Antirheumatic, anti-inflammatory, analgesic agent
Active ingredient: diclofenac resinate, equivalent to diclofenac sodium.
Pharmaceutical form and quantity of active substance per unit:
Oral drops (suspension) containing the equivalent of 15 mg/mL (1 drop = 0.5 mg) diclofenac sodium.
Excipients: Flavouring agent: tutti-frutti; saccharin sodium; vehicle excipients: hydrogenated castor oil, liquid paraffin, polacrilin.
White to pale beige homogeneous oily suspension with a fruity odour.
Diclofenac, the active ingredient of Cataflam, is a non-steroidal agent with pronounced antirheumatic, anti inflammatory, analgesic and antipyretic activity.
Inhibition of prostaglandin biosynthesis by diclofenac has been demonstrated experimentally and this is considered fundamental to its mechanism of action. Prostaglandins play a major role in causing inflammation, pain and fever. In rheumatic diseases, the anti inflammatory and analgesic properties of diclofenac elicit a clinical response characterized by marked relief of signs and symptoms such as pain at rest, pain on
movement, morning stiffness and swelling of the joints, and by improved function. In posttraumatic and postoperative inflammatory conditions, Cataflam Oral Drops rapidly relieve both spontaneous pain and pain on movement, and reduce inflammatory swelling and wound oedema. In clinical trials Cataflam has also been found to exert a pronounced analgesic effect in moderate and severe pain of nonrheumatic origin.
In vitro it does not suppress proteoglycan biosynthesis in cartilage at concentrations equivalent to those attained in humans.
Diclofenac is absorbed from the suspension rapidly and completely after passing through the stomach. Ingestion with food does not reduce the amount of drug absorbed but might affect the rate of absorption.
Peak plasma concentration is attained within two hours after ingestion of a single dose of Cataflam Oral Drops equivalent to 50 mg diclofenac sodium. Plasma concentration shows a linear relation to dose.
Concentrations attained in children after equivalent doses (mg/kg bodyweight) are similar to those attained in adults. Repeated administration does not alter the drug's pharmacokinetic behaviour. Accumulation does not occur if the recommended interval is respected between doses.
Diclofenac is 99.7% bound to serum proteins, mainly albumin (99.4%). Its apparent volume of distribution has been calculated as 0.12-0.17 L/kg. Diclofenac penetrates the synovial fluid, where the concentration reaches a peak 2-4 hours after the peak plasma concentration. The apparent half-life of elimination from synovial fluid is 3-6 hours. The concentration in synovial fluid is higher than in plasma as early as two hours after the peak plasma level has been attained and remains higher for up to 12 hours.
Biotransformation of diclofenac is partly by glucuronidation of the intact molecule but mainly by single and multiple hydroxylation and methoxylation. This results in several phenolic metabolites (3'-hydroxy-, 4'-hydroxy-, 5-hydroxy-,4',5-dihydroxy- and 3'-hydroxy4'- methoxy-diclofenac), most of which are subsequently converted to glucuronide conjugates. Two of the phenolic metabolites are pharmacologically active but to a much smaller extent than diclofenac itself.
Total body clearance of diclofenac from plasma is 263 ± 56 mL/min (mean ± SD). Its terminal half-life in plasma is 1-2 hours. Four of the metabolites, including the two that are active, also have short plasma halflives of 1-3 hours. One of the metabolites (3'-hydroxyl-4'-methoxy-diclofenac) has a much longer plasma half-life but is virtually inactive. About 60% of the dose is excreted in the urine as metabolites as against less than 1% as unchanged substance. The rest of the dose is eliminated as metabolites via the bile in the faeces.
Pharmacokinetics in special clinical situations
No relevant age-dependent differences in the drug's absorption, metabolism or excretion have been observed. In patients with renal
impairment the drug's single-dose kinetics do not suggest that there is any accumulation of unchanged substance with the usual dosage schedule. In patients with a creatinine clearance of < 10 mL/min, theoretical steady-state plasma levels of the metabolites are about 4 times higher than in normal subjects.
However, the metabolites are ultimately eliminated via the bile.
In patients with hepatic impairment (chronic hepatitis or compensated cirrhosis), the kinetics and metabolism of diclofenac are the same as in patients without liver disease.
Post-traumatic and postoperative pain, inflammation and swelling, e.g. following dental or orthopaedic surgery. As an adjunct in acute painful inflammatory infections of the ear, nose or throat, e.g. pharyngotonsillitis, otitis. In keeping with standard therapeutic principles, the underlying disease should be treated with specific therapy as appropriate.
Cataflam Oral Drops are particularly suitable for paediatric use because they enable the dosage to be individually tailored to bodyweight within the recommended range (1 drop = 0.5 mg). Children aged 1 year or over should be given 0.5-2 mg/kg bodyweight daily in 2-3 divided doses, depending on the severity of the disorder. For the treatment of juvenile rheumatoid arthritis the daily dosage can be increased up to a maximum of 3 mg/kg, given in divided
doses. Cataflam drops should not be given to children under 1 year of age.
Cataflam Oral Drops are also a means whereby adults with dysphagic disorders can take diclofenac. The usual starting dose is 200-300 drops daily, i.e.100 drops (=approx. 1½ teaspoonfuls) 2-3 times daily. 150-200 drops daily are normally sufficient in mild cases and for children over 14 years of age.