Dicloplast

Diclofenac Diethylamine Transdermal Patch

Each 50 cm2 Transdermal Patch contains:

Diclofenac Diethylamine IP 100 mg

Transdermal Patch

Diclofenac Diethylamine 100 mg/50 cm²

FOR EXTERNAL USE ONLY

4.1 Therapeutic indications

DicloPLAST® is indicated for the treatment of mild to moderate pain due to osteoarthritis or soft tissue injury.

4.2 Posology and method of administration

Adults and adolescents from 16 years

One Patch to be applied for one day or as directed by the physician

Duration of use

DicloPLAST® is for short-term treatment. The duration of use should not exceed 7 days. The therapeutic benefit of longer use has not been established.

If there is no improvement, during the recommended duration of treatment or a worsening of symptoms, a doctor should be consulted.

DicloPLAST® is to be used for the shortest duration necessary to control symptoms depending on the indication.

Elderly patients and patients with renal or hepatic impairment

This medication should be used with caution in elderly patients who are more prone to adverse events.

Paediatric population

Safety and effectiveness of DicloPLAST® has not been established in pediatric patients.

Method of administration

Cutaneous (Transdermal) use only.

Instructions for using DicloPlast Transdermal Patch:

• DicloPLAST® should be applied on non-hairy area.
• DicloPLAST® should be applied only to intact non-diseased skin and should not be worn when bathing or showering.
• Clean the application area with water & dry it before applying DicloPLAST®.
• Do not cut DicloPLAST®. This may reduce the efficacy.
• If necessary, the medicated patch can be held in place using a net bandage.
• The DicloPLAST® must not be used together with an occlusive dressing.

4.3 Contraindications

• Hypersensitivity to the active substance or to any of the excipients.
• In patients with hypersensitivity to acetylsalicylic acid or other non-steroidal anti-
• inflammatory drugs [NSAIDs].
• In patients who have previously experienced asthma, angioedema, urticaria or acute rhinitis
• when taking acetylsalicylic acid or any other NSAIDs.
• In patients with active peptic ulcer.
• On damaged skin, whatever the lesion involved: exudative dermatitis, eczema, infected
• lesion, burn or wound.
• During the last trimester of pregnancy.
• Children: The use in children is contraindicated.

4.4 Special warnings and precautions for use

DicloPLAST® must not come into contact with or be applied to the eyes or mucous membranes. It should be applied only to intact non-diseased skin, and not to skin wounds or open injuries. Topical diclofenac can be used with non-occlusive bandages but should not be used with an airtight occlusive dressing. Undesirable effects can be reduced by using the lowest effective dose for the shortest possible period of time. Bronchospasm can occur in patients who suffer or have previously suffered from bronchial asthma or allergies. Treatment must be stopped immediately if a skin rash develops after applying the medicated patches. Patients should be warned against exposure to sunlight or solarium radiation after removal of the DicloPLAST® in order to reduce the risk of photosensitisation. The possibility of systemic adverse events from application of diclofenac medicated patch cannot be excluded if the preparation is used on large areas of skin and over a prolonged period. Although the systemic effects are expected to be minimal, the medicated patch should be used with caution in patients with impaired renal, cardiac or hepatic function, or a history of peptic ulcer, inflammatory bowel disease or haemorrhagic diathesis. Non-steroidal anti-inflammatory drugs should be used with caution in elderly patients as they are more likely to experience undesirable effects. No other medicinal products containing diclofenac or any other non-steroidal anti-inflammatory drugs (NSAIDs) should be used concomitantly, neither topically nor systemically. Paediatric population DicloPLAST® is not recommended for use in children.

4.5 Drug Interactions

Non-steroidal anti-inflammatory drugs may interact with blood pressure lowering drugs, and may possibly enhance the effects of anticoagulants, although the chance of either of these occurring with a topically administered preparation is extremely remote. Concurrent aspirin or other NSAIDs may result in an increased incidence of adverse reactions. Since systemic absorption of diclofenac during labelled use of the DicloPLAST® is very low, the risk of developing clinically relevant drug-drug interactions is negligible.

4.6 Use in special populations

Fertility

There are no data available on the use of topical formulations of diclofenac and its effects on fertility in humans. The systemic concentration of diclofenac is lower after topical administration, compared to oral formulations. As for other NSAIDs, the oral use of diclofenac may impair female fertility and is not recommended in women attempting to conceive.

