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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to evaluate and compare the antiemetic effectiveness and tolerability of Navoban (tropisetron) and Zofran (ondansetron) following high-dose (> or = 50 mg/m2) cisplatin chemotherapy. In a randomised, multi-centre, double-blind, double-dummy, parallel group study, 117 evaluable chemotherapy-naive patients who received Navoban were compared with 114 who received Zofran. Patient diary cards were used to assess both acute (Day 1) and delayed (Days 2-6) nausea and vomiting. Total control of acute vomiting was achieved in 54% of Navoban and 65% of Zofran patients (p = 0.052), and total control of acute nausea in 66% and 62% respectively (p = 0.655). Total control of delayed vomiting was achieved in 44% of Navoban patients and 46% of Zofran patients (p = 0.765), and of delayed nausea in 56% and 47% respectively (p = 0.207). Both reactions combined were totally prevented during the entire 6-day trial period in 22% of Navoban and 24% of Zofran patients (NS), while a further 42% of patients in both groups remained largely free from both nausea and emesis. The few adverse reactions (e.g. headache, constipation, diarrhoea) were mainly mild and typical of the 5-HT3-receptor antagonists. In conclusion, there were no significant differences in efficacy and tolerability between Navoban 5 mg once daily and the highest recommended dose of Zofran (32 mg on Day 1, followed by 8 mg three times a day).
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PMID:Is Navoban (tropisetron) as effective as Zofran (ondansetron) in cisplatin-induced emesis? The French Navoban Study Group. 774 65

The 5-HT3 antagonism property of metoclopramide, acting on receptors presumably located in the trigeminovascular system, is the theoretical basis of its remarkable success, as a single intravenous agent, in the treatment of migraine attacks. The specific anti-migraine activity of oral metoclopramide is, most probably, applicable only when its plasma level is equivalent to 10 mg injected intravenously. The clinical effective dose of ergotamine, beginning from the minimal dose of 1 mg, correlates well with its affinity for 5-HT1B and 5-HT1D receptors, and the rank order of clinical potency of ergotamine is superior to sumatriptan. The presumed synergic power of drugs that interact with both 5-HT1 and 5-HT3 receptors is examined, in order to formulate a highly potent, low headache recurrence, oral combination.
Headache
PMID:Application of metoclopramide specificity in migraine attacks therapy. 792 30

Granisetron, a potent and selective 5-hydroxytryptamine receptor (5-HT3) antagonist was reported to be an effective antiemetic agent both in animal studies and in patients given highly emetogenic chemotherapy. A sample of 43 patients with breast cancer was accrued from September to November 1992 in a phase II study to assess the efficacy of granisetron in patients receiving FEC (5-FU, epirubicin, cyclophosphamide). Each patient received 3 mg intravenous granisetron as a single dose just prior to chemotherapy. Oral metoclopromide was prescribed to each patient as a rescue anti-emetic. The emetic episodes and degree of nausea were evaluated on a daily basis. Good control of emesis (0-2 episodes of vomiting) and nausea (mild or no nausea) was in the range 77%-98% and 77%-93% respectively. There was a complete response (no emetic episodes throughout the 6-day period) in 16 patients (37.2%). Onset of emesis tends to occur on day 1 and tend to subside after day 3; 85% of patients had onset of emesis in the first 2 days after chemotherapy. Control of emesis and nausea tends to improve after day 3, which could be the result of the reduced emetogenicity of the combination FEC with time. Altogether, 77% had good control of acute emesis; control of delayed emesis was better with 84% achieving a major response on day 2 after chemotherapy, which improved to more than 90% after day 4. Granisetron was generally tolerated with headache being the most common side-effect followed by constipation and flushing. This study suggests that granisetron is an effective and well-tolerated anti-emetic agent, which deserves randomised trials to elucidate its efficacy further.
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PMID:Control of emesis by intravenous granisetron in breast cancer patients treated with 5-FU, epirubicin and cyclophosphamide. 803 7

