Citanest (Prilocaine)



Prilocaine HCl

Prilocaine HCl – Epinephrine

Local Anesthetic for Infiltration and Nerve Block

Action And Clinical Pharmacology: Mechanism of Action: Prilocaine stabilizes the neuronal membrane and prevents the initiation and transmission of nerve impulses thereby, effecting local anesthetic action. Local anesthetics of the amide type are thought to act within sodium channels of the nerve membrane.

Onset of Action: When used for infiltration anesthesia in dental patients, the time of onset of Citanest 4% Forte averages 2 minutes with a duration of soft tissue anesthesia of approximately 2 hours. Operative anesthesia lasts up to 45 minutes. When used for infiltration anesthesia, Citanest 4% Plain has a rapid onset time of approximately 2 to 3 minutes and a duration of approximately 1 to 1.5 hours for soft tissue anesthesia. Citanest 4% Plain has a short duration for operative anesthesia of approximately 15 minutes.

When used for inferior alveolar nerve block the time of onset of Citanest 4% Forte averages approximately 2 to 4 minutes with an average duration of soft tissue anesthesia of approximately 3 hours providing 1.5 hours of operative anesthesia.

When used for mandibular block anesthesia, Citanest 4% Plain requires 5 minutes or more to take full effect. The duration of soft tissue anesthesia is approximately 2.5 hours while operative anesthesia has a duration of 1 to 1.5 hours.

Hemodynamics: Prilocaine, like other local anesthetics, may also have effects on excitable membranes in the brain and myocardium. If excessive amounts of drug reach systemic circulation rapidly, symptoms and signs of toxicity will appear, emanating from the central nervous and cardiovascular systems.

CNS toxicity (see Overdose: Symptoms and Treatment) usually precedes the cardiovascular effects since it occurs at lower plasma concentrations. Direct effects of local anesthetics on the heart include slow conduction, negative inotropism and eventually cardiac arrest.

Pharmacokinetics and Metabolism: Prilocaine is between 40 to 55% protein bound in plasma, mainly to alpha1-acid glycoprotein.

Prilocaine redistributes rapidly from the blood and has a large apparent distribution volume of between 190 and 260 L. The terminal elimination half-life of prilocaine is 1.6 h.

Prilocaine readily passes the placenta and free plasma concentrations are similar in both fetus and mother. In the presence of fetal acidosis, plasma concentrations may be slightly higher in the fetus due to ion trapping. Information concerning the elimination half-life of prilocaine in neonates is not available.

In the liver, prilocaine is primarily metabolized by amide hydrolysis to o-toluidine and N-propylamine. o-Toluidine is subsequently hydroxylated to 2-amino-3-hydroxytoluene and 2-amino-5-hydroxytoluene, metabolites which are believed to be responsible for the occurrence of methemoglobinemia (see Contraindications).

Indications And Clinical Uses: In dentistry for the production of local anesthesia by infiltration or nerve block.

Contra-Indications: Patients with a known history of hypersensitivity to local anesthetics of the amide type or to other components of the solution. Patients with congenital or idiopathic methemoglobinemia.

Manufacturers’ Warnings In Clinical States: Local anesthetics should only be employed by clinicians who are well versed in diagnosis and management of dose-related toxicity and other acute emergencies that might arise from the block to be employed and then only after ensuring the immediate availability of oxygen, other resuscitative drugs, cardiopulmonary equipment and the personnel needed for proper management of toxic reactions and related emergencies (see also Adverse Effects and Precautions). Delay in proper management of dose-related toxicity, underventilation from any cause, and/or altered sensitivity may lead to the development of acidosis, cardiac arrest and possibly, death.

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.

Citanest 4% Forte contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

Precautions: The safety and effectiveness of prilocaine depends on proper dosage, correct technique, adequate precautions and readiness for emergencies. Standard textbooks should be consulted for specific techniques and precautions for various dental anesthetic procedures.

Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use (see Warnings and Overdose: Symptoms and Treatment). The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels and serious adverse effects. Injections should be made slowly, with frequent aspirations before and during the injection to avoid intravascular injection.

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 condition. Prilocaine should also be used with caution in patients with epilepsy, impaired cardiac conduction, bradycardia, impaired hepatic function and in severe shock.

