Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A total of 25 patients with metastatic renal cancer were treated on a phase II protocol with 5 days of continuous-infusion fluorodeoxyuridine (FUDR), (0.1 mg/kg daily) together with high-dose oral leucovorin (100 mg 4 h) and daily x6 high-dose interferon-alpha 2b (30 x 10(6) IU/m2). Despite the good performance status of the patients and the inclusion of 14 previously untreated patients in the cohort, no response was observed among the 20 evaluable patients. Toxicities included high fever, moderate anemia, transient leukopenia, transient and mild elevations of transaminases, and moderate to severe nausea, vomiting, diarrhea, and mucositis. There were also two episodes each of confusion, fluid retention, and pancreatitis and one episode of increased creatinine levels. During the study three deaths occurred, two of which were possibly therapy-related. Despite previous reports of activity of FUDR in metastatic renal cancer, the present regimen cannot be recommended.
 ...
PMID:Continuous-infusion fluorodeoxyuridine with leucovorin and high-dose interferon: a phase II study in metastatic renal-cell cancer. 146 58

Most antiviral drugs are nucleoside analogues with potential teratogenic, embryotoxic, carcinogenic and antiproliferative activities. They must be administered with caution during pregnancy, because some are known teratogens (e.g. amantadine) and a similar propensity cannot be entirely excluded for others (e.g. aciclovir). Their adverse effects mostly involve bone marrow depression (e.g. granulocytopenia with ganciclovir, anaemia with zidovudine) or neurotoxicity (e.g. seizures with interferon-alpha, peripheral neuropathy with zalcitabine), although gastrointestinal effects are also seen. Idiosyncratic reactions include didanosine-induced acute pancreatitis. Only inosine pranobex is largely free from toxicity. Idoxuridine must be administered topically, given the severity of its systemic adverse effects. Drug interactions involving antiviral agents mostly reflect shared toxicity with other agents (e.g. neutropenia with ganciclovir and zidovudine, pancreatitis with didanosine and alcohol), although renal excretion or hepatic metabolism may be implicated. Given the possibility of severe adverse reactions and drug interactions, antiviral chemotherapy should only be used for potentially serious virus infections. Topical administration avoids systemic adverse effects but not mutagenic risks, and may result in exposure of individuals other than the patient (e.g. aerosolised ribavirin).
 ...
PMID:Adverse effects and drug interactions of clinical importance with antiviral drugs. 801

A nonrandomized trial was undertaken to evaluate the combination of didanosine and interferon-alpha (INF-alpha) in human immunodeficiency virus (HIV)-infected patients. Thirty-six volunteers with >200 x 10(6) CD4 cells/L received didanosine (one 100-, 250-, or 375-mg sachet twice daily) for at least 6 weeks, following which IFN-alpha (1, 5, 10, or 15 MU/day) was begun. Didanosine (one 375-mg sachet twice daily) was substituted for zidovudine in 14 additional patients who had received IFN-alpha and zidovudine for 7-45 months. Thirty-five patients completed the 34-week study. Clinical or chemical pancreatitis was the most common (6 patients) dose-limiting toxicity. CD4 cell counts increased with didanosine but declined following the addition of IFN-alpha; CD4 cell percents tended to increase and remain elevated. Thus, combination therapy with didanosine and IFN-alpha can be safely administered to patients with HIV infection. The clinical benefit of this combination therapy will require further evaluation.
 ...
PMID:Combination therapy with didanosine and interferon-alpha in human immunodeficiency virus-infected patients: results of a phase I/II trial. 860 61

Dyslipidemia, characterized by elevated serum levels of triglycerides and reduced levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol, has been recognized in patients with human immunodeficiency virus (HIV) infection. It is thought that elevated levels of circulating cytokines, such as tumor necrosis factor-alpha and interferon-alpha, may alter lipid metabolism in patients with HIV infection. Protease inhibitors, such as saquinavir, indinavir and ritonavir, have been found to decrease mortality and improve quality of life in patients with HIV infection. However, these drugs have been associated with a syndrome of fat redistribution, insulin resistance, and hyperlipidemia. Elevations in serum total cholesterol and triglyceride levels, along with dyslipidemia that typically occurs in patients with HIV infection, may predispose patients to complications such as premature atherosclerosis and pancreatitis. It has been estimated that hypercholesterolemia and hypertriglyceridemia occur in greater than 50% of protease inhibitor recipients after 2 years of therapy, and that the risk of developing hyperlipidemia increases with the duration of treatment with protease inhibitors. In general, treatment of hyperlipidemia should follow National Cholesterol Education Program guidelines; efforts should be made to modify/control coronary heart disease risk factors (i.e. smoking; hypertension; diabetes mellitus) and maximize lifestyle modifications, primarily dietary intervention and exercise, in these patients. Where indicated, treatment usually consists of either pravastatin or atorvastatin for patients with elevated serum levels of LDL-C and/or total cholesterol. Atorvastatin is more potent in lowering serum total cholesterol and triglycerides compared with other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, but it is also associated with more drug interactions compared with pravastatin. Simvastatin and lovastatin are significantly metabolized by cytochrome P450 enzymes (CYP3A4) and are therefore not recommended for coadministration with protease inhibitors. A fibric acid derivative (gemfibrozil or fenofibrate) should be used in patients with primary hypertriglyceridemia. However, it must be kept in mind that protease inhibitors, such as nelfinavir and ritonavir, induce enzymes involved in the metabolism of the fibric acid derivatives and may, therefore, reduce the lipid-lowering activity of coadministered gemfibrozil or fenofibrate. In certain patients HMG-CoA reductase inhibitors may be used in combination with fibric acid derivatives but patients should be carefully monitored for liver and skeletal muscle toxicity. Select patients may experience improvements in serum lipid levels when their offending protease inhibitor(s) is/are exchanged for efavirenz, nevirapine, or abacavir; however each patient's virologic and immunologic status must be taken closely into consideration.
 ...
PMID:Management of protease inhibitor-associated hyperlipidemia. 1472 85

A patient treated with interferon-alpha and ribavirin for hepatitis C, who developed acute pancreatitis, is presented here along with a literature review. A 45-year-old Caucasian man was admitted to the intensive care unit because of an acute pancreatitis. According to the adverse drug reaction probability scale, it is probable that pancreatitis was induced by treatment (interferon and ribavirin) for chronic hepatitis C (CHC) commenced 2 months ago. We performed a literature search of all available English-language articles published on MEDLINE between January 1966 and July 2008 using the key terms "acute pancreatitis", "interferon" and "ribavirin"; only four papers were found with a total of 13 reported cases demonstrating acute pancreatitis developed during treatment for CHC. Looking out for the minimal clinical signs and symptoms of acute pancreatitis in patients with CHC using interferon and ribavirin can help to detect this relevant and rare adverse drug reaction early.
 ...
PMID:Acute pancreatitis during interferon-alpha and ribavirin treatment for hepatitis C. 2168 14