We evaluated the efficacy and safety of oral ondansetron, a selective antagonist of 5-HT3 receptors, for the treatment of nausea and vomiting associated with cyclophosphamide-based chemotherapy (> 500 mg/m2). In this trial 324 chemotherapy-naive cancer patients, mostly females with breast cancer, were randomized to receive either placebo or ondansetron 1 mg, 4 mg, or 8 mg three times per day for 3 days. There were no differences in the doses of cyclophosphamide, doxorubicin, and methotrexate between the study groups. All ondansetron dose groups were superior to the placebo control group (p < .001) for all measured efficacy parameters (complete response, number of emetic episodes, therapeutic failures, need of rescue antiemetics). No emetic episodes were reported by 9 (12%), 29 (37%), 48 (64%), and 47 (66%) of the placebo patients and the 1-mg, 4-mg, and 8-mg dose of ondansetron patients, respectively. Nausea was reduced and food intake was improved for all the ondansetron groups. A more severe emetic response was observed in patients receiving cyclophosphamide and doxorubicin combination chemotherapy. In this subgroup of patients, 66%, 38%, 25%, and 16% of the placebo group and 1-mg, 4-mg, and 8-mg ondansetron patients, respectively, required rescue antiemetics. No significant toxic effects were observed in this study. A higher incidence of headaches and gastrointestinal complaints (constipation, abdominal pain) were observed in the three ondansetron groups. In conclusion, oral ondansetron is an effective and well-tolerated antiemetic treatment in the management of cancer patients receiving ambulatory cyclophosphamide-based chemotherapy. These results support the view that serotonin and 5-HT3 receptors play an important role in cyclophosphamide-induced nausea and vomiting.
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PMID:Efficacy of oral ondansetron, a selective antagonist of 5-HT3 receptors, in the treatment of nausea and vomiting associated with cyclophosphamide-based chemotherapies. Ondansetron Study Group. 814 Nov 6

Dolasetron mesylate (MDL 73,147EF), a new serotonin receptor (5-HT3) antagonist was administered to 164 cancer patients naive or non-naive to chemotherapy, in single, rising doses of 10, 20, 30, 40, or 50 mg i.v. 15 minutes prior to an infusion of cisplatin. The severity of nausea and number of episodes of emesis were recorded during the 24-hour period following cisplatin administration. There were significant differences between the dose groups, sex, and naive and non-naive patients. There were also significant dolasetron dose-dependent differences for no emesis (p = .01), less than 3 emetic episodes (p = .01), time-to-onset of nausea (p = .04), and time-to-onset of emesis (p = .003). The severity of symptoms was greater for females, for patients with previous chemotherapy, and with shorter duration of cisplatin infusion. Adjustment for these variables and the study center reduced the associations between the dose of dolasetron mesylate and the outcome variables. The principal adverse events were headache (11%) and diarrhea (6%). Dolasetron mesylate was well tolerated; a single dose of 40 or 50 mg controlled acute nausea and vomiting induced by highly emetogenic chemotherapy in the majority, in particular in chemotherapy-naive and male patients. In conclusion, 50 mg and a larger dose merit study in controlled trials with stratification for sex and previous chemotherapy.
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PMID:Acute antiemetic efficacy and safety of dolasetron mesylate, a 5-HT3 antagonist, in cancer patients treated with cisplatin. European Dolasetron Study Group. 814 Nov 14

Tropisetron is a novel, potent and highly selective 5-HT3 receptor antagonist, which is active in the treatment of nausea and vomiting induced by highly emetogenic chemotherapeutic drugs such as cisplatin. Tropisetron selectively blocks the excitation of the presynaptic 5-HT receptors of the peripheral neurones involved in the emetic reflex, and may have other direct actions in the CNS on 5-HT3 receptors, mediating the actions of vagal inputs to the area postrema. Toxicological studies show that tropisetron is generally well tolerated by all animal species investigated and no specific organ toxicity was observed, other than slight loss of body weight development. In man, tropisetron metabolism is linked to the cytochrome P-450 2D6 isoenzyme system, which determines the polymorphism of debrisoquine/sparteine metabolism. As a result, there are phenotypical populations of extensive and poor metabolizers. The two main adverse events in human volunteer tolerability studies with tropisetron were headache and constipation. These adverse events tended to be slightly more intense and to last longer in poor metabolizers, compared with extensive metabolizers. Tropisetron had similar pharmacokinetic characteristics in elderly patients and renal patients, compared with healthy subjects. From a toxicological and pharmacokinetic point of view, therefore, daily doses of 5 mg tropisetron can be administered to both poor and extensive metabolizers, as well as to special populations, without any particular precautions.
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PMID:Pharmacology, toxicology and human pharmacokinetics of tropisetron. 836 93

