Efficacy and safety of an oral formulation of cetirizine and prolonged-release pseudoephedrine versus xylometazoline nasal spray in nasal congestion.

The aim of this study was to compare the decongestant properties and tolerability of the sympathomimetic xylometazoline hydrochloride 0.1% (CAS 1218-35-5, XMZ) and an oral formulation of cetirizine hydrochloride 5 mg and pseudoephedrine hydrochloride 120 mg (CAS 83881-51-0 and 90-82-4, CTZ/PSE; Cirrus). Thirty-six asymptomatic patients suffering from perennial allergic rhinitis from house dust mite were randomized to this open two-period crossover study. Patients received the study medications for four days each. In each period, treatments were taken twice a day. On day 1 in each period, immediately after the first dose of medication, patients were challenged with Dermatophagoides pteronyssinus extract 1 in the Vienna Challenge Chamber for 5 h. Primary efficacy parameters were nasal congestion evaluated by digital analysis of nasal cavity photographs and nasal airflow. Furthermore amounts of nasal secretions, nasal and ocular symptoms were recorded. In addition, 5 independent Ear-Nose-Throat specialists also assessed nasal cavity photographs. Statistical analyses were conducted at the 5% level of significance. Digital analysis of the nasal cavity photographs as well as nasal airflow measurements did not differentiate XMZ from CTZ/PSE. Ratings of the photographs of the nasal cavity emphasized the rapid onset of XMZ. No clinically relevant adverse events were recorded. This rapid onset of action but short-lived effect of topical xylometazoline 0.1% should be balanced against the consistent and prolonged effect of systemic cetirizine/pseudoephedrine combination in the treatment of perennial allergic rhinitis as no significant differences between these 2 medications were noted regarding their decongestant properties. With the exception of nasal obstruction, all subjective symptoms as well as the global condition were significantly better under CTZ/PSE. Amounts of nasal secretions during these sessions were significantly lower with CTZ/PSE.

The influence of female sex hormones on nasal reactivity in seasonal allergic rhinitis.

BACKGROUND: This study aimed to investigate whether the hormone peaks of estrogen and progesterone could influence the extent of the allergic reaction in grass-pollen-allergic women. METHODS: Twenty-three allergic women with seasonal allergic rhinitis due to grass pollen were included in this trial. Twelve were taking oral contraceptives (OC) (control group), and 11 were taking no pill (target group). The subjects were challenged with grass pollen by nasal provocation test around day 14 of their menstrual cycle (ovulation day) and again at the end of the cycle (day 27). The primary criteria were the subjective nasal symptoms rhinorrhea, nasal blockage, itching, and sneezing. A further criterion was the objectively measured nasal mucosal swelling, assessed by active anterior rhinomanometry. All criteria were evaluated before and 15 min after provocation, and the hormone status was determined on each investigation day. RESULTS: Comparisons of symptoms between the groups resulted in P values of > 0.05 for all symptoms at both visits except the symptom blocked nose, which was significantly lower (P=0.03) in the patients with OC intake at visit 2, and the symptom sneezing, which showed a significantly (P=0.02) higher increase in patients taking OC at the end of the cycle. The flow decrease reached a greater extent in the target group than in the controls. CONCLUSIONS: These results indicate a correlation of the hormonal situation and the nasal allergic reactivity. OC intake led to an intensifying of neurogenic symptoms near the end of pill intake, a result which could be due to a protective effect of the endogenous progesterone, in contrast to the orally administered hormones.

Comparative tolerability of second generation antihistamines.

Second generation histamine H1 receptor antagonists, the so-called 'nonsedating' antihistamines, have high potency and additional antiallergic properties as well as H1 antagonism and are associated with fewer adverse effects compared with the first generation antihistamines. A number of drugs in this class are approved for use: acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, loratadine, mizolastine and terfenadine. All of them have a more favourable risk-benefit ratio with regard to the CNS adverse effects. Even those second generation antihistamines that are not actually 'nonsedating' are less impairing than their predecessors, but not one of them is entirely devoid of CNS activity. Under certain circumstances some antihistamines may affect cardiac repolarisation resulting in cardiovascular adverse effects. Serious cardiovascular effects have been reported with terfenadine and astemizole when they are used in high dosages or when they are given to 'at risk' patients. Animal models indicate that there might be a potential risk of cardiovascular adverse effects with other antihistamines as well. However, up to now there is no clinical evidence for this assumption, despite some confusing reports. Likewise there has been much discussion about a link between these agents and carcinogenicity. However, there is no evidence that any of the second generation antihistamines increase the risk of tumour growth in humans. Small children, elderly patients and persons with chronic renal or liver impairment are special groups in which the individual adverse effects of the second generation antihistamines must be kept in mind. The dosage for an individual has to be modified with respect to their metabolic situation. Despite the fact that some of the second generation antihistamines are listed in the US Food and Drug Administration pregnancy risk classification as class B, the use of second generation antihistamines should be avoided during pregnancy and they should never be administered to nursing mothers. Taking into account their negligible CNS activity, the low incidence of cardiovascular adverse effects, their lack of anticholinergic effects and other benefits, this class of antiallergic drugs represents a definite advance in therapy.

