The butterbur extract petasin has no effect on skin test reactivity induced by different stimuli: a randomized, double-blind crossover study using histamine, codeine, methacholine, and aeroallergen solutions.

BACKGROUND: Petasin (Ze 339) was recently introduced on the market as a potent herbal antiallergic drug for treatment of respiratory allergies such as hay fever. Few clinical studies have been performed so far addressing the clinical effectiveness of Ze 339. OBJECTIVE: To evaluate the antiallergic properties of Ze 339 using skin prick tests with different stimuli, such as codeine, histamine, methacholine, and a relevant inhalant allergen. METHODS: A randomized, double-blind, placebo-controlled study was performed in which Ze 339 was compared to acrivastine, a short-acting antihistamine, in 8 patients with respiratory allergy and in 10 nonatopic, healthy volunteers. Antiallergic activity of Ze 339 was determined by analyzing inhibitory potency in skin prick tests with codeine, histamine, methacholine, and an inhalant allergen. Wheal-and-flare reactions were assessed 90 minutes after a double dose of Ze 339, acrivastine, or placebo. An interval of at least 3 days was left between the skin tests. RESULTS: Acrivastine was identified as the only substance that significantly inhibited skin test reactivity to all solutions analyzed in all study subjects. In contrast, no significant inhibition could be demonstrated for Ze 339 with any test solution. Moreover, the results of Ze 339 did not differ significantly from placebo. CONCLUSIONS: In this study we found no antiallergic, particularly antihistaminic, effect of Ze 339 in skin tests using a variety of stimuli often used to evaluate immediate skin test reactivity. The mechanism by which Ze 339 is effective in the treatment of seasonal allergic rhinitis still needs to be elucidated.

Evaluation and comparison of five matrix excipients for the controlled release of acrivastine and pseudoephedrine.

For treatment of allergic rhinitis, acrivastine with pseudoephedrine in Semprex-D conventional capsules requires dosing every 6-8 hours. This study was designed to develop a controlled release matrix tablet of acrivastine and pseudoephedrine and evaluate 5 different matrix excipients for their in vitro controlled-release profiles. Compritol 888ATO, Eudragit RS, Methocel K100M, Polyox WSR301 and Precirol ATO5 were used alone or in varying combinations for the formulation of controlled release matrix tablets. In vitro drug dissolution and mathematical modeling were used to characterize drug release rate and extent. All tablet formulations yielded quality matrix preparations with satisfactory tableting properties. Due to the aqueous solubility of pseudoephedrine and the size of the dose, none of the matrix excipients used alone prolonged drug release significantly to meet the desired twice-daily administration frequency. The use of two excipients in combination, however, significantly decreased the dissolution rate of both active ingredients. A combined lipid-based Compritol and hydrophilic Methocel produced optimal controlled drug release for longer than 8 hours for both acrivastine and pseudoephedrine.

Onset-of-action for antihistamine and decongestant combinations during an outdoor challenge.

BACKGROUND: Medications containing a combination antihistamine-decongestant are commonly used for allergic rhinitis yet onset-of-action comparisons for symptom relief after a single dose have not been performed. OBJECTIVE: To determine the onset of symptom relief and efficacy of antihistamine-decongestant medications (acrivastine-pseudoephedrine and loratadine-pseudoephedrine) compared with placebo in an outdoor park. METHODS: This study was conducted during the spring of 1997 using a double-blind, placebo-controlled design. Patients completed baseline rhinitis symptom diaries from 7:30 to 9:30 AM. Subjects with qualifying symptom scores received one dose of either acrivastine-pseudoephedrine, loratadine-pseudoephedrine, or placebo at 10:00 AM. Symptom diaries were recorded for the next 4 hours. RESULTS: Of 593 patients randomized to treatment, 592 were included in efficacy analysis. Acrivastine-pseudoephedrine and loratadine-pseudoephedrine demonstrated a mean onset-of-action by 45 and 30 minutes respectively for total symptom and rhinitis symptom scores for the five sites. Onset-of-action for nasal congestion scores was 45 minutes for both medications. Sites having higher pollen exposure (>100 pollen grains over 6 hours) demonstrated a difference between the antihistamine combinations: acrivastine-pseudoephedrine had an onset of action at 45 minutes for total symptom and rhinitis symptom scores, and 15 minutes for nasal congestion scores whereas loratadine-pseudoephedrine had onset-of-action for nasal congestion score of 105 minutes but failed to reach significance at any timepoint for total symptom and rhinitis symptom scores. CONCLUSIONS: Both antihistamine-decongestant combinations demonstrate an onset-of-action within 60 minutes of administration but under conditions of higher pollen exposure, the acrivastine combination was more effective for total symptoms, rhinitis symptoms, and nasal congestion with an onset-of-action within 45 minutes for rhinitis symptoms and 15 minutes for congestion.

Efficacy of acrivastine plus pseudoephedrine for symptomatic relief of seasonal allergic rhinitis due to mountain cedar.

