100 mg/5 ml,
1000 mg/50 ml
For the use of a Registered Medical Practitioner or a Hospital or a Institution only.
LIDOSOL-PF (Lidocaine Hydrochloride) is a class I B antiarrhythmic and local anaesthetic of the amide type. Chemically, Lidocaine Hydrochloride is 2-(Diethylamino)-2’,6’-acetoxylidide monohydrochloride monohydrate. Its molecular formula is C14H22N2O HCl H2O and its molecular weight is 288.81.
STRUCTURAL FORMULA :
Its structural formula is :
LIDOSOL-PF is a sterile, clear, colourless solution filled in Amber coloured ampoule of suitable size.
Each ml contains :
Lidocaine Hydrochloride (anhydrous) USP 20 mg
Water for Injection USP q.s.
Lidocaine is a local anaesthetic of the amide type. It is used to provide local anaesthesia at various sites in the body and it acts by inhibiting the ionic refluxes required for the initiation and conduction of impulses, thereby stabilising the neuronal membrane. In addition to blocking conduction in nerve axons in the peripheral nervous system, Lidocaine has important effects on the central nervous system and cardiovascular system. After absorption Lidocaine may cause stimulation of the CNS followed by depression and in the cardiovascular system, it acts primarily on the myocardium where it may produce decreases in electrical excitability, conduction rate and force of contraction.
The mode of action of the antiarrhythmic effect of Lidocaine Hydrochloride appears to be similar to that of procaine, procainamide, and quinidine. Ventricular excitability is depressed and the stimulation threshold of the ventricle is increased during diastole. The sinoatrial node is, however, unaffected. In contrast to the latter three drugs, Lidocaine Hydrochloride in therapeutic doses does not produce a significant decrease in arterial pressure or in cardiac contractile force. In larger doses, Lidocaine Hydrochloride may produce circulatory depression, but the magnitude of the change is less than that found with comparable doses of procainamide. Neither drug appreciably affects the duration of the absolute refractory period.
Lidocaine is readily absorbed from the gastrointestinal tract, from mucous membranes, and through damaged skin. Absorption through intact skin is poor. It is rapidly absorbed from injection sites including muscle. After an intravenous dose lidocaine is rapidly and widely distributed into highly perfused tissues followed by redistribution into skeletal muscle and adipose tissue. Lidocaine is bound to plasma proteins, including a1-acid glycoprotein (AAG). The extent of binding is variable but is about 66 %. Plasma protein binding of lidocaine depends in part on the concentrations of both lidocaine and AAG. Any alteration in the concentration of AAG can greatly affect plasma concentrations of lidocaine. Plasma concentrations decline rapidly after an intravenous dose with an initial half-life of less than 30 minutes; the elimination half-life is 1 to 2 hours but may be prolonged if infusions are given for longer than 24 hours or if hepatic blood flow is reduced.
Lidocaine is largely metabolised in the liver and any alteration in liver function or hepatic blood flow can have a significant effect on its pharmacokinetics and dosage requirements. First-pass metabolism is extensive and bioavailability is about 35 % after oral doses. Metabolism in the liver is rapid and about 90 % of a given dose is dealkylated to form monoethylglycinexylidide and glycinexylidide. Both of these metabolites may contribute to the therapeutic and toxic effects of lidocaine and since their half-lives are longer than that of lidocaine, accumulation, particularly of glycinexylidide, may occur during prolonged infusions. Further metabolism occurs and metabolites are excreted in the urine with less than 10 % of unchanged lidocaine. Reduced clearance of lidocaine has been found in patients with heart failure, alcoholic liver disease, or chronic or viral hepatitis. Drugs that alter hepatic blood flow or induce drug-metabolising microsomal enzymes can also affect the clearance of lidocaine. Renal impairment does not affect the clearance of lidocaine but accumulation of its active metabolites can occur. Lidocaine crosses the placenta and blood-brain barrier; it is distributed into breast milk.
