To be sold by retail on the prescription of a RMP only

1. Generic name
Lidocaine & Prilocaine Gel
Lidocaine & prilocaine gel
2. Qualitative and quantitative composition
Composition:
Lidocaine IP.......................2.50 % w/w
Prilocaine IP......................2.50 % w/w
Sorbic Acid IP……………..0.08 % w/w
(As Preservative)
Gel base..................................q.s.
3. Dosage form and strength
Gel, for topical use.
4. Clinical particulars
4.1 Therapeutic indication
As a topical anaesthetic for use on normal intact skin for local anaesthesia.
4.2 Dosage And Administration
Adult Patients - Intact Skin
Lidocaine and Prilocaine gel
A thick layer of Lidocaine and Prilocaine gel is applied to intact skin and covered with an occlusive dressing:
Major Dermal Procedures: For more painful dermatological procedures involving a larger skin area such as split thickness skin graft harvesting, apply 2 grams of Lidocaine and
Prilocaine gel per 10 cm2 of skin and allow to remain in contact with the skin for at least 2 hours.
Adult Male Genital Skin: As pretreatment prior to local anesthetic inltration, apply a thick layer of Lidocaine and Prilocaine gel (1 g/10 cm2) to the skin surface for 15
minutes. Local anesthetic inltration should be performed immediately after removal of Lidocaine and Prilocaine gel.
Dermal analgesia can be expected to increase for up to 3 hours under occlusive dressing and persist for 1 to 2 hours after removal of the cream. The amount of lidocaine and
prilocaine absorbed during the period of application can be estimated from the information in Table 1, ** footnote, in Individualization of Dose.
Adult Female Patients - Genital Mucous Membranes
For minor procedures on the female external genitalia, such as removal of condylomata acuminata, as well as for use as pretreatment for local anesthetic inltration, apply a thick
layer (5 to 10 grams) of Lidocaine and Prilocaine gel for 5 to 10 minutes.
Occlusion is not necessary for absorption, but may be helpful to keep the cream in place. Patients should be lying down during the Lidocaine and Prilocaine gel application,
especially if no occlusion is used. The procedure or the local anesthetic inltration should be performed immediately after removal of Lidocaine and Prilocaine gel.
Pediatric Patients - Intact Skin
The following are the maximum recommended doses, application areas and application times for Lidocaine and Prilocaine gel based on a child's age and weight:

Age and Body Weight Maximum Total Maximum Maximum

Requirements Dose of EMLA Application Area Application Time
2
0 up to 3 months or < 5 kg 1g 10 cm 1 hour
3 up to 12 months and > 5 kg 2g 20 cm2 4 hour
3 up to 6years > 10 kg 10 g 100 cm
2
4 hour
7 to 12 years and > 20 kg 20 g 200 cm 2
4 hour
Please note: If a patient greater than 3 months old does not meet the minimum weight requirement, the maximum total dose of (lidocaine 2.5% and prilocaine 2.5%) should be
restricted to that which corresponds to the patient's weight.
Practitioners should carefully instruct caregivers to avoid application of excessive amounts of Lidocaine and Prilocaine gel when applying Lidocaine and Prilocaine gel to the skin
of young children, care must be taken to maintain careful observation of the child to prevent accidental ingestion of Lidocaine and Prilocaine gel, the occlusive dressing, or the
anesthetic disc. A secondary protective covering to prevent inadvertent disruption of the application site may be useful.
Lidocaine and Prilocaine gel should not be used in neonates with a gestational age less than 37 weeks nor in infants under the age of twelve months who are
receiving treatment with methemoglobin-inducing agents.
When (lidocaine 2.5% and prilocaine 2.5%) is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all formulations must
be considered (see Individualization of Dose). The amount absorbed in the case of (lidocaine 2.5% and prilocaine 2.5%) is determined by the area over which it is applied
and the duration of application under occlusion (see Table 2, ** footnote, in Individualization of Dose).
Although the incidence of systemic adverse reactions with (lidocaine 2.5% and prilocaine 2.5%) is very low, caution should be exercised, particularly when applying it over large
areas and leaving it on for longer than 2 hours. The incidence of systemic adverse reactions can be expected to be directly proportional to the area and time of exposure (see
Individualization of Dose).
