Lidocaine and prilocaine (oral mucosal)

Other local anesthetics or agents structurally related to local anesthetics ( 7.1 ) Drugs That May Cause Methemoglobinemia When Used With ORAQIX ( 7.2 )

7.1 Other Local Anesthetics or Agents Structurally Related to Local Anesthetics Oraqix should be used with caution in combination with dental injection anesthesia, other local anesthetics, or agents structurally related to local anesthetics, e.g., Class 1 antiarrhythmics such as tocainide and mexiletine, as the toxic effects of these drugs are likely to be additive and potentially synergistic.

7.2 Drugs That May Cause Methemoglobinemia When Used With ORAQIX 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, isofamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sufonamides Antimalarials chloroquine, primaquine Anticonvulsants Phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine

8.1 Pregnancy Pregnancy Category B .Reproduction studies have been performed in rats with lidocaine, prilocaine and a 1:1 (weight:weight) mixture of the two compounds. There was no evidence of harm to the fetus at subcutaneous doses of up to 30 mg/kg lidocaine (estimated exposure was approximately equivalent to the expected lidocaine exposure at the maximum recommended human dose of Oraqix (lidocaine and prilocaine periodontal gel) 2.5% / 2.5% on a mg/m 2 basis).

Following intramuscular prilocaine doses of up to 300 mg/kg (estimated exposure was approximately 11 times the expected prilocaine exposure at the maximum recommended human dose of Oraqix gel on a mg/m 2 basis), there was no evidence of impaired fertility or harm to the fetus. Similarly, subcutaneous administration of a lidocaine and prilocaine mixture of 40 mg/kg of each compound (estimated exposures were approximately 1.5 times the expected lidocaine and prilocaine exposures at the maximum recommended human dose of Oraqix gel on a mg/m 2 basis) produced no teratogenic, embryotoxic, or fetotoxic effects. Reproductive toxicology studies of lidocaine were also conducted in rabbits.

There was no evidence of harm to the fetus at a dose of 5 mg/kg, s.c. (60 mg/m 2 ). Treatment of rabbits with 15 mg/kg (180 mg/m 2 ) produced evidence of maternal toxicity and evidence of delayed fetal development, including a non-significant decrease in fetal weight (7%) and an increase in minor skeletal anomalies (skull and sternebral defects, reduced ossification of the phalanges). The effects of lidocaine and prilocaine on post-natal development was examined in rats treated for 8 months with 10 or 30 mg/kg, s.c. lidocaine or prilocaine (60 mg/m 2 and 180 mg/m 2 on a body surface area basis, respectively up to 1.4-fold the maximum recommended exposure for a single procedure).

This time period encompassed 3 mating periods. There was no evidence of altered post-natal development in any offspring; however, both doses of either drug reduced the average number of pups per litter surviving until weaning of offspring from the first 2 mating periods. In a separate study, the effect of prilocaine on pre- and postnatal development was examined in rats treated with up to 60 mg/kg, s.c. (up to 2.8 times the maximum recommended human dose of prilocaine in Oraqix gel on a mg/m 2 basis) from Day 6 of gestation to weaning. There was no evidence of altered post-natal development, viability, or reproductive capacity in any offspring.

All the above calculations of exposure are assuming 100% bioavailability of lidocaine and prilocaine…

8.3 Nursing Mothers Lidocaine and, possibly, prilocaine are excreted in breast milk. Caution should be exercised when Oraqix is administered to nursing women.