Because amide-type local anesthetics such as prilocaine are metabolized by the liver, these drugs, especially repeat doses, should be used cautiously 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 AV conduction produced by these drugs.

Local anesthetic procedures should not be used when there is inflammation and/or sepsis in the region of the proposed injection.

Solutions containing epinephrine should be used with caution in patients whose medical history and physical evaluation suggest the existence of untreated hypertension, poorly controlled thyrotoxicosis, diabetes, ischemic heart disease, heart block, cerebral vascular insufficiency and peripheral vascular disorder. These solutions should also be used cautiously in areas of the body supplied by end arteries, such as digits, or otherwise having a compromised blood supply (see also Drug Interactions).

Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient’s state of consciousness should be performed after each local anesthetic injection. It should be kept in mind at such times that restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, depression or drowsiness may be early warning signs of CNS toxicity.

Many drugs used during the conduct of anesthesia are considered potential triggering agents for familial malignant hyperthermia. It has been shown that the use of amide local anesthetics in malignant hyperthermia is safe. However, there is no guarantee that neural blockade will prevent the development of malignant hyperthermia during surgery. It is also difficult to predict the need for supplemental general anesthesia. Therefore a standard protocol for the management of malignant hyperthermia should be available.

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.

Methemoglobinemia: A few instances of cyanosis have been reported following the administration of more than 400 mg of prilocaine. It would be necessary to inject 5 cartridges of Citanest 4% solution to produce an average methemoglobin value of 1%. Since methemoglobin values of less than 20% generally do not produce any clinical symptoms of hypoxia, the routine use of prilocaine solutions for normal dental procedures should not be associated with any side effects related to methemoglobinemia. The usual clinical signs of methemoglobinemia are cyanosis of the nail beds and lips. Although the possibility of methemoglobinemia occurring in dental patients is extremely rare, it should be remembered that methemoglobinemia can be treated easily and reversed rapidly by the use of 1 to 2 mg/kg body weight of methylene blue administered i.v. over a 5-minute period (see Adverse Effects and Overdose: Symptoms and Treatment).

Caution should be exercised when administering prilocaine concomitantly with other medications which are potential producers of methemoglobin (e.g., sulfonamides, antimalarials, and certain nitric compounds).

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 caused by inadvertent injection to an artery. These reactions may be similar to systemic toxicity seen with unintentional intravascular injections of larger doses. Inadvertent injections into an artery can cause cerebral symptoms even at low doses. Confusion, convulsions, respiratory depression and/or respiratory arrest, and cardiovascular stimulation or depression leading to cardiac arrest have been reported. Patients receiving these blocks should have their circulation and respiration monitored and be constantly observed.

Drug Interactions: See also under Methemoglobinemia.

Prilocaine should be used with caution in patients receiving other agents structurally related to amide-type local anesthetics, since the toxic effects are additive.

Citanest 4% Forte, which contains epinephrine, should not be used concomitantly with ergot-type oxytocic drugs, because a severe persistent hypertension may occur and cerebrovascular and cardiac accidents are possible. Likewise, Citanest 4% Forte or solutions containing Citanest 4% Plain and another vasoconstrictor should be used with extreme caution in patients receiving MAO inhibitors or antidepressants of the triptyline or imipramine types, because severe prolonged hypertension may result. In situations when concurrent therapy is necessary, careful patient monitoring is essential. Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine.

If sedatives are employed to reduce patient apprehension, they should be used in reduced doses, since local anesthetic agents, like sedatives, are CNS depressants which in combination may have an additive effect.

Solutions containing epinephrine should be used with caution in patients undergoing general anesthesia with inhalation agents such as halothane, due to the risk of serious cardiac arrhythmias.

Information for the Patient: 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 mucosa 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.

Pregnancy : Although the safe use of prilocaine during pregnancy has not been established with respect to possible adverse effects upon fetal development, it is reasonable to assume that Citanest has been administered to a large number of pregnant women and women of childbearing age. No specific disturbances to the reproductive process have so far been reported, e.g., no increased incidence of malformations or other direct or indirect harmful effects on the fetus.

Methemoglobinemia in the neonate has been reported after the administration of prilocaine to the mother in doses exceeding 600 mg.

