Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nevirapine (NVP) is a nonnucleoside reverse transcriptase inhibitor widely used in combination with other antiretroviral agents for the treatment of human immunodeficiency virus disease. To establish its safety profile, we conducted a review of data from prospective US and international clinical trials involving a total of 906 adult patients and 468 pediatric patients treated with NVP. Drug-related adverse events were similar in adults and children, with rash and nausea most frequently reported in adults and rash and granulocytopenia most frequently reported in children. A separate analysis of rash based on data from adult patients in controlled trials demonstrated a 16% rate of NVP-attributable rash in these patients. Of patients with NVP-associated rash, 65% developed rash within the first 6 weeks of therapy, and it has been shown that a lower lead-in dose (200 mg/d vs the standard 400 mg/d) for the first 2 weeks of NVP treatment reduces the frequency of drug-associated rash. Serious rash (Stevens-Johnson syndrome [SJS] or SJS/toxic epidermal necrolysis transition syndrome) occurred with an incidence of 0.3% and clinical hepatitis with an incidence of 1.0% among NVP-treated patients in clinical trials. Adverse event data from long-term clinical trials demonstrated a lower incidence of NVP-related adverse events than in short-term trials of NVP therapy. An analysis of abnormal laboratory findings using thresholds similar to those found in the prescribing information for other commonly used antiretroviral agents and data from controlled trials in adults showed that the most frequently observed laboratory abnormalities were elevations in liver function test results. Approximately 50,000 patients in the United States had been treated with marketed NVP at the time of writing, and postmarketing surveillance has supported the overall safety profile observed in clinical trials. NVP has been shown to be well tolerated in both adult and pediatric patients.
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PMID:Safety profile of nevirapine, a nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus infection. 991 3

Carbamazepine is a commonly prescribed anticonvulsant medication that affects various levels of the nervous system. We report a case of temporary sensorineural hearing loss in a patient after overdosing with 36 g of carbamazepine. Six days after the overdose, the patient complained of bilateral hearing loss and tinnitus. Audiograms revealed a 30- to 40-dB sensorineural hearing loss bilaterally. Another audiogram 2 weeks later showed a complete recovery in both ears accompanied by a clinical resolution in audiovestibular symptoms. Carbamazepine is used to treat partial and generalized seizures, trigeminal neuralgia, and bipolar illness. Adverse effects are not common but most frequently include dizziness, drowziness, nausea, and skin rashes; rare complications are agranulocytosis, bradycardia, and heart block. Documented hearing loss as a side effect of carbamazepine has not been reported, to our knowledge.
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PMID:Carbamazepine-induced sensorineural hearing loss. 1003 90

Quetiapine is an atypical antipsychotic with clozapine-like pharmacology but without associated agranulocytosis. We report our complete experience with quetiapine for the treatment of drug-induced psychosis (DIP) in Parkinson's disease (PD). Thirty-five patients with PD and DIP aged 75 years (range, 58-89) with a mean PD duration of 8.4 years on an average of 427 mg levodopa per day received a mean dose of 40.6 mg quetiapine daily. Twenty of 24 neuroleptic-naive patients reported marked improvement of psychosis without a decline in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS-motor). Ten patients had a baseline and 4-week follow-up assessment using the Mini-Mental Status Examination (MMSE) and Brief Psychiatric Rating Scale (BPRS). The improvement in BPRS score (32.6 versus 22.8) was clinically and statistically significant (p = 0.024). Three of 24 were unable to tolerate quetiapine because of orthostatic hypotension, headache, nausea, and persistence of hallucinations. One patient died of an unrelated cause. We also tried to switch 11 psychiatrically stable patients on clozapine (eight) and olanzapine (three). Five patients made this transition without a loss of effect as measured on BPRS and MMSE. Six did not (five on clozapine, one on olanzapine) because of confusion, erratic behavior, and increased hallucinations. No crossover failure had worsened PD except for increased tremor in one. Quetiapine is useful and well-tolerated as a first drug to treat DIP in PD but must be used cautiously to replace other atypical antipsychotic drugs.
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PMID:Quetiapine for the treatment of drug-induced psychosis in Parkinson's disease. 1034 74