Individualization of Dose: The dose of Lidocaine and Prilocaine gel which provides effective analgesia depends on the duration of the application over the treated area.
All pharmacokinetic and clinical studies on intact skin employed a thick layer of Lidocaine and Prilocaine gel (1-2 g/10 cm2).
The duration of application prior to venipuncture was 1 hour. The duration of application prior to taking split thickness skin grafts was 2 hours. Although a thinner application may be
efcacious, such has not been studied and may result in less complete analgesia or a shorter duration of adequate analgesia.
The systemic absorption of lidocaine and prilocaine is a side effect of the desired local effect. The amount of drug absorbed depends on surface area and duration of application.
The systemic blood levels depend on the amount absorbed and patient size (weight) and rate of systemic drug elimination. Long duration of application, large treatment area,
small patients, or impaired elimination may result in high blood levels. The systemic blood levels are typically a small fraction (1/20 to 1/36) of the blood levels which produce
toxicity. Table 2 which follows gives maximum recommended doses, application areas and application times for infants and children.
Table 1: EMLAP GEL MAXIMUM RECOMMENDED DOSE, APPLICATION AREA, AND APPLICATION TIME BY AGE AND WEIGHT*
For Infants and Children
Based on Application to Intact Skin
Age and Body Weight Maximum Total Maximum Maximum
Requirements Dose of EMLA Application Area** Application Time
0 up to 3 months or < 5 kg 1g 10 cm2 1 hour
3 up to 12 months and > 5 kg 2g 20 cm
2
4 hour
3 up to 6years > 10 kg 10 g 100 cm
2
4 hour
7 to 12 years and > 20 kg 20 g 200 cm2 4 hour
Please note: If a patient greater than 3 months old does not meet the minimum weight requirement, themaximum total dose of EMLAP GEL should be restricted to that which
corresponds to the patient's weight.
* These are broad guidelines for avoiding systemic toxicity in applying EMLAP GEL to patients with normal intact skin and with normal renal and hepatic function.
** For more individualized calculation of how much lidocaine and prilocaine may be absorbed, physicians can use the following estimates of lidocaine and prilocaine absorption for
children and adults:
The estimated mean(±SD) absorption of lidocaine is 0.045(±0.016) mg/cm2/hr.
The estimated mean(±SD) absorption of prilocaine is 0.077(±0.036) mg/cm2/hr.
An IV antiarrhythmic dose of lidocaine is 1 mg/kg (70 mg/70 kg) and gives a blood level of about 1 μg/mL.
Toxicity would be expected at blood levels above 5 μg/mL. Smaller areas of treatment are recommended in a debilitated patient, a small child or a patient with impaired elimination.
Decreasing the duration of application is likely to decrease the analgesic effect.
4.3 CONTRAINDICATIONS
Lidocaine and prilocaine gel is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type or to any other component of the product.
4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE
General
Allergy
Allergic and anaphylactic reactions associated with lidocaine or prilocaine can occur. These reactions may be characterized by urticaria, angioedema, bronchospasm, and shock.
If these reactions occur they should be managed according to standard clinical practice.
Methemoglobinemia
Prilocaine can cause elevated methemoglobin levels particularly in conjunction with methemoglobin inducing agents. Methemoglobinemia has also been associated with amino-
or nitro-derivatives of benzene e.g. aniline, dapsone and lidocaine although reports on the link between lidocaine treatment and methemoglobinemia are limited.
Methemoglobinemia is well documented in relation to prilocaine and lidocaine combination treatment and correlated with exposure to prilocaine and the plasma levels of its
metabolite o-toluidine.
Patients with glucose-6-phosphate dehydrogenase deciency or congenital or idiopathic methemoglobinemia are more susceptible to drug-induced methemoglobinemia.
Lidocaine and Prilocaine Gel) should not be used in those patients with congenital or idiopathic methemoglobinemia.
Patients taking drugs associated with drug-induced methemoglobinemia are also at greater risk for developing methemoglobinemia. Treatment with Lidocaine and Prilocaine Gel
should be avoided in patients with any of the above conditions or with a previous history of problems in connection with prilocaine treatment.
