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- Material and Methods
Background: Cutaneous adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs), in particular urticaria/angiedema syndrome, represent a frequent problem in clinical practice. To date laboratory tests for the diagnosis of these adverse reactions are not available. A patient with an adverse drug reaction to NSAIDs needs an alternative drug to assume if necessary. Nimesulide is a highly prescribed nonsteroidal anti-inflammatory drug (NSAID) world-wide. It is also described as one of the most tolerated NSAID. In this paper we present data on the tolerability of benzydamine in nimesulide-sensitive patients.
Patients and methods: One hundred and thirty-seven patients with nimesulide-induced urticaria were submitted to a single-blind, placebo-controlled peroral challenge with increasing doses of benzydamine.
Results: One hundred and thirty-four out of 137 (98%) patients tolerated benzydamine without adverse effects, only three (2%) experienced immediate systemic urticaria (1 at the first dose and 2 at the second dose).
Conclusion: Benzydamine is a well tolerated drug in patients with nimesulide-induced urticaria and it may represent a valid alternative NSAID in nimesulide-sensitive patients.
Nonsteroidal anti-inflammatory drugs (NSAIDs), together with antimicrobials, are the drug categories with the highest number of cutaneous reactions (1). In particular, NSAIDs may elicit adverse reactions such as urticaria/angiedema, bronchial asthma, rhinithis, and anaphylaxis. Pathogenic mechanisms are still obscure. The inhibition of prostaglandin endoperoxide H synthase (PGHS) 1 and/or 2 enzymes, which is a pharmacological effect of these drugs, has been proposed in the case of bronchial asthma. The inhibition of these enzymes may create an imbalance between PGHS (1 and/or 2) and 5-lipoxygenase (5-LO) in the arachidonic acid cascade with a lower production of the bronchodilator prostaglandin (PG) E2, (2, 3) and with a relatively higher production of the bronchoconstrictors leukotrienes (LT) C4 and D4.
The other clinical manifestations are classified as drug allergy or nonallergic drug hypersensitivity (position paper). In the drug allergy immunological mechanisms have been shown to be either antibidy or cell mediated. In the literature the documented NSAIDs allergy refer mostly to pyrazolone derivatives, (4–6) aspirin,(7, 8) anthranilic-acid derivatives,(9) and diclofenac (10).
In the majority of cases it is not possible to demonstrate an immunological mechanism. These are nonallergic drug hypersensitivity reactions and, to date, little or nothing is known about the pathogenetic mechanisms (11).
It is a frequent problem in clinical practice, to find an alternative NSAID in subjects who refer an adverse drug reaction to NSAIDs. The choice is usually focused on classes of NSAIDs other than those responsible for the adverse reaction and that offer the least amount of adverse reactions.
At the moment there are no NSAIDs absolutely void of adverse reactions.
Acetaminophen and nimesulide are NSAIDs that appear to have fewer side-effects than most members of the class of NSAIDs (12–14).
Benzydamine is a nonsteroidal anti-inflammatory drug that acts partly through an inhibitory effect on the phospholipase A2 by diminishing the liberation of arachidonic acid from phospholipids, and partly as a weak inhibitor of PGHS 1 and/or 2 by reducing the production of PGs (15, 16).
In this paper we present data on a single-blind, placebo-controlled peroral challenge with benzydamine in patients with nimesulide-induced urticaria.
- Top of page
- Material and Methods
NSAIDs are the most frequently consumed drugs world-wide. Adverse reactions to NSAIDs is a very important problem in clinical practice. Nimesulide is one of the most frequently prescribed NSAID, perhaps owing to its tolerability and efficacy. It is considered a tolerable NSAID and, along with acetaminophen, it seems to be responsible for the lowest number of adverse drug reactions among NSAIDs (12, 14). Nevertheless, in clinical practice, the number of patients who have adverse reactions to this drug is beginning to increase (13). Thus, finding of tolerable NSAID generally speaking is of great interest as well as a valid alternative to nimesulide because it is believed to be a tolerable NSAID.
The data reported here suggest that nimesulide is a tolerable NSAID. In fact 115 out of 137 patients (84%) had a positive history of urticaria to other NSAIDs apart from nimesulide, thus only 22 patients (16%) had an adverse reaction exclusively towards nimesulide. For this reason we can say that the patients in this study may be considered particularly reactive against NSAIDs.
Benzydamine is an NSAID with anti-inflammatory, antipyretic and anti edema activity. It is considered a weak inhibitor of PGHS 1–2 enzymes.
We have tested the hypotheses that benzydamine may be a tolerable NSAID and then it could be a valid alternative in NSAIDs-sensitive subjects, and, in particular, may represent a valid alternative in nimesulide-sensitive patients.
The results we have obtained are in favour of this hypotheses, in fact in this study population we have obtained only three (2%) positives out of 137 peroral challenges to benzydamine. This is a very low percentage, especially considering that the population of this study may be considered highly reactive against NSAIDs. These results clearly demonstrate that benzydamine is a tolerable NSAID and may represent a valid alternative in NSAIDs sensitive patients.
Moreover within the patients of group B (54 patients) who all had a positive peroral challenge with nimesulide only two (4%) had positive peroral challenge with benzydamine. This was probably the aim of this study because it suggests that benzydamine does not cross react with nimesulide.
As described by Stevenson and collegues, (21) the new class of NSAIDs which selectively inhibits PGHS-2 enzyme, are better tolerated than other NSAIDs in aspirin-sensitive patients.
Our data allow us to conclude that benzydamine is a tolerable NSAID and together with other NSAIDs such as floctafenine (17) and meloxicam (18–19) whose tolerability has been demonstrated, it may be considered a valid alternative in patients with NSAIDs adverse reactions. Moreover, it may be considered a valid alternative in those patients highly reactive to NSAIDs and in those who react against nimesulide as well.