Source: FDA, National Drug Code (US) Revision Year: 2020
Local anesthetics should only be administered 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 insuring 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 Adverse Reaction (6) and Overdosage (10)]. 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.
The clinician should take the appropriate measures to avoid an intravascular injection [see Administration (2.2)]. In addition, it is essential for the clinician to know how to recognize and treat undesirable effects, systemic toxicity and other complications. If signs of acute systemic toxicity or total spinal block are observed, the injection of the local anesthetic must be stopped immediately [see Overdosage (10)].
Hypotension and bradycardia are well known side effects of all local anesthetics [see Adverse Reaction (6) and Overdosage (10)].
A serious, undesirable effect of spinal anesthesia is high or total spinal block, with consequent cardiovascular and respiratory depression. Cardiovascular depression is induced by an extended block of the sympathetic nervous system, which may induce severe hypotension and bradycardia to the point of cardiac arrest. Respiratory depression is induced by the block of the respiratory musculature and the diaphragm. Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient’s state of consciousness should be accomplished after CLOROTEKAL injection.
Patients over 65 years, particularly those with hypertension, may be at increased risk for experiencing the hypotensive effects of CLOROTEKAL. Blood pressure should, therefore, be carefully monitored after CLOROTEKAL injection. Hypotension may be controlled by vasoconstrictors in dosages depending on the severity of hypotension and response of treatment.
Neurological damage may occur after spinal anesthesia, manifesting as paresthesia, loss of sensitivity, motor weakness, paralysis, cauda equina syndrome. Occasionally these symptoms persist and can be permanent. Carefully evaluate patients with underlying neuromuscular disorders and consider the risk-benefit ratio prior to treatment.
Carefully and constantly monitor cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient’s state of consciousness after local anesthetic injection. Restlessness, headache, anxiety, incoherent speech problems, lightheadedness, paresthesia, numbness and tingling of the mouth and lips, hearing problems, tinnitus, dizziness, blurred vision, convulsions, loss of consciousness tremors, depression, or drowsiness may be early warning signs of central nervous system toxicity [see Adverse Reactions (6.2) and Overdosage (10)].
CLOROTEKAL is contraindicated in patients hypersensitive to drugs of the PABA ester group. Allergic type reactions may occur as a result of sensitivity to the local anesthetic or to other formulation ingredients. 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, anaphylaxis 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 [see Adverse Reactions (6.2)].
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.
Some patients require special attention in order to reduce the risk of serious undesirable effects, even when locoregional anesthesia constitutes the optimum choice for the surgical intervention:
Because ester-type local anesthetics are hydrolyzed by plasma cholinesterase produced by the liver, use CLOROTEKAL cautiously in patients with advanced hepatic disease [see Use in Specific Populations (8.6)].
Local anesthetics 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.
The following serious adverse reactions are described, or described in greater detail, in other sections:
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
During clinical investigations, a total of 111 patients undergoing various surgical procedures received CLOROTEKAL. Patients were administered a dose ranging from 30 to 50 mg of CLOROTEKAL.
Taking into consideration data for 50 mg dose only, the most common adverse reaction in these studies, (incidence greater than or equal to 10%) following CLOROTEKAL administration was procedural pain.
The common adverse reactions (incidence greater than or equal to 2% to less than 10%) following CLOROTEKAL administration were injection site pain and hypotension.
The less common/rare adverse reactions (incidence less than 2%) following CLOROTEKAL administration were anesthetic complication, nausea, headache and hyperglycemia.
All Treatment Emergent Adverse Reactions in clinical studies comparing CLOROTEKAL (dose 50 mg) to Bupivacaine 0.5% (10 mg) are shown in Table 1.
