Versatis - Package Leaflet
Active ingredients: Lidocaine
Versatis 5% medicated plaster
Why is Versatis used? What is it for?
Versatis contains lidocaine, a local analgesic, which works by reducing pain in the skin. It has been prescribed to you to treat pain caused by post-herpetic neuralgia. This condition is generally characterized by localized symptoms such as burning, stabbing, or stabbing pain.
Contraindications When Versatis should not be used
Do not use Versatis
- if you are allergic to lidocaine or any of the other ingredients of this medicine (listed in section 6)
- if you have had an allergic reaction to other lidocaine-like products, such as bupivacaine, etidocaine, mepivacaine or prilocaine
- on broken skin or open wounds.
Precautions for use What you need to know before taking Versatis
Talk to your doctor or pharmacist before using Versatis If you have severe liver disease or have severe heart or kidney problems, you should talk to your doctor before using Versatis. Versatis should be applied to the skin after the shingles lesions have healed. It should not be applied to or near the eyes or mouth.
Lidocaine is metabolised into numerous compounds in the liver. One such compound is 2.6 xylidine, which has been shown to cause tumors in rats when given continuously at very high doses. The value of these data in humans is not known.
Children and adolescents
Versatis has not been studied in patients under 18 years of age. Therefore, use in these patients is not recommended.
Interactions Which drugs or foods may change the effect of Versatis
Tell your doctor or pharmacist if you are taking or have recently taken or might take any other medicines.
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant or are planning to have a baby, or if you are breast-feeding, ask your doctor or pharmacist for advice before using this medicine. Versatis should not be used during pregnancy unless clearly necessary. There are no studies on the use of the patch during breastfeeding. When using Versatis, only a small amount of the active ingredient, lidocaine, may be present in the blood. An effect on breastfed babies is unlikely.
Driving and using machines
An effect of Versatis on the ability to drive or use machines is unlikely. Therefore it is possible to drive or work on machinery while using Versatis.
Versatis contains propylene glycol, methyl parahydroxybenzoate and propyl parahydroxybenzoate.
The patches contain propylene glycol (E1520) which can cause skin irritation. In addition, they contain methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216) which can cause allergic reactions. Sometimes allergic reactions can appear after using the patches for a certain period of time.
Dose, Method and Time of Administration How to use Versatis: Posology
Always use this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist. Normally the daily dosage is one to three patches the size of the area of sore skin. Versatis can be cut into smaller pieces to cover the affected area. You must not use more than 3 patches at the same time. The patches must be removed after 12 hours of application; in this way you will have a period of 12 hours without a patch. You can choose whether to apply Versatis during the day or at night. You will generally feel some pain relief from the first day of use, but it may take up to 2-4 weeks for the pain relieving effect of Versatis to be complete. If after this time the pain is still very intense, tell your doctor, as the benefit of the treatment must be weighed against the potential risks (see "warnings and precautions").
Your doctor will check at regular intervals whether Versatis is working.
Before applying Versatis on the affected area
- if the painful area of the skin is covered with hair or hair, it should be cut with scissors. They should not be shaved.
- The skin must be clean and dry.
- Creams or lotions can be used on the treated skin only during the period when the patch is not applied.
- If you have just taken a bath or shower, you should wait until your skin has cooled before applying the patch.
Apply the patch
Step 1: Open the pouch and remove one or more patches
- tear or cut the envelope along the dotted line
- if using scissors, be careful not to damage the patches
- take one or more patches, depending on the size of the painful area of skin
Step 2: Close the envelope
- close the bag tightly after use
- the patch contains water and may dry out if the pouch is not closed properly
Step 3: Cut the patch if necessary
- if necessary, before removing the film, cut the patch to the size necessary to cover the painful part of the skin.
Step 4: Remove the film
- remove the transparent film from the patch
- try not to touch the sticky part of the patch
Step 5: Apply the patch and press firmly on the skin
- apply up to three patches to the painful area of the skin
- press the patch onto the skin
- press and hold the patch for at least 10 seconds so that the patch adheres well to the skin
- make sure that all of the patch, including the edges, adheres to the skin.
Leave the patch on for only 12 hours
It is important that Versatis is only applied to the skin for 12 hours. For example, if you feel more pain during the night, you can apply the patch at 7pm and remove it at 7am. If you experience more pain during the day, you can apply Versatis at 7 in the morning and take it off at 7 in the evening.
