Chloroprocaine

Chloroprocaine
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]

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Overview

Chloroprocaine is a local anesthetic that is FDA approved for the {{{indicationType}}} of local anesthesia. Common adverse reactions include neurologic: dizziness.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

• Dosage varies with anesthetic procedure, vascularity of tissues, depth of anesthesia, degree of muscle relaxation required, duration of anesthesia, and physical condition of patient
• Local anesthesia: maximum single doses (without epinephrine), 11 mg/kg, not to exceed 800 mg.
• Local anesthesia: maximum single doses (with epinephrine 1:200,000), 14 mg/kg, not to exceed 1000 mg.
• Local anesthesia: (brachial plexus) 30 to 40 mL (600 to 800 mg) as a 2% solution [1]
• Local anesthesia: (caudal epidural) 15 to 25 mL of 2% or 3% methylparaben-free (MPF) solution, repeated every 40-60 min.
• Local anesthesia: (digital, without epinephrine) 3 to 4 mL (30 to 40 mg) as a 1% solution (without epinephrine).
• Local anesthesia: (infraorbital) 0.5 to 1 mL (10 to 20 mg) as a 2% solution.
• Local anesthesia: (lumbar epidural) 2 to 2.5 mL per segment of 2% or 3% methylparaben-free (MPF) solution; usual total volume 15 to 25 mL; repeat doses of 2 to 6 mL less than original dose may be given at 40 to 50 min intervals.
• Local anesthesia: (mandibular) 2 to 3 mL (40 to 60 mg) as a 2% solution.
• Local anesthesia: (paracervical) 3 mL per each of 4 sites as a 1% solution, total dose up to 120 mg.
• Local anesthesia: (pudendal) 10 mL on each side as a 2% solution, total dose 400 mg.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information about Off-Label Guideline-Supported Use of Chloroprocaine in adult patients.

Non–Guideline-Supported Use

There is limited information about Off-Label Non–Guideline-Supported Use of Chloroprocaine in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

• Dosage must be individualized based on age and weight of patient.
• Local anesthesia: (infiltration) older than 3 years of age, 0.5% to 1% solution; max 11 mg/kg .
• Local anesthesia: (nerve blocks) older than 3 years of age, 1% to 1.5% solution; max 11 mg/kg .

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information about Off-Label Guideline-Supported Use of Chloroprocaine in pediatric patients.

Non–Guideline-Supported Use

There is limited information about Off-Label Non–Guideline-Supported Use of Chloroprocaine in pediatric patients.

Contraindications

• Chloroprocaine and Chloroprocaine-MPF Injections are 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.

Warnings

• Local anesthetics should only be employed by clinicians who are well versed in diagnosis and management of dose related toxicity and other acute emergencies which might arise from the block to be employed, and then only after ensuring the immediate availability of oxygen, other resuscitative drugs, cardiopulmonary resuscitative equipment, and the personnel resources needed for proper management of toxic reactions and related emergencies (see also adverse reactions 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. Chloroprocaine (chloroprocaine HCl Injection, USP) contains methylparaben and should not be used for lumbar or caudal epidural anesthesia because safety of this antimicrobial preservative has not been established with regard to intrathecal injection, either intentional or unintentional. Chloroprocaine-MPF Injection contains no preservative; discard unused injection remaining in vial after initial use.
• Intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures is an unapproved use, and there have been post-marketing reports of chondrolysis in patients receiving such infusions. The majority of reported cases of chondrolysis have involved the shoulder joint; cases of gleno-humeral chondrolysis have been described in pediatric and adult patients following intra-articular infusions of local anesthetics with and without epinephrine for periods of 48 to 72 hours. There is insufficient information to determine whether shorter infusion periods are not associated with these findings. The time of onset of symptoms, such as joint pain, stiffness and loss of motion can be variable, but may begin as early as the 2nd month after surgery. Currently, there is no effective treatment for chondrolysis; patients who experienced chondrolysis have required additional diagnostic and therapeutic procedures and some required arthroplasty or shoulder replacement.
• Vasopressors should not be used in the presence of ergot-type oxytocic drugs, since a severe persistent hypertension may occur.
• To avoid intravascular injection, aspiration should be performed before the anesthetic solution is injected. The needle must be repositioned until no blood return can be elicited. However, the absence of blood in the syringe does not guarantee that intravascular injection has been avoided.
• Mixtures of local anesthetics are sometimes employed to compensate for the slower onset of one drug and the shorter duration of action of the second drug. Experiments in primates suggest that toxicity is probably additive when mixtures of local anesthetics are employed, but some experiments in rodents suggest synergism. Caution regarding toxic equivalence should be exercised when mixtures of local anesthetics are employed.