Lactation : Prilocaine may enter the breast milk, but in such small quantities that there is generally no risk of affecting the infant at therapeutic dose levels. It is not known whether epinephrine enters breast milk, but it is unlikely to affect the breast-fed infant.

Adverse Reactions: Adverse experiences following the administration of prilocaine are similar in nature to those observed with other amide local anesthetic agents. These adverse experiences are, in general, dose-related and may result from high plasma levels caused by overdosage, rapid absorption, or inadvertent intravascular injection, or may result from a hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient.

Reactions to prilocaine are very rare in the doses used in dental procedures. Psychogenic reactions to anticipation of or during the dental procedures, are however, common and may mimic the symptoms of a generalized systemic reaction to local anesthetics.

Serious adverse experiences are generally systemic in nature. The following types are those most commonly reported:

CNS: CNS manifestations are excitatory and/or depressant and may be characterized by circumoral paresthesia, lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, hyperacusis, tinnitus, blurred vision, vomiting, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, respiratory depression and arrest. The excitatory manifestations may be very brief or may not occur at all, in which case the first manifestation of toxicity may be drowsiness merging into unconsciousness and respiratory arrest.

Drowsiness following the administration of prilocaine is usually an early sign of a high prilocaine plasma level and may occur as a consequence of rapid absorption.

Cardiovascular: Cardiovascular manifestations are usually depressant and are characterized by bradycardia, hypotension, arrhythmia, and cardiovascular collapse, which may lead to cardiac arrest.

Allergic: Allergic reactions are characterized by cutaneous lesions, urticaria, edema, or in the most severe instances, anaphylactic shock. Allergic reactions of the amide type are extremely rare and may occur as a result of sensitivity either to the local anesthetic agent or to other components in the formulation.

Neurologic: The incidence of adverse neurological reactions, e.g., persistent neurological deficit, associated with the use of local anesthetics is very low. Neurological reactions may be dependent upon the particular drug used, the route of administration and the physical status of the patient. Many of these effects may be linked to the injection technique, with or without a contribution by the drug. Neurological reactions following regional nerve blocks have included persistent paresthesia and sensory disturbances.

Methemoglobinemia: Cyanosis due to the formation of methemoglobin may occur after the administration of prilocaine. The repeated administration of prilocaine, even in relatively small doses, can lead to clinically overt methemoglobinemia.

The conversion of hemoglobin to methemoglobin is caused by the prilocaine metabolite, o-toluidine, which has a long half-life and tends to accumulate, and in turn, its conversion to 4- and 6-hydroxytoluidine. Methemoglobin has risen to clinically significant levels in patients receiving high doses of prilocaine. Cyanosis occurs when the methemoglobin concentration in the blood reaches 10 to 20 g/L (6 to 12% of the normal hemoglobin concentration). Methemoglobin oxidizes only slowly back to hemoglobin, but this process can be greatly accelerated by giving methylene blue i.v. (see Overdose: Symptoms and Treatment).

The reduction in the oxygen-carrying capacity in normal patients is marginal; hence cyanosis is usually symptomless. However, in severely anemic patients it may cause significant hypoxemia. It is important to rule out other more serious causes of cyanosis such as acute hypoxemia and/or heart failure. In using the recommended dosage of Citanest, 1 to 2 mL (40 to 80 mg prilocaine) (adult dosage), the occurrence of methemoglobinemia in dental practice appears remote. However, gross overdosage in dental practice has been reported to cause methemoglobinemia.

Note: Even low concentrations of methemoglobin may interfere with pulse oximetry readings, indicating a false low oxygen saturation.

Symptoms And Treatment Of Overdose: Since prilocaine is the least toxic of the amino-amide anesthetics, it is particularly useful in situations when high dosage may be needed. This advantage, however, should be weighed against the risk of causing methemoglobinemia.

Acute emergencies are, in general, dose-related and may result from high plasma levels caused by excessive dosage, rapid absorption (i.e., rate of increase of plasma concentration) or unintentional intravascular injection, or may result from hypersensitivity or diminished tolerance on the part of the patient.Symptoms: Acute Systemic Toxicity: CNS reactions are excitatory or depressant and may be characterized by nervousness, tinnitus, twitching, euphoria, drowsiness, blurred or double vision, dizziness, convulsions, unconsciousness and possibly respiratory arrest. The excitatory reactions may be very brief or may not occur at all, in which case the first manifestation of toxicity is drowsiness merging into unconsciousness and even respiratory arrest.