Pregnancy

As the safety of Diclofenac in pregnant women has not been established large dose or long-term use of this drug in pregnant women should be avoided.

The systemic concentration of diclofenac is lower after topical administration, compared to oral formulations. With reference to experience from treatment with pharmaceutical forms with systemic uptake, the following is recommended:

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5 %. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period.

During the first and second trimester of pregnancy, diclofenac should not be given unless clearly necessary. If diclofenac is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:

- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

- renal dysfunction, which may progress to renal failure with oligo-hydroamniosis; the mother and the neonate, at the end of pregnancy, to:

- possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.

- inhibition of uterine contractions resulting in delayed or prolonged labour. Consequently, diclofenac is contraindicated during the third trimester of pregnancy.

Breastfeeding

Like other NSAIDs, diclofenac is excreted into breast milk in small amounts. However, at therapeutic doses of diclofenac medicated patches no effects on the suckling child are anticipated.

Because of a lack of controlled studies in lactating women, the product should only be used during lactation under advice from a healthcare professional. Under this circumstance, DicloPLAST® should not be applied on the breasts of nursing mothers, nor elsewhere on large areas of skin or for a prolonged period of time.

4.7 Effects on ability to drive and use machines

DicloPLAST® has no influence on the ability to drive and use machines.

4.8 Undesirable effects

The following frequency categories are used for reporting undesirable effects:

Systemic plasma diclofenac levels measured during labelled use of the transdermal patches are very low compared to those obtained after oral intake of diclofenac. The risk of developing systemically induced side effects (like gastric, hepatic and renal disorders) during use of the patch therefore appears to be low. However, in particular when the transdermal patch is used on a large area of skin and over a prolonged period of time, systemic side effects may occur.

Reporting of suspected adverse reactions

• Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to: medico@zuventus.com
• Website: http://www.zuventus.co.in/safety.aspx

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

The low systemic absorption of topical diclofenac renders overdoses unlikely. Should significant systemic undesirable effects occur following incorrect use or accidental overdose (e.g. in children), the precautions appropriate for poisoning with non-steroidal anti-inflammatory drugs should be taken.

Pharmacotherapeutic group: Topical products for joint and muscular pain; Anti-inflammatory preparations, non-steroids for topical use ATC code: M02AA15

5.1 Mechanism of Action

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID). In pharmacologic studies, diclofenac has shown anti-inflammatory, analgesic, and antipyretic activity. As with other NSAIDs, its ability to inhibit prostaglandin synthesis, is involved in its anti-inflammatory activity, as well as contribute to its efficacy in relieving pain associated with inflammation.

5.2 Pharmacodynamic properties

DicloPLAST® Patch applied to intact skin provides local analgesia by releasing diclofenac Diethylamine from the patch into the skin.

5.3 Pharmacokinetic properties

Absorption

Diclofenac is absorbed slowly and incompletely from cutaneous formulations. The plasma concentrations of diclofenac at steady state are characterised by continuous absorption of diclofenac from the patch, regardless of whether the patch is applied in the morning or in the evening. Following cutaneous application, diclofenac may be absorbed into a dermal depot, from where it is released slowly into the central compartment. The systemic absorption of topical products is about 2-10% of that obtained with same dose administered orally. The mean peak plasma concentration is approximately 1 ng/ml. The observed therapeutic efficacy is mainly explained by therapeutically relevant drug tissue concentrations beneath the site of application. Penetration to the site of action may vary with the extent and nature of the condition and depending on the site of application and action.

Distribution

Plasma protein binding of diclofenac is high at 99%.

Biotransformation and Elimination

Metabolism and elimination are similar after cutaneous and oral use. Following rapid hepatic metabolism (hydroxylation and binding to glucuronic acid), ⅔ of the active substance is eliminated renally and ⅓ by the biliary route.

6.1 Animal Toxicology or Pharmacology

Non-clinical data based on conventional studies of safety pharmacology, genotoxicity and carcinogenic potential reveal no special hazards for humans beyond those already outlined in other sections of this prescribing information. In animal studies, chronic toxicity of diclofenac following systemic administration mainly manifested as gastrointestinal lesions and ulcers. In a 2-year toxicity study, rats treated with diclofenac showed a dose-related increase in thrombotic occlusion of the cardiac vessels.