The development of methemoglobinemia is generally dose-related. Levels of methemoglobin observed after application of the Lidocaine and Prilocaine Gel in clinical trials did not
exceed normal values (i.e. <2% of the individual patient's total hemoglobin). The individual maximum level of methemoglobin in blood ranged from 0.8% to 1.7% following
administration of the maximum dose of 8.5 g Lidocaine and Prilocaine Gel.
Ear/Nose/Throat
Lidocaine and Prilocaine Gel should not be used in clinical situations where it can penetrate or migrate into the middle ear. Tests on laboratory animals (guinea pigs) have shown
that a cream formulation containing lidocaine and prilocaine has an ototoxic effect. When the same animals were exposed to the cream formulation in the external auditory canal,
no abnormalities were observed. Minor structural damage to the tympanic membrane in guinea pigs was observed when a lidocaine-prilocaine cream formulation was applied
directly to the membrane.
Care should be taken to avoid excess Lidocaine and Prilocaine from spreading to the oropharyngeal mucosa.
Patients treated with class III anti-arrhythmic drugs (e.g., amiodarone, bretylium, sotalol, dofetilide) should be under close surveillance and ECG monitoring considered, because
cardiac effects may be additive.
Precautions
Lidocaine and Prilocaine Gel must not be injected. It is for external use only.
Allergic and anaphylactic reactions associated with lidocaine or prilocaine can occur. These reactions may be characterized by urticaria, angioedema, bronchospasm, and shock.
If these reactions occur they should be managed by conventional means.
Repeated doses of Lidocaine and Prilocaine Gel may increase blood levels of lidocaine and prilocaine. Lidocaine and Prilocaine Gel should be used with caution in patients who
may be more sensitive to the systemic effects of lidocaine and prilocaine including acutely ill, debilitated, or elderly patients.
Lidocaine and Prilocaine Gel should not be applied to open wounds.
Lidocaine and Prilocaine Gel coming in contact with the eye should be avoided because animal studies have demonstrated severe eye irritation. A loss of protective reexes may
allow corneal irritation and potential abrasion. If eye contact occurs, immediately rinse the eye with water or saline and protect it until normal sensation returns. In addition, the
patient should be evaluated by an ophthalmologist, as indicated.
Patients allergic to paraaminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross sensitivity to lidocaine and/or prilocaine. However, Lidocaine
and Prilocaine Gel should be used with caution in patients with a history of drug sensitivities, especially if the etiologic agent is uncertain.
Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at greater risk of developing toxic plasma concentrations of lidocaine
and prilocaine.
Information for Patients
Patients should be cautioned to avoid injury to the treated area, or exposure to extreme hot or cold temperatures, until complete sensation has returned.
This medication should not be used for any other condition than that for which it is prescribed.
4.5 DRUG INTERACTIONS
Lidocaine and Prilocaine Gel should be used with caution in combination with dental injection anesthesia, other local anesthetics, or agents structurally related to local
anesthetics, e.g., Class 1 antiarrhythmics such as tocainide and mexiletine, as the toxic effects of these drugs are likely to be additive and potentially synergistic.
Patients taking drugs associated with drug-induced methemoglobinemia such as sulfonamides, acetaminophen, acetanilide, aniline dyes, benzocaine, chloroquine, dapsone,
naphthalene, nitrates and nitrites, nitrofurantoin, nitroglycerin, nitroprusside, pamaquine, para-aminosalicylic acid, phenacetin, phenobarbital, phenytoin, primaquine, and
quinine are also at greater risk for developing methemoglobinemia.
4.6 USE IN SPECIAL POPULATIONS (SUCH AS PREGNANT WOMEN, LACTATING WOMEN, PAEDIATRIC PATIENTS, GERIATRIC PATIENTS ETC.)
Pregnancy
There are no adequate and well-controlled studies to evaluate Lidocaine and Prilocaine Gel during pregnancy. Animal reproduction studies are not always predictive of human
response. Lidocaine and Prilocaine Gel should be used during pregnancy only if the benets outweigh the risks.
