Drugs
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Review
Tropisetron: an update of its use in the prevention of chemotherapy-induced nausea and vomiting.
Tropisetron is a serotonin (5-hydroxytryptamine; 5-HT) antagonist that is primarily used in the prevention of chemotherapy-induced nausea and vomiting. Antagonism of 5-HT3 binding sites in the peripheral and central nervous system is the probable mechanism of prevention of acute nausea and vomiting. Effects on delayed nausea and vomiting are less well understood as these are probably not mediated solely by 5-HT3 receptors. Tropisetron monotherapy is effective for the control of acute, and to a lesser extent delayed, nausea and vomiting in patients receiving moderately to severely emetogenic chemotherapy. The combination of dexamethasone and tropisetron is more effective than monotherapy. Complete control of cisplatin-induced nausea and vomiting was obtained in 69 to 97% of patients receiving the combination compared with 46 to 80% receiving tropisetron monotherapy in randomised trials. There were generally no significant differences between the control of acute or delayed nausea and vomiting provided by tropisetron, ondansetron or granisetron in randomised, comparative trials. The antiemetic efficacy of tropisetron was maintained over multiple cycles of chemotherapy. Most comparative studies showed tropisetron monotherapy to be more effective than metoclopramide in controlling acute nausea and vomiting, with the exception of 1 study which showed similar efficacy. However, high dose metoclopramide plus dexamethasone provided similar control of delayed emesis to tropisetron plus dexamethasone. Tropisetron is also effective in children, including those who responded poorly to previous antiemetic treatment. Tropisetron and ondansetron generally have similar efficacies in this population. The drug enhanced patients' quality of life and was well tolerated by adults and children alike. The recommended oral and IV dosage of tropisetron is 5 mg once daily; there is no increase in efficacy with doses >5 mg. ⋯ Tropisetron is similar to other 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting in both adults and children. It is suitable as first-line therapy (combined with a corticosteroid) for the prevention of acute nausea and vomiting in patients treated with moderately to severely emetogenic chemotherapeutic agents. This combination is also moderately effective in the prevention of delayed nausea and vomiting.
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Varicella zoster virus (VZV), the pathogen responsible for herpes zoster, belongs to the herpesvirus family and is sensitive to the antiviral drug aciclovir. However, the low oral bioavailability of aciclovir has to some extent limited its efficacy in the treatment of herpes zoster and has prompted the development of the more readily absorbed oral prodrug valaciclovir. In a large comparative study valaciclovir, (1000 mg 3 times daily for 7 days) was at least as effective as aciclovir (800 mg 5 times daily for 7 days) in controlling the symptoms of acute herpes zoster. Importantly, valaciclovir alleviated zoster-associated pain and postherpetic neuralgia significantly faster than aciclovir. A 14-day regimen of valaciclovir showed no significant advantage over the 7-day regimen. A smaller trial in Japanese patients focusing primarily on the cutaneous (rash) signs of herpes zoster confirmed the similar efficacy of valaciclovir and aciclovir in the 7-day regimen. This study did not follow all patients for a formal analysis of postherpetic neuralgia. Valaciclovir and aciclovir demonstrated similar efficacy for the control of cutaneous lesions and ocular complications in patients with zoster ophthalmicus. Preliminary results of a large controlled trial indicate that valaciclovir 1000 mg 3 times daily and famciclovir (the prodrug of penciclovir) 500 mg 3 times daily are of similar efficacy in speeding resolution of acute herpes zoster rash and shortening the duration of postherpetic neuralgia. Starting treatment later than 72 hours after rash onset did not significantly reduce the beneficial effect of valaciclovir on duration of zoster-associated pain (a continuum of pain that encompasses both acute pain and postherpetic neuralgia) in a large observational study, suggesting that valaciclovir might be effective when given later than previously thought. However, valaciclovir should ideally be given as soon as possible after symptoms appear. With the recommended regimen for the treatment of herpes zoster (1000 mg 3 times daily for 7 days) valaciclovir was well tolerated, with nausea and headache being the most commonly reported adverse events. The adverse events profile of the agent was similar to that seen with aciclovir or famciclovir. ⋯ The efficacy of valaciclovir for the treatment of herpes zoster has been confirmed and extended by follow-up studies in herpes zoster ophthalmicus, in Japanese patients, and in the wider primary care setting. Valaciclovir is at least equivalent to, and better in certain parameters than, aciclovir and appears to have similar efficacy to famciclovir 500 mg 3 times daily. Valaciclovir is a well tolerated first-line therapy with an established place in the treatment of immunocompetent patients with herpes zoster.