid using any additional local anesthetics within 96 hours after insertion of the bupivacaine implant (Xaracoll) or bupivacaine and meloxicam periarticular solution (Zynrelef) or within 168 hours after subacromial infiltration (Posimir brand). Risk C: Monitor
Cannabinoid-Containing Products: May increase tachycardic effects of Sympathomimetics. Risk C: Monitor
Chloroprocaine (Systemic): May increase hypertensive effects of Alpha-/Beta-Agonists. Risk C: Monitor
Cocaine (Topical): May increase hypertensive effects of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Risk D: Consider Therapy Modification
Dihydralazine: Sympathomimetics may decrease therapeutic effects of Dihydralazine. Risk C: Monitor
Doxofylline: Sympathomimetics may increase adverse/toxic effects of Doxofylline. Risk C: Monitor
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): May increase vasoconstricting effects of Alpha-/Beta-Agonists. Risk X: Avoid
Esketamine (Injection): May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for elevated heart rate, hypertension, and arrhythmias may be increased. Risk C: Monitor
Guanethidine: May increase hypertensive effects of Sympathomimetics. Guanethidine may increase arrhythmogenic effects of Sympathomimetics. Risk C: Monitor
Hyaluronidase: May increase vasoconstricting effects of Alpha-/Beta-Agonists. Management: Do not use hyaluronidase to enhance the dispersion or absorption of alpha-/beta-agonists. Use of hyaluronidase for other purposes in patients receiving alpha-/beta-agonists may be considered as clinically indicated. Risk D: Consider Therapy Modification
Kratom: May increase adverse/toxic effects of Sympathomimetics. Risk X: Avoid
Landiolol: Sympathomimetics may decrease therapeutic effects of Landiolol. Risk C: Monitor
Levothyroxine: May increase therapeutic effects of Sympathomimetics. Sympathomimetics may increase therapeutic effects of Levothyroxine. Levothyroxine may increase adverse/toxic effects of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Risk C: Monitor
Linezolid: May increase hypertensive effects of Sympathomimetics. Management: Consider initial dose reductions of sympathomimetic agents, and closely monitor for enhanced blood pressure elevations, in patients receiving linezolid. Risk D: Consider Therapy Modification
Lisuride: May increase hypertensive effects of Alpha-/Beta-Agonists. Risk X: Avoid
Methemoglobinemia Associated Agents: May increase adverse/toxic effects of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor
Monoamine Oxidase Inhibitors: May increase hypertensive effects of Levonordefrin. Management: Avoid the use of levonordefrin during or within 2 weeks of treatment with a monoamine oxidase inhibitor whenever possible. If levonordefrin cannot be avoided during this period, monitor closely for enhanced or prolonged increases in blood pressure. Risk D: Consider Therapy Modification
Neuromuscular-Blocking Agents: Local Anesthetics may increase neuromuscular-blocking effects of Neuromuscular-Blocking Agents. Risk C: Monitor
Pergolide: May increase hypertensive effects of Alpha-/Beta-Agonists. Risk C: Monitor
Propranolol: May increase serum concentration of Mepivacaine. Risk C: Monitor
ROPivacaine: May increase adverse/toxic effects of Local Anesthetics. Risk C: Monitor
Serotonin/Norepinephrine Reuptake Inhibitor: May increase tachycardic effects of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitor may increase vasopressor effects of Alpha-/Beta-Agonists. Management: If possible, avoid coadministration of direct-acting alpha-/beta-agonists and serotonin/norepinephrine reuptake inhibitors. If coadministered, monitor for increased sympathomimetic effects (eg, increased blood pressure, chest pain, headache). Risk D: Consider Therapy Modification
Solriamfetol: Sympathomimetics may increase hypertensive effects of Solriamfetol. Sympathomimetics may increase tachycardic effects of Solriamfetol. Risk C: Monitor
Spironolactone: May decrease vasoconstricting effects of Alpha-/Beta-Agonists. Risk C: Monitor
Sympathomimetics: May increase adverse/toxic effects of Sympathomimetics. Risk C: Monitor
Technetium Tc 99m Tilmanocept: Coadministration of Local Anesthetics and Technetium Tc 99m Tilmanocept may alter diagnostic results. Management: Avoid mixing and simultaneously co-injecting technetium Tc 99m tilmanocept with local anesthetics. This interaction does not appear to apply to other uses of these agents in combination. Risk C: Monitor
Tedizolid: May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for increased blood pressure and heart rate may be increased. Risk C: Monitor
Tricyclic Antidepressants: May increase vasopressor effects of Alpha-/Beta-Agonists. Management: Avoid, if possible, the use of alpha-/beta-agonists in patients receiving tricyclic antidepressants. If combined, monitor for evidence of increased pressor effects and consider reductions in initial dosages of the alpha-/beta-agonist. Risk D: Consider Therapy Modification
Vasopressin: Alpha-/Beta-Agonists (Direct-Acting) may increase hypertensive effects of Vasopressin. The effect of other hemodynamic parameters may also be enhanced. Risk C: Monitor
Animal reproduction studies have not been conducted with this combination.
It is not known if mepivacaine or levonordefrin is present in breast milk. The manufacturer recommends that caution be exercised when administering mepivacaine/levonordefrin to breastfeeding women. Usual infiltration doses of mepivacaine with levonordefrin given to breastfeeding mothers has not been shown to affect the health of the breastfed infant.
Mepivacaine: Local anesthetics bind selectively to the intracellular surface of sodium channels to block influx of sodium into the axon. As a result, depolarization necessary for action potential propagation and subsequent nerve function is prevented. The block at the sodium channel is reversible. When drug diffuses away from the axon, sodium channel function is restored and nerve propagation returns.
Levonordefrin: Prolongs the duration of the anesthetic actions of mepivacaine by causing vasoconstriction (alpha-adrenergic receptor agonist) of the vasculature surrounding the nerve axons. This prevents the diffusion of mepivacaine away from the nerves resulting in a longer retention in the axon.
Onset of action: Upper jaw: 30 to 120 seconds; Lower jaw: 1 to 4 minutes
Duration: Upper jaw: 1 to 2.5 hours; Lower jaw: 2.5 to 5.5 hours
Protein binding: Mepivacaine: ~75%
Metabolism: Mepivacaine: Primarily hepatic via N-demethylation, hydroxylation, and glucuronidation
Excretion: Mepivacaine: Urine (90% to 95% as metabolites)