BACKGROUND: Acrivastine is a second-generation H1-antagonist chemically related to triprolidine, but more polar and with less central nervous system penetration than triprolidine. OBJECTIVE: The efficacy of the antihistamine-decongestant combination product (Semprex-D capsules) containing acrivastine 8 mg plus pseudoephedrine HCl 60 mg was evaluated for the treatment of seasonal allergic rhinitis symptoms. METHODS: A total of 676 patients sensitive to mountain cedar pollen was enrolled into a 6-center, randomized, double-blind, placebo-controlled, parallel, 4-group study designed to compare acrivastine + pseudoephedrine, acrivastine, pseudoephedrine, and placebo. Patients with demonstrable diary symptom scores at baseline took study medication (4 doses/day) and recorded symptom scores twice daily for 2 weeks. The effectiveness of the acrivastine + pseudoephedrine combination was examined relative to the individual components and placebo in terms of changes in diary symptom scores. RESULTS: Over the 2-week period, the combination of acrivastine plus pseudoephedrine was significantly more effective than (1) acrivastine, pseudoephedrine, and placebo (P < .001) for relief of all symptoms; (2) pseudoephedrine (P < .001) for relieving allergy symptoms, ie, running nose, sneezing, itchy nose/throat and tearing; and (3) acrivastine (P < .001) for reducing nasal congestion. Relative to placebo, small increases in adverse experience rates were observed with acrivastine + pseudoephedrine for dry mouth, insomnia, somnolence, and headache. CONCLUSION: These findings in a large clinical trial demonstrate (1) the efficacy of acrivastine and (2) that each component of the combination of acrivastine 8 mg plus pseudoephedrine HCl 60 mg contributes to the overall efficacy, thereby supporting the conclusion that the combination is rational, safe, and effective for the treatment of allergic rhinitis.

Efficacy of acrivastine with pseudoephedrine in treatment of allergic rhinitis due to ragweed.

BACKGROUND: Semprex-D capsules contain acrivastine 8 mg (a second generation H1-antagonist) plus pseudoephedrine HCl 60 mg and were developed to satisfy the needs of allergy suffers who prefer combination products designed to provide broader symptom relief. Approval of combination products by the US Food and Drug Administration requires demonstration that each component contributes to the overall effectiveness. OBJECTIVE: The objective of the study was to demonstrate that both acrivastine and pseudoephedrine share in the efficacy of the combination in relieving allergy symptoms in patients sensitive to ragweed pollen. METHODS: This was a double-blind, randomized, placebo-controlled, parallel groups, balanced design, multicenter (13 sites) study. Patients 12 years of age or older with skin test reactivity to ragweed were recruited. Patients who qualified for the study were dispensed either (1) acrivastine + pseudoephedrine, (2) acrivastine, (3) pseudoephedrine, or (4) placebo with instructions to take one capsule 4 times daily and to record allergy symptom scores in a symptom diary 3 times daily for 14 days. Assessments of health, global allergy symptoms, protocol compliance, adverse events, and vital signs were also documented. RESULTS: A total of 702 patients were enrolled in this study. Over the 2-week period, the combination of acrivastine + pseudophedrine was significantly more effective than acrivastine, pseudoephedrine, and placebo for relief of all symptoms (P range .01 to .001); pseudoephedrine for treating symptoms responsive to antihistamines (P = .003); and acrivastine for treating symptoms responsive to nasal decongestants (P < .001). Relatively small increases in adverse experience rates were observed for the combination relative to the placebo. CONCLUSIONS: These findings in a large clinical trial demonstrate that each component of the combination of acrivastine 8 mg plus pseudoephedrine HCl 60 mg contributes to the overall efficacy, thereby supporting the conclusion that the combination is rational, safe, and effective for the treatment of allergic rhinitis.

Efficacy of acrivastine in the treatment of allergic rhinitis during natural pollen exposure: onset of action.

In a placebo-controlled, randomized, and double-blind 1-day field study, the efficacy and onset of action of capsule acrivastine 8 mg were evaluated in 42 patients suffering from allergic rhinoconjunctivitis elicited by natural grass pollen exposure. Before and for 2 h after treatment, the patients scored the severity of five rhinoconjunctivitis symptoms every 10 min on a 0-5 scale (0 = no symptoms; 5 = very severe symptoms). The number of sneezes was recorded, and every 30 min, measurements of nasal peak flow were made. Before treatment, there was no difference in median total symptom score (mTSS) between the acrivastine group (A) and the placebo group (P) (12 and 12, respectively). Time of onset was estimated by an exponential decay model to be 19 min (95% confidence interval 0-39 min). A statistically significant difference in percent reduction of mTSS between A and P was observed for the first time 46 min after treatment start (A = 22%, P = 0%, P < 0.05). A 50% reduction in total symptom score (TSS) was achieved within 60 min by 38% in A and 17% in P (NS), and within 80 min in 52% and 17%, respectively (P < 0.05). The median time for 50% reduction in TSS (MT50) was 80 min for A and > 120 min for P (P < 0.01). The symptom score of sneezing and number of sneezes were evaluated for periods of 30 min. The difference between A and P became statistically significant from 31-60 and 61-90 min, respectively (P < 0.05 and P < 0.01). Objective and subjective determinants in the different time intervals were well correlated. Improvement of nasal congestion was observed in A at 91-120 min, as measured by nasal peak flow.

Time of onset of action of acrivastine in the skin of pollen-allergic subjects. A double-blind, randomized, placebo-controlled comparative study.

The purpose of this study was to assess the time of onset of action of acrivastine in suppressing the wheal response to histamine (10 mg/ml) and allergen (10,000 and 100,000 BU/ml) in the skin prick test. Ten subjects with a well-documented allergy to pollen received single doses of 8 mg of acrivastine and placebo according to a randomized, double-blind, placebo-controlled, crossover treatment design. Duplicate skin prick tests were performed 0, 15, 20, 25, 30, and 60 min after medication. The results demonstrated a statistically significant suppression of the wheal reactions 15-20 min after medication, depending on the reaction producers used. The sum of all three producers showed a statistically significant effect on the wheal reaction 15 min after medication. The upper 95% confidence limit for time lag from dosing of acrivastine until reduction from placebo level commences was 6.5 min. The study substantiates that orally administered acrivastine has a rapid onset of action in the skin of allergic subjects. The results indicate that allergen SPT is a more sensitive tool for studying antihistaminergic activity than histamine SPT.