Axcel Lignocaine-P

White to off white coloured, water miscible cream.

Pharmacology: Pharmacodynamics: Mechanism of Action: Axcel Lignocaine-P Cream provides dermal anaesthesia through the release of lidocaine and prilocaine from the cream into the epidermal and dermal layers of the skin and the accumulation of lidocaine and prilocaine in the vicinity of dermal pain receptors and nerve endings. Lidocaine and prilocaine are amide-type local anaesthetic agents. They both stabilize neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby producing local anaesthesia. The quality of anaesthesia depends upon the application time and the dose.
Axcel Lignocaine-P Cream is applied to intact skin under an occlusive dressing. The time needed to achieve reliable anaesthesia of intact skin is 1-2 hours, depending on the type of procedure. In clinical studies of Axcel Lignocaine-P Cream on intact skin, no differences in safety or efficacy (including anaesthetic onset time) were observed between geriatric patients (aged 65-96 years) and younger patients. The duration of anaesthesia following the application of Axcel Lignocaine-P Cream for 1-2 hours is at least 2 hours after removal of the dressing. The depth of cutaneous anaesthesia increases with application time. In 90% of patients the anaesthesia is sufficient for the insertion of a biopsy punch (4mm diameter) to a depth of 2mm after 60min and 3mm after 120min Axcel Lignocaine-P Cream treatment. Axcel Lignocaine-P Cream is equally effective and has the same anaesthetic onset time across the range of light to dark pigmented skin (skin types I to VI).
The use of Axcel Lignocaine-P Cream prior to measles-mumps-rubella or intramuscular diphtheria pertussis-tetanus-inactivated poliovirus-Haemophilus influenzae b or Hepatitis B vaccines does not affect mean antibody titres, rate of seroconversion, or the proportion of patients achieving protective or positive antibody titres post immunization, as compared to placebo treated patients. Absorption from the genital mucosa is more rapid and onset time is shorter than after application to the skin. After a 5-10 min application of Axcel Lignocaine-P Cream to female genital mucosa the average duration of effective analgesia to an argon laser stimulus which produced a sharp, pricking pain was 15-20 min (individual variations in the range 5-45 min). Reliable anaesthesia for the cleansing of leg ulcers is achieved after an application time of 30 minutes in most patients. An application time of 60 minutes may improve the anaesthesia further. The cleansing procedure should start within 10 minutes of removal of the cream. Clinical data from a longer waiting period are not available. Axcel Lignocaine-P Cream reduces the postoperative pain for up to 4 hours after debridement. Axcel Lignocaine-P Cream reduces the number of cleansing sessions required to achieve a clean ulcer compared to debridement with placebo cream. No negative effects on ulcer healing or bacterial flora have been observed.
Axcel Lignocaine-P Cream produces a biphasic vascular response involving initial vasoconstriction followed by vasodilatation at the application site (see Side Effects). Irrespective of the vascular response, Axcel Lignocaine-P Cream facilitates the needle procedure compared to placebo cream. In patients with atopic dermatitis, a similar but shorter vascular reaction is seen, with erythema occurring after 30-60 minutes, indicating more rapid absorption through the skin (see Precautions).
Pharmacokinetics: The systemic absorption of lidocaine and prilocaine from Axcel Lignocaine-P Cream is dependent upon the dose, area of application and application time. Additional factors include thickness of the skin (which varies in different areas of the body), other conditions such as skin diseases, and shaving. Following application to leg ulcers, the characteristics of the ulcers may also affect the absorption.
Intact skin: Following application to the thigh in adults (60g cream/400cm² for 3 hours), the extent of absorption was approx 5% of lidocaine and prilocaine. Maximum plasma concentrations (mean 0.12 and 0.07μg/ml) were reached approx 2-6 hours after application. The extent of systemic absorption was approx 10% following application to the face (10g/100cm² for 2 hours). Maximum plasma levels (mean 0.16 and 0.06μg/ml) were reached after approx 1.5-3 hours. Plasma levels of lidocaine and prilocaine in both geriatric and non-geriatric patients following application of Axcel Lignocaine-P Cream to intact skin are very low and well below potentially toxic levels.
Children: Following the application of 1.0g Axcel Lignocaine-P Cream in neonates below 3 months of age, to approx 10cm² for one hour, the maximum plasma concentrations of lidocaine and prilocaine were 0.135μg/ml and 0.107μg/ml respectively. Following the application of 2.0g Axcel Lignocaine-P Cream in infants between 3 and 12 months of age, to approx 16cm² for four hours, the maximum plasma concentrations of lidocaine and prilocaine were 0.155μg/ml and 0.131μg/ml respectively. Following the application of 10.0g of Axcel Lignocaine-P Cream in children between 2 and 3 years of age, to approx 100cm² for two hours, the maximum plasma concentrations of lidocaine and prilocaine were 0.315μg/ml and 0.215μg/ml respectively. Following the application of 10.0-16.0g Axcel Lignocaine-P Cream in children between 6 and 8 years of age, to approx 100-160cm² for two hours, the maximum plasma concentrations of lidocaine and prilocaine were 0.299μ g/ml and 0.110μg/ml respectively.
Genital mucosa: After the application of 10g Axcel Lignocaine-P Cream for 10 minutes to vaginal mucosa, maximum plasma concentrations of lidocaine and prilocaine (mean 0.18μg/ml and 0.15μg/ml respectively) were reached after 20-45 minutes.
Leg ulcer: Following a single application of 5 to 10g of Axcel Lignocaine-P Cream to leg ulcers with an area of up to 64cm² for 30 minutes, the maximum plasma levels of lidocaine (range 0.05-0.25μg/ml, one individual value of 0.84μg/ml) and of prilocaine (0.02-0.08μg/ml) were reached within 1-2.5 hours. After an application time of 24 hours to leg ulcers with an area of up to 50-100cm², the maximum plasma levels of lidocaine (0.19-0.71μg/ml) and of prilocaine (0.06-0.28μg/ml) were usually reached within 2-4 hours. Following repeated application of 2-10g Axcel Lignocaine-P Cream to leg ulcers with an area of up to 62 cm² for 30-60 minutes 3-7 times a week for up to 15 doses during a period of one month, there was no apparent accumulation in plasma of lidocaine and its metabolites monoglycinexylidide and 2,6-xylidine or of prilocaine and its metabolite ortho-toluidine. The maximum observed plasma levels for lidocaine, monoglycinexylidide and 2,6-xylidine were 0.41, 0.03 and 0.01μg/ml respectively. The maximum observed plasma levels for prilocaine and ortho-toluidine were 0.08 μg/ml and 0.01μg/ml respectively.