Bath, shower and swimming
Since contact of Versatis with water must be avoided, any baths, showers or swimming can be done during the time the patch is not applied. After bathing or showering, the skin should be allowed to cool before applying. apply the patch.
If the patch falls off
Very rarely the patch may come off or not adhere well. If so, try reattaching it to the same area. If it does not stick, remove it completely and apply a new patch, always on the same area.
How to remove Versatis
To change the patch, take off the old patch slowly. If it doesn't come off easily, you can wet it with hot water for a few minutes before taking it off.
Overdose What to do if you have taken too much Versatis
If you forget to remove the patch after 12 hours
Take off the patch as soon as you remember. The new patch can be applied after 12 hours.
If you use more patches than you should
If you use more patches than necessary or keep them on for too long, the risk of side effects may increase.
If you forget to apply Versatis
If you forgot to put on a new patch after 12 hours without the previous patch, apply the new patch as soon as you remember.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Versatis
Like all medicines, this medicine can cause side effects, although not everybody gets them. If there is any irritation or burning sensation while applying the patch, the patch should be removed. Do not apply another patch to that area until the irritation has healed.
Very common side effects that may affect more than 1 in 10 people are listed below.
These include changes in the skin at or near the patch application area and may include redness, rash, itching, burning, dermatitis and blisters.
Uncommon side effects that may affect up to 1 in 100 people are listed below.
Skin alterations and wounds
Very rare side effects which may affect up to 1 in 10,000 people are listed below.
Open wounds, severe allergic reactions and allergy.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at http://www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the pouch and carton after EXP. The expiry date refers to the last day of that month. Do not keep in the refrigerator or freezer. Close the bag carefully after first opening. After opening the pouch, the patches must be used within 14 days. Do not use this medicine if you notice that the pouch is damaged. If so, the patch may have dried out and therefore not adhere well.
How to remove Versatis
The patches used still contain active ingredient which could be dangerous for others. Fold the old patches in half, with the sticky side on the inside, and throw them away so they stay out of the reach of children.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What Versatis contains
- the active ingredient is lidocaine
- each 10 cm x14 cm patch contains 700 mg (5% w / w) of lidocaine
- the other components in the patch (excipients) are: glycerol, liquid crystallizable sorbitol, carmellose sodium, propylene glycol (E1520), urea, heavy kaolin, tartaric acid, gelatin, polyvinyl alcohol, aluminum glycinate, edetate disodium, methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216), polyacrylic acid, sodium polyacrylate, purified water.
The support layer and the adhesive layer: polyethylene terephthalate (PET).
Description of what Versatis looks like and contents of the pack
The medicated plasters are 14 cm long and 10 cm wide. They are white, of soft material and bear the inscription "lidocaine 5%". The patches are packaged in resealable pouches, each containing 5 patches.
Each pack contains 5, 10, 20, 25 or 30 patches packed in 1, 2, 4, 5 or 6 pouches respectively.
Not all packs are commercially available.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
VERSATIS 5% MEDICATED PATCH
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 10cm x14cm patch contains 700 mg (5% w / w) of lidocaine (50 mg of lidocaine / gram of adhesive base)
Excipients with known effect:
Methyl parahydroxybenzoate 14 mg
Propyl parahydroxybenzoate 7 mg
Propylene glycol 700 mg
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
White hydrogel patch, containing adhesive material applied to a non-woven polyethylene terephthalate support bearing the embossed wording "Lidocaine 5%" and covered with a protective film of polyethylene terephthalate.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Versatis is indicated for the symptomatic treatment of neuropathic pain associated with previous Herpes Zoster infection (post-herpetic neuralgia, NPH) in adults.
04.2 Posology and method of administration
Adults and the elderly
The painful area must be covered with the patch, applied once a day for no more than 12 hours within 24 hours. Only the patches necessary for effective treatment should be applied. If necessary, the patch can be cut into smaller parts with scissors before removing the protective film. In total, no more than three patches should be applied at the same time.
The patch should be applied to intact, dry and non-irritated skin (after healing of herpetic lesions).
Each patch cannot be applied for more than 12 hours. The free interval from the next application should be at least 12 hours. The patch can be applied during the day or during the night.
