Dentipatch

Overdose

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 CNS excitation. Convulsions 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 jeopardize 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 Dentipatche.

Lidocaine overdose from cutaneous absorption is rare, but could occur. If there is any suspicion of lidocaine overdose (see ADVERSE REACTIONS, Systemic Reactions), drug blood concentration should be checked. The management of overdose includes close monitoring, supportive care, and symptomatic treatment. Dialysis is of negligible value in the treatment of acute overdose with lidocaine.

In the absence of massive topical overdose or oral ingestion, evaluation of symptoms of toxicity should include consideration of other etiologies for the clinical effects, or overdosage from other sources of lidocaine or other local anesthetics.

The oral LD50 of lidocaine HCl is 459 (346-773) mg/kg (as the salt) in non-fasted female rats and 214 (159-324) mg/kg (as the salt) in fasted female rats, which are equivalent to roughly 4000 mg and 2000 mg, respectively, in a 60 to 70 kg man based on the equivalent surface area dosage conversion factors between species.

Contraindications

Known hypersensitivity to anaesthetics of the amide type

Complete heart block

Hypovolaemia

Dentipatch is contraindicated in patients with a known history of sensitivity to local anesthetics of the amide type, or to any other component of the product.

Incompatibilities

Dentipatche solution for injection should not be mixed with other preparations unless compatibility is known.

Pharmaceutical form

Undesirable effects

Blood and Lymphatic System Disorders

Dentipatche may also produce methaemoglobinaemia.

Immune system disorders

Hypersensitivity reactions (allergic or anaphylactoid reactions, anaphylactic shock) - see also Skin & subcutaneous tissue disorders) are rare. They may be characterised by cutaneous lesions,

Skin testing for allergy to Dentipatche is not considered to be reliable.

Localised nerve damage at the site of injection (very rare).

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.

CNS (central 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 Dentipatche and other similar agents. The majority of cases have been associated with hyperbaric concentrations of Dentipatche or prolonged spinal infusion.

Psychotic reactions have been reported following infusion for the control of arrhythmia.

Eye disorders

Blurred vision, diplopia and transient amaurosis may be signs of Dentipatche 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

Tinnitus, hyperacusis

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 anesthesia. Isolated cases of bradycardia and cardiac arrest have also been reported.

Profound hypotension may be associated with B blockade, widespread sympathetic block from spinal or epidural block, intercostal nerve block administration or supine hypotension in pregnancy.

The major adverse effects on the CNS and CVS are primarily due to the absorption of Dentipatche into the systemic circulation.

Ventricular fibrillation occurs less frequently than that seen with bupivacaine.

Respiratory, thoracic or mediastinal disorders

Dyspnoea, bronchospasm and respiratory depression

Gastrointestinal

Nausea, vomiting.

Skin and subcutaneous tissue disorders

Rash, urticaria, oedema (including angioedema, face oedema)

Prolonged neural blockade following epidural may be due to delayed spread. Permanent neural blockade may be more likely associated with hypotension and cord ischaemia.

Following regional blockade as when Dentipatche is injected intrathecally or extradurally, hypotension, hypoventilation, Horners Syndrome and hypoglycaemia may be seen. The degree of these effects will depend on the dose and the height of the block. Urinary retention may occur following sacral or lumbar epidural block. It should not outlast the duration of the block. Apnoea and coma followed by aphasia and hemiparesis may occur following stellate ganglion block. The probable cause is a direct injection of Dentipatche into the vertebral or carotid arteries.

Profound lethargy and death have been reported following the injection of only 10 - 32 mg of Dentipatche for dental blocks.

The initial CNS toxic effects are demonstrated by a gradual onset of drowsiness or inebriation similar to alcoholic intoxication. Balance is disturbed, dizziness or light-headedness, nervousness, circumoral pins and needles (circumoral paraesthesia), tongue numbness, tinnitus, hyperacusis, visual disturbances, restlessness and twitching may occur. Severe intoxication of rapid onset may immediately lead to convulsions followed by circulatory depression. Major overdosage may depress all systems simultaneously.