Adverse Reactions

Clinical Trials Experience

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 or to other formulation ingredients, such as the antimicrobial preservative methylparaben, contained in multiple dose vials. These reactions are characterized by signs such as urticaria, pruritus, 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.

Postmarketing Experience

There is limited information regarding Chloroprocaine Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Chloroprocaine Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

• Animal reproduction studies have not been conducted with chloroprocaine. It is also not known whether chloroprocaine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Chloroprocaine should be given to a pregnant woman only if clearly needed. This does not preclude the use of chloroprocaine at term for the production of obstetrical anesthesia.

Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Chloroprocaine in women who are pregnant.

Labor and Delivery

• Local anesthetics rapidly cross the placenta, and when used for epidural, paracervical, pudendal or caudal block anesthesia, can cause varying degrees of maternal, fetal and neonatal toxicity (see Clinical Pharmacology and Pharmacokinetics).
• The incidence and degree of toxicity depend upon the procedure performed, the type and amount of drug used, and the technique of drug administration. Adverse reactions in the parturient, fetus and neonate involve alterations of the central nervous system, peripheral vascular tone and cardiac function.
• Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves. Elevating the patient’s legs and positioning her on her left side will help prevent decreases in blood pressure. The fetal heart rate also should be monitored continuously, and electronic fetal monitoring is highly advisable.
• Epidural, paracervical, or pudendal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. In one study, paracervical block anesthesia was associated with a decrease in the mean duration of first stage labor and facilitation of cervical dilation. However, epidural anesthesia has also been reported to prolong the second stage of labor by removing the parturient’s reflex urge to bear down or by interfering with motor function. The use of obstetrical anesthesia may increase the need for forceps assistance.
• The use of some local anesthetic drug products during labor and delivery may be followed by diminished muscle strength and tone for the first day or two of life. The long-term significance of these observations is unknown.
• Careful adherence to recommended dosage is of the utmost importance in obstetrical paracervical block. Failure to achieve adequate analgesia with recommended doses should arouse suspicion of intravascular or fetal intracranial injection. Cases compatible with unintended fetal intracranial injection of local anesthetic injection have been reported following intended paracervical or pudendal block or both. Babies so affected present with unexplained neonatal depression at birth which correlates with high local anesthetic serum levels and usually manifest seizures within six hours. Prompt use of supportive measures combined with forced urinary excretion of the local anesthetic has been used successfully to manage this complication.
• Case reports of maternal convulsions and cardiovascular collapse following use of some local anesthetics for paracervical block in early pregnancy (as anesthesia for elective abortion) suggest that systemic absorption under these circumstances may be rapid. The recommended maximum dose of each drug should not be exceeded. Injection should be made slowly and with frequent aspiration. Allow a 5-minute interval between sides.
• There are no data concerning use of chloroprocaine for obstetrical paracervical block when toxemia of pregnancy is present or when fetal distress or prematurity is anticipated in advance of the block; such use is, therefore, not recommended.
• The following information should be considered by clinicians who select chloroprocaine for obstetrical paracervical block anesthesia:

