Senso® is indicated for relief of pain associated with post-herpetic neuralgia.

Apply Senso® to intact skin to cover the most painful area. Apply up to three plasters, only once for up to 12 hours within a 24-hour period. Plasters may be cut into smaller sizes with scissors prior to removal of the release liner. 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.

1.1  Warnings:

Risk of Methemoglobinemia

Cases of methemoglobinemia have been reported in association with local anesthetic use. Although all patients are at risk for methemoglobinemia, patients

with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition. If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended.

Signs of methemoglobinemia may occur immediately or may be delayed some hours after exposure, and are characterized by a cyanotic skin discoloration and/or abnormal coloration of the blood. Methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. Discontinue Senso® and any other oxidizing agents. Depending on the severity of the signs and symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration. A more severe clinical presentation may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.

Accidental Exposure in Children

Even a used Senso® plaster 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 Senso® plaster, although the risk with this formulationhas not been evaluated. It is important for patients to store and dispose of Senso® out of the reach of children, pets and others.

Excessive Dosing

Excessive dosing by applying Senso® 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. Lidocaine toxicity could be expected at lidocaine blood concentrations above 5μg/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 plasters, smaller patients, or impaired elimination may all contribute to increasing the blood concentration of lidocaine. With recommended dosing of Senso®, the average peak blood concentration is about 0.13μg/mL, but concentrations higher than 0.25μg/mL have been observed in some individuals.

Precautions: General

Hepatic Disease:

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

Allergic Reactions:

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

Non-intact Skin:

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

External Heat Sources:

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

Eye Exposure:

The contact of Senso® 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.

Senso® 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.

Local Anesthetics:

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

1.1  Fertility:

The effect of Senso® on fertility has not been studied.

Pregnancy:

Category B. Senso® (Lidocaine 700 mg medicated plaster) 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, Senso® should be used during pregnancy only if clearly needed.

Lactation:

Senso® 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 Senso® is administered to a nursing woman.

The effect of Senso® on ability to drive and use machines has not been studied.

1.1.1  Adverse reactions:

Application Site Reactions

During or immediately after treatment with Senso®, 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 Reactions

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.

Other Adverse Events

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 (Dose-Related) Reactions

Systemic adverse reactions following appropriate use of Senso® are unlikely, due to the small dose absorbed. 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.

1.1.2  Clinical Studies Experience:

Single-dose treatment with Senso® was compared to treatment with vehicle plaster (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. Senso® performed statistically better than vehicle plaster in terms of pain intensity from 4 to 12 hours

.

Multiple-dose, two-week treatment with Senso® was compared to vehicle plaster (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 Senso® prior to the study. The constant type of pain was evaluated but not the pain induced by sensory stimuli (dysesthesia). Statistically significant differences favoring Senso® 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.

1.1.3  Post-marketing Experience:

The post-marketing experience of Senso® has not been shown.

Lidocaine overdose from cutaneous absorption is rare, but could occur. If there is any suspicion of lidocaine overdose, 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.

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 Senso® is

sufficient to produce an analgesic effect, but less than the amount necessary to produce a complete sensory block.

1.1  Absorption:

The amount of lidocaine systemically absorbed from Senso® is directly related to both the duration of application and the surface area over which it is applied. In a pharmacokinetic study, three Senso® plasters 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 plasters. The results are summarized in Table 1.

Table 1. Absorption of lidocaine from Senso®

Normal volunteers (n = 15, 12-hour wearing time)

                                                                              Dose                                                                             

When Senso® 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 plaster. 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 plasters 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 Senso® plasters simultaneously for 12 hours per day in healthy volunteers (n = 15)

Distribution:

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 Senso®, 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.

Metabolism:

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 Senso® (lidocaine plaster 5%). Following intravenous administration, MEGX and GX concentrations in serum range from 11 to 36% and from 5 to 11% of lidocaine concentrations, respectively.

Excretion:

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).

1.1  Carcinogenesis

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 Senso®.

Mutagenesis

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

Dihydroxyaluminum aminoacetate, Disodium edetate, Glycerin, Kaolin, Methylparaben, Polyacrylic acid, Polyvinyl alcohol, Propylene glycol, Propylparaben, Sodium carboxymethylcellulose, Sodium polyacrylate, Sodium polyacrylate starch, Sorbitol solution, Tartaric acid, and Urea.

Not applicable.

Store Senso® at below 30°C and protect from light. Keep Senso® out of the sight and reach of children.

Do not use Senso® after the expiry date which is stated on the sachet and carton after EXP. The expiry date refers to the last day of that month.

Do not refrigerate or freeze.

After first opening: Keep the sachet tightly closed to protect from light.

The Senso® are packed in sealable aluminium foil pouch, each containing 1 plaster. Each carton contains 5, 10, 20, 25 or 30 plasters, respectively.

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