During or immediately after treatment with Dentipatch (lidocaine patch 5%), the skin at the site of application may develop blisters, bruising, burning sensation, depigmentation, dermatitis, discoloration, edema, erythema, exfoliation, irritation, papules, petechia, pruritus, vesicles, or may be the locus of abnormal sensation. These reactions are generally mild and transient, resolving spontaneously within a few minutes to hours.

Allergic and anaphylactoid reactions associated with lidocaine, although rare, can occur. They are characterized by angioedema, bronchospasm, dermatitis, dyspnea, hypersensitivity, laryngospasm, pruritus, shock, and urticaria. If they occur, they should be managed by conventional means. The detection of sensitivity by skin testing is of doubtful value.

Due to the nature and limitation of spontaneous reports in postmarketing surveillance, causality has not been established for additional reported adverse events including:

Asthenia, confusion, disorientation, dizziness, headache, hyperesthesia, hypoesthesia, lightheadedness, metallic taste, nausea, nervousness, pain exacerbated, paresthesia, somnolence, taste alteration, vomiting, visual disturbances such as blurred vision, flushing, tinnitus, and tremor.

Systemic adverse reactions following appropriate use of Dentipatch are unlikely, due to the small dose absorbed (see CLINICAL PHARMACOLOGY, Pharmacokinetics). Systemic adverse effects of lidocaine are similar in nature to those observed with other amide local anesthetic agents, including CNS excitation and/or depression (light-headedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, vomiting, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, respiratory depression and arrest). Excitatory CNS reactions may be brief or not occur at all, in which case the first manifestation may be drowsiness merging into unconsciousness. Cardiovascular manifestations may include bradycardia, hypotension and cardiovascular collapse leading to arrest.

Preclinical safety data

No further relevant information other than that which is included in other sections of the Summary of Product Characteristics.

Therapeutic indications

Dentipatche is a local anaesthetic of the amide group. Dentipatche solution for injection is indicated for use in infiltration anaesthesia, intravenous regional anaesthesia and nerve blocks.

Dentipatch is indicated for relief of pain associated with post-herpetic neuralgia. It should be applied only to intact skin.

Pharmacodynamic properties

ATC Code:N01BB02

Dentipatche is a local anaesthetic of the amide type. It is used to provide local anaesthesia by nerve blockade at various sites in the body and in the control of dysrhythmias. 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, Dentipatche has important effects on the central nervous system and cardiovascular system. After absorption, Dentipatche 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. It has a rapid onset of action (about one minute following intravenous injection and fifteen minutes following intramuscular injection) and rapidly spreads through the surrounding tissues. The effect lasts about ten to twenty minutes and about sixty to ninety minutes following intravenous and intramuscular injection respectively.

Lidocaine is an amide-type local anesthetic agent and is suggested to stabilize neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of impulses.

The penetration of lidocaine into intact skin after application of Dentipatch is sufficient to produce an analgesic effect, but less than the amount necessary to produce a complete sensory block.

Pharmacokinetic properties

The concentration of Dentipatche in the blood will be determined by its rate of absorption from the site of injection, the rate of tissue distribution and the rate of metabolism and excretion.

The systemic absorption of Dentipatche is determined by the site of injection, the dosage and its pharmacological profile. The maximum blood concentration occurs following intercostal nerve blockade followed in order of decreasing concentration, the lumbar epidural space, brachial plexus site and subcutaneous tissue. The total dose injected regardless of the site is the primary determinant of the absorption rate and blood levels achieved. There is a linear relationship between the amount of Dentipatche injected and the resultant peak anaesthetic blood levels.

The lipid solubility and vasodilator activity will also influence its rate of absorption. This is seen in the epidural space where Dentipatche is absorbed more rapidly than prilocaine.

Dentipatche is distributed throughout the total body water. Its rate of disappearance from the blood can be described by a two or three compartment model. There is a rapid disappearance (alpha) phase which is believed to be related to uptake by rapidly equilibrating tissues (i.e. tissues with a high vascular perfusion). The slower phase is related to distribution, to slowly equilibrating tissues (Betaphase) and to its metabolism and excretion (Gamma phase).