Cardiovascular reactions are depressant and may be characterized by hypotension, myocardial depression, bradycardia and possibly cardiac arrest. Signs and symptoms of depressed cardiovascular function may commonly result from a vasovagal reaction, particularly if the patient is in an upright position. Less commonly, they may occur as a direct effect of the drug. Failure to recognize premonitory signs such as sweating, a feeling of faintness, changes in pulse or sensorium, may result in progressive cerebral hypoxia and seizure or serious cardiovascular collapse.

Cardiovascular effects are usually only seen in the most severe cases and are generally preceded by signs of toxicity in the central nervous system.

Acidosis or hypoxia in the patient may increase the risk and severity of toxic reactions. Such reactions involve the CNS and the cardiovascular system.

Treatment: Treatment of Acute Toxicity: The immediate treatment of acute systemic toxicity is as follows: a) Put the patient in a supine position. Raise the legs 30 to 45° above the horizontal level. b) Ensure a patent airway. If ventilation is inadequate, ventilate the patient, with oxygen if available. This is important since toxicity increases with acidosis. c) The treatment of convulsions consists in ensuring a patent airway and arresting convulsions. Should convulsions persist despite adequate ventilation, 5 to 15 mg diazepam or 50 to 200 mg thiopental should be administered i.v. to arrest the convulsions. Since this treatment may also depress respiration, the means of mechanically supporting or controlling ventilation should be available. d) Supportive treatment of circulatory depression may require the administration of i.v. fluids and, when appropriate, a vasopressor (e.g., ephedrine 5 to 10 mg i.v. and repeated, if necessary, after 2 to 3 minutes), as governed by the clinical situation. e) If the patient is unresponsive and the carotid pulse rate is totally absent, start external cardiac massage and mouth to mouth resuscitation.

Treatment of Acute Methemoglobinemia: If clinical methemoglobinemia occurs, it can be rapidly treated by a single i.v. injection of a 1% methylene blue solution, 1 mg/kg body weight, over a 5-minute period. Cyanosis will disappear in about 15 minutes. This dose should not be repeated as methylene blue in high concentrations acts as a hemoglobin oxidant.

Dosage And Administration: The dosage of Citanest 4% Plain and Citanest 4% Forte varies and depends on the area of the oral cavity to be anesthetized, the vascularity of the oral tissues and the technique of anesthesia. The total dose must be adjusted to the age, size and physical status of the patient. The lowest dosage that results in effective local anesthesia should be administered. Injections should be made slowly with careful aspiration before and intermittently during injection to avoid inadvertent intravascular injection, which may have toxic effects. For specific techniques and procedures of a local anesthesia in the oral cavity, refer to standard textbooks.

Citanest 4% Plain is recommended for use in maxillary infiltration anesthesia for procedures lasting approximately 15 minutes. Citanest 4% Plain 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, Citanest 4% Forte is recommended.

Citanest 4% Plain is also recommended for those dental procedures in which it is desirable to use a local anesthetic that does not contain a vasoconstrictor agent, e.g., in those patients for whom vasoconstrictor agents are not indicated.

There are no practical clinical differences between Citanest 4% Plain and Citanest 4% Forte when used for inferior alveolar blocks.

Adults: For most routine dental procedures, initial dosages of 1 to 2 mL of Citanest 4% Plain or Citanest 4% Forte (40 to 80 mg prilocaine) will usually provide adequate infiltration or major nerve block anesthesia. No more than 400 mg (10 mL) should be administered per procedure.

Children: In children under 10 years of age it is rarely necessary to administer more than one-half cartridge (0.9 to 1 mL or 36 to 40 mg prilocaine) of Citanest 4% Plain or Citanest 4% Forte per procedure.

Due to the specific need for bone penetration, dental local anesthetics contain high concentrations of active drug, e.g., 40 mg/mL prilocaine for Citanest. A combination of high pressure induced by the use of a dental cartridge system and a rapid rate of injection may lead to complications (see Overdose: Symptoms and Treatment) even after the injection of small amounts of local anesthetic. This is due to the high concentration, especially following accidental intravascular injection, when the injected drug could travel in a retrograde manner along the vessel and, in cases of intra-arterial injection in the head and neck area, reach the brain without the same degree of dilution that occurs with an i.v. injection. It must also be noted that epinephrine, when added to a local anesthetic solution is less active as a localizing agent in the highly vascular oral environment than elsewhere in the body.