• Fetal bradycardia (generally a heart rate of less than 120 per minute for more than 2 minutes) has been noted by electronic monitoring in about 5 to 10 percent of the cases (various studies) where initial total doses of 120 mg to 400 mg of chloroprocaine were employed. The incidence of bradycardia, within this dose range, might not be dose related.
• Fetal acidosis has not been demonstrated by blood gas monitoring around the time of bradycardia or afterwards. These data are limited and generally restricted to non-toxemic cases where fetal distress or prematurity was not anticipated in advance of the block.
• No intact chloroprocaine and only trace quantities of a hydrolysis product, 2-chloro-4-aminobenzoic acid, have been demonstrated in umbilical cord arterial or venous plasma following properly administered paracervical block with chloroprocaine.
• The role of drug factors and non-drug factors associated with fetal bradycardia following paracervical block are unexplained at this time.

Nursing Mothers

• 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 chloroprocaine is administered to a nursing woman.

Pediatric Use

• 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 HCl without epinephrine would be 250 mg. Concentrations of 0.5–1% are suggested for infiltration and 1–1.5% 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.

Geriatic Use

• Clinical studies of Nesacaine and Nesacaine-MPF did not include sufficient numbers of subjects 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
• This drug and its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function.

Gender

There is no FDA guidance on the use of Chloroprocaine with respect to specific gender populations.

Race

There is no FDA guidance on the use of Chloroprocaine with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Chloroprocaine in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Chloroprocaine in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Chloroprocaine in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Chloroprocaine in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Chloroprocaine Administration in the drug label.

Monitoring

There is limited information regarding Chloroprocaine Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Chloroprocaine and IV administrations.

Overdosage

• Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use of local anesthetics or to unintended subarachnoid injection of local anesthetic solution (see ADVERSE REACTIONS, WARNINGS and PRECAUTIONS).
• In mice, the intravenous LD50 of chloroprocaine HCl is 97 mg/kg and the subcutaneous LD50 of chloroprocaine HCl is 950 mg/kg.

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, as well as underventilation or apnea due to unintentional subarachnoid injection of drug solution, 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 the use of anesthetics, with these anticonvulsant drugs. Supportive treatment of circulatory depression may require administration of intravenous fluids and, when appropriate, a vasopressor dictated by the clinical situation (such as ephedrine to enhance myocardial contractile force).
• If not treated immediately, both convulsions and cardiovascular depression can result in hypoxia, acidosis, bradycardia, arrhythmias and cardiac arrest. Underventilation or apnea due to unintentional subarachnoid injection of local anesthetic solution may produce these same signs and also lead to cardiac arrest if ventilatory support is not instituted. If cardiac arrest should occur, standard cardiopulmonary resuscitative measures should be instituted. Recovery has been reported after prolonged resuscitative efforts.
• 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.

Pharmacology

Chloroprocaine

File:Chloroprocaine.svg
Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
ATC code	N01BA04 (WHO)
Identifiers
IUPAC name 2-diethylaminoethyl-4-amino-2-chloro-benzoate
CAS Number	133-16-4 Y
PubChem CID	8612
DrugBank	DB01161 Y
ChemSpider	8293 Y
UNII	5YVB0POT2H
KEGG	D07678 Y
ChEBI	CHEBI:3636 Y
ChEMBL	ChEMBL1179047 N
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C13H19ClN2O2
Molar mass	270.755 g/mol
3D model (JSmol)	Interactive image
SMILES O=C(OCCN(CC)CC)c1ccc(cc1Cl)N
InChI InChI=1S/C13H19ClN2O2/c1-3-16(4-2)7-8-18-13(17)11-6-5-10(15)9-12(11)14/h5-6,9H,3-4,7-8,15H2,1-2H3 Y Key:VDANGULDQQJODZ-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Mechanism of Action

• Chloroprocaine, like other local anesthetics, blocks the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows:

1. Pain
2. Temperature
3. Touch
4. Proprioception
5. Skeletal muscle tone

Structure

• Nesacaine and Nesacaine-MPF Injections are sterile non pyrogenic local anesthetics. The active ingredient in Nesacaine and Nesacaine-MPF Injections is chloroprocaine HCl (benzoic acid, 4-amino-2-chloro-2-(diethylamino) ethyl ester, monohydrochloride), which is represented by the following structural formula:

File:FILENAME.jpg

This image is provided by the National Library of Medicine.