Dentipatche is distributed less rapidly than prilocaine (an amide drug of similar potency and duration of action) but equally as with mepivacaine. Its distribution is throughout all body tissues. In general, the more highly perfused organs will show higher concentrations of Dentipatche. The highest percentage of this drug will be found in skeletal muscle. This is because of the mass of muscle rather than an affinity.

Dentipatche undergoes enzymatic degradation primarily in the liver. Some degradation may take in tissues other than liver. The main pathway involves oxidative de-ethylation to monoethylglycinexylidide followed by a subsequent hydrolysis to xylidine.

The excretion occurs via the kidney with less than 5% in the unchanged form appearing in the urine. The renal clearance is inversely related to its protein binding affinity and the pH of the urine. This suggests by the latter that excretion of Dentipatche occurs by non-ionic diffusion..

Dentipatch should be used with caution in patients receiving Class I antiarrhythmic drugs (such as tocainide and mexiletine) since the toxic effects are additive and potentially synergistic.

When Dentipatch is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all formulations must be considered.

Even a used Dentipatch patch contains a large amount of lidocaine (at least 665 mg). The potential exists for a small child or a pet to suffer serious adverse effects from chewing or ingesting a new or used Dentipatch patch, although the risk with this formulation has not been evaluated. It is important for patients to store and dispose of Dentipatch out of the reach of children, pets and others. (See Handling And Disposal)

Excessive dosing by applying Dentipatch to larger areas or for longer than the recommended wearing time could result in increased absorption of lidocaine and high blood concentrations, leading to serious adverse effects (see ADVERSE REACTIONS, Systemic Reactions). Lidocaine toxicity could be expected at lidocaine blood concentrations above 5 μg/mL. The blood concentration of lidocaine is determined by the rate of systemic absorption and elimination. Longer duration of application, application of more than the recommended number of patches, smaller patients, or impaired elimination may all contribute to increasing the blood concentration of lidocaine. With recommended dosing of Dentipatch, the average peak blood concentration is about 0.13 μg/mL, but concentrations higher than 0.25 μg/mL have been observed in some individuals.

Patients with severe hepatic disease are at greater risk of developing toxic blood concentrations of lidocaine, because of their inability to metabolize lidocaine normally.

Patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross sensitivity to lidocaine. However, Dentipatch should be used with caution in patients with a history of drug sensitivities, especially if the etiologic agent is uncertain.

Application to broken or inflamed skin, although not tested, may result in higher blood concentrations of lidocaine from increased absorption. Dentipatch is only recommended for use on intact skin.

Placement of external heat sources, such as heating pads or electric blankets, over Dentipatch patches is not recommended as this has not been evaluated and may increase plasma lidocaine levels.

The contact of Dentipatch with eyes, although not studied, should be avoided based on the findings of severe eye irritation with the use of similar products in animals. If eye contact occurs, immediately wash out the eye with water or saline and protect the eye until sensation returns.

A minor metabolite, 2, 6-xylidine, has been found to be carcinogenic in rats. The blood concentration of this metabolite is negligible following application of Dentipatch.

Lidocaine HC1 is not mutagenic in Salmonella/mammalian microsome test nor clastogenic in chromosome aberration assay with human lymphocytes and mouse micronucleus test.

The effect of Dentipatch on fertility has not been studied.

Pregnancy Category B

Dentipatch (lidocaine patch 5%) has not been studied in pregnancy. Reproduction studies with lidocaine have been performed in rats at doses up to 30 mg/kg subcutaneously and have revealed no evidence of harm to the fetus due to lidocaine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Dentipatch should be used during pregnancy only if clearly needed.

Dentipatch has not been studied in labor and delivery. Lidocaine is not contraindicated in labor and delivery. Should Dentipatch be used concomitantly with other products containing lidocaine, total doses contributed by all formulations must be considered.

Dentipatch has not been studied in nursing mothers. Lidocaine is excreted in human milk, and the milk: plasma ratio of lidocaine is 0.4. Caution should be exercised when Dentipatch is administered to a nursing woman.

Safety and effectiveness in pediatric patients have not been established.

Lidocaine overdose from cutaneous absorption is rare, but could occur. If there is any suspicion of lidocaine overdose (see ADVERSE REACTIONS, Systemic Reactions), drug blood concentration should be checked. The management of overdose includes close monitoring, supportive care, and symptomatic treatment. Dialysis is of negligible value in the treatment of acute overdose with lidocaine.