9-Aminocamptothecin (9-AC) is a camptothecin derivative with broad antitumor activity in preclinical studies. Prior investigations suggested that prolonged maintenance of 9-AC lactone plasma concentrations above 10 nmol/l and frequent administration of the drug are important determinants of antitumor activity. Our phase II study, therefore, examined a 5-day continuous infusion of 9-AC weekly for 3 weeks in patients with advanced colorectal cancer. Eighteen patients previously untreated for metastatic disease received 480 microg/m2/day of 9-AC. No responses were observed in 17 evaluable patients. Severe toxicities included granulocytopenia, nausea, vomiting and diarrhea. The median absolute granulocyte count (AGC) nadir was 2,300/microl (range 0-9,000/microl) and occurred on day 10. Eight patients received an escalated dose of 600 microg/m2/day. The median AGC nadir at the escalated dose was 1,500/microl (range: 300-2,700/microl) and occurred on day 22. The median number of courses given was 2 (range: 1-8); and the median time to disease progression was 8 weeks (range: 1-40 weeks). 9-AC administered by this schedule lacked antitumor activity in patients with advanced colorectal carcinomas.
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PMID:Phase II trial of 9-aminocamptothecin (NSC 603071) administered as a 120-hr continuous infusion weekly for three weeks in metastatic colorectal carcinoma. 1042 69

We reported previously that the addition of recombinant Escherichia coli human granulocyte-macrophage colony stimulating factor (GM-CSF) to a 5-fluorouracil (5-FU) and leucovorin (LV) regimen seemed to ameliorate diarrhea and permit increased 5-FU dose intensity (J. L. Grem et al., J. Clin. Oncol., 12: 560-568, 1994). We then tested the effect of GM-CSF given with a more toxic regimen of 5-FU/LV/IFN-alpha (IFN alpha-2a). Thirty-one patients with a good performance status and no prior chemotherapy for systemic disease received IFN alpha(-2a (5 MU/m2 s.c., days 1-7), 5-FU (370 mg/m2 i.v., days 2-6), LV (500 mg/m2 i.v., days 2-6), and GM-CSF (Saccharomyces cerevisiae 250 microg/m2 s.c., days 7-18) every 3 weeks. Toxicities and 5-FU dose intensity were compared with that observed in our prior Phase II trial with 5-FU/LV/IFN alpha-2a (J. L. Grem et al., J. Clin. Oncol., 11: 1737-1745, 1993). In comparison with the prior Phase II study, the WBC and granulocyte nadirs in the present trial were significantly higher. When trends in toxicity grades for all cycles were compared, stratifying for 5-FU dose, the incidence and severity of mucositis, skin rash, WBC toxicity, and granulocyte toxicity were significantly lower in the present trial, whereas nausea/vomiting and fatigue were significantly worse. The delivered 5-FU dose intensity for all cycles of therapy appeared to be significantly higher in the present trial. Six of 28 evaluable patients had a partial response (21.4%), and 13 (46%) had stable disease for > or =12 weeks. Despite treatment-related toxicity, patient quality of life did not worsen during the study. No correlation was observed between thymidylate synthase content in primary tumor specimens and response, time to treatment failure, or survival. The addition of GM-CSF appeared to decrease the severity of leukopenia, granulocytopenia, mucositis, and skin rash when compared with our prior experience with this regimen of 5-FU/LV/IFN alpha-2a, at the cost of greater nausea/vomiting and fatigue. The potential impact of increased 5-FU dose intensity on clinical response, however, remains to be determined.
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PMID:A pilot study of interferon alpha-2a, fluorouracil, and leucovorin given with granulocyte-macrophage colony stimulating factor in advanced gastrointestinal adenocarcinoma. 1049 10

