MEPIVACAINE HYDROCHLORIDE W/ LEVONORDEFRIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MEPIVACAINE HYDROCHLORIDE W/ LEVONORDEFRIN (MEPIVACAINE HYDROCHLORIDE W/ LEVONORDEFRIN).
Local anesthetic that blocks voltage-gated sodium channels in neuronal membranes, preventing propagation of action potentials and transmission of pain signals.
| Metabolism | Primarily hepatic via N-demethylation by CYP1A2; minor metabolism by CYP3A4. Metabolites excreted renally. |
| Excretion | Mepivacaine is primarily metabolized in the liver via N-demethylation and hydroxylation. Less than 5% is excreted unchanged in urine. Hepatic clearance accounts for >90% of elimination; renal excretion of metabolites accounts for the remainder. Fecal elimination is minimal (<2%). |
| Half-life | Terminal elimination half-life is approximately 2-3 hours in adults. In neonates, half-life is prolonged (8-10 hours due to immature hepatic function). Clinical context: Short half-life reduces risk of systemic accumulation with repeated doses. |
| Protein binding | Approximately 75-85% bound to alpha-1-acid glycoprotein (orosomucoid) and less extensively to albumin. Binding is concentration-dependent. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 0.8-1.0 L/kg, indicating extensive tissue distribution. Higher Vd in infants (2-3 L/kg) due to larger extracellular fluid compartment. |
| Bioavailability | Mepivacaine is not administered orally due to extensive first-pass metabolism. For local infiltration or regional administration, bioavailability is essentially 100% at the site of administration. Intravenous bioavailability is 100% by definition. |
| Onset of Action | Onset of action after infiltration or nerve block is 3-5 minutes. For epidural administration, onset is 5-10 minutes. Onset after subcutaneous infiltration is 1-2 minutes. |
| Duration of Action | Duration of anesthesia depends on dose and administration site. Without epinephrine, duration is 0.75-1 hour for infiltration; with levonordefrin (1:20,000), duration is prolonged to 2-3 hours for infiltration and 3-4 hours for nerve blocks. Levonordefrin provides vasoconstriction to prolong effect. |
| Molecular Weight | 282.8 |
Dental infiltration or nerve block: 1-2 cartridges (36-72 mg mepivacaine; 0.009-0.018 mg levonordefrin) of 2% solution with 1:20,000 levonordefrin; maximum dose: 4.4 mg/kg mepivacaine (not to exceed 300 mg) per appointment.
| Dosage form | INJECTABLE |
| Renal impairment | GFR ≥ 50 mL/min: no adjustment. GFR 30-49 mL/min: consider reducing dose by 25% due to potential accumulation of metabolites. GFR < 30 mL/min: avoid or use with caution; reduce dose by 50% and monitor for CNS toxicity. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: consider 50% dose reduction. Child-Pugh C: contraindicated due to impaired metabolism and risk of toxicity. |
| Pediatric use | Children: 1.1-1.8 mg/kg mepivacaine (0.54-0.9 mg/lb) as 2% solution with 1:20,000 levonordefrin; maximum 4.4 mg/kg (not exceeding 300 mg). For example, 20 kg child: 22-36 mg mepivacaine (1.1-1.8 mL of 2% solution). |
| Geriatric use | Elderly patients (≥65 years): use lowest effective dose due to increased sensitivity, potential renal impairment, and comorbidities. Maximum single dose: 4.4 mg/kg (not exceeding 300 mg); reduce dose by 50% if GFR < 50 mL/min. Monitor cardiovascular status due to levonordefrin. |
| 1st trimester | Limited data; use only if clearly needed. Avoid in early pregnancy if possible due to potential fetal bradycardia. |
| 2nd trimester | May be used for dental procedures with caution; monitor fetal heart rate if prolonged exposure. |
| 3rd trimester | Use with caution; may cause uterine contractions or fetal bradycardia. Avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for MEPIVACAINE HYDROCHLORIDE W/ LEVONORDEFRIN (MEPIVACAINE HYDROCHLORIDE W/ LEVONORDEFRIN).
| Placental transfer | Crosses placenta; fetal serum levels approximately 60-80% of maternal levels. |
| Breastfeeding | Excreted in breast milk in small amounts; unlikely to cause adverse effects in infants. Use lowest effective dose and shortest duration. Monitor infant for drowsiness. |
■ FDA Black Box Warning
Not available.
| Serious Effects |
Hypersensitivity to mepivacaine or levonordefrinSevere hypotensionCardiovascular disease (e.g., severe hypertension, arrhythmias)Concurrent use of MAOIs or tricyclic antidepressants (due to levonordefrin)Cocaine or methamphetamine useSevere hepatic impairment
| Precautions | Risk of central nervous system toxicity (seizures, CNS depression), Cardiovascular toxicity (arrhythmias, hypotension) with high doses or rapid absorption, Avoid in patients with severe liver disease, May cause methemoglobinemia, especially in patients with glucose-6-phosphate dehydrogenase deficiency |
| Food/Dietary | Avoid high-tyramine foods (aged cheese, cured meats, fermented products) as concurrent MAO-A inhibition from levonordefrin may cause hypertensive crisis. Limit caffeine intake (stimulant additive effect on heart rate). |
Loading safety data…
| Lactation Rating |
| L2 (Safer) |
| Teratogenic Risk | Mepivacaine hydrochloride with levonordefrin is classified as FDA Pregnancy Category C. In animal studies, mepivacaine has been associated with adverse fetal effects at high doses, but no well-controlled human studies exist. Levonordefrin is a vasoconstrictor; systemic absorption may reduce uterine blood flow, potentially causing fetal hypoxia. Risk in the first trimester is unknown; second and third trimester use may be associated with fetal bradycardia and acidosis if high doses are administered or inadvertent intravascular injection occurs. Use only if clearly needed. |
| Fetal Monitoring | Monitor maternal vital signs (heart rate, blood pressure) and fetal heart rate continuously during administration, especially after large doses or in high-risk pregnancies. Watch for signs of systemic toxicity (e.g., CNS excitement, seizures, cardiac depression). Administer with caution in patients with preeclampsia or impaired placental perfusion. |
| Fertility Effects | No specific human data exist regarding effects of mepivacaine or levonordefrin on fertility. Animal studies have not shown significant impairment. Temporary local anesthetic effects are not expected to affect fertility. |
| Clinical Pearls | For dental procedures, limit dose to 1 cartridge (1.8 mL) per appointment due to levonordefrin's α-adrenergic effects. Avoid in patients with sulfite allergy (bisulfite preservative). Use with caution in severe cardiovascular disease, pheochromocytoma, or hyperthyroidism due to levonordefrin. Onset 2-3 min, duration 60-90 min (infiltration). |
| Patient Advice | Report any history of heart disease, high blood pressure, or sulfite allergy before injection. · You may feel temporary increased heart rate or palpitations due to the vasoconstrictor. · Numbness may last several hours; avoid chewing gum or eating until sensation returns. · Seek immediate medical attention if you experience chest pain, severe headache, or difficulty breathing. · Use only as directed by your dentist; do not exceed prescribed dose. |