DailyMed Label: Prilocaine Hydrochloride with Epinephrine

DailyMed Label: Prilocaine Hydrochloride

2010

DailyMed Prescription

Prilocaine Hydrochloride

prilocaine hydrochloride

Septodont Inc.

NDC: 0362-9014

NDC: 0362-9014

Prilocaine Hydrochloride Injection, USP, 4% is a sterile, non pyrogenic isotonic solution that contains a local anesthetic agent and is administered parenterally by injection. See INDICATIONS AND USAGE for specific uses. The quantitative composition is shown in Table 1. Prilocaine Hydrochloride Injection, USP, 4% contains prilocaine HCl, which is chemically designated as propanamide, N-(2-methyl-phenyl) -2- (propylamino)-, monohydrochloride and has the following structural formula: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. The specific quantitative composition is shown in Table 1. TABLE 1. COMPOSITION Product Identification Formula (mg/mL) Prilocaine HCl pH Prilocaine Hydrochloride Injection, USP, 4% 40.0 6.0 to 7.0 Note: Sodium hydroxide or hydrochloric acid may be used to adjust the pH of Prilocaine Hydrochloride Injection, USP, 4%. Chemical Structure

Prilocaine Hydrochloride Injection, USP, 4% is indicated for the production of local anesthesia in dentistry by nerve block or infiltration techniques. Only accepted procedures for these techniques as described in standard textbooks are recommended.

The dosage of Prilocaine Hydrochloride Injection, USP, 4% varies and depends on the physical status of the patient, the area of the oral cavity to be anesthetized, the vascularity of the oral tissues, and the technique of anesthesia. The least volume of injection that results in effective local anesthesia should be administered. For specific techniques and procedures of local anesthesia in the oral cavity, refer to standard textbooks. There are no practical clinical differences between prilocaine with and without epinephrine when used for inferior alveolar blocks. Prilocaine Hydrochloride Injection, USP, 4% is recommended for use in maxillary infiltration anesthesia for procedures in which the painful aspects can be completed within 15 minutes after the injection. Prilocaine Hydrochloride Injection, USP, 4% is therefore especially suited to short procedures in the maxillary anterior teeth. For long procedures, or those involving maxillary posterior teeth where soft tissue numbness is not troublesome to the patient, Prilocaine HCl 4% with epinephrine 1:200,000 is recommended. For most routine procedures, initial dosages of 1 to 2 mL of Prilocaine Hydrochloride Injection, USP, 4% will usually provide adequate infiltration or major nerve block anesthesia. The maximum recommended dose that should ever be administered within a two-hour period in normal healthy adults should be calculated based upon the patient's weight as follows: Weight Maximum recommended dose <150 lbs 4 mg/lb (<70 kg) (8 mg/kg) ≥150 lbs 600 mg (15 mL) or (≥70 kg) 8 cartridges In children under 10 years of age it is rarely necessary to administer more than one-half cartridge (40 mg) of Prilocaine Hydrochloride Injection, USP, 4% per procedure to achieve local anesthesia for a procedure involving a single tooth. In maxillary infiltration, this amount will often suffice to the treatment of two or even three teeth. In the mandibular block, however, satisfactory anesthesia achieved with this amount of drug will allow treatment of the teeth in an entire quadrant. ASPIRATION PRIOR TO INJECTION IS RECOMMENDED, since it reduces the possibility of intravascular injection, thereby keeping the incidence of side effects and anesthetic failure to a minimum. NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit. Solutions that are discolored and/or contain particulate matter should not be used. Any unused portion of a cartridge should be discarded. In patients weighing <150 lbs (70 kg), no more than 4 mg/lb (8 mg/kg) should be administered. In patients weighing <150 lbs, no more than 600 mg (8 cartridges) of prilocaine HCl should be administered as a single injection. It is difficult to recommend a maximum dose of any drug for children since this varies as a function of age and weight. For children of less than ten years who have a normal lean body mass and normal body development, the maximum dose may be determined by the application of one of the standard pediatric drug formulas (e.g., Clark's rule). For example, in a child of five years weighing 50 lbs., the dose of prilocaine hydrochloride should not exceed 150 to 200 mg (6.6 to 8.8 mg/kg or 3 to 4 mg/lb of body weight) when calculated according to Clark's rule.

Prilocaine is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type and in those rare patients with congenital or idiopathic methemoglobinemia.