Efficacy and safety relative to placebo of an oral formulation of cetirizine and sustained-release pseudoephedrine in the management of nasal congestion.

BACKGROUND: The aim of this study was to assess the clinical efficacy of an oral formulation of cetirizine 5 mg with sustained-release pseudoephedrine (PSE) 120 mg relative to placebo in patients with nasal congestion. METHODS: Twenty-four patients with perennial rhinitis due to house-dust-mite (HDM) allergy were recruited in this crossover study. A treatment period of 1 week, in which cetirizine/PSE was administered twice daily, was followed by a washout period of at least 2 weeks and a further period of 1 week in which the alternative treatment was given to each patient. Immediately after the first dose of each medication (day 1), nasal congestion and related symptoms were assessed during a 7-h challenge with HDM feces, with the Vienna Challenge Chamber (VCC), to investigate onset of action of the preparation. A second challenge of 3-h duration, carried out at least 12 h after the final dose, was undertaken after 1 week (mean) of twice-daily treatment to assess residual effects of the formulation after achievement of steady state. RESULTS: The oral formulation of cetirizine/PSE was significantly (P<0.001) superior to placebo in improving nasal obstruction during both challenges. The improvement in nasal airflow and nasal patency was significantly greater with cetirizine/PSE than with placebo (P<0.02). In addition, subjective assessment of nasal symptoms showed that cetirizine/PSE was significantly superior to placebo in both challenges for the sum of nasal obstruction scores (P<0.01). Both medications were well tolerated, and no serious adverse events occurred during the study. CONCLUSIONS: In this study, cetirizine/PSE relieved nasal congestion and other objective and subjective symptoms to a significantly greater extent than placebo. No serious adverse events occurred, and both regimens were equally well tolerated.

Effect of continuous allergen challenge on clinical symptoms and mediator release in dust-mite-allergic patients.

This study investigated the early, prolonged immediate, and late-phase reactions of dust-mite-sensitive subjects undergoing long-term challenge in the Vienna challenge chamber (VCC) in terms of clinical symptoms and inflammatory mediator level patterns in nasal lavage fluids. A concentration of 70 ng Der p 1/m3 of air (feces of Dermatophagoides) was maintained over 8 h in the VCC. To show the clinical impact of this challenge model, the effect of a histamine H1-receptor antagonist that also has some antiallergic properties (loratadine) was also investigated. The study followed a double-blind, placebo-controlled, crossover design. Medication was given orally over 7 days before the provocation at a dose of 10 mg once daily. All 12 patients, whose dust-mite sensitivity was confirmed by disease history, skin prick test, and RAST, completed the challenge session. The documentation of the chosen parameters was performed every 30 min. Subjective nasal and ocular symptoms were assessed via a visual analog scale of 100 mm, nasal flow was recorded by active anterior rhinomanometry, and mediator release was evaluated with nasal lavages. Clinical aspect: the whole sample population showed a rise of nasal and ocular symptom severity and a nasal flow reduction, which were perceptibly, but not significantly attenuated by active drug treatment. Mediator pattern: in each patient, prostaglandin (PG)D2 and leukotriene (LT)C4 levels peaked within the first 2 h of provocation, PGD2 then moving toward baseline levels, and LTC4 then again rising continuously. Eosinophil cationic protein (ECP) exhibited a constant level increase over the whole provocation period, and tryptase levels did not change significantly. Whereas the area under the curve values of tryptase and ECP were higher in drug-treated patients than the placebo group, the early PGD2 peak occurring during the first two challenge hours seemed to be mitigated by loratadine. These results reveal that there is no link between the clinical symptoms, the drug efficacy, and the released mediators (LTC4, PGD2, ECP, and tryptase).