CHLOROPROCAINE HYDROCHLORIDE

Chloroprocaine Hydrochloride Injection, USP is a sterile non-pyrogenic local anesthetic. The active ingredient is chloroprocaine HCl (benzoic acid, 4-amino-2-chloro-2-(diethylamino) ethyl ester, monohydrochloride), which is represented by the following structural formula: Molecular Formula: C 13 H 19 ClN 2 O 2 • HCl M. W. 307.22 Chloroprocaine Hydrochloride Injection, USP is available in a 2% and 3% solution for infiltration, nerve block, caudal and epidural anesthesia ( not for spinal anesthesia). Each mL of the 20 mg/mL, 2%, solution contains; 20 mg of Chloroprocaine HCl, USP, 4.7 mg of Sodium Chloride, USP, and Sodium Hydroxide and/or Hydrochloric Acid to adjust pH. The pH range is 2.7 to 4.0. Each mL of the 30 mg/mL, 3%, solution contains; 30 mg of Chloroprocaine HCl, USP, 3.3 mg of Sodium Chloride, USP, and Sodium Hydroxide and/or Hydrochloric Acid to adjust pH. The pH range is 2.7 to 4.0. Chloroprocaine HCl Injection, USP, should not be resterilized by autoclaving. structural formula

Chloroprocaine hydrochloride injection 2% and 3%, in single dose vials, without methylparaben preservative, without EDTA, is indicated for the production of local anesthesia by infiltration, peripheral and central nerve block, including lumbar and caudal epidural blocks. Chloroprocaine hydrochloride injection is not to be used for subarachnoid administration.

Chloroprocaine may be administered as a single injection or continuously through an indwelling catheter. As with all local anesthetics, the dose administered varies with the anesthetic procedure, the vascularity of the tissues, the depth of anesthesia and degree of muscle relaxation required, the duration of anesthesia desired, and the physical condition of the patient. The smallest dose and concentration required to produce the desired result should be used. Dosage should be reduced for children, elderly and debilitated patients and patients with cardiac and/or liver disease. The maximum single recommended doses of chloroprocaine in adults are: without epinephrine, 11 mg/kg, not to exceed a maximum total dose of 800 mg; with epinephrine (1:200,000), 14 mg/kg, not to exceed a maximum total dose of 1000 mg. For specific techniques and procedures, refer to standard textbooks. There have been adverse event reports of chondrolysis in patients receiving intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures. Chloroprocaine hydrochloride injection is not approved for this use. (See WARNINGS and DOSAGE AND ADMINISTRATION ). Caudal and Lumbar Epidural Block: In order to guard against adverse experiences sometimes noted following unintended penetration of the subarachnoid space, the following procedure modifications are recommended: Use an adequate test dose (3 mL of chloroprocaine hydrochloride injection 3% or 5 mL of chloroprocaine hydrochloride injection 2%) prior to induction of complete block. This test dose should be repeated if the patient is moved in such a fashion as to have displaced the epidural catheter. Allow adequate time for onset of anesthesia following administration of each test dose. Avoid the rapid injection of a large volume of local anesthetic injection through the catheter. Consider fractional doses, when feasible. In the event of the known injection of a large volume of local anesthetic injection into the subarachnoid space, after suitable resuscitation and if the catheter is in place, consider attempting the recovery of drug by draining a moderate amount of cerebrospinal fluid (such as 10 mL) through the epidural catheter. As a guide for some routine procedures, suggested doses are given below: Infiltration and Peripheral Nerve Block: Chloroprocaine HCl Injection, USP Anesthetic Procedure Solution Concentration % Volume (mL) Total Dose (mg) Mandibular 2 2 to 3 40 to 60 Infraorbital 2 0.5 to 1 10 to 20 Brachial plexus 2 30 to 40 600 to 800 Digital (without epinephrine) 1 3 to 4 30 to 40 Pudendal 2 10 on each side 400 Paracervical (see also PRECAUTIONS ) 1 3 per each of 4 sites up to 120 Caudal and Lumbar Epidural Block: For caudal anesthesia, the initial dose is 15 to 25 mL of a 2% or 3% solution. Repeated doses may be given at 40 to 60 minute intervals. For lumbar epidural anesthesia, 2 to 2.5 mL per segment of a 2% or 3% solution can be used. The usual total volume of chloroprocaine hydrochloride injection is from 15 to 25 mL. Repeated doses 2 to 6 mL less than the original dose may be given at 40 to 50 minute intervals. The above dosages are recommended as a guide for use in the average adult. Maximum dosages of all local anesthetics must be individualized after evaluating the size and physical condition of the patient and the rate of systemic absorption from a particular injection site. Pediatric Dosage: 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 over 3 years of age who have a normal lean body mass and normal body development, the maximum dose is determined by the child’s age and weight and should not exceed 11 mg/kg (5 mg/lb). For example, in a child of 5 years weighing 50 lbs (23 kg), the dose of chloroprocaine hydrochloride without epinephrine would be 250 mg. Concentrations of 0.5 to 1% are suggested for infiltration and 1 to 1.5% for nerve block. In order to guard against systemic toxicity, the lowest effective concentration and lowest effective dose should be used at all times. Some of the lower concentrations for use in infants and smaller children are not available in prepackaged containers; it will be necessary to dilute available concentrations with the amount of 0.9% sodium chloride injection necessary to obtain the required final concentration of chloroprocaine injection. Preparation of Epinephrine Injections: To prepare a 1:200,000 epinephrine chloroprocaine hydrochloride injection, add 0.1 mL of a 1 to 1000 Epinephrine Injection, USP to 20 mL of Chloroprocaine Hydrochloride Injection. Chloroprocaine is incompatible with caustic alkalis and their carbonates, soaps, silver salts, iodine and iodides. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever injection and container permit. As with other anesthetics having a free aromatic amino group, chloroprocaine hydrochloride injection is slightly photosensitive and may become discolored after prolonged exposure to light. It is recommended that these vials be stored in the original outer containers, protected from direct sunlight. Discolored injection should not be administered. If exposed to low temperatures, chloroprocaine hydrochloride injection may deposit crystals of chloroprocaine hydrochloride which will redissolve with shaking when returned to room temperature. The product should not be used if it contains undissolved (e.g., particulate) material.