The safety and effectiveness of prilocaine depend on proper dosage, correct technique, adequate precautions, and readiness for emergencies. Standard textbooks should be consulted for specific techniques and precautions for various regional anesthetic procedures. Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use. (See WARNINGS and ADVERSE REACTIONS .) The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels and serious adverse effects. Repeated doses of prilocaine may cause significant increases in blood levels with each repeated dose because of slow accumulation of the drug or its metabolites. Tolerance to elevated blood levels varies with the status of the patient. Debilitated, elderly patients, acutely ill patients, and children should be given reduced doses commensurate with their age and physical status. Prilocaine should also be used with caution in patients with severe shock or heart block. Cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient's state of consciousness should be monitored after each local anesthetic injection. Restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, depression or drowsiness should alert the practitioner to the possibility of central nervous system toxicity. Signs and symptoms of depressed cardiovascular function may commonly result from a vasovagal reaction, particularly if the patient is in an upright position. (See ADVERSE REACTIONS, Cardiovascular System ). Since amide-type local anesthetics are metabolized by the liver, prilocaine should be used with caution in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at greater risk of developing toxic plasma concentrations. Prilocaine should also be used with caution in patients with impaired cardiovascular function since they may be less able to compensate for functional changes associated with the prolongation of A-V conduction produced by these drugs. Many drugs used during the conduct of anesthesia are considered potential triggering agents for familial malignant hyperthermia. Since it is not known whether amide-type local anesthetics may trigger this reaction and since the need for supplemental general anesthesia cannot be predicted in advance, it is suggested that a standard protocol for the management of malignant hyperthermia should be available. Early unexplained signs of tachycardia, tachypnea, labile blood pressure, and metabolic acidosis may precede temperature elevation. Successful outcome is dependent on early diagnosis, prompt discontinuance of the suspect triggering agent(s) and institution of treatment, including oxygen therapy, indicated supportive measures and dantrolene (consult dantrolene sodium intravenous package insert before using). Prilocaine should be used with caution in persons with known drug sensitivities. Patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross sensitivity to prilocaine. Small doses of local anesthetics injected into the head and neck area, including retrobulbar, dental and stellate ganglion blocks, may produce adverse reactions similar to systemic toxicity seen with unintentional intravascular injections of larger doses. Confusion, convulsions, respiratory depression and/or respiratory arrest, and cardiovascular stimulation or depression have been reported. These reactions may be due to intra-arterial injection of the local anesthetic with retrograde flow to the cerebral circulation. Patients receiving these blocks should have their circulation and respiration monitored and be constantly observed. Resuscitative equipment and personnel for treating adverse reactions should be immediately available. Dosage recommendations should not be exceeded. (See DOSAGE AND ADMINISTRATION .) The patient should be informed of the possibility of temporary loss of sensation and muscle function following infiltration or nerve block injections. The patient should be advised to exert caution to avoid inadvertent trauma to the lips, tongue, cheek mucosae, or soft palate when these structures are anesthetized. The ingestion of food should therefore be postponed until normal function returns. The patient should be advised to consult the dentist if anesthesia persists, or if a rash develops. Concurrent administration of vasopressor drugs and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents. Prilocaine may contribute to the formation of methemoglobinemia in patients treated with other drugs known to cause this condition (see methemoglobinemia subsection of WARNINGS ). The intramuscular injection of prilocaine may result in an increase in creatine phosphokinase levels. Thus, the use of this enzyme determination, without isoenzyme separation, as a diagnostic test for the presence of acute myocardial infarction may be compromised by the intramuscular injection of prilocaine. Studies of prilocaine in animals to evaluate the carcinogenic and mutagenic potential or the effect on fertility have not been conducted. Chronic oral toxicity studies of ortho-toluidine, a metabolite of prilocaine, in mice (150 to 4800 mg/kg) and rats (150 to 800 mg/kg) have shown that ortho-toluidine is a carcinogen in both species. The lowest dose corresponds to approximately 50 times the maximum amount of ortho-toluidine to which a 50 kg subject would be expected to be exposed following a single injection (8 mg/kg) of prilocaine. Ortho-toluidine (0.5 mg/mL) showed positive results in Escherichia coli DNA repair and phage-induction assays. Urine concentrates from rats treated with ortho-toluidine (300 mg/kg, orally) were mutagenic for Salmonella typhimurium with metabolic activation. Several other tests, including reverse mutations in five different Salmonella typhimurium strains with or without metabolic activation and single strand breaks in DNA of V79 Chinese hamster cells, were negative. Reproduction studies have been performed in rats at doses up to 30 times the human dose and revealed no evidence of impaired fertility or harm to the fetus due to prilocaine. There are, however, no adequate and well-controlled studies in pregnant women. Animal reproduction studies are not always predictive of human response. General consideration should be given to this fact before administering prilocaine to women of childbearing potential, especially during early pregnancy when maximum organogenesis takes place. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when prilocaine is administered to a nursing woman. Dosages in children should be reduced, commensurate with age, body weight, and physical condition. (See DOSAGE AND ADMINISTRATION .)