• The solutions are adjusted to pH 2.7–4.0 by means of sodium hydroxide and/or hydrochloric acid. Filled under nitrogen.
• Nesacaine and Nesacaine-MPF Injections should not be resterilized by autoclaving.

Pharmacodynamics

• Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems. At blood concentrations achieved with normal therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal. However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block and ultimately to cardiac arrest. In addition, with toxic blood concentrations myocardial contractility may be depressed and peripheral vasodilation may occur, leading to decreased cardiac output and arterial blood pressure.
• Following systemic absorption, toxic blood concentrations of local anesthetics can produce central nervous system stimulation, depression, or both. Apparent central stimulation may be manifested as restlessness, tremors and shivering, which may progress to convulsions. Depression and coma may occur, possibly progressing ultimately to respiratory arrest.
• However, the local anesthetics have a primary depressant effect on the medulla and on higher centers. The depressed stage may occur without a prior stage of central nervous system stimulation.

Pharmacokinetics

• The rate of systemic absorption of local anesthetic drugs is dependent upon the total dose and concentration of drug administered, the route of administration, the vascularity of the administration site, and the presence or absence of epinephrine in the anesthetic injection. Epinephrine usually reduces the rate of absorption and plasma concentration of local anesthetics and is sometimes added to local anesthetic injections in order to prolong the duration of action.
• The onset of action with chloroprocaine is rapid (usually within 6 to 12 minutes), and the duration of anesthesia, depending upon the amount used and the route of administration, may be up to 60 minutes.
• Local anesthetics appear to cross the placenta by passive diffusion. However, the rate and degree of diffusion varies considerably among the different drugs as governed by:

(1) the degree of plasma protein binding, (2) the degree of ionization, and (3) the degree of lipid solubility. * Fetal/maternal ratios of local anesthetics appear to be inversely related to the degree of plasma protein binding, since only the free, unbound drug is available for placental transfer.  Thus, drugs with the highest protein binding capacity may have the lowest fetal/maternal ratios.  The extent of placental transfer is also determined by the degree of ionization and lipid solubility of the drug.  Lipid soluble, nonionized drugs readily enter the fetal blood from the maternal circulation.

Depending upon the route of administration, local anesthetics are distributed to some extent to all body tissues, with high concentrations found in highly perfused organs such as the liver, lungs, heart, and brain.

Various pharmacokinetic parameters of the local anesthetics can be significantly altered by the presence of hepatic or renal disease, addition of epinephrine, factors affecting urinary pH, renal blood flow, the route of administration, and the age of the patient. The in vitro plasma half-life of chloroprocaine in adults is 21 ± 2 seconds for males and 25 ± 1 seconds for females. The in vitro plasma half-life in neonates is 43 ± 2 seconds.

Chloroprocaine is rapidly metabolized in plasma by hydrolysis of the ester linkage by pseudocholinesterase. The hydrolysis of chloroprocaine results in the production of ß-diethylaminoethanol and 2-chloro-4-aminobenzoic acid, which inhibits the action of the sulfonamides (see PRECAUTIONS).

The kidney is the main excretory organ for most local anesthetics and their metabolites. Urinary excretion is affected by urinary perfusion and factors affecting urinary pH.

Nonclinical Toxicology

There is limited information regarding Chloroprocaine Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Chloroprocaine Clinical Studies in the drug label.

How Supplied

There is limited information regarding Chloroprocaine How Supplied in the drug label.

Storage

There is limited information regarding Chloroprocaine Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Chloroprocaine Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Chloroprocaine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Chloroprocaine Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Chloroprocaine Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.