Lidocaine and prilocaine cross the placental barrier and may be absorbed by the fetal tissues. It is reasonable to assume that lidocaine and prilocaine have been used in a large
number of pregnant women and women of child-bearing age. No specic 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 fetus. However, care should be given during early pregnancy when maximum organogenesis takes place.
Nursing Mothers
Lidocaine and, possibly, prilocaine are excreted in breast milk. Caution should be exercised when Lidocaine and Prilocaine Gel is administered to nursing women.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Very young children are more susceptible to methemoglobinemia. There have been reports of clinically
signicant methemoglobinemia in infants and children following excessive applications of lidocaine 2.5% topical cream.
Geriatric Use
Of the total number of subjects in clinical studies of Lidocaine and Prilocaine Gel, 7% were aged 65 and over, while 1% were aged 75 and over. No overall differences in safety or
effectiveness were observed between these subjects and younger subjects. Other reported clinical experience has not identied differences in responses between elderly and
younger patients, but greater sensitivity of some older individuals cannot be ruled out.
In general, dose selection for and elderly patient should be cautious, usually starting at the low end of the dosing range, reecting the greater frequency of decreased hepatic,
renal, or cardiac function, and of concomitant disease or other drug therapy.
4.7 EFFECTS ON ABILITY TO DRIVE AND USE MACHINES
Not available.
4.8 UNDESIRABLE EFFECTS
Adverse Drug Reaction Overview
The clinical safety database included 559 subjects, 391 of whom were exposed to Lidocaine and Prilocaine Gel and 168 to placebo gel. In a crossover study, 170 patients exposed
to Lidocaine and Prilocaine Gel also received an injection of 2% lidocaine with epinephrine.
The most frequent adverse reactions in clinical trials were local reactions in the oral cavity. The frequency and type of reactions were similar for Lidocaine and Prilocaine Gel and
placebo-treatment patients. The treatment-emergent adverse events observed in three placebo controlled parallel studies (B1 – B3) are summarized in Table 1.
Table 2: Treatment-Emergent Adverse Events for Lidocaine and Prilocaine Gel in placebo controlled parallel studies (B1 – B3) (1% and more frequent than placebo)
Lidocaine and Prilocaine Gel Placebo
Adverse Event
n = 169 (case, %) n = 168 (case, %)
Application Site Reaction 25 (15) 20 (12)
Headache 4 (2) 3 (2)
Taste Perversion 4 (2) 1 (1)
Accident and/or Injury 2 (1) 2 (1)
Application Site Edema 2 (1) 1 (1)
Respiratory Infection 2 (1) 0 (0)

103320 20185660 Page 1 of 2

Dimensions: 120 x 400 mm

SGraphic
S ADesigners
RT S PANTONE CODES

Black

Version No: 00

Date: 16.02.2022

Change History:
New Artwork (01.02.2022)
Correction done (03-02-2022)
Correction done (04-02-2022)
Corrections done (09-02-2022)
Corrections done (16-02-2022)
Allergic Reactions
In rare cases, local anesthetics have been associated with allergic reactions and in the most severe instances; anaphylactic shock (see Warnings and Precautions, Sensitivity,
Allergy) Allergic reactions were not reported during clinical studies with Lidocaine and Prilocaine Gel. Very rare cases of anaphylactic or anaphylactoid reactions associated with
the use of Lidocaine and Prilocaine Gel have been reported.
Allergic and anaphylactoid reactions associated with lidocaine or prilocaine can occur. They are characterized by urticaria, angioedema, bronchospasm, and shock. If they occur
they should be managed by conventional means. The detection of sensitivity by skin testing is of doubtful value.
During postmarketing experience serious and life threatening systemic adverse events, including methemoglobinemia, central nervous system toxicity and cardiovascular
collapse, have occurred when Lidocaine and Prilocaine cream was applied to large areas of skin for topical analgesia during cosmetic procedures (e.g., laser depilation).
Significant: Allergic and anaphylactic reactions, eye irritation, numbness of oral mucosa (periodontal gel); erectile dysfunction and male genital hypoaesthesia.
Gastrointestinal disorders: Nausea, taste perversion, throat irritation.