In previous trials, the orally active iron chelator deferiprone (L1) has been associated with sporadic agranulocytosis, milder forms of neutropenia and other side-effects. To determine the incidence of these events, we performed a multicentre prospective study of the chelator. Blood counts were performed weekly, and confirmed neutropenia mandated discontinuation of therapy. Among 187 patients with thalassaemia major, the incidence of agranulocytosis (neutrophils < 0.5 x 109/l) was 0.6/100 patient-years, and the incidence of milder forms of neutropenia (neutrophils 0.5-1.5 x 109/l) was 5.4/100 patient-years. All cases of neutropenia resolved after interruption of therapy. Neutropenia occurred predominantly in non-splenectomized patients. Nausea and/or vomiting occurred early in therapy, was usually transient and caused discontinuation of deferiprone in three patients. Mild to moderate joint pain and/or swelling did not require permanent cessation of deferiprone and occurred more commonly in patients with higher ferritin levels. Mean alanine transaminase (ALT) levels rose during therapy. Increased ALT levels were generally transient and occurred more commonly in patients with hepatitis C. Persistent changes in immunological studies were infrequent, although sporadic abnormalities occurred commonly. Mean zinc levels decreased during therapy. Ferritin levels did not change in the overall group but decreased in those patients with baseline levels > 2500 microgram/l. This study characterized the safety profile of deferiprone, and, under the specific conditions of monitoring, demonstrated that agranulocytosis is less common than previously predicted.
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PMID:Safety profile of the oral iron chelator deferiprone: a multicentre study. 1069 60

Pentostatin (Nipent; SuperGen, San Ramon, CA), which is highly lymphocytotoxic, is an active agent in hairy cell leukemia. We therefore initiated a trial of this agent in T-cell lymphomas. Pentostatin was administered at a dose of 3.75 or 5.0 mg/m2/d intravenously for 3 days every 3 weeks to heavily pretreated patients with cutaneous and peripheral T-cell lymphomas. To date, there are 24 evaluable patients in the trial. Seventeen of these individuals have responded (complete or partial remission). The most common toxicities included granulocytopenia, nausea, renal insufficiency, CD4 suppression, and delayed herpes zoster. Pentostatin is an active agent in this group of diseases and merits further exploration.
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PMID:Pentostatin (Nipent) in T-cell lymphomas. 1087 55

It has been reported that 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11) and its active metabolite, 7-ethyl-10-hydroxy-camptothecin (SN-38), have absorption characteristics of weakly basic drugs, suggesting that alkalization of the intestinal lumen might reduce reabsorption and its attendant side effects. Furthermore, stasis of stools containing these compounds is thought to induce damage to the intestinal mucosa. The prevention of CPT-11-induced side effects by oral alkalization (OA) combined with control of defecation (CD) was estimated in a case-control study of lung cancer patients. Coinciding with day 1 of CPT-11 infusion and for 4 days thereafter, OA and CD were practiced utilizing orally administered sodium bicarbonate, magnesium oxide, basic water and ursodeoxycholic acid. OA involved the daily use of all four therapeutics, and CD required doses of up to 4.0 g/day of magnesium oxide and 2 L/day of excess basic water. From three ongoing prospective phase I/II studies, we selected 37 consecutive patients who were treated with CPT-11 in combination with cisplatin in the presence of OA and CD (group B). Thirty-two control subjects who were matched to the background characteristics of the case patients were treated with the same regimen in the absence of OA and CD (group A). Toxicities induced by the CPT-11/cisplatin combination were evaluated and analyzed in group A and group B in a case-control format. The use of OA and CD resulted in significantly higher stool pH (p < 0.0001), while reducing the incidence of delayed diarrhea (> or = grade 2: group A 32.3% versus group B 9.4%; p = 0.005), nausea (p = 0.0001), vomiting (p = 0.001) and myelotoxicity, especially granulocytopenia (p = 0.03) and lymphocytopenia (p = 0.034). In addition, dose intensification was well tolerated in patients receiving OA and CD, allowing dose escalation from 35.6 +/- 6.0 to 39.9 +/- 5.6 mg/m(2)/week (p < 0.001). Tumor response rates for non-small cell lung cancer were 59.3% (16/27 patients) in group B compared with 38.5% (10/26 patients) in group A. Multivariate analysis revealed that the risk of CPT-11-induced delayed diarrhea greater than grade 2 was associated with OA and CD (odds ratio for delayed diarrhea, 0.14 with use of OA and CD; 95% confidence interval, 0.05 to 0.4; p = 0.0002) and age (odds ratio, 1.08 per increase in age; 95% confidence interval, 1.02 to 1.15; p = 0.009). OA and CD appear to be useful in preventing the dose-limiting side effects of CPT-11 noted in clinical practice, mainly nausea, vomiting, granulocytopenia and especially delayed diarrhea. Risk factors statistically associated with delayed diarrhea include advanced age and the use of CPT-11 without OA and CD.
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PMID:Prevention of irinotecan (CPT-11)-induced diarrhea by oral alkalization combined with control of defecation in cancer patients. 1129 Oct 56

