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.

For cutaneous use only

Adults: Clofen should be rubbed gently into the skin. Depending on the size of the affected site to be treated 2-4g (a circular shaped mass approximately 2.0-2.5cm in diameter) should be applied 3-4 times daily. After application, the hands should be washed unless they are the site being treated. It is recommended that treatment be limited to 14 days.

If the condition does not improve or worsens within 7 days of starting treatment, patient should consult their doctor to exclude an alternative underlying cause of pain.

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

Children and adolescents below 14 years: There are insufficient data on efficacy and safety available for 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.

Precautions

The possibility of systemic adverse events from application of diclofenac cannot be excluded if the preparation is used at higher dosage or over a prolonged period. These include gastrointestinal disturbances and bleeding, irritability, fluid retention, rash, hepatitis, renal dysfunction, anaphylaxis and rarely blood dyscrasias, bronchospasm and erythema multiforme. This product should only be used with great caution in patients with a history of peptic ulcer, gastrointestinal bleeding, hepatic or renal insufficiency, or bleeding diathesis, or intestinal inflammation. Circulating levels of the active drug substance are low but the theoretical risk in these patients should be considered.

Discontinue the treatment if a skin rash develops after applying the product.

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

Diclofenac should be applied only to intact, non-diseased skin and not to skin wounds or open injuries. It should not be used with occlusion. It should not be allowed to come into contact with the eyes or mucous membranes, and should never be ingested.

Patients with a history of, or active, peptic ulceration. Some possibility of gastrointestinal 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, bronchial asthma. 

Diclofenac is usually well tolerated. Local irritation, erythema, pruritus or dermatitis, desquamation and discoloration commonly occur. Bullous or vesicular eruptions are rarely reported. Skin photosensitivity has very rarely been reported. Patients should be warned against excessive exposure to sunlight in order to reduce the incidence of photosensitivity.

Information concerning excipients

Clofen creamagel contains propylene glycol, which may cause skin irritation.

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

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/fetal 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-fetal 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 fetus 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.

Lactation

Like other NSAIDs, diclofenac passes into breast milk in small amounts. However, at therapeutic doses of diclofenac 1.16% 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, diclofenac 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).

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

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 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000), not known:  cannot be estimated from the available data. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Diclofenac is usually well tolerated. Local irritation, erythema, pruritus or dermatitis, desquamation and discoloration commonly occur. Bullous or vesicular eruptions are rarely reported. Skin photosensitivity has very rarely been reported.

To report any side effect(s):

§ Saudi Arabia:

The National Pharmacovigilance Centre (NPC):

-        SFDA Call Centre: 19999

-        E-mail: npc.drug@sfda.gov.sa

-        Website: https://ade.sfda.gov.sa/

§ Other GCC States:

-        Please contact the relevant competent authority.

Signs and symptoms

The low systemic absorption of topical diclofenac renders overdosage unlikely. However, undesirable effects, similar to those observed following an overdose of diclofenac tablets can be expected if topical diclofenac is ingested (1 tube of 100g contains the equivalent of 1000mg diclofenac sodium). In the event of accidental ingestion, resulting in significant systemic side-effects, general therapeutic measures normally adopted to treat poisoning with non-steroidal anti-inflammatory drugs should be used.

Treatment

Management of overdosage with NSAIDs essentially consists of supportive and symptomatic measures. There is no typical clinical picture resulting from diclofenac overdosage. Supportive and symptomatic treatment should be given for complications such as hypotension, renal failure, convulsions, gastro-intestinal irritation, and respiratory depression; specific therapies such as forced diuresis, dialysis or haemoperfusion are probably of no help in eliminating NSAIDs due to their high rate of protein binding and extensive metabolism.

Further management should be as clinically indicated or as recommended by the national poisons centres, where available.

Pharmacotherapeutic group: Topical products for joint and muscular pain, anti-inflammatory preparations, non-steroids for topical use (ATC code M02A A15)

Mode of action: Diclofenac is a potent non-steroidal anti-inflammatory (NSAID) with pronounced analgesic, anti-inflammatory and antipyretic properties. Diclofenac exerts its therapeutic effects primarily through inhibition of prostaglandin synthesis by cyclo-oxygenase 2 (COX-2).

Diclofenac creamagel is an anti-inflammatory and analgesic preparation designed for topical application. In inflammation and pain of traumatic or rheumatic origin, diclofenac relieves pain, decreases swelling, and shortens the time to return to normal function. Due to an aqueous-alcoholic base the creamagel exerts a soothing and cooling effect.

Clinical data have demonstrated that diclofenac 1.16% reduces acute pain one hour after initial application (p < 0.0001 versus placebo). Ninety-four percent (94%) of patients responded to creamagel 1.16% after 2 days of treatment versus 8% with placebo

(p <0.0001) Resolution of both pain and functional impairment were achieved after 4 days of treatment with diclofenac1.16% (p < 0.0001 versus placebo).

Absorption:

The quantity of diclofenac absorbed through the skin is proportional to the size of the treated area, and depends on both the total dose applied and the degree of skin hydration. Absorption amounts to about 6 % of the applied dose of diclofenac after topical application of 2.5 g diclofenac on 500 cm² skin, determined by reference to the total renal elimination, compared with diclofenac tablets. A 10-hour occlusion leads to a three-fold increase in the amount of diclofenac absorbed.

Distribution:  

Diclofenac concentrations have been measured from plasma, synovial tissue and synovial fluid after topical administration of diclofenac to hand and knee joints. Maximum plasma concentrations are approximately 100 times lower than after oral administration of the same quantity of diclofenac. 99.7 % of diclofenac is bound to serum proteins, mainly albumin (99.4 %).

Diclofenac accumulates in the skin which acts as a reservoir from where there is a sustained release of drug into underlying tissues. From there, diclofenac preferentially distributes and persists in deep inflamed tissues (such as the joint) rather than in the bloodstream. Diclofenac is found in concentrations up to 20 times higher than in plasma.

Biotransformation:

Biotransformation of diclofenac involves partly glucuronidation of the intact molecule, but mainly single and multiple hydroxylation resulting in several phenolic metabolites, most of which are converted to glucuronide conjugates. Two of the phenolic metabolites are biologically active, however, to a much smaller extent than diclofenac.

Elimination:

The total systemic clearance of diclofenac from plasma is 263 ± 56 ml/min. The terminal plasma half-life is 1-2 hours. Four of the metabolites, including the two active ones, also have short plasma half-lives of 1-3 hours. One metabolite, 3'-hydroxy-4'-methoxy-diclofenac, has a longer half-life but is virtually inactive. Diclofenac and its metabolites are excreted mainly in the urine.

Characteristics in patients: No accumulation of diclofenac and its metabolites is to be expected in patients suffering from renal impairment. In patients with chronic hepatitis or non-decompensated cirrhosis, the kinetics and metabolism of diclofenac are the same as in patients without liver disease.

Preclinical studies conducted with diclofenac did not reveal any clinical relevant toxicological effects.

Note applicable

Store below 30°C

50g creamagel in a printed collapsible aluminium tube in a printed carton along with a leaflet

No special requirements