General disorders and administration site conditions: Fatigue, u-like disorder, pyrexia, local alteration in temperature sensations; application site reactions such as pruritus,
erythema, burning or stinging sensation, warmth, pallor; rarely, purpuric or petechial lesions (cream/patch); local pain, oedema, numbness, soreness, irritation, ulceration,
abscess, vesicles (periodontal gel).
Musculoskeletal and connective tissue disorders: Myalgia, arthralgia.
Nervous system disorders: Headache, dizziness.
Reproductive system and breast disorders: Genital burning sensation; hypoaesthesia, vulvovaginal burning sensation in female partners (spray solution).
Respiratory, thoracic and mediastinal disorders: Respiratory tract infection, rhinitis.
Skin and subcutaneous tissue disorders: Urticaria. Rarely: hyperpigmentation.
Potentially Fatal: Methaemoglobinaemia.
4.9 OVERDOSE
Symptoms: CNS excitation or depression (e.g. visual disturbances, hyperacusis, muscular tremors, light-headedness, general convulsions), CV manifestations (e.g.
hypotension, bradycardia, arrhythmia, CV collapse); rarely, clinically signicant methaemoglobinaemia. Management: Symptomatic and supportive treatment. May administer
anticonvulsant agents and initiate respiratory support for severe neurological symptoms (e.g. convulsions, CNS depression); initiate CV resuscitation as necessary. Administer
slow IV injection of methylthioninium Cl to treat clinically signicant methaemoglobinaemia.
5. PHARMACOLOGICAL PROPERTIES
5.1 Mechanism of action
Lidocaine and prilocaine are amide-type local anaesthetic agents. Both produce local anaesthetic activity by stabilizing the neuronal membranes and blocking the sodium ion
channels necessary for the initiation and conduction of nerve impulses, resulting in local anesthesia.
5.2 Pharmacodynamic properties
The pharmacological mode of action of lidocaine and prilocaine is well established. Like other local anaesthetics, they act directly on nerve cells to block their ability to transmit
impulses down their axons. Lidocaine and prilocaine have similar anaesthetic potency. The molecular targets of both are the voltage-dependent sodium channels of neurons. The
drugs bind selectively to the intracellular surface of sodium channels and block the entry of sodium into the cell. The blocking of sodium inux prevents the depolarisation
necessary for action potential propagation and at sufcient concentrations block impulse conduction. Since binding of lidocaine and prilocaine to sodium channels is completely
reversible, when drug administration is stopped the drug diffuses away. Restoration of active sodium pumping and continued leakage of potassium restores the membrane
potential to its polarised state. The membrane potential remains deactivated and refractory to further stimulation for a short period. Eventually nerve function is completely
restored.
Lidocaine has a rapid onset of action and anaesthesia is obtained within a few minutes, with an intermediate duration of action. Prilocaine has a slower onset of action with slightly
longer duration of action. The combination of lidocaine and prilocaine in PSD502 provides a rapid onset of action. So, application of lidocaine and prilocaine in their base forms at a
pH of 8.0, optimises penetration, maximising the depth of neural blockade and minimising time to onset of numbness.
5.3 Clinical Studies
Lidocaine and Prilocaine Gel application in adults prior to IV cannulation or venipuncture was studied in 200 patients in four clinical studies in Europe. Application for at least 1 hour
provided signicantly more dermal analgesia than placebo cream or ethyl chloride. Lidocaine and Prilocaine Gel was comparable to subcutaneous lidocaine, but was less
efcacious than intradermal lidocaine. Most patients found Lidocaine and Prilocaine treatment preferable to lidocaine inltration or ethyl chloride spray.
Lidocaine and Prilocaine Gel was compared with 0.5% lidocaine inltration prior to skin graft harvesting in one open label study in 80 adult patients in England.Application of
Lidocaine and Prilocaine Gel for 2 to 5 hours provided dermal analgesia comparable to lidocaine inltration.
Lidocaine and Prilocaine Gel application in children was studied in seven non-US studies (320 patients) and one US study (100 patients). In controlled studies, application of
Lidocaine and Prilocaine Gel for at least 1 hour with or without presurgical medication prior to needle insertion provided signicantly more pain reduction than placebo. In children
under the age of seven years, Lidocaine and Prilocaine Gel was less effective than in older children or adults.