Cytovene (ganciclovir) capsules were approved by the Food and Drug Administration (FDA) on December 22, 1994 as an alternative to the intravenous formulation for maintenance therapy of CMV retinitis in patients with HIV disease. This treatment is limited to those whose retinitis is stable following appropriate IV induction therapy, and where the risk of more rapid disease progression is balanced by the benefit of avoidance of daily infusion. FDA approval also allows physicians to prescribe the capsules off-label as a prophylaxis against CMV retinitis. Clinical studies have shown that in patients taking the Cytovene capsules, the mean time to CMV retinitis progression was 5-12 days less than in those patients on the IV formulation. The major side effects of the Cytovene capsules were the same as those associated with IV formulation: granulocytopenia, anemia, and thrombocytopenia. Side effects unique to the oral treatment include diarrhea, fever, leukopenia and nausea. The benefits of Cytovene capsules are fewer serious incidents of sepsis, fewer catheter-related infections, and a lower incidence of both anemia and leukopenia.
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PMID:Cytovene capsules approved. 1136 95

Our objective was to determine the maximum tolerated doses of tirapazamine and cyclophosphamide given i.v. in combination. Eligible patients had advanced solid tumors refractory to conventional treatment. Tirapazamine (escalated from 80 to 390 mg/m(2)) was given i.v. over 2 h and followed by cyclophosphamide over 1 h. The cyclophosphamide dose was fixed at 1000 mg/m(2) until the tirapazamine dose of 390 mg/m(2) was reached. Once that dose of tirapazamine was reached, the cyclophosphamide dose was escalated to 1250 and 1500 mg/m(2). Twenty-eight patients were enrolled. The dose-limiting toxicity was granulocytopenia. One patient had transient deafness for 2 days. Four other patients had grade 1 ototoxicity. Grade 1 and 2 muscle cramps were observed at all dose levels. Other toxic effects observed included fatigue, nausea, vomiting, headache, diarrhea, drug fever, elevated transaminases and elevated creatine phosphokinase. Three patients had stable disease and the longest time to progression was 5 months. The combination of tirapazamine and cyclophosphamide is feasible, and the dose-limiting toxicity is granulocytopenia. The use of growth factors could possibly allow escalation of tirapazamine doses in future phase II trials. Without growth factor support, the recommended doses of tirapazamine and cyclophosphamide when administered in this schedule are 260 and 1000 mg/m(2), respectively.
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PMID:Phase I trial of i.v. administered tirapazamine plus cyclophosphamide. 1145 95


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