Formulation and Clinical Evaluation of Sodium Benzoate Oral Solution for the Treatment of Urea Cycle Disorders in Pediatric Patients.

BACKGROUND: Sodium benzoate, a common food preservative, is used in the treatment of patients with urea cycle disorders (UCDs) as it stimulates ammonia removal by a non-urea cycle-based pathway. Despite its use in the clinical routine, no commercially available oral formulations currently exist. Liquid formulation is normally well accepted in pediatric age and allows precise dosage according to the children's needs. AIMS: (1) To prepare an oral sodium benzoate solution in different tastes and determine its stability, palatability, and tolerability and (2) to describe the long-term follow-up of two pediatric patients with UCDs treated with our formulation. METHODS: We prepared five oral solutions of sodium benzoate (200 mg/ml) by adding different flavoring agents. We measured drug concentration in the samples by high-performance liquid chromatography (HPLC). We evaluated palatability and tolerability with adult volunteers. Long-term drug compliance and metabolic control were appraised in two pediatric patients. RESULTS: All the oral solutions remained stable at room temperature along the 96-day test period, and they were well tolerated. The mint-flavored solution resulted the most palatable and preferred by adult volunteers. We report good drug compliance and good metabolic outcomes for both pediatric patients during the entire follow-up. CONCLUSIONS: Our study highlighted the stability and tolerability of flavored sodium benzoate oral solutions. These solutions were well accepted during a long-term follow-up and guaranteed a good metabolic control. Since taste attributes are critical to ensure acceptable medication adherence in the pediatric age, flavored liquid formulations of sodium benzoate may be an efficient strategy to achieve therapeutic outcomes in UCD pediatric patients.

Evidence-based and unlicensed indications for proton pump inhibitors and patients' preferences for discontinuation: a pilot study in a sample of Italian community pharmacies.

WHAT IS KNOWN AND OBJECTIVE: Despite the widespread use of proton pump inhibitors (PPIs), little is known about the appropriateness of treatment according to the indications reported by patients and their involvement in the process of treatment discontinuation. In patients who are unlikely to benefit, the medication should be stopped and dose tapering is recommended to reduce the risk of rebound symptoms. The aims of this pilot study were to evaluate the appropriateness of treatment according to the reported indications by PPI users, patients' preferences for drug withdrawal, and the modalities of previous attempts to discontinue the medications. METHODS: This observational study was conducted in nine community pharmacies. Each pharmacist was asked to interview a sample of patients with prescriptions for PPIs and to collect a minimum set of information about socio-demographic characteristics, drug indication, duration of drug treatment, number of drugs used for acid-related disorders, preference about drug withdrawal, previous attempts at drug discontinuation and the method of drug tapering when this was performed. RESULTS AND DISCUSSION: The study included 260 patients, 126 (48·5%) females; 81 patients received more than one drug for acid-related problems and the second medication was more frequently prescribed by a general practitioner, community pharmacist or specialist. Unlicensed indication was reported by 125 patients, and 77 patients did not receive any information about the duration of treatment. Fifty-one patients were in favour of drug discontinuation. PPI withdrawal was attempted but was unsuccessful in 12 cases. Nine patients discussed the method of drug withdrawal with their physician, and abrupt discontinuation was the most frequent suggestion. Many patients were treated with PPIs for unlicensed indications such as gastroprotection because of the number of concomitant drugs used or unspecified gastroprotection. Recommendations about the main indications and the duration of treatment are essential to avoid unnecessary prescriptions and undefined prolongation of drug use. Correct information about the method of drug discontinuation is essential for success. WHAT IS NEW AND CONCLUSION: Many patients using PPIs are treated for unlicensed indications such as non-specific gastroprotection. The use of more than one drug for acid-related disorders is frequent among PPI users although this is not supported by evidence. Patients should be given clear and appropriate information about the duration of treatment and method of drug discontinuation.

Role of Community Pharmacies for the Detection of Potentially Inappropriate Xanthine Oxidase Inhibitor Prescriptions.

BACKGROUND: Xanthine oxidase (XO) inhibitors are largely the treatment of choice for gout, but allopurinol is often inappropriately used for asymptomatic hyperuricemia. There is little evidence that allopurinol is useful in preventing cardiovascular diseases and therapeutic decisions must the balance the expected benefit with the potential harm. OBJECTIVE: To investigate the appropriateness of XO inhibitor use in relation to evidence-based indications and examine the role of community pharmacies in the detection of inappropriate prescriptions of these drugs. METHODS: This is an observational study conducted in eight community pharmacies. Each pharmacist was asked to interview a sample of patients who had received prescriptions of XO inhibitors. Patients were asked to complete a structured minimum data set that collected information on drug indication, history of gout, and presence of cardiovascular diseases. RESULTS: The study sample included 74 patients receiving XO inhibitors. About one third of patients reported being treated for asymptomatic hyperuricemia and had never had a gout attack. About half of the patients treated for asymptomatic hyperuricemia had been receiving the drug treatment for more than 3 years. Four asymptomatic hyperuricemic patients received allopurinol to treat hypertension. Among the patients treated for asymptomatic hyperuricemia, there was a higher presence of diabetes mellitus, obesity, previous myocardial infarction, and heart failure than in patients treated for an appropriate indication. CONCLUSIONS: Inappropriate use of XO inhibitors is principally related to the treatment of hyperuricemia in patients with cardiovascular diseases. Community pharmacists have a central role in pharmacovigilance, by contributing to the prevention and identification of potentially inappropriate drug prescriptions.