Selective 5-HT3 antagonists have proven to be safe and effective for the prevention of chemotherapy-induced nausea and vomiting. Dolasetron is a new highly selective addition to this class of antiemetics that has been shown to have significant antiemetic activity in patients receiving cisplatin-containing regimens. This pilot study was designed to evaluate the antiemetic efficacy of dolasetron in cancer patients receiving doxorubicin and/or cyclophosphamide. This study used an open-label, non-randomized design to evaluate the efficacy and safety of intravenous dolasetron in the prevention of emesis in patients receiving doxorubicin (25-75 mg/m2) and/or cyclophosphamide (400-1200 mg/m2). Sixty-nine patients received a single, intravenous dose of dolasetron over 15-20 min beginning 30 min prior to the start of chemotherapy. Dose levels of dolasetron studied were: 0.3, 0.6, 1.2, 1.8 and 2.4 mg/kg. Patients were monitored for emesis, nausea and adverse events for 24h after the start of chemotherapy. Overall, 61% of patients experienced complete control of emesis. No significant trend towards increased antiemetic efficacy (P = 0.076) or nausea control with increasing dolasetron dose was noted, although the power to detect significant differences was limited by the small number of patients on the 0.3-mg/kg and 2.4-mg/kg dose levels. Age, gender, and type of chemotherapy were significant predictors of complete antiemetic control. Adverse events were generally mild and included headache, chills, lightheadedness, fever, diarrhea, dizziness, and asymptomatic prolongation of ECG intervals. Intravenous dolasetron is safe and effective in the prevention of emesis induced by doxorubicin and/or cyclophosphamide.
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PMID:Dose-ranging evaluation of the antiemetic efficacy of intravenous dolasetron in patients receiving chemotherapy with doxorubicin or cyclophosphamide. 867 51

The potent serotonin receptor (5-HT3) antagonists are new highly selective agents for the prevention and control of chemotherapy-induced nausea and vomiting that have been shown to be comparable to or more effective than traditional metoclopramide regimens. This study was designed to compare the antiemetic efficacy of dolasetron and metoclopramide in chemotherapy-naive and non-naive cancer patients receiving high-dose cisplatin-containing chemotherapy. This multicentre, double-blind, randomized trial compared the efficacy and safety of single i.v. doses of dolasetron mesilate salt (1.2 or 1.8 mg/kg) and metoclopramide (7 mg/kg) in 226 patients for the prevention of acute emesis and nausea associated with the administration of high-dose (> or = 80 mg/m2) cisplatin. Efficacy and safety were evaluated for 24 h. Complete responses were achieved by 57%, 48%, and 35% of patients given dolasetron mesilate 1.8 mg/kg (P = 0.0009 vs metoclopramide), dolasetron mesilate 1.2 mg/kg (P = 0.0058 vs metoclopramide), and metoclopramide, respectively. Overall, dolasetron was significantly more effective than metoclopramide for time to first emetic episode, nausea, patient satisfaction, and investigator global assessment of efficacy. Males, chemotherapy-naive patients, and alcoholics had higher response rates. Dolasetron was well tolerated, with mild-to-moderate headache most commonly reported. Twelve percent of patients receiving metoclopramide reported extrapyramidal symptoms compared with 0% of patients receiving dolasetron. In conclusion, dolasetron mesilate was effective for the prevention of CINV with high-dose cisplatin. Single i.v. doses of dolasetron mesilate were more effective than 7 mg/kg metoclopramide in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy. In addition, 1.8 mg/kg dolasetron mesilate consistently produced the highest response rates and appears to be the most effective dose for further clinical development.
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PMID:A double-blind, multicentre comparison of intravenous dolasetron mesilate and metoclopramide in the prevention of nausea and vomiting in cancer patients receiving high-dose cisplatin chemotherapy. 901 Sep 86