In the absence of massive topical overdose or oral ingestion, evaluation of symptoms of toxicity should include consideration of other etiologies for the clinical effects, or overdosage from other sources of lidocaine or other local anesthetics.

The oral LD50 of lidocaine HCl is 459 (346-773) mg/kg (as the salt) in non-fasted female rats and 214 (159-324) mg/kg (as the salt) in fasted female rats, which are equivalent to roughly 4000 mg and 2000 mg, respectively, in a 60 to 70 kg man based on the equivalent surface area dosage conversion factors between species.

Dentipatch is contraindicated in patients with a known history of sensitivity to local anesthetics of the amide type, or to any other component of the product.

Lidocaine is an amide-type local anesthetic agent and is suggested to stabilize neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of impulses.

The penetration of lidocaine into intact skin after application of Dentipatch is sufficient to produce an analgesic effect, but less than the amount necessary to produce a complete sensory block.

The amount of lidocaine systemically absorbed from Dentipatch is directly related to both the duration of application and the surface area over which it is applied. In a pharmacokinetic study, three Dentipatch patches were applied over an area of 420 cm² of intact skin on the back of normal volunteers for 12 hours. Blood samples were withdrawn for determination of lidocaine concentration during the application and for 12 hours after removal of patches. The results are summarized in Table 1.

Table 1 : Absorption of lidocaine from Dentipatch Normal volunteers (n= 15, 12-hour wearing time)

When Dentipatch is used according to the recommended dosing instructions, only 3 ± 2% of the dose applied is expected to be absorbed. At least 95% (665 mg) of lidocaine will remain in a used patch. Mean peak blood concentration of lidocaine is about 0.13 μg/mL (about 1/10 of the therapeutic concentration required to treat cardiac arrhythmias). Repeated application of three patches simultaneously for 12 hours (recommended maximum daily dose), once per day for three days, indicated that the lidocaine concentration does not increase with daily use. The mean plasma pharmacokinetic profile for the 15 healthy volunteers is shown in Figure 1.

Figure 1 : Mean lidocaine blood concentrations after three consecutive daily applications of three Dentipatch patches simultaneously for 12 hours per day in healthy volunteers (n = 15).

When lidocaine is administered intravenously to healthy volunteers, the volume of distribution is 0.7 to 2.7 L/kg (mean 1.5 ± 0.6 SD, n=15). At concentrations produced by application of Dentipatch, lidocaine is approximately 70% bound to plasma proteins, primarily alpha-1-acid glycoprotein. At much higher plasma concentrations (1 to 4 μg/mL of free base), the plasma protein binding of lidocaine is concentration dependent. Lidocaine crosses the placental and blood brain barriers, presumably by passive diffusion.

It is not known if lidocaine is metabolized in the skin. Lidocaine is metabolized rapidly by the liver to a number of metabolites, including monoethylglycinexylidide (MEGX) and glycinexylidide (GX), both of which have pharmacologic activity similar to, but less potent than that of lidocaine. A minor metabolite, 2, 6-xylidine, has unknown pharmacologic activity but is carcinogenic in rats. The blood concentration of this metabolite is negligible following application of Dentipatch (lidocaine patch 5%). Following intravenous administration, MEGX and GX concentrations in serum range from 11 to 36% and from 5 to 11% of lidocaine concentrations, respectively.

Lidocaine and its metabolites are excreted by the kidneys. Less than 10% of lidocaine is excreted unchanged. The half-life of lidocaine elimination from the plasma following IV administration is 81 to 149 minutes (mean 107 ± 22 SD, n = 15). The systemic clearance is 0.33 to 0.90 L/min (mean 0.64 ± 0.18 SD, n = 15).

Single-dose treatment with Dentipatch was compared to treatment with vehicle patch (without lidocaine), and to no treatment (observation only) in a double-blind, crossover clinical trial with 35 post-herpetic neuralgia patients. Pain intensity and pain relief scores were evaluated periodically for 12 hours. Dentipatch performed statistically better than vehicle patch in terms of pain intensity from 4 to 12 hours.

