Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection, as hydrochloride:
Nesacaine: 1% (30 mL); 2% (30 mL) [contains disodium edta, methylparaben]
Solution, Injection, as hydrochloride [preservative free]:
Nesacaine-MPF: 2% (20 mL); 3% (20 mL) [methylparaben free]
Generic: 2% (20 mL); 3% (20 mL)
Solution, Intrathecal, as hydrochloride [preservative free]:
Clorotekal: 1% (5 mL)
Pharmacology
Mechanism of Action
Chloroprocaine is an ester-type local anesthetic, which stabilizes the neuronal membranes and prevents initiation and transmission of nerve impulses thereby affecting local anesthetic actions. Chloroprocaine reversibly prevents generation and conduction of electrical impulses in neurons by decreasing the transient increase in permeability to sodium. The differential sensitivity generally depends on the size of the fiber; small fibers are more sensitive than larger fibers and require a longer period for recovery. Sensory pain fibers are usually blocked first, followed by fibers that transmit sensations of temperature, touch, and deep pressure. High concentrations block sympathetic somatic sensory and somatic motor fibers. The spread of anesthesia depends upon the distribution of the solution. This is primarily dependent on the volume of drug injected.
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: Depends upon route of administration; high concentrations found in highly perfused organs such as liver, lungs, heart, and brain
Metabolism
Rapidly hydrolyzed by plasma enzymes to 2-chloro-4-aminobenzoic acid and beta-diethylaminoethanol (80% conjugated before elimination)
Excretion
Urine (minimal as unchanged drug in urine; metabolites: Chloro-aminobenzoic acid and beta-diethylaminoethanol primarily excreted unchanged)
Onset of Action
6 to 12 minutes
Duration of Action
Up to 60 minutes (patient, type of block, concentration, and method of anesthesia dependent)
Half-Life Elimination
In vitro, plasma: Neonates: 43 ± 2 seconds; Adults: 21 ± 2 seconds (males), 25 ± 1 second (females)
Use in Specific Populations
Special Populations: Hepatic Function Impairment
Pharmacokinetic parameters can be significantly altered.
Special Populations: Elderly
Pharmacokinetic parameters can be significantly altered.
Use: Labeled Indications
Local anesthesia:
Chloroprocaine (with preservatives):
Production of local anesthesia by infiltration and peripheral nerve block.
Chloroprocaine (without preservatives):
Production of local anesthesia by infiltration and peripheral nerve block, as well as epidural and caudal administration; production of local anesthesia by subarachnoid block (spinal anesthesia) in adults (Clorotekal only).
Note: Due to chloroprocaine’s fast onset and short duration of action, it is most often used to establish adequate epidural anesthesia (eg, in a parturient prior to delivery) or possibly, for peripheral nerve block in a patient undergoing short (<60 minutes) ambulatory surgery that is not anticipated to produce significant postoperative pain (Alley 2014; Miller 2010).
Limitations of use: Nesacaine, Nesacaine-MPF: The manufacturer recommends against using either formulation (ie, with or without preservatives) for subarachnoid administration (ie, spinal anesthesia); however, the use of chloroprocaine without preservatives (Nesacaine-MPF) has been safely used off-label for spinal anesthesia (Goldblum 2013; Miller 2010; Yoos 2005). Do not use chloroprocaine with preservatives (Nesacaine) for epidural or spinal anesthesia.
Contraindications
Hypersensitivity to chloroprocaine, other para aminobenzoic acid (PABA) ester type anesthetics, or any component of the formulation.
Additional contraindications described in the Clorotekal labeling (clinically, some may be applicable to other products): Contraindications specific to spinal anesthesia (eg, decompensated cardiac insufficiency, hypovolemic, shock, coagulopathy); IV regional anesthesia; serious cardiac conduction problems; local infection at the site of proposed lumbar puncture; septicemia.
Dosage and Administration
Dosing: Adult
Local anesthesia: Use the smallest dose and concentration required to produce the desired result. Dosage varies with anesthetic procedure, the vascularity of the tissues, depth of anesthesia required, degree of muscle relaxation required, duration of anesthesia, and physical condition of the patient. Use reduced doses in debilitated patients and patients with cardiovascular disease. During epidural administration, a test dose (3 mL of 3% or 5 mL of 2%) is recommended prior to induction of complete block and all reinforcing doses with continuous catheter technique.
