ALMIRAL Gel Ref.[28121] Active ingredients: Diclofenac

The possibility of systemic adverse events from application of Almiral gel cannot be excluded if the preparation is used on large areas of skin and over a prolonged period (see the product information on systemic forms of diclofenac).

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

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

Almiral gel 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.

Side effects include itching, reddening or smarting of the skin or skin rash. Photosensitivity reactions have been observed in isolated cases.

Asthma has been rarely reported in patients using topical non steroidal anti-inflammatory drugs (NSAID) preparations.

Application over extensive areas for prolonged periods or application in excess of recommended dosage may give rise to systemic effects. 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.

Almiral gel contains propylene glycol, which may cause skin irritation.

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

However, the following interactions occur with oral forms of Almiral:

Lithium and digoxin: Diclofenac may increase plasma concentrations of lithium and digoxin.

Anticoagulants: Although clinical investigations do not appear to indicate that diclofenac has an influence on the effect of anticoagulants, there are isolated reports of an increased risk of haemorrhage with the combined use of diclofenac and anticoagulant therapy. Therefore, to be certain that no change in anticoagulant dosage is required, close monitoring of such patients is required. As with other non-steroidal anti-inflammatory agents, diclofenac in a high dose can reversibly inhibit platelet aggregation.

Antidiabetic agents: Clinical studies have shown that diclofenac can be given together with oral antidiabetic agents without influencing their clinical effect. However there have been isolated reports of hypoglycaemic and hyperglycaemic effects which have required adjustment to the dosage of hypoglycaemic agents.

Ciclosporin: Cases of nephrotoxicity have been reported in patients receiving concomitant cyclosporin and NSAIDs, including diclofenac. This might be mediated through combined renal antiprostaglandin effects of both the NSAID and cyclosporin.

Methotrexate: Cases of serious toxicity have been reported when methotrexate and NSAIDs are given within 24 hours of each other. This interaction is mediated through accumulation of methotrexate resulting from impairment of renal excretion in the presence of the NSAID.

Quinolone antimicrobials: Convulsions may occur due to an interaction between quinolones and NSAIDs. This may occur in patients with or without a previous history of epilepsy or convulsions. Therefore, caution should be exercised when considering the use of a quinolone in patients who are already receiving an NSAID.

Other NSAIDs and steroids: Co-administration of diclofenac with other systemic NSAIDs and steroids may increase the frequency of unwanted effects. Concomitant therapy with aspirin lowers the plasma levels of each, although the clinical significance is unknown.

Diuretics: Various NSAIDs are liable to inhibit the activity of diuretics. Concomitant treatment with potassium-sparing diuretics may be associated with increased serum potassium levels, hence serum potassium should be monitored.

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/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.

Breastfeeding

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

Patients who experience dizziness or other central nervous system disturbances, including visual disturbances, while taking NSAIDs should refrain from driving or operating machinery.

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.

Table 1:

Almiral gel is usually well tolerated. Itching, reddening or smarting of the skin, or skin rash, commonly occurs. Photosensitivity reactions have very rarely been observed.

Systemic absorption of Almiral gel is low compared with plasma levels obtained following oral forms of Almiral. However, where diclofenac gel is applied to a relatively large area of skin and over a prolonged period, the possibility of systemic side effects cannot be completely excluded.

Asthma has very rarely been reported in patients using topical NSAID preparations.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions is an important way to gather more information to continuously monitor the benefit / risk balance of the medicinal product. Any suspected adverse reactions should be reported to Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy / phs Fax: + 357 22608649.

None stated.