[Assessment of inappropriate prescriptions in psychiatric in-patients]. / Evaluation des prescriptions médicales non conformes dans un service de psychiatrie adulte.

OBJECTIVE: To evaluate occurrence of the inappropriate prescriptions in a psychiatric department. METHODOLOGY: In this prospective survey over a two-month period, the medical orders were analysed. Inappropriate prescription was defined as any discrepancy with summary of product characteristics (SPC) or our hospital treatment guidelines. RESULTS: One hundred inpatients (72 women, mean age 37.5+/-15 years) were included. We reviewed 495 medication orders, which represent 1875 prescribed drugs. We found 2636 discrepancies with SPC or our hospital treatment guidelines. The proportion of discrepancies related to legal informations was 21.28% and them related to pharmacotherapy was 55.04%. The proportion of discrepancy per patient was estimated to 4.93%. CONCLUSION: Our study shows a high proportion of inappropriate prescriptions, none of them having induced adverse-drug effects.

Adverse effects of voriconazole: analysis of the French Pharmacovigilance Database.

BACKGROUND: The most common adverse effects of voriconazole reported during clinical trials were disturbances of vision (30% of pts.), skin rashes (17.3%), and elevations in hepatic enzymes level (approximately 10% of pts.; varying with enzymes). However, postmarketing data concerning safety of voriconazole are limited. OBJECTIVE: To describe voriconazole adverse drug effects (ADEs) after 4 years of the drug's availability in France and determine their occurrence. METHODS: All cases of ADEs including voriconazole reported to the French Pharmacovigilance Database between 2002 and 2005 were analyzed. For each case, the following data were recorded: age, sex, indication, concomitant disease, concomitant medications, and ADE description. Causality link between voriconazole and ADEs was performed using the Naranjo probability scale. RESULTS: A total of 227 ADE cases were reported in 178 adults and 9 children (<12 y), with 66% occurring in males. The patients' median age was 49.6 (2-80) years. ADEs included liver function test abnormalities (23%), visual disturbances (18%), skin rashes (17%), neurologic disturbances (14%), cardiovascular events (10%), hematologic disorders (8%), and renal disturbances (4%). Other less commonly identified ADEs included headache, nausea, vomiting, and diarrhea. Drug-drug interactions were observed in 7 cases. According to the Naranjo criteria, 84% of ADEs were classified as possible, 7% as probable, 5% as highly probable, and 4% as doubtful. CONCLUSIONS: Most ADEs found in this study are well documented in the literature, except for cardiac complications, which are rarely reported. Few ADEs related to drug interactions were observed; however, due to the extensive metabolism of voriconazole by cytochrome P450 isoenzymes, clinicians should be aware of potential interactions between voriconazole and other drugs metabolized through this pathway.

Neurotoxicity related to valganciclovir in a child with impaired renal function: usefulness of therapeutic drug monitoring.

OBJECTIVE: To report a case of neurotoxicity related to antiviral drugs, discuss the involvement of concomitant medications, and document the pharmacokinetics of ganciclovir (administered as valganciclovir) in a child with impaired renal function. CASE SUMMARY: A 13-year-old boy with acute lymphoblastic leukemia was treated for cytomegalovirus retinitis with valganciclovir 450 mg every 2 days in the course of hematopoietic stem cell transplantation. Concomitant medication included omeprazole, furosemide, and acetaminophen. During treatment, when creatinine clearance decreased to 20 mL/min, the child presented with acute neurotoxicity, consisting of mental confusion and hallucinations, which resolved when all medications were stopped. Valganciclovir therapeutic monitoring showed high ganciclovir concentrations in the plasma (3.85 microg/mL) and cerebrospinal fluid (2.6 microg/mL) 48 hours after the last valganciclovir dose. After recovery of neurologic function, valganciclovir was resumed at a lower dosage (225 mg twice a week) with therapeutic drug monitoring and was well tolerated. However, the cytomegalovirus infection was not resolved. The leukemia relapsed, and the patient had terminal renal failure and died. The Naranjo probability scale indicated a probable relationship between valganciclovir and neurotoxicity. DISCUSSION: Drugs taken by this child (acyclovir, valganciclovir, omeprazole) have been reported to induce neurotoxicity, with the pharmacokinetics of the first 2 being altered by renal failure. At the time when acyclovir was first administered, symptoms of neurotoxicity were already apparent. Moreover, plasma concentrations of ganciclovir were very high during the course of the neurotoxicity. Thus, the adverse effects seemed related to an overdosage of valganciclovir and were worsened by the addition of acyclovir. CONCLUSIONS: This case is informative because few clinical and pharmacokinetic data are available concerning the use of valganciclovir in children. A study should be performed to determine the proper pediatric dose of valganciclovir with and without renal impairment to prevent the occurrence of adverse effects.