Lidocaine and Prilocaine was compared with placebo in the laser treatment of facial port-wine stains in 72 pediatric patients (ages 5-16). Lidocaine and Prilocaine was effective in
providing pain relief during laser treatment.
Lidocaine and Prilocaine alone was compared to Emlap Gel followed by lidocaine inltration and lidocaine inltration alone prior to cryotherapy for the removal of male genital
warts. The data from 121 patients demonstrated that Lidocaine and Prilocaine was not effective as a sole anesthetic agent in managing the pain from the surgical procedure.
The administration of Lidocaine and Prilocaine Cream prior to lidocaine inltration provided signicant relief of discomfort associated with local anesthetic inltration and thus was
effective in the overall reduction of pain from the procedure only when used in conjunction with local anesthetic inltration of lidocaine.
Lidocaine and Prilocaine was studied in 105 full term neonates (gestational age: 37 weeks) for blood drawing and circumcision procedures. When considering the use of
Lidocaine and Prilocaine in neonates, the primary concerns are the systemic absorption of the active ingredients and the subsequent formation of methemoglobin. In clinical
studies performed in neonates, the plasma levels of lidocaine, prilocaine, and methemoglobin were not reported in a range expected to cause clinical symptoms.
Local dermal effects associated with Lidocaine and Prilocaine application in these studies on intact skin included paleness, redness and edema and were transient in nature. The
application of Lidocaine and Prilocaine to genital mucous membranes for minor, supercial surgical procedures (e.g., removal of condylomata acuminata) was studied in 80
patients in a placebo-controlled clinical trial (60 patients received Lidocaine and Prilocaine and 20 patients received placebo). Lidocaine and Prilocaine (5 to 10 g) applied
between 1 and 75 minutes before surgery, with a median time of 15 minutes, provided effective local anesthesia of mucous membranes for minor supercial surgical procedures.
The application of Lidocaine and Prilocaine to genital mucous membranes as pretreatment for local anesthetic inltration was studied in a double blind, placebo-controlled study
in 44 female patients (21 patients received Lidocaine and Prilocaine and 23 patients received placebo) scheduled for inltration prior to a surgical procedure of the external vulva
or genital mucosa. Lidocaine and Prilocaine applied to the genital mucous membranes for 5 to 10 minutes resulted in adequate topical anesthesia for local anesthetic injection.
5.4 Pharmacokinetic properties
Absorption
Lidocaine and prilocaine are absorbed from Lidocaine and Prilocaine Gel via the oral mucous membranes. After a single application of 0.9–3.5 g Lidocaine and Prilocaine Gel, the
mean (±SD) lidocaine and prilocaine Cmax values were 182 (±53) and 77 (±27) ng/mL, respectively. After a total of 8 – 8.5 g Lidocaine and Prilocaine Gel administered as
repeated applications over 3 hours, the mean (±SD) lidocaine Cmax was 284 (±122) ng/mL, ranging between 157 and 552 ng/mL. The mean lidocaine AUC∞ was 84,000
ng.min/mL. The mean (±SD) prilocaine Cmax was 106 (±45) ng/mL, ranging between 53 and 181 ng/mL. The mean prilocaine AUC∞ was 26,000 ng.min/mL.
The toxicities of lidocaine and prilocaine are thought to be additive. Systemic CNS toxicity may occur over a range of plasma concentrations of local anesthetics. CNS toxicity may
typically be found around 5000 ng/mL of lidocaine; however a small number of patients reportedly may show signs of toxicity at approximately 1000 ng/mL. Pharmacological
thresholds for prilocaine are poorly dened.
The median Tmax of lidocaine and prilocaine was 30 minutes, ranging between 20 and 40 min., after the start of a single application of 0.9 to 3.5 g Lidocaine and Prilocaine Gel,
and 200 minutes, ranging between 120 and 200 min., after a cumulative dose of 8.5g Lidocaine and Prilocaine Gel administered as repeated applications over 3 hours.
