The approved dosage of bilastine in the SmPC is 20 mg once daily. However, consensus reports have suggested that doses of non-sedating H1-antihistamines may be increased two- to four-fold the normal therapeutic dose in patients with urticaria. The Phase III clinical study performed to evaluate the efficacy of bilastine in the symptomatic treatment of urticaria exclusively used the approved 20 mg dosage. Bilastine 20 mg, 40 mg or 80 mg once daily for 7 days was effective in reducing critical temperature thresholds in 19 of 20 patients with cold contact urticaria (CCU). The increased efficacy of bilastine with four-fold up-dosing was without sedation and supports urticaria treatment guidelines. Additionally, during the clinical development programme for bilastine, supratherapeutic doses have been studied. In Phase I studies, doses up to about ten-fold higher (in single-dose and multiple-dose studies) were administered to assess pharmacokinetics, tolerability and safety. No clinically significant trends in ECG, vital signs or physical examination findings were observed. In another study, five-fold higher doses (100 mg), as well as 20 mg in combination with ketoconazole, were evaluated in a ‘Thorough QT/QTc’ study performed to assess the cardiac safety of the bilastine. Doses of bilastine up to four times the therapeutic dose (80 mg) were found to be well tolerated in CNS safety studies. The results of these studies support the fact that bilastine at therapeutic and supratherapeutic doses, and even when combined with ketoconazole, is safe from a cardiac point of view. Furthermore, bilastine 20 mg–40 mg did not cause psychomotor impairment or affect driving ability. In addition, throughout the clinical development programme, the adverse events profile of bilastine has not differed from that of placebo. Should the physician, after considering the risk-benefit ratio, decide to follow the proposed ‘Up-Dosing Guidelines’, bilastine should be considered as a possible candidate because of its excellent safety profile.
