Articaine and epinephrine

The administration of local anesthetic solutions containing epinephrine to patients receiving monoamine oxidase inhibitors, nonselective beta-adrenergic antagonists, or tricyclic antidepressants may produce severe, prolonged hypertension. Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine. Concurrent use of these agents should be avoided; however, in situations when concurrent therapy is necessary, careful patient monitoring is essential [see Warnings and Precautions (5.2) ].

Patients who are administered local anesthetics are at increased risk of developing methemoglobinemia when concurrently exposed to the following drugs, which could include other local anesthetics: Table 5.

Examples of Drugs Associated with Methemoglobinemia: Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine Monoamine Oxidase Inhibitors, Nonselective Beta-Adrenergic Antagonists, or Tricyclic Antidepressants: May produce severe, prolonged hypertension ( 7 ) Phenothiazines and Butyrophenones: May reduce or reverse the pressor effect of epinephrine ( 7 )

8.1 Pregnancy Teratogenic Effects - Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women with Articaine HCl and Epinephrine. Articaine hydrochloride and epinephrine (1:100,000) has been shown to increase fetal deaths and skeletal variations in rabbits when given in doses approximately 4 times the maximum recommended human dose (MRHD). Articaine HCl and Epinephrine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In embryo-fetal toxicity studies in rabbits, 80 mg/kg, subcutaneously (approximately 4 times the MRHD based on body surface area) caused fetal death and increased fetal skeletal variations, but these effects may be attributable to severe maternal toxicity, including seizures, observed at this dose. In contrast, no embryo-fetal toxicities were observed when articaine and epinephrine (1:100,000) was administered subcutaneously throughout organogenesis at doses up to 40 mg/kg in rabbits and 80 mg/kg in rats (approximately 2 times the MRHD based on body surface area).

In pre- and postnatal developmental studies subcutaneous administration of articaine hydrochloride to pregnant rats throughout gestation and lactation, at a dose of 80 mg/kg (approximately 2 times the MRHD based on body surface area) increased the number of stillbirths and adversely affected passive avoidance, a measure of learning, in pups. This dose also produced severe maternal toxicity in some animals. A dose of 40 mg/kg (approximately equal to the MRHD on a mg/m 2 basis) did not produce these effects. A similar study using articaine and epinephrine (1:100,000) rather than articaine hydrochloride alone produced maternal toxicity, but no effects on offspring.

8.3 Nursing Mothers It is not known whether Articaine HCl and Epinephrine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Articaine HCl and Epinephrine is administered to a nursing woman. When using Articaine HCl and Epinephrine, nursing mothers may choose to pump and discard breast milk for approximately 4 hours (based on plasma half life) following an injection of Articaine HCl and Epinephrine (to minimize infant ingestion) and then resume breastfeeding.