In animal studies on reproductive toxicity, systemically administered diclofenac caused inhibition of ovulation in rabbits and impairment of implantation and early embryonic development in rats. The gestational period and duration of parturition were prolonged by diclofenac. The embryotoxic potential of diclofenac was studied in three animal species (rat, mouse, rabbit). Foetal death and growth retardation occurred at maternotoxic dose levels. Based on the available non-clinical data, diclofenac is regarded as non-teratogenic. Doses below the maternotoxic threshold had no impact on the postnatal development of the offspring.

Conventional studies on local tolerability reveal no special hazards for humans.

DicloPLAST® is a Diclofenac Diethylamine Transdermal Patch (50 cm2) is comprised of an adhesive material containing Diclofenac Diethylamine with a unique backing layer & polymer matrix. The release liner is removed prior to topical application to the skin. Each adhesive patch contains 100 mg of Diclofenac Diethylamine in an aqueous base.

Diclofenac Diethylamine is a non-opioid analgesic chemically designated as 2-[2-(2,6-dichloroanilino)phenyl]acetic acid;N-ethylethanamine, with a molecular formula of C18H22Cl2N2O2 (molecular weight 369.3 g/mol), and the following structure:

8.1 Incompatibilities

Not applicable

8.2 Shelf life

Refer on pack

8.3 Packaging information

3 Patches per Pouch (58 x 87 mm)

8.4 Storage and handling instructions

Store in a cool place below 30°C. Protect from light & moisture. Store in the original package in order to protect from desiccation and light. Keep the sachet tightly closed in order to protect from desiccation and light. Keep out of reach of children. Used patches should be folded in half, with the adhesive side inwards. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Advise the patient to read the patient information label, as well as the Directions for Use on the product packaging. Inform patients, families, or their caregivers of the following information before initiating therapy with DicloPLAST® and periodically during the course of ongoing therapy.

Cardiovascular Thrombotic Events

Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately. Gastrointestinal Bleeding, Ulceration, and Perforation Advise patients to report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their health care provider. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, inform patients of the increased risk for and the signs and symptoms of GI bleeding.

Hepatotoxicity

Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, diarrhea, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur, instruct patients to stop DicloPLAST® and seek immediate medical therapy.

Heart Failure and Edema

Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur.

Anaphylactic Reactions

Inform patients of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat). Instruct patients to seek immediate emergency help if these occur.

Serious Skin Reactions

Advise patients to stop DicloPLAST® immediately if they develop any type of rash and to contact their healthcare provider as soon as possible.

Female Fertility

Advise females of reproductive potential who desire pregnancy that NSAIDs, including DicloPLAST®, may be associated with a reversible delay in ovulation. Fetal Toxicity Inform pregnant women to avoid use of DicloPLAST® and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus.

Avoid Concomitant Use of NSAIDs

Inform patients that the concomitant use of DicloPLAST® with other NSAIDs or salicylates (e.g., diflunisal, salsalate) is not recommended due to the increased risk of gastrointestinal toxicity, and little or no increase in efficacy. Alert patients that NSAIDs may be present in "over the counter" medications for treatment of colds, fever, or insomnia.

Use of NSAIDS and Low-Dose Aspirin

Inform patients not to use low-dose aspirin concomitantly with DicloPLAST® until they talk to their healthcare provider.

Eye Exposure

Instruct patients to avoid contact of DicloPLAST® with the eyes and mucosa. Advise patients that if eye contact occurs, immediately wash out the eye with water or saline and consult a physician if irritation persists for more than an hour.

Special Application Instructions

• Instruct patients that, if DicloPLAST® begins to peel-off, the edges of the patch may be taped down. If problems with adhesion persist, patients may overlay the patch with a mesh netting sleeve, where appropriate (e.g. to secure patches applied to ankles, knees, or elbows). The mesh netting sleeve must allow air to pass through and not be occlusive (non-breathable).
• Instruct patients not to apply DicloPLAST® to non-intact or damaged skin resulting from any etiology e.g. exudative dermatitis, eczema, infected lesion, burns or wounds.
• Instruct patients not to wear a DicloPLAST® when bathing or showering.
• Instruct patients to wash hands after applying, handling or removing the patch.