Multiple-dose, two-week treatment with Dentipatch was compared to vehicle patch (without lidocaine) in a double-blind, crossover clinical trial of withdrawal-type design conducted in 32 patients, who were considered as responders to the open-label use of Dentipatch prior to the study. The constant type of pain was evaluated but not the pain induced by sensory stimuli (dysesthesia). Statistically significant differences favoring Dentipatch were observed in terms of time to exit from the trial (14 versus 3.8 days at p-value < 0.001), daily average pain relief, and patient's preference of treatment. About half of the patients also took oral medication commonly used in the treatment of post-herpetic neuralgia. The extent of use of concomitant medication was similar in the two treatment groups.

Name of the medicinal product

Qualitative and quantitative composition

Special warnings and precautions for use

Dentipatche should be administered by persons with resuscitative skills and equipment.

Facilities for resuscitation should be available when administering local anaesthetics.

As with other local anaesthetics, Dentipatche should be used with caution in patients with epilepsy, myasthenia gravis, impaired cardiac conduction, congestive cardiac failure, bradycardia or impaired respiratory function, including where agents are known to interact with Dentipatche either to increase its availability or additive effects e.g. phenytoin or prolong its elimination e.g. hepatic or end renal insufficiency where the metabolites of Dentipatche may accumulate, or if the dose or site of administration is likely to produce high blood levels. Dentipatche is metabolised in the liver and it should be used with caution in patients with impaired hepatic function.

The effect of local anaesthetics may be reduced if the injection is made into an inflamed or infected area.

Intramuscular Dentipatche may increase creatinine phosphokinase concentrations which can interfere with the diagnosis of acute myocardial infarction. Dentipatche has been shown to be porphyrinogenic in animals and should be avoided in persons suffering from porphyria.

Hypokalaemia, hypoxia and disorder of acid-base balance should be corrected before treatment with intravenous Dentipatche begins.

Certain local anaesthetic procedures may be associated with serious adverse reactions, regardless of the local anaesthetic drug used, e.g.:

- Central nerve blocks may cause cardiovascular depression, especially in the presence of hypovolaemia, and therefore epidural anaesthesia should be used with caution in patients with impaired cardiovascular function.

- Retrobulbar injections may rarely reach the cranial subarachnoid space, causing serious / severe reactions, including cardiovascular collapse, apnoea, convulsions and temporary blindness.

- Retro- and peribulbar injections of local anaesthetics carry a low risk of persistent ocular muscle dysfunction. The primary causes include trauma and/or local toxic effects on muscles and/or nerves.

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.

- Injections in the head and neck regions may be made inadvertently into an artery, causing cerebral symptoms even at low doses.

- Paracervical block can sometimes cause foetal bradycardia/tachycardia, and careful monitoring of the foetal heart rate is necessary.

Epidural anaesthesia may lead to hypotension and bradycardia. This risk can be reduced by preloading the circulation with crystalloidal or colloidal solutions. Hypotension should be treated promptly

Dentipatche Injection is not recommended for use in neonates. The optimum serum concentration of Dentipatche required to avoid toxicity, such as convulsions and cardiac arrhythmias, in this age group is not known.

Each 5 ml of Dentipatche 1% w/v solution for injection contains approximately 13.57 mg (0.59 mmol) sodium.

Each 10 ml of Dentipatche 1% w/v solution for injection contains approximately 27.14 mg (1.18 mmol) sodium.

Even a used Dentipatch patch contains a large amount of lidocaine (at least 665 mg). The potential exists for a small child or a pet to suffer serious adverse effects from chewing or ingesting a new or used Dentipatch patch, although the risk with this formulation has not been evaluated. It is important for patients to store and dispose of Dentipatch out of the reach of children, pets and others. (See Handling And Disposal)

Excessive dosing by applying Dentipatch to larger areas or for longer than the recommended wearing time could result in increased absorption of lidocaine and high blood concentrations, leading to serious adverse effects (see ADVERSE REACTIONS, Systemic Reactions). Lidocaine toxicity could be expected at lidocaine blood concentrations above 5 μg/mL. The blood concentration of lidocaine is determined by the rate of systemic absorption and elimination. Longer duration of application, application of more than the recommended number of patches, smaller patients, or impaired elimination may all contribute to increasing the blood concentration of lidocaine. With recommended dosing of Dentipatch, the average peak blood concentration is about 0.13 μg/mL, but concentrations higher than 0.25 μg/mL have been observed in some individuals.