Chloroprocaine hydrochloride is contraindicated in patients hypersensitive (allergic) to drugs of the PABA ester group. Lumbar and caudal epidural anesthesia should be used with extreme caution in persons with the following conditions: existing neurological disease, spinal deformities, septicemia, and severe hypertension.

Systemic: The most commonly encountered acute adverse experiences that demand immediate countermeasures are related to the central nervous system and the cardiovascular system. These adverse experiences are generally dose related and may result from rapid absorption from the injection site, diminished tolerance, or from unintentional intravascular injection of the local anesthetic solution. In addition to systemic dose-related toxicity, unintentional subarachnoid injection of drug during the intended performance of caudal or lumbar epidural block or nerve blocks near the vertebral column (especially in the head and neck region) may result in underventilation or apnea (“Total Spinal”). Factors influencing plasma protein binding, such as acidosis, systemic diseases that alter protein production, or competition of other drugs for protein binding sites, may diminish individual tolerance. Plasma cholinesterase deficiency may also account for diminished tolerance to ester-type local anesthetics. Central Nervous System Reactions: These are characterized by excitation and/or depression. Restlessness, anxiety, dizziness, tinnitus, blurred vision or tremors may occur, possibly proceeding to convulsions. However, excitement may be transient or absent, with depression being the first manifestation of an adverse reaction. This may quickly be followed by drowsiness merging into unconsciousness and respiratory arrest. The incidence of convulsions associated with the use of local anesthetics varies with the procedure used and the total dose administered. In a survey of studies of epidural anesthesia, overt toxicity progressing to convulsions occurred in approximately 0.1 percent of local anesthetic administrations. Cardiovascular System Reactions: High doses, or unintended intravascular injection, may lead to high plasma levels and related depression of the myocardium, hypotension, bradycardia, ventricular arrhythmias, and, possibly, cardiac arrest. Allergic: Allergic type reactions are rare and may occur as a result of sensitivity to the local anesthetic. These reactions are characterized by signs such as urticaria, pruritis, erythema, angioneurotic edema (including laryngeal edema), tachycardia, sneezing, nausea, vomiting, dizziness, syncope, excessive sweating, elevated temperature, and possibly, anaphylactoid type symptomatology (including severe hypotension). Cross sensitivity among members of the ester-type local anesthetic group has been reported. The usefulness of screening for sensitivity has not been definitely established. Neurologic: In the practice of caudal or lumbar epidural block, occasional unintentional penetration of the subarachnoid space by the catheter may occur (see PRECAUTIONS ). Subsequent adverse observations may depend partially on the amount of drug administered intrathecally. These observations may include spinal block of varying magnitude (including total spinal block), hypotension secondary to spinal block, loss of bladder and bowel control, and loss of perineal sensation and sexual function. Arachnoiditis, persistent motor, sensory and/or autonomic (sphincter control) deficit of some lower spinal segments with slow recovery (several months) or incomplete recovery have been reported in rare instances. (See DOSAGE AND ADMINISTRATION discussion of Caudal and Lumbar Epidural Block .) Backache and headache have also been noted following lumbar epidural or caudal block.

Clinically Significant Drug Interactions The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors, tricyclic antidepressants or phenothiazines may produce severe, prolonged hypotension or hypertension. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential. Concurrent administration of vasopressor drugs (for the treatment of hypotension related to obstetric blocks) and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents. The para-aminobenzoic acid metabolite of chloroprocaine inhibits the action of sulfonamides. Therefore, chloroprocaine should not be used in any condition in which a sulfonamide drug is being employed.