INFORMATION FOR HEALTH PROFESSIONALS
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The molecular formula of procaine hydrochloride is C13H20N2O2.HCl. Its molecular weight is 272.8. The CAS Registry number of procaine hydrochloride is 51-05-8.
Procaine hydrochloride appears as colourless/white odourless crystals or a white crystalline powder. It is very soluble in water and alcohol and slightly soluble in chloroform. It is practically insoluble in ether. Procaine Hydrochloride Injection is a clear, colourless to pale yellow, sterile solution of procaine hydrochloride and sodium chloride in water for injections. Each mL contains 20 mg of procaine hydrochloride and 5.0 mg of sodium chloride in water for injections. The pH of the solution is between 3.0 and 5.5.
Procaine is an ester-type local anaesthetic, which blocks the generation and conduction of nerve impulses by decreasing the permeability of the nerve membrane to ions, thereby inhibiting depolarisation. The loss of nerve functions generally occurs in the order of loss of autonomic activity, followed by loss of pain sensation, other sensory functions, and finally motor activity.
Systemic absorption of procaine depends on the total dose and concentration of drug administered, the route of administration, the vascularity of the administration site, and the presence or absence of a vasoconstrictor in the injection. Systemic absorption of procaine may produce central nervous system (CNS) and cardiac effects. CNS effects are generally manifested as initial excitation followed by CNS depression. Cardiac effects include depression of cardiac conduction. Procaine also causes vasodilation.
Procaine is readily absorbed after parenteral administration. Compared to other local anaesthetics, procaine has a slow onset and short duration of action. The onset of action of parenterally administered procaine is 2-5 minutes and its duration of action is approximately 1 hour. Procaine is reported to be 6% bound to plasma proteins, and is distributed to all body tissues, with highest concentrations in the liver, lungs, heart and brain. Procaine is known to cross the placenta. Procaine is hydrolysed to para-aminobenzoic acid and diethylaminoethanol by cholinesterases in the plasma and to a lesser extent the liver. Excretion of procaine is mostly in the urine and less than 2% is excreted unchanged. The rate of renal clearance of procaine is greater in acidic urine.
Procaine Hydrochloride Injection is indicated for infiltration anaesthesia and peripheral nerve block.
Procaine Hydrochloride Injection is contraindicated in patients hypersensitive to procaine or other ester-type local anaesthetics.
Procaine Hydrochloride Injection is also contraindicated in patients with low plasma cholinesterase levels, or who are receiving anticholinesterases (see Drug Interactions ).
Procaine Hydrochloride Injection is also contraindicated when the area or site of injection is inflamed or infected.
Procaine Hydrochloride Injection is also contraindicated in patients with myasthenia gravis, severe shock or impaired cardiac conduction.
Procaine Hydrochloride Injection is also contraindicated in patients receiving sulfonamides (see Drug Interactions ).
As procaine is metabolised to produce para-aminobenzoic acid, it should be used with caution in patients who are allergic to para-aminobenzoic acid or its derivatives such as preservatives and sunscreens.
Resuscitative equipment, oxygen, drugs required for treatments of adverse reactions (eg. anticonvulsant drugs) and personnel resources needed for proper management of toxic reactions must all be readily available whenever procaine is used (see Overdosage ). Delay in proper management of dose-related toxicity, underventilation from any cause may lead to development of acidosis, cardiac arrest, and possibly death.
Clinicians should be sufficiently knowledgeable in the diagnosis and management of dose-related toxicity and acute emergencies that might arise from using procaine. Prior to use of procaine the clinician should consult the current practice guidelines and be familiar with the use of anticonvulsant drugs (see Overdosage ).
Cardiovascular vital signs, adequacy of ventilation and patient's state of consciousness should be carefully monitored after each procaine injection. Symptoms described in the Adverse Reactions (central nervous system) and Overdosage may be used as a guide of detection of early warning signs of central nervous system toxicity.
Procaine hydrochloride should be used with caution in patients with severe disturbances of cardiac rhythm, shock, heartblock or hypotension.
Procaine hydrochloride should be used with caution in patients with impaired cardiovascular function because these patients may be less able to compensate for functional changes associated with the prolongation of AV conduction produced by the drug.
Procaine Hydrochloride Injection should be used with caution in very young, elderly, acutely ill or debilitated patients, or patients with hyperthyroidism or other endocrine diseases, who may be more susceptible to the systemic toxicity of the drug.