Clorotekal: Subarachnoid block (spinal anesthesia): Intrathecal: 1%: 50 mg single dose (effective block to the T 10 level). Note: Other preservative- and antioxidant-free formulations (eg, Nesacaine-MPF) have also been used off-label (dosage range: 20 to 60 mg) for spinal anesthesia for short-duration ambulatory procedures; ensure that preservative-free products do not contain the antioxidant sodium bisulfite prior to administration (Gebhardt 2017; Hejtmanek 2011; Yoos 2005).
Nesacaine, Nesacaine-MPF:
Maximum single dose (without epinephrine): 11 mg/kg; maximum total dose: 800 mg
Maximum single dose (with epinephrine 1:200,000): 14 mg/kg; maximum total dose: 1,000 mg
Caudal block: Preservative free: 2% or 3%: 15 to 25 mL; may repeat at 40- to 60-minute intervals
Infiltration and peripheral nerve block:
Digital (without epinephrine): 1%; 3 to 4 mL; total dose: 30 to 40 mg
Infraorbital: 2%: 0.5 to 1 mL; total dose 10 to 20 mg
Mandibular: 2%: 2 to 3 mL; total dose 40 to 60 mg
Paracervical: 1%; 3 mL per each of four sites; total dose: up to 120 mg
Pudendal: 2%; 10 mL each side; total dose: 400 mg
Lumbar epidural anesthesia for Cesarean delivery: Preservative free: 3%: 15 to 25 mL total dose (includes test dose of 2 or 3 mL) (Abboud 1983; Bjornestad 2006; Chestnut 2014; Feng 2012)
Lumbar epidural anesthesia, non-parturient: Preservative-free: 2% or 3%: 2 to 2.5 mL per segment; usual total volume: 15 to 25 mL; may repeat with doses that are 2 to 6 mL less than initial dose every 40 to 50 minutes.
Dosing: Geriatric
Dosage should be reduced; refer to adult dosing.
Dosing: Pediatric
Dose varies with procedure, desired depth, and duration of anesthesia, desired muscle relaxation, vascularity of tissues, physical condition, and age of patient. The smallest dose and concentration required to produce the desired effect should be used. Decrease dose in debilitated patients and patients with cardiac disease.
Anesthesia, local injectable and peripheral nerve block: Children >3 years and Adolescents: Maximum dose without epinephrine: 11 mg/kg; for infiltration, concentrations of 0.5% to 1% are recommended; for nerve block, concentrations of 1% to 1.5% are recommended
Administration
Infiltration or peripheral nerve block: Administer locally as a single injection or continuously through an indwelling catheter (peripheral nerve block). Avoid rapid injection. Intravascular injections should be avoided; aspiration should be performed prior to administration; the needle must be repositioned until no return of blood can be elicited by aspiration; however, absence of blood in the syringe does not guarantee that intravascular injection has been avoided.
Epidural (thoracic, lumbar, or caudal) and subarachnoid block (spinal anesthesia): Do not use solutions containing preservatives. Use a filter needle to draw up solution from ampule when using Clorotekal. Do not puncture areas of the skin with signs of infection/inflammation. Intravascular injections should be avoided; aspiration should be performed prior to administration; the needle must be repositioned until no return of blood can be elicited by aspiration; however, absence of blood in the syringe does not guarantee that intravascular injection has been avoided. Clorotekal is intended for intrathecal administration only; the manufacturer recommends against using for epidural administration. Use of Clorotekal via continuous spinal catheters is not recommended (safety has not been established).
Storage
Store at 20°C to 25°C (68°F to 77°F) in original container; protect from freezing. Protect from light. Discard Clorotekal and Nesacaine-MPF following single use. Solution in vials may become discolored with prolonged exposure to light; do not administer discolored solutions. Crystals of chloroprocaine may develop when exposed to low temperatures; when the vial is returned to room temperature, the crystals will redissolve with shaking; do not use solutions that contain undissolved matter. Do not heat before use; do not autoclave. Use immediately after initial puncture of vial or after ampule opening.
