ARTICAINE HYDROCHLORIDE AND EPINEPHRINE BITARTRATE
Clinical safety rating
safeBeta-blockers may antagonize cardiac effects and cause severe hypertension Can cause angina and arrhythmias in patients with heart disease.
Beta-blockers may antagonize cardiac effects and cause severe hypertension Can cause angina and arrhythmias in patients with heart disease.
Local infiltration anesthesia for dental proceduresNerve block anesthesia for dental procedures
cardiac arrest
Articaine is an amide local anesthetic that blocks sodium ion channels in nerve cell membranes, preventing depolarization and conduction of nerve impulses. Epinephrine is a vasoconstrictor that prolongs the anesthetic effect by reducing local blood flow and systemic absorption.
| Metabolism | Articaine is primarily metabolized by plasma esterases (butyrylcholinesterase) to its inactive metabolite articainic acid. Epinephrine is metabolized by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). |
| Excretion | Articaine is primarily metabolized by plasma esterases; its inactive metabolite articainic acid is excreted renally (approximately 90% as metabolites, <2% unchanged). Epinephrine is metabolized by COMT and MAO; metabolites and small amounts unchanged are excreted in urine (~90% renal). |
| Half-life | Articaine: terminal half-life ~20 minutes (0.33 h) in plasma; clinical context: rapid elimination limits systemic toxicity. Epinephrine: short half-life ~2 minutes; clinical effect terminated by uptake and metabolism. |
| Protein binding | Articaine: ~60–80% bound to plasma proteins (primarily albumin). Epinephrine: ~50% bound to plasma proteins (albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Articaine: Vd ~1.0 L/kg (healthy adults); large Vd indicates extensive tissue distribution. Epinephrine: Vd ~0.2 L/kg (predominantly in circulation and tissues). |
| Bioavailability | Not applicable for submucosal injection (100% bioavailable locally). Oral epinephrine has negligible bioavailability due to first-pass metabolism. For systemic effects, IV administration yields 100% bioavailability. |
| Onset of Action | Submucosal infiltration or nerve block: 1–3 minutes for pulpal anesthesia due to rapid diffusion and high lipid solubility of articaine. |
| Duration of Action | Pulpal anesthesia: ~60–75 minutes for infiltration; soft tissue anesthesia: 3–5 hours. Epinephrine prolongs duration by vasoconstriction. Clinical note: shorter duration in highly vascular areas. |
| Molecular Weight | Articaine HCl: 320.84 Da; Epinephrine bitartrate: 333.29 Da |
Adults: 1:100,000 epinephrine formulation (4% articaine) administered as a submucosal local infiltration or nerve block; maximum dose 7 mg/kg (0.175 mL/kg) per appointment, not to exceed 500 mg (12.5 mL). 1:200,000 epinephrine formulation may be used; maximum dose same.
| Dosage form | INJECTABLE |
| Renal impairment | No dosage adjustment required for mild-to-moderate renal impairment; use with caution in severe renal impairment (GFR <30 mL/min) due to potential accumulation of articaine metabolite; monitor for toxicity. |
| Liver impairment | No specific guidelines; use with caution in severe hepatic impairment (Child-Pugh C) due to reduced metabolism; consider reduced doses and monitor for prolonged effects. |
| Pediatric use | Children ≥4 years: 4% articaine with 1:100,000 or 1:200,000 epinephrine; submucosal local infiltration or nerve block; maximum dose 7 mg/kg (0.175 mL/kg) per appointment, not to exceed 7 mg/kg (absolute max 500 mg). For 1:100,000 formulation, maximum epinephrine dose 0.001 mg/kg (0.001 mL/kg) per injection. |
| Geriatric use | No specific dose adjustment; consider reduced doses due to age-related decreased hepatic and renal function; monitor for prolonged anesthesia and cardiovascular effects; use lowest effective dose. |
| 1st trimester | Avoid due to potential teratogenic effects from epinephrine; articaine is a pregnancy category C drug. |
| 2nd trimester | Use only if clearly needed; consider risk-benefit; epinephrine may reduce uterine blood flow. |
| 3rd trimester | Avoid near term; epinephrine may delay labor or cause fetal hypoxia. |
Clinical note
Beta-blockers may antagonize cardiac effects and cause severe hypertension Can cause angina and arrhythmias in patients with heart disease.
| FDA category | Animal |
| Placental transfer | Articaine crosses the placenta; fetal plasma concentrations are approximately 30% of maternal levels. Epinephrine also crosses but is rapidly metabolized. |
| Breastfeeding | Articaine and epinephrine are excreted into breast milk in low amounts; however, due to potential for infant effects (e.g., cardiovascular stimulation from epinephrine), caution is advised. The American Academy of Pediatrics considers articaine compatible with breastfeeding. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | FDA Pregnancy Category C. No well-controlled studies in pregnant women. In animal studies, articaine and epinephrine have not shown teratogenic effects at clinically relevant doses. Risk to fetus cannot be ruled out. Use only if clearly needed. No specific trimester-associated risks identified; however, epinephrine may reduce uteroplacental blood flow, particularly if given with vasoconstrictors or during second/third trimester. |
| Fetal Monitoring | Monitor maternal vital signs (blood pressure, heart rate) during and after administration due to epinephrine content. Assess fetal heart rate if warranted by maternal condition or if signs of uterine hypertonus occur. In high doses or inadvertent intravascular injection, monitor for signs of maternal toxicity: CNS excitation, seizures, cardiac arrhythmias. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies have not shown impaired fertility at clinically relevant doses. Articaine and epinephrine do not directly affect reproductive organs or hormonal cycles in standard doses. |
■ FDA Black Box Warning
Not available
| Common Effects | cardiac arrest |
| Serious Effects |
Hypersensitivity to articaine or epinephrineHypersensitivity to amide-type local anestheticsSevere or uncontrolled hypertensionSevere cardiovascular disease (e.g., unstable angina, recent MI)ThyrotoxicosisConcurrent MAO inhibitor therapy or tricyclic antidepressants (risk of hypertensive crisis due to epinephrine)PheochromocytomaNarrow-angle glaucoma (epinephrine component)
| Precautions | Risk of methemoglobinemia, especially in patients with glucose-6-phosphate dehydrogenase deficiency or hemoglobin abnormalities, Use with caution in patients with cardiovascular disease, hypertension, or hyperthyroidism due to epinephrine component, Avoid intravascular injection; may cause systemic toxicity or cardiovascular collapse, Caution in patients with hepatic or renal impairment, May cause allergic reactions or hypersensitivity; cross-sensitivity with other amide anesthetics is possible |
| Food/Dietary | No known food-drug interactions. Avoid eating until numbness resolves to prevent oral trauma. |
| Clinical Pearls | Aspirate before injection to prevent intravascular administration. Maximum dose: 7 mg/kg articaine (0.175 mL/kg of 4% solution with 1:100,000 epinephrine). Avoid in patients with hepatic porphyria. Use with caution in patients with sulfite allergy (epinephrine component contains sodium metabisulfite). |
| Patient Advice | You may experience temporary numbness of the tongue, lips, or face; avoid eating or drinking until sensation returns to prevent biting yourself. · Do not drive or operate machinery for at least 2 hours after administration, or until numbness resolves. · Contact your dentist or doctor immediately if you experience chest pain, difficulty breathing, rapid heartbeat, or severe headache after injection. · Inform your healthcare provider if you have heart disease, high blood pressure, thyroid problems, or are taking MAO inhibitors or tricyclic antidepressants. |
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