The intravenous administration of LIDOSOL-PF is indicated in the treatment of ventricular tachycardia occurring during cardiac manipulation, such as surgery or catheterization, or which may occur during acute myocardial infarction, digitalis toxicity, or other cardiac diseases. LIDOSOL-PF is also used in local anaesthesia by surface infiltration, regional, epidural and caudal routes, dental anaesthesia, either alone or in combination with adrenaline.
For intravenous, intramuscular, subcutaneous injection. Not intended for use in the eye.
INSTRUCTION FOR USE OF AMPOULE :
The ampoule used in this product is equipped with O.P.C (One Point Cut) opening system. No ampoule file is needed to open the ampoule. The neck of the ampoule is prescored at the point of constriction. A coloured dot on the ampoule head helps to orientate the ampoule. Take the ampoule and face the coloured dot. Let the solution at the head of the ampoule to flow down by shaking or a gentle stroke. The ampoule opens easily by placing the thumb on the coloured dot and gently pressing downwards as shown.
In ventricular arrhythmias :
The usual adult IV bolus dose is 50-100 mg administered at a rate of approximately 25-50 mg per minute. If the desired response is not achieved, a second dose may be administered 5 minutes after completion of the first injection. Not more than 200-300 mg should be administered during a one hour period. Elderly patients and those with congestive heart failure or cardiogenic shock may require smaller bolus doses. Maintenance infusion of a 0.2 or 0.4 % solution in 5 % glucose.
20-50 micrograms/kg/minute (1-4 mg/minute in an average 70 kg adult). Slower infusion rates should be used in patients with congestive heart failure or liver disease; no dosing modification appears necessary in patients with renal failure. When arrhythmias reappear during a constant infusion of Lidocaine, a small bolus may be given to rapidly increase plasma concentration of the drug; the infusion rate is increased simultaneously. The infusion should be terminated as soon as the patients basic cardiac rhythm appears to be stable or at the earliest sign of toxicity. Infants and children may be given an initial IV bolus of 0.5-1 mg/kg. This dose may be repeated according to the response of the patient, but the total dose should not exceed 3-5 mg/kg. A maintenance IV infusion of 10-50 micrograms/kg per minute may be given via an infusion pump.
For advanced cardiac life support in children, the recommended dosage is an initial IV bolus of 1 mg/kg. If ventricular tachycardia or ventricular fibrillation is not corrected following defibrillation and an initial bolus, an IV infusion should be started at a rate of 20-50 mcg/kg per minute. Constant ECG monitoring is recommended during therapy with LIDOSOL-PF, however if this equipment is not available and a ventricular arrhythmia is suspected, a single IM dose may be administered if bradycardia is not present. The deltoid muscle is the preferred site for IM injection.
In Local Anaesthesia :
Usual doses should generally be reduced in children and in elderly or debilitated patients. To minimise the possibility of toxic reactions, children should be given Lidocaine Hydrochloride solutions in concentrations of 0.5 % or 1 %. Single doses of Lidocaine (for anaesthesia other than spinal) should not exceed 4.5 mg/kg (or 200 mg) in adults or children 12-18 years of age. Lidocaine by local infiltration for children under the age of 12 years should not exceed 3 mg/kg, repeated not more often than every 4 hours. For spinal anaesthesia, up to 100 mg of the drug may be given. For continuous epidural or caudal anaesthesia, the maximum dose should not be repeated at intervals of less than 1.5 hours. For paracervical block for obstetric analgesia (including abortion) the maximum recommended dosage (200 mg) should not be repeated at intervals of less than 1.5 hours. For IV regional anaesthesia in adults using a 0.5 % solution, the dose administered should not exceed 4 mg/kg. Solutions of 1 % Lidocaine Hydrochloride (without preservative) are used for epidural or caudal anaesthesia. To prevent intravascular or subarachnoid injection of a large epidural dose of Lidocaine, a test dose of 2-5 mls should be injected at least 5 minutes prior to administering the total dose. In epidural anaesthesia 2-3 mls of 1 % solution is usually required for each dermatome to be anaesthetised.