Surface anaesthesia of the skin in connection with needle insertion and for superficial surgical procedures.
Surface anaesthesia of leg ulcers prior to cleaning and superficial surgical procedures, e.g. removal of fibrin, pus and necroses.
Surface anaesthesia of the genital mucosa.

For external use only.
Adults: Intact skin: (See Table 1.)

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Leg ulcers: For cleaning of leg ulcers: approx. 1-2g per 10cm². The cream is applied in a thick layer to the surface of the ulcer, but not more than 10g per treatment occasion. Cover the ulcer surface with an occlusive dressing. An opened tube is intended for single use, and leftover cream should therefore be discarded after each treatment occasion. Application time: at least 30 minutes. For leg ulcers with tissue that is especially difficult to penetrate, the application time may be extended to 60 minutes. Cleaning of the ulcer should begin within 10 minutes after removal of the cream. Axcel Lignocaine-P Cream has been used on up to 15 treatment occasions during a 1-2 month period without a reduction in effect or increase in the number of local reactions.
Genital use: Skin: Use before injection of local anaesthetics: Men: 1g per 10cm². A thick layer of cream is applied to the skin. Application time: 15 minutes.
Women: 1-2g per 10cm². A thick layer of cream is applied to the skin. Application time: 60 minutes.
Mucosa: For removal of condylomata or before injection of local anaesthetics: approx. 5-10g, depending on the area treated. The whole surface including mucous membrane folds must be covered. Occlusion is not necessary. Application time: 5-10 minutes. The surgery may be begun immediately after removal of the cream.
Children: For needle insertion, removal of mollusca and other minor superficial surgical procedures: 1g per 10cm². A thick layer of cream is applied to the skin and covered with an occlusive dressing. The dose should not exceed 1 gram per 10cm² and should be adjusted according to the application area. (See Table 2.)

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Children with atopic dermatitis: reduced application time to 30 minutes.

Rare cases of clinically significant methaemoglobinaemia have been reported. Prilocaine in high doses may cause an increase in the methaemoglobin level particularly in conjunction with methaemoglobin-inducing agents (e.g., sulphonamides). Clinically significant methaemoglobinaemia should be treated with a slow intravenous injection of methylene blue. Should other symptoms of systemic toxicity occur, the signs are anticipated to be similar in nature to those following the administration of local anaesthetics by other routes. Local anaesthetic toxicity is manifested by symptoms of nervous system excitation and, in severe cases, central nervous and cardiovascular depression. Severe neurological symptoms (convulsions, CNS depression) must be treated symptomatically by respiratory support and the administration of anticonvulsive drugs.