Distribution
Lidocaine and prilocaine have an intermediate degree of plasma protein binding, mainly to 1-acid glycoprotein, with a protein binding of 70% and 40%, respectively. When
administered intravenously, the mean volume of distribution (for 60-kg person) at steady state for lidocaine and prilocaine were 90 L and 156 L, respectively. Lidocaine and
Prilocaine Gel is not intended for intravenous administration. Both lidocaine and prilocaine cross the placental and blood brain barriers, presumably by passive diffusion.
Metabolism
Lidocaine and prilocaine are mainly metabolized in the liver. Prilocaine and lidocaine are not metabolized by plasma esterases. The main metabolism of lidocaine is through N-
dealkylation to monoethylglycinexylidide (MEGX) and glycinexylidide (GX), which is mainly mediated by CYP3A4. These metabolites are hydrolyzed to 2,6GX), whic, which is
converted to 4-hydroxy-2,6-xylidine (mediated by CYP2A6), the major urinary metabolite in man. After a total of 8-8.5 g Lidocaine and Prilocaine Gel administered as repeated
applications over 3 hours, the mean (+SD) 2,6-xylidine Cmax was 18 (+8.4) ng/mL ranging between 8 and 32 ng/mL. The mean 2,6-xylidine AUCUClidine AUng.min/mL (n/mL
(UCUClidine AUCing between 8 and 32 ng/mL./mL. mean (+SD) 2,6-xylidine inaconvulsant activity similar to that of lidocaine and a somewhat longer half-life. GX has a weak
antiarrhythmic effect but lacks convulsant activity and has a half-life of about 10 h.
Prilocaine is split at the amide linkage to o-toluidine, which is converted further to 4- and 6hydroxytoluidine. The prilocaine metabolite o-toluidine and the hydroxylated metabolites
of otoluidine are excreted mainly in the urine. o-Toluidine has been shown to be carcinogenic in several animal models. After a total of 8 – 8.5 g Lidocaine and Prilocaine Gel was
administered as repeated applications over 3 hours, the mean ( total of 8 ther Cmax was 25 (±11) ng/mL ranging between 13 and 44 ng/mL. The mean o-toluidine AUCAUCne
AUCicng.min/mL. The median Tmax was 220 minutes, ranging between 90 and 240 min. In addition, o-Toluidine can cause the formation of methemoglobin (metHb) following
treatment with prilocaine. Individual maximum blood concentrations of metHb increased from 0-1.1% up to 0.8-1.7% following administration of the maximum recommended
dose of 8.5 g Lidocaine and Prilocaine Gel administrated as repeated applications over 3 hours. The Tmax of metHb ranged from 1 to 4 hours.
Elimination
Lidocaine and prilocaine have systemic clearances of 0.95 and 2.37 L/min, respectively, after intravenous administration as single agents. The terminal half-life of both drugs after
intravenous administration as single agents is 1.6 h. Lidocaine and Prilocaine Gel is not intended for intravenous administration.
However, after application of Lidocaine and Prilocaine Gel to the periodontal pockets the mean (±SD) terminal lidocaine half-life was 3.6 (±1.3) hours, ranging between 2.2 and
6.5 h. The mean (±SD) terminal prilocaine half-life was 2.8 (±1.0) hours, ranging between 2.0 to 5.7 h. For the metabolite o-toluidine the mean terminal half-life was 4.0 (±1.1)
hours, ranging between 2.0 and 5.7 hours. For the metabolite 2,60) hours, the mean terminal half-life was 8.0 (±4.0) hours, ranging between 3.7 and 18.3 hours.
Linearity
The increase in Cmax of both lidocaine and prilocaine is proportional (or less than proportional) to the dose after single application of Lidocaine and Prilocaine Gel. The Cmax after
a cumulative dose of 8.5 g Lidocaine and Prilocaine Gel administered as repeated applications over 3 hours, (i.e. the highest recommended dose, corresponding to 212.5 mg
each of lidocaine and prilocaine base), is lower than that extrapolated from the proportional increase in plasma concentrations at lower doses.