Aspiration is recommended since it reduces the possibility of intravascular injection, thereby keeping the incidence of side effects and anesthetic failures to a minimum.

For best results, it is important that cartridges be used with a syringe of appropriate size. The Astra Self-Aspirating Syringe has been designed especially for Astra cartridges.

Sterilization, Storage and Technical Procedures: Cartridges should not be autoclaved, because the rubber plunger will typically be extruded thus compromising container integrity.

If disinfection of the cartridge is desired, its immersion should be avoided due to the risk of undesirable effects on the rubber membrane and aluminum cap, and the risk of contamination of the solution. Disinfection of the rubber membrane or the entire dental cartridge should be accomplished by wiping it with a cotton pledget that has been moistened with a disinfectant. Isopropyl alcohol (91%) or ethyl alcohol (70%) is recommended. Many commercially available brands of rubbing alcohol, as well as solutions of ethyl alcohol not of USP grade, contain denaturants which are injurious to rubber and therefore are not to be used.

Quaternary ammonium salts, such as benzalkonium chloride, are electrolytically incompatible with aluminum. Cartridges which are sealed with aluminum caps should not be immersed in any solution containing these salts.

Anti-rust tablets usually contain sodium nitrate or other similar agents which may be capable of releasing metal ions from syringes, needles and aluminum sealed cartridges. Accordingly, cartridges should not be kept in such solutions.

Adequate precautions should be taken to avoid prolonged contact between local anesthetic solutions containing epinephrine (low pH) and metal surfaces (e.g., needles or metal parts of syringes), since dissolved metal ions, particularly copper ions, may cause severe local irritation (swelling, edema) at the site of injection and accelerate the degradation of epinephrine.

To avoid leakage of solutions during injection, be sure to penetrate the centre of the rubber diaphragm perpendicularly with the needle when loading the syringe. An off-centre penetration produces an oval shaped puncture that allows leakage around the needle.

In order to avoid traumatic nerve injuries leading to paresthesia in conjunction with dental nerve block, an atraumatic technique should be used. Dental cartridge systems may generate high pressures during injection, however, injected local anesthetics may travel in a retrograde manner along a nerve in cases of intraneural injection. If an accidental traumatic nerve injury has occurred, epinephrine, if present in the anesthetic solution, may aggravate the local neurotoxicity by decreasing the intraneural blood circulation. In order to minimize the risk of intraneural injection as well as fascicular injuries, the needle should always be withdrawn a little if paresthesia is elicited during injection. Furthermore, a short-bevelled needle should be considered for regional blocks (in which case a topical anesthetic may be used to reduce the pain of needle insertion), while a sharper (i.e., long-bevelled) needle can still be recommended for infiltration.

Citanest solutions should be stored at room temperature (15 to 30°C). Citanest 4% Forte should be protected from light. Do not use if solution is pinkish or darker than slightly yellow, or contains a precipitate.

Citanest 4% Plain and Citanest 4% Forte are preservative free and for single use only. Discard unused portion.

Availability And Storage: Citanest 4% Plain: Each mL of sterile, aqueous, isotonic solution contains: prilocaine HCl 40 mg. Nonmedicinal ingredients: water for injection and sodium hydroxide and/or hydrochloric acid to adjust pH to 6 to 7. Preservative-free. Dental cartridges of 1.8 mL, boxes of 50.

Citanest 4% Forte: Each mL of sterile, aqueous, isotonic solution contains: prilocaine HCl 40 mg and epinephrine (1:200 000) 0.005 mg. Nonmedicinal ingredients: sodium metabisulfite, water for injection and sodium hydroxide and/or hydrochloric acid to adjust pH to 3.3 to 5.5. Preservative-free. Dental cartridges of 1.8 mL, boxes of 50.

CITANEST® 4% PLAIN CITANEST® 4% FORTE Astra Prilocaine HCl Prilocaine HCl – Epinephrine Local Anesthetic for Infiltration and Nerve Block

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