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.
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Postherpetic neuralgia (PHN) is a chronic pain syndrome that is often refractory to treatment and can last for years, causing physical and social disability, psychological distress, and increased use of the healthcare system. In this paper we provide an update on recent developments in the treatment of PHN. We emphasise the results of recent studies that provide an evidence-based approach for treating PHN that was not available until very recently. ⋯ Based on these results, nortriptyline can now be considered the preferred antidepressant for the treatment of PHN, although desipramine may be used if the patient experiences unacceptable sedation from nortriptyline. The topical lidocaine patch, gabapentin and controlled release oxycodone all appear to be as effective as tricyclic antidepressants in the treatment of patients with PHN, and the results of these recent studies suggest that each of these treatments should be considered early in the course of treatment. Additional controlled trials are needed to compare the efficacy and tolerability of these 4 treatments- tricyclic antidepressants, gabapentin, the topical lidocaine patch and controlled release opioid analgesics--used singly and in various combinations in the treatment of patients with PHN.
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Montelukast is a cysteinyl leukotriene receptor antagonist used to treat persistent asthma in patients aged > or = 6 years. The drug has a rapid onset of action. Improvements in lung function and reductions in as-needed beta2-agonist usage are apparent within 1 day of initiating montelukast treatment in adults and adolescents (aged > or = 15 years treated with 10 mg/day) or children (aged 6 to 14 years treated with 5 mg/day) with persistent asthma as shown in clinical trials. ⋯ In conclusion, montelukast is well tolerated and effective in adults and children aged > or = 6 years with persistent asthma including those with exercise-induced bronchoconstriction and/or aspirin sensitivity. Furthermore, montelukast has glucocorticoid sparing properties. Hence, montelukast, as monotherapy in patients with mild persistent asthma, or as an adjunct to inhaled corticosteroids is useful across a broad spectrum of patients with persistent asthma.
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Celecoxib is a cyclo-oxygenase (COX) inhibitor that exhibits relative in vitro and ex vivo selectivity for COX-2 over COX-1. Results of randomised double-blind multicentre studies indicate that celecoxib is superior to placebo and has similar efficacy as conventional nonsteroidal anti-inflammatory drugs (NSAIDs) in improving the signs and symptoms of osteoarthritis and rheumatoid arthritis. Analgesic efficacy and improvements in functional status are apparent within 2 weeks of starting therapy and are maintained throughout treatment. Available data suggest that celecoxib has analgesic efficacy in patients with postsurgical dental pain, although this is yet to be confirmed. In patients with osteoarthritis of the knee, celecoxib 100 and 200 mg and naproxen 500 mg twice daily were similarly efficacious and superior to placebo. Once and twice daily celecoxib dosage regimens provided comparable efficacy. Improvements in physical function paralleled those in pain relief. Celecoxib also has efficacy in treating the signs and symptoms of osteoarthritis of the hip. The effects of celecoxib were not diminished in elderly patients with osteoarthritis of the hip or knee. All dosages of celecoxib (100 to 400 mg twice daily) and naproxen 500 mg twice daily produced significant anti-inflammatory and analgesic effects in patients with active rheumatoid arthritis. In patients with stable rheumatoid arthritis, celecoxib 200 mg twice daily showed sustained symptomatic improvements similar to those of twice daily slow-release diclofenac 75 mg over a 24-week period. Celecoxib was well tolerated in clinical trials. Upper gastrointestinal complications occurred in significantly fewer patients treated with twice daily celecoxib 25 to 400 mg than in those receiving comparator NSAIDs. There was no evidence of a dose relationship in endoscopic ulcer development and incidences in celecoxib and placebo recipients were lower than in those receiving twice daily naproxen 500 mg or ibuprofen 800 mg 3 times daily. ⋯ Celecoxib is the first COX-2 specific inhibitor approved for use in osteoarthritis and rheumatoid arthritis. Celecoxib produces significant improvements in pain and inflammation and these effects are maintained during treatment for up 24 weeks in clinical trials. Studies indicate that celecoxib has similar efficacy to conventional NSAIDs in relieving pain and improving functional status, but is associated with a lower incidence of upper gastrointestinal ulceration and complications. This promising gastrointestinal safety profile, together with sustained symptomatic relief, places celecoxib as a useful alternative for the treatment of osteoarthritis and rheumatoid arthritis, particularly in patients at high risk of developing gastrointestinal events. Although data are encouraging, its place in acute pain states remains to be established.