Comparison of the safety and efficacy of a fixed-dose combination regimen and separate formulations for pulmonary tuberculosis treatment

OBJECTIVES: Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment. METHOD: A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients’ outcomes were analyzed. ClinicalTrials.gov: NCT00979290. RESULTS: A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up. CONCLUSIONS: In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used. .

Allopurinol hypersensitivity syndrome in patients with hematological malignancies: characteristics and clinical outcomes

BACKGROUND/AIMS: Allopurinol is a urate-lowering agent that is commonly used to prevent chemotherapy-related hyperuricemia. Allopurinol hypersensitivity syndrome (AHS) is a disorder involving multiple organs, which may be accompanied by cutaneous adverse reactions. We identified the characteristics and clinical outcomes of chemotherapy-associated AHS in patients with hematological malignancies. METHODS: This retrospective single-center study included 26 AHS patients (11 with and 15 without hematological malignancies) admitted to Seoul St. Mary's Hospital. AHS was defined using the criteria of Singer and Wallace. Comparisons were made using the Mann-Whitney U test and Fisher exact test as appropriate. RESULTS: In patients with a hematological malignancy and AHS, statistically significant differences were observed in terms of younger age at onset; shorter duration of exposure; higher starting and maintenance doses of allopurinol; lower incidence of eosinophilia, leukocytosis, and underlying renal insufficiency; and more frequent occurrence of fever compared to AHS patients without a hematological malignancy. Two AHS patients with a hematological malignancy were examined for human leukocyte antigen (HLA)-B typing, but neither patient harbored the HLA-B*5801 allele. All of the patients ceased allopurinol treatment, with most patients making a full recovery. Two patients in the study died; however, these deaths were unrelated to AHS. One patient developed serious sequelae of AHS that required hemodialysis. CONCLUSIONS: Physicians who prescribe allopurinol for the prevention of chemotherapy-related hyperuricemia should be aware of the unique risk of AHS, even in patients with hematological malignancies who do not have known risk factors for AHS. Novel urate-lowering agents should be considered alternative treatments.

To study the efficacy of losartan on urinary uric acid excretion in thiazide induced hyperuricemic and hypertensive patients

The precise relationship of Hyperuricemia found in hypertensive patients is still obscure; this study is a urinary uric acid lowering intervention with Losartan in hypertensive patients induced by Thiazide diuretics. A number of pharmacological agents like loop diuretics, similarly low doses of aspirin [<3g daily] aggravate Hyperuricemia. The effect of Losartan on urinary uric acid excretion In Hypertensive patients with Thiazide induced Hyperuricemia were investigated in the Department of pharmacology and therapeutics, Basic Medical Sciences Institute Jinnah Postgraduate Medical Centre Karachi. It was randomized, open label, prospective, comparative study. Total 60 hypertensive Hyperuricemic patients were enrolled one by one in this study, selected from medical OPD and wards of Jinnah Postgraduate Medical Centre, Karachi. Patients were divided in three groups. Group-1 patients were treated with Thiazide 50 mg/day, Group-2 with Losartan + Thiazide 50 mg/day, and Group-3 with Losartan 50 mg/day. The effect on urinary uric acid level was measured, after every fortnightly. Treatment with Thiazide + Losartan group and Losartan group showed significantly increase in urinary uric acid excretion. Whereas, Thiazide group decrease in urinary uric acid level. In contrast to Thiazide and Losartan alone Thiazide + Losartan led to a greater increased in urinary uric acid excretion. The average percentage increase in urinary uric acid excretion in Thiazide + Losartan group was -13.27% and the average percentage increased in urinary uric acid excretion was 6.7% in Losartan group. Thus it can be concluded from the present study that urinary uric acid excretion was more increased in combination therapies. Ultimately Losartan decrease serum uric acid level and uricosuric effect of Losartan might be particularly useful in Hyperuricemic patients those on Thiazide diuretic [for hypertension and heart failure]

Pyrazinamide induced hyperuricaemia presenting as severe bilateral leg cramps.

Pyrazinamide is one of the first line drugs used for the treatment of tuberculosis. Hepatotoxicity and hyperuricaemia are important and common untoward effects seen after administration of pyrazinamide. The drug inhibits elimination of urates resulting in hyperuricaemia, the presenting features of which are arthralgia, arthritis or even gout. A-case of bilateral leg cramps due to hyperuricaemia following pyrazinamide therapy is reported here.