Is long-term use of benzodiazepine a risk for cancer?

The carcinogenicity of benzodiazepines (BZDs) is still unclear. We aimed to assess whether long-term benzodiazepines use is risk for cancer.We conducted a longitudinal population-based case-control study by using 12 years from Taiwan National Health Insurance database and investigated the association between BZDs use and cancer risk of people aged over 20 years. During the study period, 42,500 cases diagnosed with cancer were identified and analyzed for BZDs use. For each case, six eligible controls matched for age, sex, and the index date (ie, free of any cancer in the date of case diagnosis) by using propensity score. For appropriate risk estimation, we observed the outcomes according to their length of exposure (LOE) and defined daily dose (DDD). To mimic bias, we adjusted with potential confounding factors such as medications and comorbid diseases which could influence for cancer risk during the study period. The data was analyzed by using Cox proportional hazard regression and conditional logistic regression.The finding unveils benzodiazepines use into safe and unsafe groups for their carcinogenicity. The use of diazepam (HR, 0.96; 95%CI, 0.92-1.00), chlorodizepoxide (HR, 0.98; 95%CI, 0.92-1.04), medazepam (HR, 1.01; 95%CI, 0.84-1.21), nitrazepam (HR, 1.06; 95%CI, 0.98-1.14), oxazepam (HR, 1.05; 95%CI, 0.94-1.17) found safer among BZDs. However, clonazepam (HR, 1.15; 95%CI, 1.09-1.22) were associated with a higher risk for cancers. Moreover, specific cancer risk among BZDs use was observed significantly increased 98% for brain, 25% for colorectal, and 10% for lung, as compared with non-BZDs use.Diazepam, chlordiazepoxide, medazepam, nitrazepam, and oxazepam are safe among BZDs use for cancer risk. Our findings could help physicians to select safer BZDs and provide an evidence on the carcinogenic effect of benzodiazepines use by considering the LOE and DDD for further research.

Acute kidney injury with medazepam-hyoscine buthylbromide.

An 84-year-old female patient was admitted to our internal medicine outpatient clinic complaining of stomach ache, nausea, and vomiting. She had hepatitis C infection for 10 years that was managed with antiviral treatment. On the second day of admission, she developed anxiety and complained about dysuria. Medazepam and hyoscine butylbromide combined tablet was administered. The day after medazepam and hyoscine butylbromide administration, patient's creatinine level increased to 2.3 mg/dL (0.57-1.11 mg/dL). Medazepam and hyoscine butylbromide administration was stopped on the fourth day. After 10 days of follow-up, her creatinine levels were normalized. In this article, we present an elderly patient with acute kidney injury induced by medazepam and hyoscine butylbromide that was managed with best supportive care.

A population-based case-control teratologic study of nitrazepam, medazepam, tofisopam, alprazolum and clonazepam treatment during pregnancy.

OBJECTIVE: To study the association between nitrazepam, medazepam, tofisopam, alprazolum and clonazepam treatments during pregnancy and prevalence of different congenital abnormalities (CAs). MATERIALS AND METHODS: A matched case-control study using cases with CAs and population controls from the dataset of the nationwide Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA), 1980-1996. RESULTS: Of 38,151 pregnant women who had babies without any defects (population control group), 75 (0.20%) were treated with these five benzodiazepines during pregnancy. Of 22,865 pregnant women who delivered offspring with CAs, 57 (0.25%) had benzodiazepine treatment. The occurrence of five benzodiazepine treatments during the second and third months of gestation, i.e. in the critical period for most major CAs did not show significant differences in matched case-control pairs. CONCLUSION: Treatment with five benzodiazepines studied during pregnancy did not present detectable teratogenic risk to the fetus in humans but the amount of information was limited for different CAs.

Depression following withdrawal from long-term benzodiazepine use: a report of four cases.

Depression following withdrawal from long- or short-term use of benzodiazepines is not uncommon, yet it is under-reported in the benzodiazepine withdrawal literature. Four cases of depressive illness supervening during benzodiazepine withdrawal are reported. Depression may, it is suggested, be an integral part of the benzodiazepine withdrawal syndrome.

A comparative study of the clinical effects of oral flunitrazepam, medazepam, and placebo.

In a double-blind randomized study 40 patients received 1 mg flunitrazepam, 40 patients received 10 mg medazepam, and 40 patients received placebo p.o. the night before surgery. On the morning of surgery each patient received another identical oral dose of the product or placebo taken the previous night. On the average, the flunitrazepam group slept better, was better sedated, and was less anxious than the medazepam or placebo groups. Similarly, as a reflection of diminished autonomic reactions, the patients receiving flunitrazepam had fewer cardiovascular changes. Flunitrazepam significantly decreased the amounts of thiopentone needed for induction of anesthesia. Medazepam did not. The pronounced sedative, sleep-inducing, and anxiolytic effects of flunitrazepam appear to be of great clinical importance for its use in anesthesiology. Repeated administrations of medazepam seem to be required to produce an evident clinical effect of the drug, possibly via the slow accumulation of metabolites. The main difference between these two benzodiazepine derivatives as regards clinical response therefore seems to be pharmacokinetic in origin.