Patients with severe hepatic disease are at greater risk of developing toxic blood concentrations of lidocaine, because of their inability to metabolize lidocaine normally.

Patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross sensitivity to lidocaine. However, Dentipatch should be used with caution in patients with a history of drug sensitivities, especially if the etiologic agent is uncertain.

Application to broken or inflamed skin, although not tested, may result in higher blood concentrations of lidocaine from increased absorption. Dentipatch is only recommended for use on intact skin.

Placement of external heat sources, such as heating pads or electric blankets, over Dentipatch patches is not recommended as this has not been evaluated and may increase plasma lidocaine levels.

The contact of Dentipatch with eyes, although not studied, should be avoided based on the findings of severe eye irritation with the use of similar products in animals. If eye contact occurs, immediately wash out the eye with water or saline and protect the eye until sensation returns.

A minor metabolite, 2, 6-xylidine, has been found to be carcinogenic in rats. The blood concentration of this metabolite is negligible following application of Dentipatch.

Lidocaine HC1 is not mutagenic in Salmonella/mammalian microsome test nor clastogenic in chromosome aberration assay with human lymphocytes and mouse micronucleus test.

The effect of Dentipatch on fertility has not been studied.

Pregnancy Category B

Dentipatch (lidocaine patch 5%) has not been studied in pregnancy. Reproduction studies with lidocaine have been performed in rats at doses up to 30 mg/kg subcutaneously and have revealed no evidence of harm to the fetus due to lidocaine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Dentipatch should be used during pregnancy only if clearly needed.

Dentipatch has not been studied in labor and delivery. Lidocaine is not contraindicated in labor and delivery. Should Dentipatch be used concomitantly with other products containing lidocaine, total doses contributed by all formulations must be considered.

Dentipatch has not been studied in nursing mothers. Lidocaine is excreted in human milk, and the milk: plasma ratio of lidocaine is 0.4. Caution should be exercised when Dentipatch is administered to a nursing woman.

Safety and effectiveness in pediatric patients have not been established.

Effects on ability to drive and use machines

Where 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. Where major motor nerve block occurs e.g. Brachial plexus, epidural, spinal block. Where there is a loss of sensation resulting from nerve block to areas of muscle co-ordination or balance. Advice is that for general anaesthesia as sedative/hypnotic drugs are often used during nerve blockade.

Dosage (Posology) and method of administration

The method of administration of Dentipatche varies according to the procedure (infiltration anaesthesia, intravenous regional anaesthesia or nerve block).

The dosage should be adjusted according to the response of the patient and the site of administration. The lowest concentration and smallest dose producing the required effect should be given. The maximum dose for healthy adults should not exceed 200 mg.

Children and elderly or debilitated patients require smaller doses, commensurate with age and physical status.

Apply Dentipatch to intact skin to cover the most painful area. Apply the prescribed number of patches (maximum of 3), only once for up to 12 hours within a 24 hour period. Patches may be cut into smaller sizes with scissors prior to removal of the release liner. (See Handling And Disposal) Clothing may be worn over the area of application. Smaller areas of treatment are recommended in a debilitated patient, or a patient with impaired elimination.

If irritation or a burning sensation occurs during application, remove the patch (es) and do not reapply until the irritation subsides.

When Dentipatch is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all formulations must be considered.

Dentipatch may not stick if it gets wet. Avoid contact with water, such as bathing, swimming or showering.

Hands should be washed after the handling of Dentipatch, and eye contact with Dentipatch should be avoided. Do not store patch outside the sealed envelope. Apply immediately after removal from the protective envelope. Fold used patches so that the adhesive side sticks to itself and safely discard used patches or pieces of cut patches where children and pets cannot get to them. Dentipatch should be kept out of the reach of children.

Special precautions for disposal and other handling

For single use only.

Use immediately after opening.

If only part of an ampoule is used, discard the remaining solution.

The injection should not be used if particles are present.