PIROXICAM Gel Ref.[7941] Active ingredients: Piroxicam

A study in man examining skin biopsies following piroxicam gel administration concluded that piroxicam rapidly permeates through the stratum corneum into the epidermis/dermis after application of the gel with plasma levels being low.

A separate study in man demonstrated mean plasma concentrations of piroxicam gel to be approximately 5% of those observed after equivalent doses of oral or intramuscular piroxicam. In healthy subjects or patients following the administration of a single oral dose, the pharmacokinetics of Piroxicam are linear, with maximum plasma concentration usually being obtained in about 2 h, but this can vary from 1-6 h in different subjects. It has a low clearance rate of approximately 45 h, but the half-life can vary from 30-60 h. After repeated doses of 20 mg daily, steady–state concentrations are generally achieved in 7-12 days; with a peak plasma concentration ranging from 4.5-2.2 mg/l.

In humans it penetrates into the synovial fluid of patients with rheumatoid arthritis, osteoarthritis, and reactive synovitis where mean concentrations are approximately 40% of those in plasma; it is also demonstrable in synovial tissues. Concentrations of piroxicam in breast milk are about 1% of those in the maternal plasma at the same time. Overall, piroxicam is 99% bound to plasma protein. Pharmacokinetics of the drug do not appear to be age related, and renal function has only a limited influence on its elimination, but plasma concentrations are increased in patients with severe liver dysfunction.

Piroxicam is eliminated by biotransformation in the liver. The major route is by hydroxylation, with the resultant products being excreted alone or as a glucuronide in urine and faeces. The metabolites of piroxicam have little or no anti-inflammatory activity in animal models. Approximately 10% of an oral dose is excreted as unchanged drug in 10 days.

In reproductive toxicity studies, piroxicam increases the incidence of dystocia and delayed parturition in animals, when drug administration is continued during pregnancy. Administration of prostaglandin synthesis inhibitors has also been shown to result in increased pre- and post-implantation loss. These observations were made using parenteral dosing, and as noted in section 5.2, equilibrium plasma levels of piroxicam obtained in patients using the topical gel are only approximately 5% of those achieved using an equivalent dose of parenteral product.

In animal studies with the topical gel, there were no treatment- related adverse effects using 1 gram of gel daily for up to 30 days, nor was there evidence of photo-allergy or skin sensitisation.