The patch should be applied to the skin immediately after removing it from the pouch and removing the protective film from the hydrogel surface. Hair and hair in the application area must be cut with a pair of scissors (not shaved).
Treatment should be reassessed after 2-4 weeks. If there has been no therapeutic response to Versatis after this period (during the patch being applied and / or the patch-free period, treatment should be stopped, as, in this situation, the potential risks could exceed the benefits (see sections 4.4 and 5.1). Long-term use of Versatis in clinical trials has shown that the number of patches to be used decreases over time. Consequently, treatment should be reassessed at regular intervals in order to decide whether the number of patches needed to cover the painful area can be reduced or whether the free interval between applying the patch can be increased.
In patients with mild or moderate renal impairment, no dosage adjustments are required. Versatis should be used with caution in patients with severe renal impairment (see section 4.4)
In patients with mild or moderate hepatic impairment, no dosage adjustments are required. Versatis should be used with caution in patients with severe hepatic impairment (see section 4.4).
The safety and efficacy of Versatis in patients under 18 years of age have not been established. No data are available.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. The patch is also contraindicated in patients with known hypersensitivity to other amide-type local anesthetics, such as bupivacaine, etidocaine, mepivacaine and prilocaine.
The patch should not be applied to inflamed or damaged skin, such as active Herpes Zoster lesions, atopic dermatitis, wounds.
04.4 Special warnings and appropriate precautions for use
The patch should not be applied to the mucous membranes. Contact of the patch with the eyes should be avoided.
The patch contains propylene glycol which can cause skin irritation. It also contains methyl parahydroxybenzoate and propyl parahydroxybenzoate which can cause allergic reactions (even delayed).
The patch should be used with caution in patients with severe heart, kidney or liver damage.
One of the lidocaine metabolites, 2,6 xylidine, was observed to have a genotoxic and carcinogenic effect in rats (see section 5.3). Secondary metabolites were shown to be mutagenic. The clinical significance of this finding is unknown. Consequently, long-term treatment with Versatis is justified only by an actual therapeutic benefit for the patient (see section 4.2).
04.5 Interactions with other medicinal products and other forms of interaction
No interaction studies are available so far. In clinical trials with the patch, no clinically relevant interactions were reported.
Since the maximum plasma concentrations of lidocaine observed in clinical studies with the patch were low (see section 5.2), clinically relevant pharmacokinetic interactions are unlikely.
Although usually the absorption of lidocaine through the skin is low, the patch should be used with caution in patients receiving class I antiarrhythmics (e.g. tocainide, mexiletine) or other local anesthetics, since the risk of a systemic addition effect cannot be excluded.
04.6 Pregnancy and breastfeeding
Lidocaine passes the placental barrier. However, there are insufficient data on the use of lidocaine in pregnant women.
Animal studies do not indicate a teratogenic potential of lidocaine. (see point 5.3).
The potential risk to humans is unknown. Therefore, Versatis should not be used during pregnancy unless clearly indicated.
Lidocaine is excreted in breast milk. However, for the patch, there are no clinical studies in breastfeeding women. Since lidocaine metabolism is relatively fast and occurs almost completely in the liver, it is assumed that only a very small amount of lidocaine can be excreted in breast milk.
No clinical data on fertility are available. Animal studies have shown no effects on female fertility.
04.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive or use machines have been performed. Since systemic absorption is minimal (section 5.2), effects on the ability to drive or use machines are unlikely.
04.8 Undesirable effects
The following undesirable effects are reported in decreasing order of severity within each frequency group.
Approximately 16% of patients under treatment may experience adverse reactions. These are local reactions due to the characteristics of the drug.
The most frequently reported adverse reactions were application site reactions (such as burning sensation, dermatitis, erythema, pruritus, rash, skin irritation and blisters).
The table below lists adverse reactions reported by patients who used the patch in post-herpetic neuralgia studies. They are listed by class and frequency in the various devices. Their frequency is defined as: very common ≥ 1/10; common ≥ 1/100 to
The following reactions have been observed in patients who used the patch in a post-marketing setting
All adverse reactions were generally mild or moderate in intensity. Less than 5% of them led to discontinuation of treatment.