Known hypersensitivity to local anaesthetics of the amide type or to any of the excipients.

Patients with glucose-6-phosphate dehydrogenase deficiency or congenital or idiopathic methaemoglobinaemia are more susceptible to drug-induced methaemoglobinaemia. Due to insufficient data on absorption, Axcel Lignocaine-P Cream should not be applied to open wounds other than leg ulcers. Studies have been unable to demonstrate the efficacy of Axcel Lignocaine-P Cream for heel lancing in neonates. Care should be taken when applying Axcel Lignocaine-P Cream to patients with atopic dermatitis. A shorter application time, 15-30 minutes, may be sufficient (see Pharmacology: Pharmacodynamics: Mechanism of Action under Actions). Prior to curettage of mollusca in children with atopic dermatitis, an application time of 30 minutes is recommended. Axcel Lignocaine-P Cream should not be applied to the genital mucosa of children owing to insufficient data on absorption. However, when used in neonates for circumcision, a dose of 1.0g Axcel Lignocaine-P Cream on the prepuce has proven to be safe. Care should be taken not to allow Axcel Lignocaine-P Cream to come in contact with the eyes as it may cause eye irritation. Also the loss of protective reflexes may allow corneal irritation and potential abrasion. If eye contact occurs, immediately rinse the eye in water or sodium chloride solution and protect it until sensation returns. Axcel Lignocaine-P Cream should not be applied to an impaired tympanic membrane. Tests on laboratory animals have shown that Axcel Lignocaine-P Cream has an ototoxic effect when instilled into the middle ear. Animals with an intact tympanic membrane, however, show no abnormality when exposed to Axcel Lignocaine-P Cream in the external auditory canal. In children/neonates younger than 3 months a transient, clinically insignificant increase in methaemoglobin level is commonly observed up to 12 hours after an application of Axcel Lignocaine-P Cream. Patients treated with anti-arrhythmic drugs class III (e.g., amiodarone) should be under close surveillance and ECG monitoring considered, since cardiac effects may be additive. Lidocaine and prilocaine have bactericidal and antiviral properties in concentrations above 0.5-2%. For this reason, although one clinical study suggests that the immunization response is not affected when Axcel Lignocaine-P Cream is used prior to BCG vaccination, the results of intracutaneous injections of live vaccines should be monitored.
Until further clinical data are available, Axcel Lignocaine-P Cream should not be used in the following cases: in infants between 0 and 12 months of age receiving treatment with methemoglobin-inducing agents; in preterm infants with a gestational age less than 37 weeks.
Effects on ability to drive and use machines: Not applicable at the recommended dosage.
Use in Pregnancy & Lactation: Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.

Pregnancy: In both animals and humans, lidocaine and prilocaine cross the placental barrier and may be absorbed by the foetal tissues. It is reasonable to assume that lidocaine and prilocaine have been used in a large number of pregnant women and women of childbearing potential. No specific disturbances to the reproductive process have so far been reported, e.g., an increased incidence of malformations or other directly or indirectly harmful effects on the foetus. However, caution should be exercised when used in pregnant women.
Lactation: Lidocaine and, in all probability, prilocaine are excreted in breast milk, but in such small quantities that there is generally no risk of the child being affected at therapeutic dose levels.

Frequency of adverse events: Intact skin: (See Table 3.)

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Genital mucosa: (See Table 4.)

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Leg ulcer: (See Table 5.)

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Prilocaine in high doses may cause an increase in the methaemoglobin level particularly in conjunction with methaemoglobin-inducing agents (e.g., sulphonamides). With large doses of Axcel Lignocaine-P Cream, consideration should be given to the risk of additional systemic toxicity in patients receiving other local anaesthetics or agents structurally related to local anaesthetics, since the toxic effects are additive. Specific interaction studies with lidocaine/prilocaine and anti-arrhythmic drugs class III (e.g., amiodarone) have not been performed, but caution is advised (see Precautions).
Drugs that reduce the clearance of lidocaine (e.g., cimetidine or betablockers) may cause potentially toxic plasma concentrations when lidocaine is given in repeated high doses over a long time period. Such interactions should therefore be of no clinical importance following short term treatment with lidocaine (e.g., Axcel Lignocaine-P Cream) at recommended doses.

Keep container well closed. Do not store above 30°C. Do not freeze.

Anaesthetics - Local & General

N01BB52 - lidocaine, combinations ; Belongs to the class of amides. Used as local anesthetics.

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