Ramosetron hydrochloride as a 5-HT3 receptor antagonist-type antiemetic, which was developed in Japan. It has an indole ring which is the mother nucleus of serotonin (5-HT) and a tetrahydrobenzimidazol radical. These components are linked by a carbonyl radical. It was reported in non-clinical studies that ramosetron hydrochloride exhibited more potent and sustained antagonistic activities against 5-HT3 receptors than existing 5-HT3 receptor antagonist-type antiemetics. It was also reported that ramosetron hydrochloride inhibited vomiting by anticancer drugs in a potent and sustained manner. The phase I trial was initiated in May, 1991. Phase II and phase III trials were then conducted in a total of 357 patients at 121 institutions in Japan. The symptoms targeted in these trials were nausea and vomiting induced by anticancer drugs, such as cisplatin. Based on the results of the phase II trial, it was recommended that ramosetron hydrochloride be infected once daily at a dose of 0.3 mg. In phase III trial, a placebo-controlled double-blind study and an open trial was performed. The utility of the drug seemed to be confirmed by the results of these studies. Ramosetron hydrochloride shown an efficacy rate of 79.8% (178/223 patients) against nausea and vomiting induced by anticancer drugs, such as cisplatin when administered at a dose of 0.3 mg. The efficacy rate was 85.1% (40/47 patients) when given at a dose of 0.3 mg before the administration of anticancer drugs, such as cisplatin. The incidence of adverse effects was 2.0% (7/352 patients). Main adverse effects reported were feeling of heat, headache, and heavy feeling in the head. These adverse effects were of no clinical importance.
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PMID:[A new antiemetic ramosetron hydrochloride]. 905 Nov 43

Dolasetron (dolasetron mesilate) is a pseudopelletierine-derived 5-HT3 antagonist which has recently become available for clinical use. It is rapidly converted in vivo to its active major metabolite, hydrodolasetron, which appears to be largely responsible for its pharmacological activity. In clinical trials, single intravenous or oral doses of dolasetron were effective in preventing acute chemotherapy-induced nausea and vomiting (CINV). Intravenous doses of 1.8 mg/kg achieved complete suppression of vomiting in approximately 50% of patients receiving highly emetogenic cisplatin-containing chemotherapy and in approximately 60 to 80% of patients receiving moderately emetogenic chemotherapy. In the latter setting, oral doses of 200 mg achieved similar response rates. In comparative studies, intravenous dolasetron 1.8 mg/kg was as effective as intravenous granisetron 3 mg or ondansetron 32 mg after highly emetogenic chemotherapy, and oral dolasetron 200 mg was equivalent to multiple oral doses of ondansetron (3 or 4 doses of 8 mg) after moderately emetogenic chemotherapy. Dolasetron 1.8 mg/kg was superior to metoclopramide in preventing emesis induced by high dose cisplatin or by moderately emetogenic chemotherapy in high risk subgroups. Dolasetron has also shown efficacy in preventing radiotherapy-induced nausea and vomiting (RINV) in preliminary studies. Single intravenous or oral dolasetron doses ranging from 12.5 to 100 mg and 25 to 200 mg, respectively, were significantly more effective than placebo in preventing postoperative nausea and vomiting (PONV) in female surgical patients. A 50 mg intravenous dose was as effective in preventing PONV as ondansetron 4 mg in a mixed-gender group. Intravenously administered dolasetron was also effective in treating established PONV, although complete suppression of vomiting was achieved in < 40% of patients. Dolasetron has a tolerability profile characteristic of this class of compounds, with headache, dizziness and diarrhoea being the most commonly occurring adverse events in clinical trials. Diarrhoea is not thought to be related to dolasetron administration, being experienced mostly by patients receiving chemotherapy. Dolasetron and other 5-HT3 receptor antagonists have been associated with minor changes in ECG intervals, but these generally do not appear to be clinically important. Thus, available evidence suggests that dolasetron will provide an alternative to other 5-HT3 receptor antagonists for the management of CINV and PONV. Further studies are required to determine whether it offers any advantages over other agents in these settings and to determine the optimum dosage for preventing RINV.
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PMID:Dolasetron. A review of its pharmacology and therapeutic potential in the management of nausea and vomiting induced by chemotherapy, radiotherapy or surgery. 925 83


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