Swelling and persistent paresthesia of the lips and oral tissues may occur. Persistent paresthesias lasting weeks to months, and in rare instances paresthesia lasting greater than one year, have been reported.

Concurrent administration of vasopressor drugs and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents. Prilocaine may contribute to the formation of methemoglobinemia in patients treated with other drugs known to cause this condition (see methemoglobinemia subsection of WARNINGS ).

Prilocaine Hydrochloride Injection, USP, 4% (NDC 0362-9014-50) is dispensed in 1.8 mL cartridges, packed 50 per box. Sterilization, Storage and Technical Procedures: Cartridges should not be autoclaved, becausee the closures employed in cartridges cannot withstand autoclaving temperatures and pressures. If chemical disinfection of anesthetic cartridges is desired, either 91% isopropyl alcohol or 70% ethyl alcohol is recommended. Many commercially available brands of rubbing alcohol, as well as solutions of ethyl alcohol not of U.S.P. grade, contain denaturants that are injurious to rubber and, therefore, are not to be used. It is recommended that chemical disinfection be accomplished by wiping the cartridge cap thoroughly with a pledget of cotton that has been moistened with the recommended alcohol just prior to use. IMMERSION IS NOT RECOMMENDED. Certain metallic ions (mercury, zinc, copper, etc.) have been related to swelling and edema after local anesthesia in dentistry. Therefore, chemical disinfectants containing or releasing those ions are not recommended. Antirust tablets usually contain metal ions. Accordingly, aluminum sealed cartridges should not be kept in such solutions. Quaternary ammonium salts, such as benzalkonium chloride, are electrolytically incompatible with aluminum. Cartridges are sealed with aluminum caps and therefore should not be immersed in any solution containing these salts. To avoid leakage of solutions during injection, be sure to penetrate the center of the rubber diaphragm when loading the syringe. An off-center penetration produces an oval shaped puncture that allows leakage around the needle. Other causes of leakage and breakage included badly worn syringes, aspirating syringes with bent harpoons, the use of syringes not designed to take 1.8 mL cartridges, and inadvertent freezing. Store at 20 to 25° C (68 to 77°F) [See USP Controlled Room Temperature].

Prilocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action. When used for infiltration injection in dental patients, the time of onset of anesthesia averages less than 2 minutes with an average duration of soft tissue anesthesia of approximately 2 hours. Based on electrical stimulation studies, Prilocaine Hydrochloride Injection, USP, 4% provides a duration of pulpal anesthesia of approximately 10 minutes in maxillary infiltration injections. In clinical studies, this has been found to provide complete anesthesia for procedures lasting an average of 20 minutes. When used for inferior alveolar nerve block, the time of onset of Prilocaine Hydrochloride Injection, USP, 4% averages less than three minutes with an average duration of soft tissue anesthesia of approximately 2 1 /2 hours. Excessive blood levels may cause changes in cardiac output, total peripheral resistance, and mean arterial pressure. These changes may be attributable to a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system. Information derived from diverse formulations, concentrations and usages reveals that prilocaine is completely absorbed following parenteral administration, its rate of absorption depending, for example, upon such factors as the site of administration and the presence or absence of a vasoconstrictor agent. Prilocaine is metabolized in both the liver and the kidney and excreted via the kidney. It is not metabolized by plasma esterases. Hydrolysis of prilocaine by amidases yields ortho-toluidine and N-proylalanine. Both of these compounds may undergo ring hydroxylation. O-toluidine has been found to produce methemoglobin, both in vitro and in vivo (see ADVERSE REACTIONS ). Because prilocaine is metabolized in both the liver and kidneys, hepatic and renal dysfunction may alter prilocaine kinetics. As with other local anesthetic agents, the plasma binding of prilocaine may be dependent on drug concentration. At 0.5 to 1.0 mg/mL it is 55% protein bound. Prilocaine crosses the blood-brain and placental barriers, presumably by passive diffusion. Factors such as acidosis and the use of CNS stimulants and depressants affect the CNS levels of prilocaine required to produce overt systemic effects. In the rhesus monkey, arterial blood levels of 20 mg/mL have been shown to be the threshold for convulsive activity.

septodont NDC 0362-9014-50 Prilocaine Hydrochloride Injection, USP, 4% 40 mg/mL Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature] DO NOT PERMIT TO FREEZE Rx Only Carton contains 50 cartridges. Each cartridge contains 1.8 mL septodont Made in Canada by Novocol Pharmaceutical of Canada, Inc. PRINCIPAL DISPLAY PANEL - 40 mL Carton