Fixed-Dose Combination of NSAIDs and Spasmolytic Agents in the Treatment of Different Types of Pain—A Practical Review

This review presents the most common disease entities in which combinations of NSAIDs and spasmolytic drugs are used to reduce pain. The benefits of fixed-dose combination products (FDCs) are that they improve the response in people with insufficient monotherapy. Using the synergy or additive effect of drugs, it is possible to obtain a significant therapeutic effect and faster action with the use of smaller doses of individual drugs. In addition, one active ingredient may counteract adverse reactions from the other. Another essential aspect of the use of FDCs is the improvement of medical adherence due to the reduction in the pill burden on patients. It is also possible to develop a fixed-dosed combination product de novo to address a new therapeutic claim and be protected by patents so that the manufacturer can obtain exclusive rights to sell a particular FDC or a formulation thereof. The proposed fixed-dose combinations should always be based on valid therapeutic principles and consider the combined safety profile of all active substances included in the medicinal product. This review aims to identify which combinations of NSAIDs and spasmolytics have been developed and tested and which combinations are still under development.

Study of Serum Levels, Venous Irritation and Gastrointestinal Side-effects with Intravenous Erythromycin Lactobionate in Patients with Bronchopulmonary Infection

1 Sixteen patients with bronchopulmonary infection received 500 mg erythromycin lactobionate by intravenous infusion every 8 h for 2 days. The duration of infusion was either 30 (8 patients) or 60 min (8 patients). An inline filterset (0.22 μm) was included in the intravenous administration set in 4 patients of each infusion group. 2 Serum erythromycin levels were obtained before and at various times for 8 h after the first and fourth doses and before and immediately after the other doses. The incidence and severity of venous irritation and gastrointestinal side-effects were assessed. 3 Mean (S.D.) peak erythromycin levels for the 30 min infusion were 26.31 (6.89) μg/ml (first dose) and 26.85 (6.11) μg/ml (fourth dose) and for the 60min infusions, 23.96 (7.91) μg/ml (first dose) and 23.65 (6.55) μg/ml (fourth dose). 4 Venous irritation was experienced by 12 patients, ranging from localized discomfort to thrombophlebitis, but the severity was significantly reduced by inline filtration (P < 0.005). 5 Gastrointestinal side-effects were reported by 8 patients and 1 patient withdrew because of severe abdominal pain and nausea. These symptoms were usually relieved by spasmolytic agents and possibly could be explained by high concentrations reaching the gut wall either by biliary excretion or direct transport from blood and stimulating smooth muscle motility.