With appropriate use of the patch, systemic adverse reactions are unlikely as the systemic concentration of lidocaine is very low (see section 5.2). Systemic adverse reactions from lidocaine are similar to those observed for other amides used as local anesthetics (see section 4.9).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "Italian Medicines Agency Website: http://www.agenziafarmaco.gov.it/it/responsabili
Overdose with the patch is unlikely, but it cannot be excluded that inappropriate use of the patch, such as the simultaneous use of a large number of patches, for a longer period of application or use on broken skin, may lead to higher than normal plasma levels of lidocaine. Possible signs of systemic toxicity are similar in nature to those seen after administration of lidocaine as a local anesthetic and may include the following signs and symptoms: dizziness, vomiting, somnolence, seizures, mydriasis, bradycardia, arrhythmia and shock.
Furthermore, known interactions between systemic concentrations of lidocaine with beta-blockers, CYP3A4 inhibitors (e.g. imidazole derivatives, macrolides) and antiarrhythmic drugs may become relevant in the event of overdose.
If overdose is suspected, the patch should be removed and supportive measures undertaken if clinically necessary. There is no antidote to lidocaine.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: local anesthetics, amides
ATC code: N01BB02
Mechanism of action
Versatis has a dual mechanism of action: the pharmacological activity of lidocaine and the mechanical action of the hydrogel patch that protects the hypersensitive area.
Lidocaine contained in the Versatis patches spreads continuously into the skin, providing a local analgesic effect. The mechanism of action is related to the stabilization of neuronal membranes, which is believed to determine one down regulation of sodium channels and therefore pain reduction.
Pain management in NPH is difficult. There is evidence of the efficacy of Versatis in the symptomatic relief of the allodynamic component of NPH in some cases (see section 4.2).
The efficacy of Versatis has been demonstrated in post-herpetic neuralgia studies.
Two main controlled studies were conducted to evaluate the efficacy of 5% lidocaine medicated patches.
In the first study, patients were recruited from a previously believed population "responderThis was a cross-over study, which involved 14 days of treatment with 5% lidocaine medicated patches followed by placebo or vice versa. The primary goal was the "time to exit", that is, when patients left the study because pain relief was 2 points lower than their usual response on a 6-point scale (from worsening to complete pain relief). Of the 32 recruited patients, 30 completed the study. The "time to exit" mean for placebo was 4 days while for active drug it was 14 days (p
In the second study, 265 patients with post-herpetic neuralgia were recruited for an 8-week open-label treatment with 5% lidocaine medicated plaster. In this uncontrolled study, approximately 50% of patients responded to treatment with a reduction of at least four points on a 6-point scale (from worsening to complete relief). A total of 71 patients were randomized to receive placebo or 5% lidocaine medicated patches administered for 2-14 days. The primary end point was defined as lack of efficacy for 2 consecutive days because pain relief was two points lower than the normal response on the six-point scale (ranging from worsening to total remission) leading to discontinuation of treatment. discontinuation due to ineffectiveness occurred in 9/36 patients treated with the drug and in 16/35 patients treated with placebo.
Post-hoc analyzes of the second study showed that the initial response was independent of the duration of the pre-existing NPH condition. However, the fact that patients with longer duration NPH (> 12 months) benefit most from active treatment is supported by the finding that this group of patients dropped out of the study more frequently due to ineffectiveness when switched to placebo treatment during phase double-blind study.
In an open-label controlled study, Versatis appears to have "comparable efficacy to pregabalin in 98 patients with PHN, with a favorable safety profile.
05.2 "Pharmacokinetic properties
When the 5% lidocaine medicated plaster is used within the recommended maximum dose (3 patches applied simultaneously for 12 hours) approximately 3 ± 2% of the total applied lidocaine dose is available systemically for both single and multiple administrations.
Population kinetic analysis performed during clinical efficacy studies in NPH patients demonstrated a mean maximum lidocaine concentration of 45 ng / ml after simultaneous application of 3 patches, 12 hours a day, repeated for up to one year. This value agrees with that found in pharmacokinetic studies in patients with NPH (52 ng / mL) and in healthy volunteers (85 ng / mL and 125 ng / mL).
There was no tendency to accumulate lidocaine and its metabolites MEGX, GX and 2.6 xylidine; concentrations at steady state they are reached in the first 4 days.
Population kinetic analysis indicated that systemic exposure shows a proportionally less increase than the number of patches applied simultaneously, when their number increases from 1 to 3.