In caudal block for production of obstetric analgesia or in epidural thoracic block, 20-30 mls of a 1 % solution (200-300 mg) of the drug may be used. For epidural lumbar anaesthesia, the dose is 25-30 mls (250-300 mg) of a 1 % solution. For intercostal nerve block : 3 mls of a 1 % solution (30 mg).
For paravertebral nerve block : 3-5 mls of a 1 % solution (30-50 mg).
For pudendal nerve block (each side) : 10 mls of a 1 % solution (100 mg).
For paracervical nerve block (each side) for obstetric analgesia : 10 mls of a 1 % solution (100 mg).
For sympathetic nerve blocks : Cervical (stellate ganglion) nerve block : 5 mls of a 1 % solution (50 mg).
Lumbar nerve block : 5-10 mls of a 1 % solution (50-100 mg).
For percutaneous infiltration anaesthesia : 1-60 mls of a 0.5 % solution or 0.5 to 30 ml of a 1 % solution (5-300 mg).
For IV regional anaesthesia : 10-60 mls of 0.5 % solution (50-300 mg).
LIDOSOL-PF is contraindicated in patients with Known hypersensitivity to lidocaine or other anaesthetics of the amide type.
In ventricular arrhythmia
• Sino-atrial disorders
• All grades of atrioventricular block
• Severe myocardial depression
• Porphyria (use with caution in local anaesthesia) Local anaesthesia
• Complete heart block
WARNINGS AND PRECAUTIONS :
As with other local anaesthetics, Lidocaine should be used with caution in patients with epilepsy, myasthenia gravis, cardiac conduction disturbances, congestive heart failure, bradycardia, severe shock, impaired respiratory function or impaired renal function with a creatinine clearance of less than 10 ml/minute. Lidocaine is metabolised in the liver and it should be used with caution in patients with impaired hepatic function. Lower doses should be used in congestive cardiac failure and following cardiac surgery. Hypokalaemia, hypoxia and disorders of acid-base balance should be corrected before treatment with intravenous lidocaine begins. Facilities for resuscitation should be available when administering local anaesthetics. The effect of local anaesthetics may be reduced if the injection is made into an inflamed or infected area. Certain local anaesthetic procedures may be associated with serious adverse reactions, regardless of the local anaesthetic drug used.
The severity of such tissue reactions is related to the degree of trauma, the concentration of the local anaesthetic and the duration of exposure of the tissue to the local anaesthetic. For this reason, as with all local anaesthetics, the lowest effective concentration and dose of local anaesthetic should be used. LIDOSOL-PF Injection is not recommended for use in neonates. The optimum serum concentration of lidocaine required to avoid toxicity, such as convulsions and cardiac arrhythmias, in this age group is not known.
Pregnancy : Category B
Teratogenic effects :
Reproduction studies have been performed in rats at doses up to 6.6 times the human dose and have revealed no evidence of harm to the foetus caused by lidocaine. There are, however, no adequate and well-controlled studies in pregnant women. Animal reproduction studies are not always predictive of human response. General consideration should be given to this fact before administering lidocaine to women of childbearing potential, especially during early pregnancy when maximum organogenesis takes place.
Labour and Delivery :
Local anaesthetics rapidly cross the placenta and when used for epidural, paracervical, pudendal or caudal block anaesthesia, can cause varying degrees of maternal, foetal and neonatal toxicity. The potential for toxicity depends upon the procedure performed, the type and amount of drug used, and the technique of drug administration. Adverse reactions in the parturient, foetus and neonate involve alterations of the central nervous system peripheral vascular tone and cardiac function. Maternal hypotension has resulted from regional anaesthesia. Local anaesthetics 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 foetal heart rate also should be monitored continuously, and electronic foetal monitoring is highly advisable.
