4.1. Therapeutic indications

For the local symptomatic relief of pain and inflammation in:

- trauma of the tendons, ligaments, muscles and joints, e.g. due to sprains, strains and bruises

- localised forms of soft tissue rheumatism

4.2. Posology and method of administration

For cutaneous use only.

Adults and children 14 years and over: The gel should be rubbed gently into the skin 3-4 times daily. Depending on the size of the affected site to be treated, 2-4g (a circular shaped mass approximately 2.0-2.5cm in diameter) of gel should be applied 3-4 times a day. A period of at least 4 hours should be left between applications. The dose should not be applied more than 4 times in a 24-hour period. The maximum daily dose is 16g. Therefore, the maximum weekly dose is 112g.

After application, the hands should be washed unless they are the site being treated.

If symptoms do not improve by day 7, or if they worsen within the first 7 days, a consultation with a doctor should be sought. Consultation with a doctor is recommended if more than two major joints in the body are affected. Do not use for more than 7 days unless recommended by a doctor.

Use in the elderly: The usual adult dosage may be used.

Children and adolescents: The product should not be used in children under 14 years of age. There are insufficient data on efficacy and safety available for the children and adolescents below 14 years of age (see also contraindications section 4.3). In children aged 14 years and over, if this product is required for more than 7 days for pain relief or if the symptoms worsen the patient/parents of the adolescent is/are advised to consult a doctor.

4.3. Contraindications

- Hypersensitivity to diclofenac, acetylsalicylic acid (aspirin), other non-steroidal anti- inflammatory drugs or any of the excipients.

- Patients with or without chronic asthma in whom attacks of asthma, angioedema urticaria or acute rhinitis are precipitated by acetylsalicylic acid or other non-steroidal anti- inflammatory drugs (NSAIDs).

- The use in children and adolescents aged less than 14 years is contraindicated.

- Third trimester of pregnancy.

- Patients with renal impairment.

- Concomitant use of oral NSAIDs and other products containing diclofenac.

4.4. Special warnings and precautions for use

The occurrence of systemic undesirable effects with the topical use of diclofenac is low when compared with the frequency of undesirable effects with the oral use of diclofenac.

The possibility of systemic adverse events (those associated with the use of systemic forms of diclofenac) from application of topical diclofenac cannot be excluded if the preparation is used at higher dosage/large amounts on large areas of skin and over a prolonged period (see the product information on systemic forms of diclofenac).

Cutaneous safety of NSAIDs: Serious skin reactions, some of them fatal, have been reported very rarely, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, associated with the administration of NSAIDs (see section 4.8.). Apparently, the risk of occurrence of these reactions is higher at the beginning of the treatment and in most cases these reactions are manifested during the first month of treatment. Concomitant use of oral NSAID's should be cautioned as the incidence of untoward effects, particularly systemic side effects, may increase.

Diclofenac Sodium 1% Gel should be discontinued at the first signs of rash, mucosal injuries or other hypersensitivity manifestations.

Patients with a history of, or active, peptic ulcerations. Some possibility of gastro-intestinal bleeding in those with a significant history of this condition has been reported in isolated cases.

Like other drugs that inhibit prostaglandin synthetase activity, diclofenac and other NSAIDs can precipitate bronchospasm if administered to patients suffering from or with a previous history of asthma or allergic disease.

Topical diclofenac should be applied only to intact, non-diseased skin, and not to skin wounds or open injuries. It should not be allowed to come into contact with the eyes or mucous membranes and should not be ingested.

The area treated with Diclofenac Sodium 1% Gel should not be exposed to sunlight.

Topical diclofenac can be used with non-occlusive bandages but should not be used with an airtight occlusive dressing.

Diclofenac Sodium 1% Gel contains propylhydroxybenzoate (E216) and methylhydroxybenzoate (E218), which may cause allergic reactions (possibly delayed).

Diclofenac Sodium 1% Gel also contains propylene glycol which may cause skin irritation.