Drug Interactions
Alpha-/Beta-Agonists: Chloroprocaine may enhance the hypertensive effect of Alpha-/Beta-Agonists. Monitor therapy
Bupivacaine (Liposomal): Local Anesthetics may enhance the adverse/toxic effect of Bupivacaine (Liposomal). Management: Liposomal bupivacaine should not be administered with local anesthetics. Liposomal bupivacaine may be administered 20 minutes or more after the administration of lidocaine, but the optimal duration of dose separation for other local anesthetics is unknown Avoid combination
Ergot Derivatives: Chloroprocaine may enhance the hypertensive effect of Ergot Derivatives. Exceptions: Nicergoline. Monitor therapy
Hyaluronidase: May enhance the adverse/toxic effect of Local Anesthetics. Monitor therapy
Methemoglobinemia Associated Agents: May enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Monitor therapy
Neuromuscular-Blocking Agents: Local Anesthetics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy
Phenylephrine (Systemic): Chloroprocaine may enhance the hypertensive effect of Phenylephrine (Systemic). Monitor therapy
Sulfonamide Antibiotics: Chloroprocaine may diminish the therapeutic effect of Sulfonamide Antibiotics. Management: Avoid concurrent use of chloroprocaine and systemic sulfonamide-based antimicrobials whenever possible. Consider therapy modification
Technetium Tc 99m Tilmanocept: Local Anesthetics may diminish the diagnostic effect of Technetium Tc 99m Tilmanocept. Management: Avoid mixing and simultaneously co-injecting technetium Tc 99m tilmanocept with local anesthetics. This interaction does not appear to apply to other uses of these agents in combination. Monitor therapy
Adverse Reactions
>10%: Central nervous system: Procedural pain (16%)
1% to 10%:
Cardiovascular: Hypotension (5%)
Central nervous system: Headache (<2%)
Endocrine & metabolic: Hyperglycemia (<2%)
Gastrointestinal: Nausea (<2%)
Local: Injection site pain (4%)
Frequency not defined.
Cardiovascular: Syncope, ventricular arrhythmia
Central nervous system: Central nervous system depression, central nervous system stimulation, increased body temperature
Dermatologic: Diaphoresis, erythema
Gastrointestinal: Loss of anal sphincter control
Hypersensitivity: Anaphylactoid reaction, angioedema
Respiratory: Laryngeal edema, respiratory arrest, sneezing
<1%, postmarketing, and/or case reports: Akathisia, anaphylaxis, anxiety, arachnoiditis, auditory impairment, back pain, blurred vision, bradycardia, burning sensation, cardiac arrest, cardiac arrhythmia, cardiac insufficiency, cauda equine syndrome, chondrolysis of articular cartilage, diplopia, dizziness, drowsiness, dysesthesia, dyspnea, erythema multiforme, fecal incontinence, feeling hot, groin pain, hypersensitivity reaction, hypertension, hypoesthesia, limb pain, localized numbness (perineal; causing sexual dysfunction), loss of consciousness, malaise, motor dysfunction, myoclonus, oral hypoesthesia, oral paresthesia, paresthesia, peripheral neuropathy, photophobia, presyncope, prolonged emergency from anesthesia, pruritus, respiratory arrest, respiratory depression, restlessness, seizure, sexual disorder, speech disturbance, spinal cord injury, tachycardia, tinnitus, tremor, urinary incontinence, urinary retention, urticaria, visual disturbance, vomiting
Warnings/Precautions
Concerns related to adverse effects:
- Cardiovascular effects: Local anesthetics, at high systemic concentrations, are commonly associated with hypotension and bradycardia especially with inadvertent intravascular administration. Perform preventive measures (eg, limiting cumulative dose, use ultrasound or direct visualization for catheter placement). Careful and constant monitoring of the patient's cardiovascular vital signs should be done during and following each local anesthetic injection (Cox 2003; Dickerson 2014). In the event of cardiovascular collapse and/or severe CNS toxicity, treatment in accordance with the American Society of Regional Anesthesia and Pain Medicine’s Checklist for Treatment of Local Anesthetic Toxicity is recommended (Neal [ASRA 2012]).
- CNS toxicity: Careful and constant monitoring of the patient's state of consciousness should be done following each local anesthetic injection; at such times, restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, depression, or drowsiness may be early warning signs of CNS toxicity. Use extreme caution in patients with existing neurological disease. Seizures due to systemic toxicity leading to cardiac arrest have also been reported, presumably following unintentional intravascular injection. In the event of cardiovascular collapse and/or severe CNS toxicity, treatment in accordance with the American Society of Regional Anesthesia and Pain Medicine’s Checklist for Treatment of Local Anesthetic Toxicity is recommended (Neal [ASRA 2012]).
- Intra-articular infusion related chondrolysis: Continuous intra-articular infusion of local anesthetics after arthroscopic or other surgical procedures is not an approved use; chondrolysis (primarily in the shoulder joint) has occurred following infusion, with some cases requiring arthroplasty or shoulder replacement.
- Methemoglobinemia: Has been reported with local anesthetics; clinically significant methemoglobinemia requires immediate treatment along with discontinuation of the anesthetic and other oxidizing agents. Onset may be immediate or delayed (hours) after anesthetic exposure. Patients with G6PD deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, exposure to oxidizing agents or their metabolites, or infants <6 months of age are more susceptible and should be closely monitored for signs and symptoms of methemoglobinemia (eg, cyanosis, headache, rapid pulse, shortness of breath, lightheadedness, fatigue).