Procaine Hydrochloride Injection should also be used with caution in patients with reduced hepatic blood flow (such as in liver disease) or renal disease, since the risk of systemic toxicity is increased due to decreased clearance of the drug.
Procaine should be used with caution in patients with a genetic predisposition to malignant hyperthermia as the safety of local anaesthetic agents in these patients has not been fully established. A standard protocol for the management of malignant hyperthermia should be available.
Category B2
It is known that Procaine hydrochloride crosses the placenta. However, limited studies on pregnant women have shown that the frequencies of malformations and congenital anomalies were not increased among the children of women who had been treated with procaine during the pregnancy. Please see below for use of Procaine during labour.
Labour: Paracervical or pudendal anaesthesia may produce changes in uterine contractility and/or maternal expulsive efforts. Maternal hypotension may occur during regional anaesthesia. Administration of local anaesthetics by paracervical nerve block during labour has been associated with a high incidence of foetal acidosis and bradycardia and has occasionally resulted in perinatal death. The risk of foetal bradycardia appears to be increased with prematurity, toxaemia of pregnancy, and foetal distress. Possible inadvertent foetal intracranial injection has reportedly occurred following attempted paracervical and/or pudendal block. This results in unexplained neonatal depression at birth, associated with high serum concentration of local anaesthetic, and seizures usually occurring within 6 hours. Prompt use of supportive measures and forced urinary excretion of the local anaesthetic has reportedly been effective for managing this complication.
It is not known whether procaine hydrochloride is distributed into breast milk. Problems in humans have not been documented, but due to lack of data the use of procaine hydrochloride is not recommended in lactating patients.
Anticholinesterases
Concurrent use of procaine hydrochloride and anticholinesterase agents may
result in increased systemic toxicity since anticholinesterases inhibit the
breakdown of procaine hydrochloride.
Antimyasthenics
Concurrent use of procaine hydrochloride and antimyasthenics may result in loss
of control of symptoms of myasthenia gravis due to antagonism of the effects of
antimyasthenics on skeletal muscle. Temporary dosage adjustment of
antimyasthenics may be required. Also antimyasthenics may have
anticholinesterase activity (see under Drug Interactions -
Anticholinesterases ).
CNS depressant medications
Concurrent use of procaine hydrochloride and CNS depressant medications may
result in additive depressant effects.
Hyaluronidase
Hyaluronidase may increase the diffusion rate of procaine hydrochloride,
resulting in a decreased time of onset, but an increase in systemic toxicity.
Neuromuscular blocking agents (such as suxamethonium chloride)
Concurrent use of procaine hydrochloride and neuromuscular blocking agents may
result in prolongation or enhancement of the neuromuscular blockade.
Sulfonamides
Concurrent use of procaine hydrochloride and sulfonamides may result in a
reduction of the antibacterial action of the sulfonamide.
Acetazolamide
Concurrent use of acetazolamide and procaine hydrochloride may extend the plasma
half-life of procaine.
Procaine Hydrochloride is reported to be physically incompatible with the following drugs: aminophylline, amylobarbitone sodium, chloramphenicol, chlorothiazide sodium, magnesium sulfate, nitrofurantoin, phenobarbitone sodium, pentobarbitone, phenytoin sodium, amphotericin, quinalbarbitone sodium, sodium bicarbonate, sodium iodide, sulfadiazine, thiopentone.
Procaine hydrochloride is also reported to be incompatible with alkaline solutions, and iodine.
Adverse reactions of local anaesthetics, usually result from high plasma concentrations caused by inadvertent intravascular injection, excessive dosage, excessive rate of injection, slow metabolic degradation, or injection into highly vascular tissue. The adverse effects of procaine hydrochloride are characteristic of those associated with other ester-type local anaesthetics. The effects are generally characterised by allergic skin reactions, CNS depression usually preceded by CNS stimulation, and cardiac depression.
CNS manifestations are excitatory and/or depressant and may be characterised by light-headedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred vision, vomiting, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, respiratory depression and/or arrest, agitation, difficulty swallowing and slurred speech.
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 administration is usually an early sign of a high blood level of the drug and may occur as a result of rapid absorption.
High doses or inadvertent intravascular injection may lead to high plasma levels and related depression of the myocardium, decreased cardiac output, heartblock, hypotension, bradycardia, ventricular arrhythmias which may lead to cardiac arrest.
Regional anaesthesia may lead to maternal hypotension.
