Treatment of chronic anal fissure with topical nitroglycerin ointment 0.4%: a prospective clinical study

Abstract

Of all of the available topical treatments for the treatment of anal fissure, nitroglycerin (NTG) ointment has been the most widely popularised. However, the different studies carried out with this ointment have been with customised compounded prescription medications prepared by pharmacists. There has been a disparity in the results arising from the inconsistency of the product, depending on the pharmacy and the methodology used in the research, namely different means of application, doses and concentrations [1]. Azarnoff et al. [2] have suggested that this heterogeneity of results existed because, to date, the studies that were conducted used formulas prepared in pharmacies (where it is not possible to ensure the exact concentration or the homogeneity of the whole tube), and thus, the dose was not exact. In one study of 24 pharmacies in the USA, it was observed that 46% of the pharmacies failed to comply with the exact formula (concentration and/or dose) prescribed, which created differences in the results reported regarding pain reduction due to NTG ointment and migraine associated with treatment. This problem has been solved with the recent appearance on the market of the first NTG ointment for commercial use Rectogesic (glyceryl trinitrate 0.4%), where both the concentration and the dose (dosifier) are precise. In our experience with Rectogesic in 120 patients, initial fissure healing was achieved in 87 patients (72.5%). In 6 cases, a relapse of the fissure occurred 4 months after treatment was completed. Therefore, the final healing rate was 67.5% (81 patients).There are few articles reported in the literature with this new formula that correct for the methodological defects mentioned above. However, we can assume that the long-term recurrence rate is high since anal pressures in repose revert to the pre-treatment values in the first 8 weeks after healing [3]. Nevertheless, we should expect the treatment to cause an initial improvement in the symptoms in most patients. On occasion, the treatment may produce incapacitating proctalgia with serious effects on quality of life. But, for the majority of patients, this treatment makes it possible to avoid irreversible resection of the internal anal sphincter and the postoperative consequences. Since the introduction of topical nitrates, the number of surgical interventions performed for anal fissure has fallen by 72% in England and 61% in Scotland [4]. As regards side effects, the risk of migraine (20–70%) is four times greater than with the placebo, as observed in the medical literature [5]. Nevertheless, although headaches may be serious, they tend to be temporary or transitory (in the first 30 min) and only necessitate withdrawal from the treatment in approximately 10% of the patients. When headaches do occur, they can be treated with mild analgesics before applying the ointment. To reduce the incidence of this side effect, the product should be applied with the finger protected by a finger cot in order to limit the absorption to the anal area and to reduce the absorption of the product through the skin of the finger. In our sample of 120 patients, headaches occurred in 63 patients (52.5%), but most were self-limiting or were relieved by oral analgesics. We must take into account the fact that the intensity of the migraine is always less than the pain caused by the anal fissure; therefore, it is not common for patients to abandon the treatment as a consequence of this side effect. J. Perez-Legaz A. Arroyo (&) J. Ruiz-Tovar A. Lopez-Delgado A. Frangi P. Moya J. Santos F. Candela R. Calpena Alicante, Spain e-mail: arroyocir@hotmail.com