Mitoxantrone is a dihydroxyanthracenedione derivative which as intravenous mono- and combination therapy has demonstrated therapeutic efficacy similar to that of standard induction and salvage treatment regimens in advanced breast cancer, non-Hodgkin's lymphoma, acute nonlymphoblastic leukaemia and chronic myelogenous leukaemia in blast crisis; it appears to be an effective alternative to the anthracycline component of standard treatment regimens in these indications. Mitoxantrone is also effective as a component of predominantly palliative treatment regimens for hepatic and advanced ovarian carcinoma. Limited studies suggest useful therapeutic activity in multiple myeloma and acute lymphoblastic leukaemia. Regional therapy of malignant effusions, hepatic and ovarian carcinomas has also been very effective, with a reduction in systemic adverse effects. Mitoxantrone inhibits DNA synthesis by intercalating DNA, inducing DNA strand breaks, and causing DNA aggregation and compaction, and delays cell cycle progression, particularly in late S phase. In vitro antitumour activity is concentration- and exposure time-proportional, and synergy with other antineoplastic drugs has been demonstrated in murine tumour models. Leucopenia may be dose-limiting in patients with solid tumours, whereas stomatitis may be dose-limiting in patients with leukaemia. Other adverse effects are usually of mild or moderate severity although cardiac effects, particularly congestive heart failure, may be of concern, especially in patients with a history of anthracycline therapy, mediastinal irradiation or cardiovascular disease. Mitoxantrone displays an improved tolerability profile compared with doxorubicin and other anthracyclines, although myelosuppression may occur more frequently. Thus, mitoxantrone is an effective and better tolerated alternative to the anthracyclines in most haematological malignancies, in breast cancer and in advanced hepatic or ovarian carcinoma. Further studies may consolidate its role in the treatment of these and other malignancies.

1080 Stiderberg M, Lundgren R, Angstrom T. Effect of cetirizine on histamine-induced bronchoconstriction and bronchoalveolar cells. Allergy 46: 217-221,1991 Spyropoulou-Vlahou M, Stavropoulos-Giokas A, Filippou M, Koyas A, Kontou-Fili K. Clinical and laboratory results confirm the efficacy of cetirizine 2HCI in seasonal allergic rhinitis. Acta Therapeutica 16: 71-78, 1990 Tashkin DP, Brik A, Gong Jr H. Cetirizine inhibition of histamineinduced bronchospasm. Annals of Allergy 59 (Part II): 49-52, 1987 Tjwa MKT, Widjaja P, DelBono L, Pichler WJ, Backhouse CI, et al. Loratadine compared to cetirizine in patients with seasonal allergic rhinitis. Abstract. Allergy 47 (Suppl.): 174, 1992 van Neste D, Coussement C, Ghys L, Rihoux J-P. Agonist-antagonist interactions in the skin: comparison of effects of loratadine and cetirizine on skin vascular responses to prick tests with histamine and substances P. Journal of Dermatological Science 4: 172-179, 1992 Varney V, Gaga M, Frew AJ, De Vos C, Kay AB. The effect of a single oral dose of prednisolone or cetirizine on inflammatory cells infiltrating allergen-induced cutaneous late-phase reactions in atopic subjects.

Zolpidem is an imidazopyridine, a chemically novel nonbenzodiazepine hypnotic agent which acts at the benzodiazepine omega 1-receptor subtype in the brain. With a rapid onset of action and short elimination half-life, it reduces the latency to and prolongs the duration of sleep in patients with insomnia, yet has no major effects on sleep stages when given in dosages of 5 to 20 mg nightly. Rebound effects on withdrawal of the drug have not been observed. Unlike benzodiazepines, zolpidem has no myorelaxant or anticonvulsant effects and its effects on anxiety appear to be minor. While zolpidem aids sedation, and may reduce memory or psychomotor function within the first 2 hours after administration of single oral doses, its use as a surgical premedicant remains to be established. Adverse effects are predominantly CNS and gastrointestinal in nature. Altered pharmacokinetics may lead to an increase in dose-proportionate adverse effects in the elderly and in patients with renal dysfunction. Limited evidence to date suggests that the dependence liability of zolpidem is minimal. Thus, zolpidem is an interesting alternative to benzodiazepines in the treatment of insomnia, with properties that potentially offer worthwhile advantages in this therapeutic area if they are confirmed with wider clinical experience.

Glimepiride is a conveniently administered alternative to other sulphonylureas in patients with type 2 diabetes mellitus not well controlled by diet alone. Its possible tolerability advantages and use in combination with other oral antidiabetic drugs require further study. Glimepiride is also reported to reduce exogenous insulin requirements in patients with secondary sulphonylurea failure when administered in combination with insulin.

Levofloxacin can be administered in a once-daily regimen as an alternative to other fluoroquinolones in the treatment of infections of the urinary tract, skin and soft tissues. Its more interesting use is as an alternative to established treatments of respiratory tract infections. S. pneumoniae appears to be more susceptible to levofloxacin than to ciprofloxacin or ofloxacin. Other newer fluoroquinolone agents that also have enhanced in vitro antipneumococcal activity may not share the well established tolerability profile of levofloxacin, which also appears to improve on that of some older fluoroquinolones.