Hypersensitivity or allergic reactions due to use of procaine are rare. These reactions may be characterised by urticaria, skin rash, redness and hives.
More serious allergic reactions include pruritus (the symptom of itching, an uncomfortable sensation leading to the urge to scratch which often results in secondary infection), angioedema (an acute painless, dermal, subcutaneous or submucosal swelling of short duration involving the face, neck, lips, larynx, hands feet, genitalia, or viscera) and anaphylaxis (an exaggerated, life-threatening hypersensitivity reaction which may be a localised wheal and flare of generalised itching, hyperaemia, angioedema, and in severe cases vascular collapse, asthma and bronchitis, and shock).
It should be noted that although skin testing in patients with suspected drug sensitivity has been recommended, the usefulness of screening for sensitivity is at present controversial. Moreover, the testing itself can cause severe or anaphylactic reactions.
The following reactions may also occur: transient burning at the injection site, skin discolouration, tissue irritation, neurolysis, neuritis, tissue necrosis, prolonged burning pain and sloughing.
Dosage of procaine hydrochloride varies with the anaesthetic procedure, the degree of anaesthesia required, and the individual patients response. The smallest dose and lowest concentration required to give the desired effect should be used.
Resuscitative equipment, oxygen and other resuscitative drugs must be immediately available when procaine hydrochloride, is used.
| Adult dose: | |
|---|---|
| Infiltration anaesthesia: | 250-600 mg as a 0.25% or 0.5% solution |
| Peripheral nerve block: | 500 mg as a 0.5%, 1% or 2% solution. Doses up to 1 g have been used. |
Paediatric dose: |
The paediatric dose has not been established. |
Procaine hydrochloride may be diluted with 0.9% sodium chloride, sterile water
for injection or 10% glucose.
Procaine hydrochloride is reported to be chemically stable and compatible at a concentration of 1g/L with the following solutions: glucose 2.5% in water, glucose 5% in water, glucose 10% in water, glucose 5% in sodium chloride 0.9%, glucose 10% in sodium chloride 0.9%, glucose 5% in lactated Ringers solution, glucose 10% in lactated Ringers solution, lactated Ringer's injection, Ringers injection, sodium chloride 0.9%, and sodium lactate 1/6 M.
Acute emergencies associated with the use of local anaesthetics are generally related to high plasma levels or to unintended subarachnoid injection of the local anaesthetic solution (see Adverse Reactions and Precautions ).
With accidental intramuscular injections, the toxic effect may occur within several minutes. However, peak plasma concentrations and toxic signs will be delayed. Toxic reactions mainly involve the central nervous and cardiovascular systems.
Acute toxicity. CNS toxicity is a graded response with symptoms and signs of escalating severity. The first symptoms are circumoral paraesthesia, numbness of the tongue, light-headedness, hyperacousis and tinnitus. Visual disturbance and muscular tremors are more serious and precede the onset of generalised convulsions. These signs must not be mistaken for neurotic behaviour.
Unconsciousness and grand mal convulsions may follow. These may last from a few seconds to several minutes. Hypoxia and hypercarbia occur rapidly following convulsions due to the increased muscular activity, together with the interference with normal respiration and loss of the airway. In severe cases, apnoea may occur. Acidosis increases the toxic effects of local anaesthetics.
Recovery is due to redistribution of the local anaesthetic drug from the central nervous system and metabolism. Recovery may be rapid unless large amounts of the drug have been injected.
Cardiovascular toxicity. Cardiovascular toxicity indicates a more severe situation. Hypotension, bradycardia, arrhythmia and even cardiac arrest may occur as a result of huge systemic concentrations of local anaesthetics.
Cardiovascular toxic effects are generally preceded by signs of toxicity in the central nervous system, unless the patient is receiving a general anaesthetic or is heavily sedated with drugs such as a benzodiazepine or a barbiturate.
If signs of acute systemic toxicity appear, injection of the local anaesthetic should be stopped immediately.
Treatment of overdose involves the following measures:
The following specific treatments are recommended:
| Strength | Pack size |
|---|---|
| 40 mg in 2 mL (2%) | 5 x 2 mL ampoules |
| 100 mg in 5 mL (2%) | 5 x 5 mL ampoules |
Store below 25°C. Protect from light.
Prescription Medicine
Mayne Pharma (NZ) Limited
23 Haining Street
Te Aro
Wellington
New Zealand
1 October 2006