[Prescription and safety of dimethindene maleate micropellet capsules in Hungary]. / Dimethinden maleat-tartalmú, késleltetett felszívódású mikropellet kapszula alkalmazása és biztonságossága Magyarországon.

INTRODUCTION: Dimethindene maleate, the active substance of the extended-release Fenistil 24 capsule, is a first-generation histamine receptor antagonist, which is marketed in 10 European countries. In Hungary approximately 200,000 boxes are sold yearly from this product, which is mainly used for treatment of symptoms associated with allergic diseases (urticaria, itch, hay fever) The aim of the present study was to gather information with the help of medical doctors about the indications, efficacy and primarily the safety of use, observed side effects and frequency of adverse events associated with this product. METHOD: During the study 4574 questionnaires were evaluated out of the 5578 filled by 249 doctors. Responses were included into the evaluation only if the address and type of polyclinic of the doctor filling the questionnaire, indication of the use of the product could be precisely identified and the patient returned for control visit at least once. RESULTS: Based on the study results in Hungary in most cases the product is prescribed according to the indications and dosing schedule given in the SPC. In this study participating doctors found the drug to be effective in 95% of cases. Unexpected, new adverse events were not observed during the study. Approximately 22% of patients reported adverse events, tiredness and sleepiness being the most frequent ones. Occurrence of sedative adverse events was more frequent among those who were prone to tiredness (51 vs. 17%). The adverse events most frequently were reported 10-12 hours after intake. The average length of treatment was 4 weeks or less. The medicine is taken usually at night, before going to sleep. CONCLUSIONS: In Hungary in most cases the product is prescribed according to the indications and dosing schedule given in the current approved Summary of Product Characteristics.

[Dimethindene maleate administered via intramuscular route in man: local and systemic tolerance]. / Maléate de dimétindène, administré par voie intramusculaire chez l'homme: tolérance locale et systémique.

Local and systemic tolerance of dimethindene maleate was studied in 10 healthy volunteers by the intramuscular route (4 mg in 4 ml solvent). Subjective perception of pain and other reported side effects were registered and objective signs at the injection site were assessed repeatedly. Hematologic and biochemical tests were performed before and after completion of the study. Two volunteers complained about local pain immediately and one hour after the injection. An other volunteer developed a small hematoma within 48 hours after injection. No other side effects or adverse reactions were noted. Good tolerance of dimethindene maleate after intramuscular application could thus be established.

A new antihistamine hc20-511 compared with dimetinden (fenistil retard) in the treatment of chronic urticaria and other pruritic dermatoses.

The new antihistamine, HC20-511 (Sandoz), was compared with Dimetinden (Fenistil retard) in a single-blind comparative study in 42 patients with dermatoses, 28 of whom suffered from chronic urticaria. HC20-511 had a better effect, especially in chronic urticaria, where pruritus, erythema and papules quickly disappeared. The effect appeared somewhat faster than and lasted as long as that of Dimetinden, although HC20-511 is not a retard-preparation unlike the Dimetinden preparation used for comparison. HC20-511 also caused less side effects.

Dimethindene maleate in the treatment of sunburn. A double-blind, placebo-controlled pilot study.

The efficacy of topical dimethindene maleate (DMM, CAS 31614-69-5, Fenistil Gel) in the treatment of sunburn was evaluated in a placebo-controlled, 1-period crossover trial in 24 healthy volunteers. An UV-erythema (sunburn) of a well-defined intensity and extent was experimentally induced on three different skin test-areas by means of UV-A/B irradiation with three times the minimal erythema dose (MED). About 24 h after irradiation, one skin test-area was subjected to a 1-h occlusive treatment with DMM gel, the second test area was subjected to treatment with a placebo gel and the third one remained untreated. As objective-quantitative indicators of tenderness, a key symptom of sunburn, sensory and pain thresholds to CO2-Laser stimulation and laser somatosensory evoked potentials (SEPs) in Vertex-EEG were assessed about 1.5 h postdose. The reaction times (RTs) to painless and painful CO2-laser stimulation (sensory and pain threshold level, respectively) on the DMM-treated area were significantly longer than RTs to stimulation on the placebo-treated area. Thresholds in terms of laser energy showed no differences between the treatments. The SEP N1-amplitude on the DMM-area was markedly decreased in comparison to placebo. With regard to subjective sensations of pain, itching and tenderness assessed by means of visual analogue scales (VAS), no clinically relevant differences between treatments were observed after sole UV-irradiation. After additional laser stimulation tenderness was--objectively but not subjectively--decreased on the DMM-area versus placebo. Both gel preparations were well tolerated.