After intravenous administration of lidocaine to healthy volunteers, the volume of distribution was 1.3 ± 0.4 L / kg (mean ± S.D., n = 15). The volume of distribution is not age dependent, it is reduced in patients with congestive heart disease and increased in patients with liver disease. At plasma concentrations determined by patch application, approximately 70% of lidocaine binds to plasma proteins. Lidocaine crosses the placental and blood-brain barrier probably by passive diffusion.
Lidocaine is rapidly metabolised in the liver to a number of metabolites. The major metabolic pathway of lidocaine is N-dealkylation to monoethylglycinxylidide (MEGX) and glycinxylidide (GX), both of which are less active than lidocaine and are available at low concentrations. These metabolites are hydrolyzed to 2,6-xylidine which is converted, by conjugation, to 4-hydroxy-2,6-xylidine.
The pharmacological activity of the metabolite 2,6-xylidine is unknown, but it shows carcinogenic potential in rats (see section 5.3). A population kinetic analysis revealed a mean maximum concentration for 2,6-xylidine of 9 ng / ml after repeated daily applications up to 1 year. This finding is confirmed by a phase I pharmacokinetic study. Data on lidocaine metabolism in the skin are not available.
Lidocaine and its metabolites are excreted by the kidney. More than 85% of the dose is recovered in the urine in the form of metabolites or active substance. Less than 10% of the dose of lidocaine is excreted unchanged. The main metabolite in the urine is a conjugate of 4-hydroxy-2,6-xylidine. , which represents approximately 70 - 80% of the dose excreted in the urine. In humans, 2,6-xylidine is excreted in the urine at concentrations less than 1% of the dose. The mean elimination half-life of lidocaine after application of the patch in healthy volunteers, is 7.6 hours. The excretion of lidocaine and its metabolites may be delayed in the case of cardiac, renal or hepatic insufficiency.
05.3 Preclinical safety data
Effects in preclinical general toxicity studies were observed only at doses considered sufficiently in excess of the maximum achievable human exposure, indicating low clinical relevance.
Lidocaine hydrochloride was not genotoxic in the studies in vitro or in vivo. Its metabolite produced by hydrolysis, 2,6-xylidine, showed genotoxic activity in several tests, especially after metabolic activation.
Carcinogenicity studies with lidocaine have not been performed. Studies carried out on the metabolite 2,6-xylidine, mixed in the diet of male and female rats, have shown treatment-related cytotoxicity: hyperplasia of the olfactory epithelium of the nose, carcinomas and adenomas in the nasal cavities have also been observed. at the liver and subcutaneous level. Since the risk to humans is unclear, long-term treatment with lidocaine should be avoided.
Lidocaine had no effect on overall reproductive capacity, female fertility or embryo-fetal development / teratogenesis in rats subjected to plasma concentrations up to 50 times those observed in patients. Animal studies regarding male fertility, childbirth or postnatal development are not complete.
06.0 PHARMACEUTICAL INFORMATION
Glycerol, liquid crystallizable sorbitol, carmellose sodium, propylene glycol (E1520), urea, heavy kaolin, tartaric acid, gelatin, polyvinyl alcohol, aluminum glycinate, edetate disodium, methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216), polyacrylic acid, sodium polyacrylate, purified water.
Polyethylene terephthalate (PET)
06.3 Period of validity
After opening the pouch the patch must be used within 14 days.
06.4 Special precautions for storage
Do not refrigerate or freeze. Keep the pouch closed after first opening.
06.5 Nature of the immediate packaging and contents of the package
Resealable bags made of paper / polyethylene / aluminum / ethylene acid meta-acrylic co-polymer, containing 5 patches.
Each pack contains 5, 10, 20, 25 or 30 patches.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
After use, the patch still contains active ingredient. After removing it, the patch should be folded in half, with the adhesive layer inwards so that the self-adhesive layer is not exposed and must be discarded.
The unused or discarded patch should be disposed of according to local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
AIC HOLDER: GRÜNENTHAL ITALIA S.r.l. via Carlo Bo 11 20143 Milan
08.0 MARKETING AUTHORIZATION NUMBER
10 medicated plasters 5% AIC n. 040335022
30 medicated plasters 5% AIC n. 040335059
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first registration: March 2012
Date of last renewal: 5.01.2012
10.0 DATE OF REVISION OF THE TEXT
May 30, 2015