Citanest Plain

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.

• DENTAL PRACTITIONERS WHO EMPLOY LOCAL ANESTHETIC AGENTS SHOULD BE WELL VERSED IN DIAGNOSIS AND MANAGEMENT OF EMERGENCIES THAT MAY ARISE FROM THEIR USE.
• RESUSCITATIVE EQUIPMENT, OXYGEN AND OTHER RESUSCITATIVE DRUGS SHOULD BE AVAILABLE FOR IMMEDIATE USE.
• Methemoglobinemia Cases of methemoglobinemia have been reported in association with local anesthetic use.
• Although all patients are at risk for methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition.
• If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended.
• Signs of methemoglobinemia may occur immediately or may be delayed some hours after exposure, and are characterized by a cyanotic skin discoloration and/ or abnormal coloration of the blood.
• Methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death.
• Discontinue CITANEST and any other oxidizing agents.
• Depending on the severity of the signs and symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration.
• A more severe clinical presentation may require treatment with methylene blue exchange transfusion, or hyperbaric oxygen.
• To minimize the likelihood of intravascular injection, aspiration should be performed before the local anesthetic solution is injected.
• If blood is aspirated, the needle must be repositioned until no return of blood can be elicited by aspiration.
• Note, however, that the absence of blood in the syringe does not assure that intravascular injection will be avoided.
• General 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.
• (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.
• Use in the Head and Neck Area 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 .) Information for Patients/Patient Counseling Information Inform patients that use of local anesthetics may cause methemoglobinemia, a serious condition that must be treated promptly.
• Drug/Laboratory Test Interactions 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.
• Carcinogenesis, Mutagenesis, Impairment of Fertility 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.
• Use in Pregnancy Teratogenic Effects Pregnancy Category B 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.
• Nursing Mothers It is not known whether this drug is excreted in human milk.
• Pediatric Use Dosages in children should be reduced, commensurate with age, body weight, and physical condition.
• (See DOSAGE AND ADMINISTRATION .)
• General 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.
• (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.

• in Pregnancy Teratogenic Effects Pregnancy Category B 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.

• Clinically Significant Drug Interactions 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 Concurrent administration of vasopressor drugs and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents.

• Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use of local anesthetics (see ADVERSE REACTIONS , WARNINGS , and PRECAUTIONS ).
• Management of Local Anesthetic Emergencies The first consideration is prevention, best accomplished by careful and constant monitoring of cardiovascular and respiratory vital signs and the patient’s state of consciousness after each local anesthetic injection.
• At the first sign of change, oxygen should be administered.
• The first step in the management of convulsions consists of immediate attention to the maintenance of a patent airway and assisted or controlled ventilation with oxygen and a delivery system capable of permitting immediate positive airway pressure by mask.
• Immediately after the institution of these ventilatory measures, the adequacy of the circulation should be evaluated, keeping in mind that drugs used to treat convulsions sometimes depress the circulation when administered intravenously.
• Should convulsions persist despite adequate respiratory support, and if the status of the circulation permits, small increments of an ultra-short acting barbiturate (such as thiopental or thiamylal) or a benzodiazepine (such as diazepam) may be administered intravenously.
• The clinician should be familiar, prior to use of local anesthetics, with these anticonvulsant drugs.
• Supportive treatment of circulatory depression may require administration of intravenous fluids and, when appropriate, a vasopressor as directed by the clinical situation (eg, ephedrine).
• If not treated immediately, both convulsions and cardiovascular depression can result in hypoxia, acidosis, bradycardia, arrhythmias and cardiac arrest.
• If cardiac arrest should occur, standard cardiopulmonary resuscitative measures should be instituted.
• Endotracheal intubation, employing drugs and techniques familiar to the clinician, may be indicated, after initial administration of oxygen by mask, if difficulty is encountered in the maintenance of a patent airway or if prolonged ventilatory support (assisted or controlled) is indicated.
• Dialysis is of negligible value in the treatment of acute overdosage with prilocaine.
• The development of methemoglobinemia is generally dose related but may occur at any dose in susceptible individuals.
• While methemoglobin values of less than 20% do not generally produce any clinical symptoms, the appearance of cyanosis at 2 to 4 hours following administration should be evaluated in terms of the general health status of the patient.
• Methemoglobinemia can be reversed when indicated by intravenous administration of methylene blue at a dosage of 1 to 2 mg/kg given over a five minute period.
• The subcutaneous LD50 of prilocaine HCl in female mice is 550 (359 to 905) mg/kg.