4.1. Therapeutic indications

For the treatment of actinic keratosis (AK) in adults.

4.2. Posology and method of administration

Use in Adults: Solaraze is applied locally to the affected area twice daily, with the gel smoothed into the skin gently. The amount needed depends on the size of the affected area. Normally 0.5 grams (the size of a pea) of the gel is used on a 5 cm × 5 cm lesion site. The maximum daily amount of 8 grams of gel allows simultaneous treatment of up to 200 cm² skin surface area.

The usual duration of therapy is from 60 to 90 days. Maximum efficacy has been observed with treatment duration towards the upper end of this range. Complete healing of the lesion(s) or optimal therapeutic effect may not be evident for up to 30 days following cessation of therapy.

Use in the Elderly: The usual adult dose may be used.

Paediatric Population: AK is a condition not generally seen within the paediatric population and was not studied. Therefore, dosage recommendations and indications for the use of Solaraze have not been established for use in children and adolescents. No data are available.

Method of administration

For cutaneous use.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Because of cross-reactions, the gel must not be used by patients who have experienced hypersensitivity reactions such as symptoms of asthma, allergic rhinitis or urticaria, to acetylsalicylic acid or other non-steroidal anti-inflammatory agents.

The use of the medicinal product is contraindicated during the third trimester of pregnancy (see Section 4.6).

4.4. Special warnings and precautions for use

The likelihood of systemic adverse reactions occurring following the topical application of <Invented name> is very small compared to the frequency of adverse reactions with oral diclofenac, owing to low systemic absorption with Solaraze. However, the possibility of systemic adverse events from application of topical diclofenac cannot be excluded if the preparation is used on large areas of skin and over a prolonged period (see product information on systemic forms of diclofenac). This medicinal product should be used with caution in patients with a history of and/or active gastrointestinal ulceration or bleeding, or reduced heart, liver or renal function, since isolated cases of systemic adverse reactions consisting of renal affection, has been reported with topically administered antiphlogistics.

It is known that nonsteroidal anti-inflammatory drugs (NSAIDs) can interfere with platelet function. Although the likelihood of systemic side effects is very low, caution should be used in patients with intracranial haemorrhage and bleeding diathesis.

Direct sunlight, including solarium, should be avoided during treatment. If sensitivity skin reactions occur, discontinue use.

Solaraze should not be applied to skin wounds, infections or exfoliative dermatitis. It should not be allowed to come into contact with the eyes or mucous membranes and should not be ingested.

The treatment should be discontinued if a generalised skin rash develops after applying the medicinal product.

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

This medicinal product contains 10 mg benzyl alcohol in each g. Benzyl alcohol may cause allergic reactions and mild local irritation.

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

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

4.6. Fertility, pregnancy and lactation

Pregnancy: 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 the dose and duration of therapy.

• Animal studies have shown reproductive toxicity. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and postimplantation 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 (< 30 % of the body surface) and duration of treatment as short as possible (not longer than 3 weeks).

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

• Functional renal injury in the foetus. From the 12th week: oligohydramnios (usually reversible after the end of treatment), or anamnios (particularly with prolonged exposure). After birth: kidney failure may persist (particularly with late or prolonged exposure).

• Pulmonary and cardiac toxicity in the foetus (pulmonary hypertension with premature closure of the ductus arteriosus). This risk exists from the beginning of the 6th month and increases if administration is close to full term.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the mother and the neonate, 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.

• Increased risk of oedema formation in the mother.

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

Breastfeeding:

Like other NSAIDs, diclofenac passes into breast milk in small amounts. However, at the recommended therapeutic doses of Solaraze 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, Solaraze 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).

4.7. Effects on ability to drive and use machines

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

4.8. Undesirable effects

Most frequently reported adverse reactions include skin reactions such as contact dermatitis, erythema and rash or application site reactions such as inflammation, irritation, pain and blistering. In studies there appeared to be no age specific increase or pattern of reactions.

Adverse reactions are listed in Table 1 according to Medical Dictionary for Regulatory Activities (MedDRA) system organ class and in decreasing frequency defined as follows: 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: frequency cannot be estimated from the available data.

Table 1: Treatment-related adverse reactions reported by body system and frequency

Infections and infestations

Very rare:

Rash pustular

Immune system disorders

Very rare:

Topical application of large amounts may result in systemic effects including all types of hypersensitivity (including urticaria, angioneurotic oedema)

Nervous system disorders

Common:

Hyperesthesia, hypertonia, localised paraesthesia

Eye disorders

Common:

Conjunctivitis

Uncommon:

Eye pain, lacrimation disorder

Vascular disorders

Uncommon:

Haemorrhage

Respiratory, thoracic and mediastinal disorders

Very rare:

Asthma

Gastrointestinal disorders

Uncommon:

Abdominal pain, diarrhoea, nausea

Very rare:

Gastrointestinal haemorrhage

Skin and subcutaneous tissue disorders

Common:

Dermatitis (including contact dermatitis), eczema, dry skin, erythema, oedema, pruritus, rash, scaly rash, skin hypertrophy, skin ulcer, vesiculobullous rash

Uncommon:

Alopecia, face oedema, maculopapular rash, seborrhoea

Rare:

Dermatitis bullous

Very rare:

Photosensitivity reaction

Renal and urinary disorders

Very rare:

Renal failure

General disorders and administration site conditions

Common:

Application site reactions (including inflammation, irritation, pain and tingling or blistering at the treatment site)

Temporary hair discolouration at the application site has been reported. This is usually reversed on stopping treatment.

Patch testing of previously treated patients indicate a 2.18 % probability of allergic contact dermatitis sensitisation (type IV) to diclofenac with as yet unknown clinical relevance. Cross-reactivity to other NSAIDs is not likely. Serum testing more than 100 patients indicated no presence of type I anti-diclofenac antibodies.

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 the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Due to the low systemic absorption of Solaraze, overdose is extremely unlikely as a result of topical use. However, the skin should be rinsed with water. There have been no clinical cases of ingestion of Solaraze inducing overdosage.

In the event of accidental ingestion (100 g Solaraze gel contain the equivalent of 3000 mg diclofenac sodium) resulting in significant systemic adverse reactions, general therapeutic measures normally adopted to treat poisoning with non-steroidal anti-inflammatories should be used.

Supporting and symptomatic treatment should be given for complications such as renal failure, convulsions, gastrointestinal irritation and respiratory depression. Gastric decontamination and the use of activated charcoal should be considered, especially within a short time of ingestion.

Specific therapies such as forced diuresis and dialysis will probably not be therapeutic in eliminating NSAIDs due to their high rate of protein binding.