4.5. Interaction with other medicinal products and other forms of interaction

Diuretics, Angiotensin Converting Enzyme Inhibitors (ACE inhibitors) and Angiotensin II Antagonists (AAII): NSAIDs may decrease the effectiveness of diuretics and other antihypertensive medicinal products. In some patients with impaired renal function (e.g., dehydrated patients or elderly with impaired renal function) the co-administration of an ACEI or AIIA and cyclooxygenase inhibitor agents may result in the progression of renal function deterioration, including the possibility of acute renal insufficiency, which is usually reversible. The occurrence of these interactions should be considered in patients applying diclofenac, particularly if in large areas of the skin and for prolonged periods, in combination with ACEI or AIIA. Consequently, this drug combination should be used with caution, especially in elderly patients. Patients should be properly hydrated and the need to monitor the renal function after the beginning of the concomitant therapy and periodically thereafter should be analysed.

Since systemic absorption of diclofenac from a topical application is very low such interactions are very unlikely.

4.6. Fertility, pregnancy and lactation

Pregnancy

There are no clinical data from the use of Diclofenac 1% Gel during pregnancy. Even if systemic exposure is lower compared with oral administration, it is not known if the systemic Diclofenac 1% Gel exposure reached after topical administration can be harmful to an embryo/fetus. During the first and second trimester of pregnancy, Diclofenac 1% Gel should not be used unless clearly necessary. If used, the dose should be kept as low and duration of treatment as short as possible.

During the third trimester of pregnancy, systemic use of prostaglandin synthetase inhibitors including diclofenac may induce cardiopulmonary and renal toxicity in the fetus. At the end of the pregnancy prolonged bleeding time in both mother and child may occur, and labour can be delayed. Therefore, Diclofenac 1% Gel is contraindicated during the last trimester of pregnancy (see Section 4.3).

The systemic concentration of diclofenac is lower after topical administration, compared to oral formulations. With reference to experience from treatment with NSAIDs 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:

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

o renal dysfunction, which may progress to renal failure with oligo- hydroamniosis;

• the mother and the neonate, at the end of pregnancy, to:

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

o inhibition of uterine contractions resulting in delayed or prolonged labour.

Consequently, diclofenac is contraindicated during the third trimester of pregnancy (see section 4.3).

Breast-feeding

Like other NSAIDs, diclofenac passes into breast milk in small amounts. However, at therapeutic doses of topical diclofenac 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, this medicinal product should not be applied on the breasts of nursing mothers, nor elsewhere on large areas of skin or for a prolonged period of time (see section 4.4).

Fertility

There are no data available on the use of topical formulations of diclofenac and its effects on fertility in humans.

4.7. Effects on ability to drive and use machines

Cutaneous application of topical diclofenac has no or negligible influence on the ability to drive and use machines.

4.8. Undesirable effects

Adverse reactions (Table 1) are ranked under heading of frequency, the most frequent first, using the following convention: very common (> 1/10); common (> 1/100, <1/10); uncommon (>1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); very rare (<1/10,000), not known: cannot be estimated from the available data.

Table 1 – Adverse Reactions

Immune system disorder:

Very rare:

Hypersensitivity (including urticaria), angioneurotic oedema.

Infections and infestations:

Very rare:

Rash pustular.

Respiratory, thoracic and mediastinal disorders:

Very rare:

Asthma.

Skin and subcutaneous tissue disorders:

Common:

Rare:

Very rare:

Not known:

Rash, eczema, erythema, dermatitis (including contact dermatitis), pruritus.

Dermatitis bullous.

Photosensitivity reaction.

Burning sensation at the application site.

Dry skin.

Although less likely with the topical administration, some side effects normally associated with systemically administered diclofenac may also occur.

The prolonged use of diclofenac in a relatively extensive area can cause systemic side effects such as nausea, vomiting, diarrhoea or epigastric pain.

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 Yellow Card Scheme at wwww.mhra.gov.uk/yellowcard or search for 'MHRA Yellow Card' in the Google Play or Apple App Store.

4.9. Overdose

The low systemic absorption of topical diclofenac renders overdose very unlikely.

However, undesirable effects similar to those observed following an overdose of Diclofenac tablets can be expected if Topical diclofenac is inadvertently ingested (1 tube of 100 g contains the equivalent of 1,000 mg diclofenac sodium).

In the event of accidental ingestion resulting in significant systemic adverse effects, general therapeutic measures normally adopted to treat poisoning with non-steroidal anti-inflammatory medicines should be used. Gastric decontamination and the use of activated charcoal should be considered, especially within a short time of ingestion.