Lidocaine (topical)

Antiarrhythmic Drugs: When BONDLIDO is used in patients receiving Class I antiarrhythmic drugs (such as tocainide or mexiletine), the toxic effects are additive and potentially synergistic. Consider risk/benefit during concomitant use ( 7.1 ). Local Anesthetics: When BONDLIDO is used concomitantly with other products containing local anesthetic agents, the effects are additive. The amount absorbed from all formulations must be considered for safe use ( 7.2 ).

7.1 Antiarrhythmic Drugs When BONDLIDO is used in patients receiving Class I antiarrhythmic drugs (such as tocainide or mexiletine), the toxic effects are additive and potentially synergistic. Consider risk/benefit during concomitant use.

7.2 Local Anesthetics When BONDLIDO is used concomitantly with other products containing local anesthetic agents, the effects are additive. The amount absorbed from all formulations must be considered for safe use.

7.3 Drugs That May Cause Methemoglobinemia When Used with BONDLIDO 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: 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

8.1 Pregnancy Risk Summary The limited human data with lidocaine in pregnant woman are not sufficient to inform drug-associated risk for major birth defects and miscarriage. The use of lidocaine for labor neuraxial analgesia has not been associated with an increased incidence of adverse fetal effects either during delivery or during the neonatal period [see Data ]. Should BONDLIDO be used concomitantly with other products containing lidocaine, consider total drug doses contributed by all formulations.

In a published animal reproduction study, pregnant rats administered lidocaine by continuous subcutaneous infusion at a dose approximately 12 times the maximum recommended daily dose (MRDD) of 400 mg in BONDLIDO during the period of organogenesis resulted in lower fetal body weights. In a published animal reproduction study, pregnant rats administered lidocaine, containing 1:100,000 epinephrine, injected into the masseter muscle of the jaw or into the gum of the lower jaw at approximately 0.14 times the MRDD on Gestation Day 11 resulted in developmental delays in neonates [see Data ]. The background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies carry some risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data In 22 parturient women given 1.5% lidocaine epidural anesthesia, there were no effects on neonatal behavior, using the early neonatal neurobehavioral scale (ENNS). Neuraxial analgesia also did not affect fetal heart rate, beat-to-beat variability, or uterine activity.

Animal Data Reproductive studies with lidocaine have been performed in rats at doses up to 30 mg/kg (0.73 times the maximum recommended daily dose [MRDD] of 400 mg from BONDLIDO on a mg/m 2 basis) subcutaneously and have revealed no evidence of harm to the fetus due to lidocaine. In a published study, lidocaine administered to pregnant rats by continuous subcutaneous infusion during the period of organogenesis at 100, 250, and 500 mg/kg/day, did not produce any structural abnormalities, but did result in lower fetal weights at 500 mg/kg/day dose (approximately 12 times the MRDD on a mg/m 2 basis) in the absence of maternal toxicity.

In a published study, lidocaine containing 1:100,000 epinephrine at a dose of 6 mg/kg (approximately 0.14 times the MRDD on a mg/m 2 basis) injected into the masseter muscle of the jaw or into the gum of the…