Epidural, spinal, paracervical, or pudendal anaesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. In one study, paracervical block anaesthesia was associated with a decrease in the mean duration of first stage labour and facilitation of cervical dilation. However, spinal and epidural anaesthesia have also been reported to prolong the second stage of labour by removing the parturient’s reflex urge to bear down or by interfering with motor function. The use of obstetrical anaesthesia may increase the need for forceps assistance. The use of some local anaesthetic drug products during labour 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. Foetal bradycardia may occur in 20 to 30 % of patients receiving paracervical nerve block anaesthesia with the amide-type local anaesthetics and may be associated with foetal acidosis. Foetal heart rate should always be monitored during paracervical anaesthesia. The physician should weigh the possible advantages against risks when considering paracervical block in prematurity, toxemia of pregnancy and foetal distress. 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 foetal intracranial injection. Cases compatible with unintended foetal intracranial injection of local anaesthetic solution 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 anaesthetic serum levels, and often manifest seizures within six hours. Prompt use of supportive measures combined with forced urinary excretion of the local anaesthetic has been used successfully to manage this complication.
Case reports of maternal convulsions and cardiovascular collapse following use of some local anaesthetics for paracervical block in early pregnancy (as anaesthesia 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.
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 lidocaine is administered to a nursing woman.
Paediatric Use :
Dosages in paediatrics patients should be reduced, commensurate with age, body weight and physical condition.
INTERACTIONS AND INCOMPATIBILITIES :
The clearance of Lidocaine may be reduced by beta-adrenoceptor blocking agents (e.g. propranolol) and cimetidine, requiring a reduction in the dosage of Lidocaine. Increase in serum levels of lidocaine may also occur with anti-viral agents (e.g. amprenavir, atazanavir, darunavir, lopinavir). Lidocaine should be used with caution in patients receiving other local anaesthetics or agents structurally related to amidelocal anaesthetics (e.g. anti-arrhythmics, such as mexiletine), since the systemic toxic effects are additive. Specific interaction studies with lidocaine and class III anti-arrhythmic drugs (e.g. amiodarone) have not been performed, but caution is advised. There may be an increased risk of ventricular arrhythmia in patients treated concurrently with antipsychotics which prolong or may prolong the QT interval (e.g. pimozide, sertindole, olanzapine, quetiapine, zotepine), or 5HT3 antagonists (e.g. tropisetron, dolasetron). Concomitant use of quinupristin/dalfopristin should be avoided. There may be an increased risk of enhanced and prolonged neuromuscular blockade in patients treated concurrently with muscle relaxants (e.g. suxamethonium).
Lidocaine caused precipitation of Amphotericin, Methohexitone Sodium and Sulphadiazine Sodium in Glucose Injection. It is recommended that admixtures of Lidocaine & Glyceryl trinitrate should be avoided.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES :
When outpatient anaesthesia affects areas of the body involved in driving or operating machinery, patients should be advised to avoid these activities until normal function is fully restored.
SIDE EFFECTS :
In common with other local anaesthetics, adverse reactions to Lidocaine are rare and are usually the result of raised plasma concentrations due to accidental intravascular injection, excessive dosage or rapid absorption from highly vascular areas, or may result from a hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient. Systematic toxicity mainly involves the central nervous system and/or the cardiovascular system.
Immune system disorders :
Hypersensitivity reactions (allergic or anaphylactoid reactions, anaphylactic shock). Skin testing for allergy to Lidocaine is not considered to be reliable.
Nervous & Psychiatric disorders :
Neurological signs of systemic toxicity include dizziness or light-headedness, nervousness, tremor, circumoral paraesthesia, tongue numbness, drowsiness, convulsions, coma. Nervous system reactions may be excitatory and or depressant. Signs of CNS stimulation may be brief, or may not occur at all, so that the first signs of toxicity may be confusion and drowsiness, followed by coma and respiratory failure. Neurological complications of spinal anaesthesia include transient neurological symptoms such as pain of the lower back, buttock and legs. These symptoms usually develop within twenty-four hours of anaesthesia and resolve within a few days. Isolated cases of arachnoiditis or cauda equina syndrome, with persistent paraesthesia, bowel and urinary dysfunction, or lower limb paralysis have been reported following spinal anaesthesia with lidocaine and other similar agents. The majority of cases have been associated with hyperbaric concentrations of lidocaine or prolonged spinal infusion.
