Source: Υπουργείο Υγείας (CY) Revision Year: 2019 Publisher: MEDOCHEMIE LTD, 1-10 Constantinoupoleos street, 3011 Limassol, Cyprus
Pharmacotherapeutic group: Antiinflammatory preparations, non-steroids for topical use, Topical products for joint and muscular pain
ATC code: M02AA15
Diclofenac is a non-steroidal anti-inflammatory (NSAID) with pronounced analgesic, anti-inflammatory and antipyretic properties. Inhibition of prostaglandin synthesis is the primary mechanism of action of diclofenac.
Almiral gel is an anti-inflammatory and analgesic preparation designed for topical application. In inflammation and pain of traumatic or rheumatic origin, Almiral gel relieves pain, decreases swelling, and shortens the time to return to normal function.
Clinical data have demonstrated that diclofenac gel reduces acute pain one hour after initial application (p<0.0001 versus placebo gel). Ninety-four percent (94%) of patients responded to diclofenac gel after 2 days of treatment versus 8% with placebo gel (p<0.0001). Resolution of both pain and functional impairment were achieved after 4 days of treatment with diclofenac gel (p<0.0001 versus placebo gel).
Due to an aqueous-alcoholic base it exerts a soothing and cooling effect.
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 gel 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.
Diclofenac concentrations have been measured from plasma, synovial tissue and synovial fluid after topical administration of diclofenac gel 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 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, where it is found in concentrations up to 20 times higher than in plasma.
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.
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.
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 data from acute and repeated dose toxicity studies, as well as from genotoxicity, mutagenicity, and carcinogenicity studies with diclofenac revealed no specific hazard for humans at the intended therapeutic doses. There was no evidence that diclofenac had a teratogenic potential in mice, rats or rabbits. Diclofenac had no influence on the fertility of parent animals in rats. The prenatal, perinatal and postnatal development of the offspring was not affected.
Diclofenac gel was well tolerated in a variety of studies. There was no potential for phototoxicity and diclofenac-containing gel caused no skin sensitization.
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