[Assessment of renal abnormalities in 107 HIV patients treated with tenofovir]. / Evaluation de la tolérance rénale du ténofovir dans une cohorte de 107 patients.

OBJECTIVES: The objectives of our study were to assess frequency, severity and outcome of renal abnormalities, as well as to determine the risk of developing hypophosphataemia in HIV-infected patients receiving tenofovir. METHODS: An observational study was conducted in real-life conditions, during a 6-month period, in 107 HIV patients receiving tenofovir. RESULTS: Mild-to-moderate hypophosphataemia (<0.77 mmol/L) occurred during follow-up, at least once in 43% of patients and at least twice in 27%. Antiretroviral therapy including ritonavir + lopinavir was significantly associated with the occurrence of hypophosphataemia (relative risk = 2.6; p = 0.03). Frequency of abnormal proteinuria was 22%. CONCLUSION: Creatinine clearance, phosphataemia, proteinuria and glycosuria should be closely monitored in patients receiving tenofovir therapy.

Reasons for early abacavir discontinuation in HIV-infected patients.

OBJECTIVE: To determine incidence of and reasons for discontinuation of abacavir within the first 6 months of therapy. METHODS: Retrospective study performed in the cohort of HIV-infected adults who started abacavir in a medical unit between 1997 and December 2000. All adverse drug reactions (ADRs) (especially hypersensitivity) observed in this cohort were reported. The association between drugs and complications were evaluated, using the French method to assess unexpected and toxic drug reactions. According to the variables studied, statistical analysis was performed using the chi2 test, Fisher's exact test, Mann-Whitney, Wilcoxon, or Kruskal-Wallis tests. RESULTS: All 331 patients treated with abacavir during this time period were included in this study. Early discontinuation of abacavir was observed in 34.1% of patients, the main reasons being adverse effects (20.8%), virologic failure (3.3%), drug holidays (2.7%), poor adherence (2.7%), and death (1.8%). Adverse effects were mostly represented by hypersensitivity reactions. After retrospective analysis, abacavir was stopped for likely hypersensitivity in 8.5% of patients, for doubtful hypersensitivity in 4.2%, and for other adverse effects in 8.1% of patients. CONCLUSIONS: This study shows that abacavir is mainly stopped during the first 6 months of therapy for ADRs. The rate of likely hypersensitivity reaction observed in this study (8.5%) is higher than that observed in clinical trials (5%). After retrospective evaluation, the causality assessment of abacavir is not always certain.

Adverse drug events associated with hospital admission.

OBJECTIVE: To increase the knowledge base on the frequency, causality, and avoidability of adverse drug events (ADEs) as a cause for admission in internal medicine or when occurring during hospitalization. METHODS: A prospective study was performed for 6 periods of 8 days each. Epidemiologic data (e.g., age, gender, medical history), drug utilization, and adverse drug reactions on patients hospitalized during these periods were collected by a pharmacy student. RESULTS: A total of 156 patients (70 men and 86 women) were included in the study. The patients' mean age +/- SD was 66.5 +/- 18.1 years and mean length of stay was 13.2 +/- 9 days. Renal and hepatic insufficiency and previous history of drug intolerance were observed in 17.9%, 10.2%, and 2% of the hospitalized patients, respectively. Thirty-eight ADEs occurred in 32 patients; in 15 cases, ADEs were identified as the reason for admission, 10 cases occurred during hospitalization, and 13 cases were present at admission, but were not the cause of admission. The most frequent ADEs involved the neurologic (23.6%), renal (15.7%), and hematologic (13.1%) systems. Among these 38 ADEs, 22 were considered avoidable (57.9%); 20 of these were associated with therapeutic errors (inappropriate administration, drug-drug interactions, dosage error, drug not stopped despite the onset of ADEs). Patients with ADEs stayed longer in the hospital and took more drugs both before and during their hospital stay (p < 0.05). CONCLUSIONS: Most of the ADEs observed in this study were avoidable. The risk/benefit ratio of administered drugs could be improved with better knowledge of the patients' medical history and the risk factors of ADEs.