Eye disorders :
Blurred vision, diplopia and transient amaurosis may be signs of lidocaine toxicity. Bilateral amaurosis may also be a consequence of accidental injection of the optic nerve sheath during ocular procedures. Orbital inflammation and diplopia have been reported following retro- or peribulbar anaesthesia.
Ear and labyrinth disorders :
Cardiac and vascular disorders :
Cardiovascular reactions are depressant and may manifest as hypotension, bradycardia, myocardial depression, cardiac arrhythmias and possibly cardiac arrest or circulatory collapse. Hypotension may accompany spinal and epidural anaesthesia. Isolated cases of bradycardia and cardiac arrest have also been reported.
Respiratory, thoracic or mediastinal disorders :
Dyspnoea, bronchospasm, respiratory depression, respiratory arrest.
Skin & subcutaneous tissue disorders :
Rash, urticaria, angioedema, face oedema.
OVERDOSAGES AND TREATMENT OF OVERDOSAGE :
Symptoms of acute systemic toxicity :
Central nervous system toxicity presents with symptoms of increasing severity. Patients may present initially with circumoral paraesthesia, numbness of the tongue, light-headedness, hyperacusis and tinnitus. Visual disturbance and muscular tremors or muscle twitching 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, which may last from a few seconds to several minutes. Hypoxia and hypercapnia occur rapidly following convulsions due to 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.
Effects on the cardiovascular system may be seen in severe cases. Hypotension, bradycardia, arrhythmia and cardiac arrest may occur as a result of high systemic concentrations, with potentially fatal outcome. Recovery occurs as a consequence of redistribution of the local anaesthetic drug from the central nervous system, and metabolism and may be rapid unless large amounts of the drug have been injected.
Treatment of acute toxicity :
If signs of acute systemic toxicity appear, injection of the anaesthetic should be stopped immediately. Treatment will be required if convulsions and CNS depression occurs. The objectives of treatment are to maintain oxygenation, stop the convulsions and support the circulation. A patent airway should be established and oxygen should be administered, together with assisted ventilation (mask and bag) if necessary. The circulation should be maintained with infusions of plasma or intravenous fluids. Where further supportive treatment of circulatory depression is required, use of a vasopressor agent may be considered although this involves a risk of central nervous system excitation. If the convulsions do not stop spontaneously in 15 - 20 seconds, they may be controlled by the intravenous administration of Diazepam or Thiopentone Sodium, bearing in mind that anti-convulsant drugs may also depress respiration and the circulation. Prolonged convulsions may jeopardise the patient’s ventilation and oxygenation and early endotracheal intubation should be considered. If cardiac arrest should occur, standard cardiopulmonary resuscitation procedures should be instituted. Continual optimal oxygenation and ventilation and circulatory support as well as treatment of acidosis are of vital importance. Dialysis is of negligible value in the treatment of acute overdosage with Lidocaine.
PHARMACEUTICAL PRECAUTIONS :
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Store below 30°C (86°F), protected from light.
Do not refrigerate.
SHELF LIFE :
24 months from the date of manufacture.
LIDOSOL-PF is supplied as 100 mg of Lidocaine Hydrochloride USP in 5 ml solution.
5 Ampoules per Box.
Disclaimer : For the use of a Registered Medical Practitioner or a Hospital or a Institution only. Also it is not intended to be used by healthcare professionals or patients for the purpose of prescribing or administering these products. Questions regarding the complete and current content of product labeling / specification / presentation should be directed to SGPharma.