Lidocaine and tetracaine

Antiarrhythmic Drugs : Use with caution in patients receiving Class I antiarrhythmic drugs (such as tocainide and mexiletine) because the systemic toxic effects are thought to be additive and potentially synergistic with lidocaine and tetracaine. ( 7.1 )

7.1 Antiarrhythmic Drugs PLIAGLIS should be used with caution in patients receiving Class I antiarrhythmic drugs (such as tocainide and mexiletine) since the systemic toxic effects are thought to be additive and potentially synergistic with lidocaine and tetracaine.

7.2 Local Anesthetics When PLIAGLIS is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all formulations should be considered since the systemic toxic effects are thought to be additive and potentially synergistic with lidocaine and tetracaine.

7.3 Drugs That May Cause Methemoglobinemia When Used with PLIAGLIS 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 There are no available data on PLIAGLIS use in pregnant women to determine a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Available data from an epidemiologic study and case series with parenteral lidocaine use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Published data on tetracaine use in pregnant women are not sufficient to determine any drug-associated risks.

The amount of lidocaine and tetracaine systemically absorbed from PLIAGLIS is low compared to the parenteral route of administration and is not expected to result in significant fetal exposure. Systemic exposure of PLIAGLIS is directly related to both the duration of application and the surface area over which it is applied [ see Clinical Pharmacology (12.3) ] . In a published animal reproduction study, pregnant rats administered lidocaine by continuous subcutaneous infusion at doses approximately 1.3 times the maximum recommended human dose (MRHD) of 53 grams of PLIAGLIS 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 on Gestation Day 11 at 0.02 times the MRHD of PLIAGLIS resulted in developmental delays in neonates. Subcutaneous administration of tetracaine to pregnant rats and rabbits during organogenesis did not produce adverse embryofetal effects at 0.03 times the MRHD of PLIAGLIS (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, 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 Animal Data Lidocaine administered by subcutaneous injection to pregnant rats during organogenesis was not teratogenic at doses up to 60 mg/kg (0.16 times the level of lidocaine contained in the MRHD of 53 grams of PLIAGLIS based on a mg/m 2 body surface area (BSA) comparison). Lidocaine administered by subcutaneous injection to pregnant rabbits during organogenesis was not teratogenic at doses up to 15 mg/kg (0.08 times the level of lidocaine in the MRHD of PLIAGLIS on a mg/m 2 basis).

In a published study, lidocaine administered to…