Influences of dimethindene maleate in a new formulation on oculo and psychomotor performance using the oculodynamic test (ODT) in volunteers.

Most antihistamines are assumed to possess a more or less pronounced sedative potential in addition to their antihistaminic properties. Therefore, a single-blind three-way crossover study was designed to assess the influence of single-dose dimethindene maleate (new "once a day formulation") on vigilance and performance vs. loratadine as reference and vs. placebo. Drug effects on performance were tested in 18 healthy volunteers by the oculodynamic test [ODT, i.e. choice reaction task (CRT), combined with recording of electrooculography (EOG) and cardiovascular parameters] and effects on subjective well-being by visual analogue scales (VAS). Main target parameters for evaluation of CNS-effects are latency and subjective perception of sedation (VAS). Neither statistically significant nor clinically relevant differences in all objective and subjective target variables (ODT and VAS) between active drugs and placebo, after single-dose administration were found. The same holds for accessory EOG, CRT and vital parameters under workload.

[Antipruritic effect of antihistaminic and local anesthetic topical agents after iontophoretic histamine stimulation]. / Antipruritugener Effekt antihistaminerger und lokalanästhetischer Externa nach iontophoretischem Histaminreiz.

No adequate topical therapy is available for pruritus. As little is known about the local influence of antihistamines and topical anaesthetics on the pruritic effect of histamine, we studied these agents in 12 volunteers. The antipruritic effect of 15-min topical application of dimethindene maleate (Fenistil gel) and different agents (Optiderm, EMLA, Xylocaine-Salbe 5%) on subsequent focal histamine stimulus (20 mC) given by iontophoresis was evaluated. The results were compared with those of pretreatment with the corresponding placebo creams and observations on skin. Wheal and flare areas were evaluated planimetrically. Itch or pain ratings were entered on a scale every minute over a 24-min period. The examination also comprised alloknesis, i.e. elicitation of perifocal itch sensation by usually non-itch-inducing (e.g. mechanical) stimuli. Remarkably, all topically applied substances, regardless of antihistaminic or anaesthetic potential, reduced the area of alloknesis significantly. This is likely to be a result of diminished excitability of the cutaneous mechanoreceptors. Itching was significantly reduced by all active substances, including the placebo cream corresponding to Optiderm, which might be due to the presence of urea.

Effects of dimethindene maleate on psychomotor performance in the oculodynamic test compared with placebo and loratadine.

The effects of dimethindene maleate (CAS 3614-69-5) on the central nervous system-as sustained release pellets (Fenistil OAD; OAD = once a day) and sustained release tablets (Fenistil retard) with an immediate release fraction-were investigated by means of the oculodynamic test (ODT) and visual analogue scales and compared to loratadine (CAS 79794-75-5) and placebo. In the confirmatory part of the study 18 healthy volunteers were included in a single-blind, randomised, 3-way change-over design with Fenistil OAD, loratadine, and placebo. An additional, fourth exploratory arm with Fenistil retard was run in 6 (out of the 18) subjects after completing the main part of the study. The ODT includes electro-oculography, choice reaction task, and cardiologic parameters under workload. Visual analogue scales were used for subjective ratings on well-being and drug effects concerning wakefulness (sedation), excitation, dizziness, performance, effort, and dry mouth. The results show no relevant differences between either of the active drugs and placebo. Therefore it can be stated that after a single dose there is no sedating effect of dimethindene maleate compared to loratadine or placebo.