6. NONCLINICAL PROPERTIES
6.1 Animal toxicology or pharmacology
In animal studies the toxicity noted after high doses of either lidocaine or prilocaine, alone or in combination, consisted of effects on the central nervous and cardiovascular
systems. When lidocaine and prilocaine were combined, only additive effects were seen, with no indication of synergism or unexpected toxicity. Both active substances were
shown to have a low oral acute toxicity, providing a good safety margin in the event that EMLA Cream is inadvertently swallowed. In studies on reproduction toxicity, embryotoxic
or fetotoxic effects of lidocaine were detected at doses of 25 mg/kg s.c. in the rabbit and for prilocaine starting at doses of 100 mg/kg i.m. in the rat. At doses below the maternal
toxic range in the rat, lidocaine has no effect on the postnatal development of the offspring. An impairment of the fertility of male or female rats by lidocaine or prilocaine was not
observed. Lidocaine crosses the placental barrier by means of simple diffusion. The ratio of the embryofetal dose to the maternal serum concentration is 0.4 to 1.3.
Neither local anaesthetic showed a genotoxic potential in either in vitro or in vivo genotoxicity tests. Cancer studies have not been performed with either lidocaine or prilocaine
alone or in combination, due to the indication and duration of therapeutic use of these active substances.
A metabolite of lidocaine, 2,6-dimethylaniline, and a metabolite of prilocaine, , a metabolite of prilocaine, negenotoxic activity. These metabolites have been shown to have
carcinogenicity potential in preclinical toxicological studies evaluating chronic exposure. Risk assessments comparing the calculated maximum human exposure from
intermittent use of lidocaine and prilocaine, with the exposure used in preclinical studies, indicate a wide margin of safety for clinical use.
Local tolerance studies using a 1:1 (w/w) mixture of lidocaine and prilocaine as an emulsion, cream or gel indicated that these formulations are well tolerated by intact and
damaged skin and mucosal membranes.
A marked irritative reaction was seen after single ocular administration of a 50 mg/g lidocaine + prilocaine 1:1 (w/w) emulsion, in an animal study. This is the same concentration of
local anaesthetics and a similar formulation as for EMLA Cream. This ocular reaction may have been inuenced by the high pH of the formulation of the emulsion (approximately
9), but is probably also partly a result of the irritative potential of the local anaesthetics themselves.
7. Description
Lidocaine 2.5% and Prilocaine 2.5% is a gel which is a eutectic mixture of lidocaine and prilocaine in a ratio of 1:1 by weight. This eutectic mixture has a melting point below room
temperature and therefore both local anesthetics exist as a liquid oil rather than as crystals.
Lidocaine is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl), has an octanol: water partition ratio of 43 at pH 7.4, and has the following structure:

Prilocaine is chemically designated as propanamide, N-(2-methylphenyl)-2-(propylamino), has an octanol: water partition ratio of 25 at pH 7.4, and has the following structure:

8. Pharmaceutical particulars
8.1 Incompatibilities
Not applicable.
8.2 SHELF LIFE
18 months
8.3 PACKAGING INFORMATION
Tube of 30 gms.
8.4 STORAGE INSTRUCTIONS
Store at a temperature not exceeding 30°C. Do not freeze.
Keep out of reach of children.
9. PATIENT COUNSELLING INFORMATION
Lidocaine and Prilocaine Gel must be applied to the target area in a dose and duration as directed by the Physician. Lidocaine and Prilocaine Gel is for TOPICAL USE ONLY. DO
NOT INJECT.
Patients should be cautioned to avoid injury to the treated area, or exposure to extreme hot or cold temperatures, until complete sensation has returned.
This medication should not be used for any other condition than that for which it is prescribed.
10. Details of manufacturer
Pure & Cure Healthcare Pvt. Ltd.
Plot No. 26A, 27-30, Sector-8A,
IIE, SIDCUL, Ranipur,
Haridwar - 249403 (Uttarakhand).
11. Details of permission or licence number with date
31/UA/2013, 27th January, 2022
12. Date of revision
Feb 2022

For further Information, please write to Medical Information cell, Branded Formulations,
Dr. Reddy's laboratories Ltd.,
7-1-27, Ameerpet, Hyderabad - 500016.
Toll Free No.:1800 425 0014.
email: customerservices@drreddys.com,
® Registered Trademark

103320 20185660 Page 2 of 2