Table 1. Treatment-Emergent Adverse Events (TEAEs) in Controlled Trials (Phase 2 and Phase 3 Trials):
| System Organ Class Preferred Term | Chloroprocaine 10 mg/mL (50 mg) N = 81 n (%) | Bupivacaine 0.5% (10 mg) N=64 n (%) |
|---|---|---|
| Subjects with Any TEAE | 17 (21.0) | 3 (4.7) |
| Injury, Poisoning and Procedural Complications | 13 (16.0) | 0 (0.0) |
| Procedural Pain | 13 (16.0) | 0 (0.0) |
| General Disorders and Administration Site Conditions | 3 (3.7) | 2 (3.1) |
| Injection Site Pain | 3 (3.7) | 2 (3.1) |
| Vascular Disorders | 4 (4.9) | 1 (1.6) |
| Hypotension | 4 (4.9) | 1 (1.6) |
Note: Subjects are summarized according to the product they actually received. The denominator for calculating the proportions is the number of subjects in each treatment group and overall.
TEAE = Treatment-Emergent Adverse Event (both related and non-related).
The following adverse reactions have been identified during post-approval of use of CLOROTEKAL outside of the United States. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure (Table 2).
Table 2. Post-Marketing Reports of Adverse Drug Reactions:
| System Organ Class | Adverse Reactions |
|---|---|
| Immune System Disorders | Hypersensivity (including urticaria, pruritus, erythema multiforme, angioedema with possible airway obstruction), anaphylaxis |
| Injury, Poisoning and Procedural Complications | Urinary retention postoperative, delayed recovery from anesthesia, anesthetic complication |
| General Disorders and Administration Site Conditions | Feeling hot, malaise |
| Musculoskeletal and Connective Tissue Disorders | Back pain, groin pain, pain in extremity |
| Nervous System Disorders | Restlessness, paresthesia, dizziness, tremor, seizure, oral paresthesia, oral hypoesthesia, hearing disability, visual disorders, blurred vision, tinnitus, speech disorders, loss of consciousness, peripheral neuropathy, somnolence, unintentional total spinal block, urinary and anal incontinence, perineal disorder and sexual dysfunction, arachnoiditis, akathisia, presyncope, burning sensation, spinal cord injury, cauda equina syndrome, hypoesthesia, dysesthesia, motor dysfunction, myoclonus, phantom pain, headache |
| Eye Disorders | Diplopia, photophobia |
| Cardiac Disorders | Bradycardia, tachycardia, arrhythmia, myocardial depression, cardiac arrest |
| Psychiatric Disorders | Anxiety |
| Vascular Disorders | Hypertension, hypotension |
| Respiratory, Thoracic and Mediastinal Disorders | Respiratory depression, dyspnea, respiratory arrest |
| Gastrointestinal Disorders | Nausea, vomiting |
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, avoid use in any condition in which a sulfonamide drug is being employed [see Clinical Pharmacology (12.3)].
No studies have been performed on interactions between chloroprocaine and class III antiarrhythmics (e.g., amiodarone). Carefully monitor these patients for cardiovascular effects.
The combination of various local anesthetics may result in additive effects affecting the cardiovascular system and the central nervous system. Monitor these patients for signs and symptoms of local anesthetic toxicity.
The limited available data with chloroprocaine use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. There are no animal reproduction studies for chloroprocaine. There are risks to the mother and the fetus associated with use of chloroprocaine during labor and delivery (see Clinical Considerations).
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
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 (12.3)]. 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.
Spinal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. Spinal 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.
Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves. The fetal heart rate also should be monitored continuously, and electronic fetal monitoring is highly advisable.
There are no data on the presence of chloroprocaine in human milk, the effects on the breastfed infant, or the effects on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CLOROTEKAL and any potential adverse effects on the breastfed infant from CLOROTEKAL or from the underlying maternal condition.
Safety and effectiveness in pediatric patient have not been established.
Patients over 65 years, particularly those with hypertension, may be at increased risk of developing hypotension while undergoing spinal anesthesia with CLOROTEKAL.
Clinical studies of CLOROTEKAL 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 an elderly patient will have greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see Warnings and Precautions (5) and Clinical Pharmacology (12.3)].
Since ester-type local anesthetics are hydrolyzed by plasma cholinesterase produced by the liver, the risk of toxic reactions might be greater in patients with advanced hepatic disease [see Clinical Pharmacology (12.3)].
This drug and its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions might be greater in patients with impaired renal function [see Clinical Pharmacology (12.3)].
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