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Therapeutic Category
- Non-steroidal anti-inflammatory drugs
- DERMATOLOGICAL DRUGS
- Pharmaceutical Form : Emulgel
- Composition : Each 1 g contains: Diclofenac diethylammonium 23.2 mg Equivalent to Diclofenac sodium 20 mg
- Active Substance : Diclofenac Sodium
MECHANISM OF ACTION:
Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) with pronounced analgesic, anti-inflammatory and antipyretic properties. Inhibition of prostaglandin synthesis is the primary mechanism of action of diclofenac.
This medicine is an anti-inflammatory and analgesic preparation designed for topical application. In inflammation and pain of traumatic or rheumatic origin, this medicine relieves pain, decreases swelling, and shortens the time to return to normal function.
Due to an aqueous-alcoholic base the gel also exerts a cooling effect.
PHARMACOKINETICS:
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. After topical application to approximately 400 cm2 of skin, the extent of systemic exposure as determined by plasma concentration of this medicine (2 applications/day) was equivalent to diclofenac 1.16% gel (4 applications/day). The relative bioavailability of diclofenac (AUC ratio) for this medicine versus tablet was 4.5% on day 7 (for equivalent diclofenac sodium dose). Absorption was not modified by a moisture and vapour permeable bandage.
Distribution:
Diclofenac concentrations have been measured from plasma, synovial tissue and synovial fluid after application of topical diclofenac to hand and knee joints. Maximum plasma concentrations were 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 penetrates inflamed areas, preferentially distributing to and persisting in deep inflamed tissues such as joints, where it 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.
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
– Localized forms of soft tissue rheumatism.
CONTRAINDICATIONS:
- Patients with or without chronic asthma in whom attacks of asthma, urticaria or acute rhinitis are precipitated by aspirin or other non-steroidal anti-inflammatory agents.
- Hypersensitivity to diclofenac, acetylsalicylic acid or other non-steroidal anti-inflammatory drugs.
- Hypersensitivity to any other ingredient of the gel.
- Concomitant use of other products containing diclofenac.
- Concomitant use of oral NSAIDS.
- During the last trimester of pregnancy.
SPECIAL WARNINGS AND PRECAUTIONS FOR USE:
The possibility of systemic adverse events from application of this medicine cannot be excluded if the preparation is used on large areas of skin and over a prolonged period.
This medicine 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 taken by mouth.
Patients with a history of, or active, peptic ulceration. 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 bronchial asthma. Discontinue the treatment if a skin rash develops after applying the product.
This medicine contains propylene glycol, which may cause mild, localised skin irritation in some people. It also contains butylhydroxytoluene which may cause local skin reactions (e.g. contact dermatitis) or irritation to the eyes and mucous membranes.
DRUG INTERACTIONS:
Systemic absorption of diclofenac from topical application is very low and no drug interactions during treatment with this medicine have been reported.
Pregnancy:
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 ductusarteriosus and pulmonary hypertension)
- Renal dysfunction, which may progress to renal failure with oligohydroamniosis
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 this medicine 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 medicine should not be applied on the breasts of nursing mothers, nor elsewhere on large areas of skin or for a prolonged period of time.
UNDESIRABLE EFFECTS:
Undesirable effects include mild and passing skin reactions at the site of application. In very rare instances, allergic reactions may occur.
Rash pustular, Hypersensitivity (including urticaria), angioedema, Asthma, Dermatitis (including contact dermatitis), rash, erythema, eczema, pruritus.
Dermatitis bullous, Photosensitivity reaction.
DOSAGE AND METHOD OF ADMINISTRATION:
Adults and children 14 years and over: The gel 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 2 times a day (preferably morning and evening). The maximum daily dose is 8g. Therefore, the maximum weekly dose is 56g.
The gel can be used for up to 14 days under pharmacy supervision.
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 is recommended. Do not use for more than 14 days unless recommended by a doctor.
Use in the elderly: The usual adult dosage may be used.
Children and adolescents: There are insufficient data on efficacy and safety available for the children and adolescents below 14 years of age. 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.
Overdose:
The low systemic absorption of topical diclofenac renders overdoses very unlikely.
However undesirable effects can be expected if this medicine is inadvertently ingested (e.g. 1 tube of 50 g contains the equivalent of 1 g 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 lavage and the use of activated charcoal should be considered, especially within a short time of ingestion.
STORAGE CONDITIONS: Do not store above 30°C.
PACKAGING: 30 – 50 g