- Respiratory effects: Local anesthetics have been associated with rare occurrences of sudden respiratory arrest. Careful and constant monitoring of the patient's respiratory (adequacy of ventilation) vital signs should be done following each local anesthetic injection.
Disease-related concerns:
- Cardiovascular disease: Use extreme caution in patients with cardiovascular disease, including severe hypertension, hypotension, heart block, and severe cardiac decompensation.
- Hepatic impairment: Use with caution in patients with severe hepatic impairment.
- Myasthenia gravis: Use with extreme caution in patients with myasthenia gravis; may cause significant weakness (Haroutiunian 2009).
- Plasma cholinesterase disorders: Use with caution in patients with genetic deficiency of plasma cholinesterase.
- Renal impairment: Use with caution in patients with severe renal impairment.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Acutely ill patients: Use with caution in acutely ill; reduce dose consistent with age and physical status.
- Debilitated patients: Use with caution in debilitated patients; reduce dose consistent with age and physical status.
- Elderly: Use with caution in the elderly; reduce dose consistent with age and physical status.
- Pediatric: Use with caution in children; reduce dose consistent with age and physical status.
Other warnings/precautions:
- Administration: Intravascular injections should be avoided; aspiration should be performed prior to administration; the needle must be repositioned until no return of blood can be elicited by aspiration; however, absence of blood in the syringe does not guarantee that intravascular injection has been avoided.
- Epidural (thoracic, lumbar, or caudal) and intrathecal/spinal administration: Do not use solutions containing preservatives. Use extreme caution in patients with spinal deformities, neurologic disease, septicemia, and severe hypertension when used for thoracic, lumbar, and caudal epidural administration. With intrathecal/spinal administration, neurologic damage may occur after anesthesia (eg, paresthesia, loss of sensitivity, motor weakness, paralysis, cauda equina syndrome); symptoms may persist and may be permanent; carefully evaluate patients with underlying neuromuscular disorders while considering risk vs. benefit prior to treatment. Use with caution or avoid epidural or intrathecal/spinal administration in patients with bleeding disorders (congenital or acquired) and severe anemia (Horlocker 2010). Clorotekal (a product with specific FDA approval for intrathecal/spinal administration) is contraindicated in patients with serious cardiac conduction abnormalities, local infection at proposed lumbar puncture site, or septicemia; contraindications to intrathecal/spinal anesthesia should be taken into consideration.
- Trained personnel: Clinicians using local anesthetic agents should be well trained in diagnosis and management of emergencies that may arise from the use of these agents. Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use.
Monitoring Parameters
Cardiovascular and respiratory status; mental status; vital signs; signs of CNS toxicity
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal reproduction studies have not been conducted. Local anesthetics rapidly cross the placenta and may cause varying degrees of maternal, fetal, and neonatal toxicity. Close maternal and fetal monitoring (heart rate and electronic fetal monitoring advised) are required during obstetrical use. Maternal hypotension has resulted from regional anesthesia. Positioning the patient on her left side and elevating the legs may help. Epidural, paracervical, or pudendal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. The use of some local anesthetic drugs during labor and delivery may diminish muscle strength and tone for the first day or two of life. Administration as a paracervical block is not recommended with toxemia of pregnancy, fetal distress, or prematurity. Administration of a paracervical block early in pregnancy has resulted in maternal seizures and cardiovascular collapse. Fetal bradycardia and acidosis also have been reported. Fetal depression has occurred following unintended fetal intracranial injection while administering a paracervical and/or pudendal block.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience injection site irritation. Have patient report immediately to prescriber signs of acidosis (confusion, fast breathing, fast heartbeat, abnormal heartbeat, severe abdominal pain, nausea, vomiting, fatigue, shortness of breath, or loss of strength and energy), signs of methemoglobinemia (blue or gray color of the lips, nails, or skin; abnormal heartbeat; seizures; severe dizziness or passing out; severe headache; fatigue; loss of strength and energy; or shortness of breath), sneezing, sweating a lot, severe anxiety, lightheadedness, confusion, fatigue, agitation, headache, change in speech, numbness or tingling in the mouth, tremors, dizziness, passing out, noise or ringing in the ears, depression, blurred vision, change in balance, seizures, slow heartbeat, fast heartbeat, chest pain, sexual dysfunction, leaking of urine, leaking of stool, back pain or paralysis in lower half of body (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
