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The New England Journal of Medicine Jan 1980
Topics: Administration, Oral; Adult; Diazoxide; Drug Evaluation; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Injections, Intra-Arterial; Pulmonary Artery
PubMed: 7350437
DOI: 10.1056/NEJM198001103020204 -
Rate of Serious Adverse Events Associated with Diazoxide Treatment of Patients with Hyperinsulinism.Hormone Research in Paediatrics 2019Diazoxide is the first line and only Federal Drug Agency approved pharmacological agent for the treatment of hyperinsulinism. Its use has increased over the years to... (Clinical Trial)
Clinical Trial Comparative Study
INTRODUCTION
Diazoxide is the first line and only Federal Drug Agency approved pharmacological agent for the treatment of hyperinsulinism. Its use has increased over the years to include patients with various genetic forms of hyperinsulinism, perinatal stress hyperinsulinism and infants of diabetic mothers with more babies than ever being exposed to this therapy.
METHODS
We performed a retrospective analysis of 194 patients with hyperinsulinism in our clinic and looked for those who had experienced serious adverse events (SAE) including pulmonary hypertension and neutropenia. We compared the rates of SAE in the different types of hyperinsulinism.
RESULTS
Out of 194 patients with hyperinsulinism, 165 (85.1%) were treated with diazoxide. There were 17 SAEs in 16 patients including 8 cases of pulmonary hypertension and 8 of neutropenia. These data show that overall the frequency of SAE associated with diazoxide use is 9.7%, but that those with perinatal stress hyperinsulinism have a much higher rate than those with genetic forms of hyperinsulinism (16.7 vs. 3.6%; p = 0.01). We also found diazoxide is associated with pulmonary hypertension (4.8% of patients treated). Although more patients with perinatal stress hyperinsulinism (7.6%) were affected than genetic hyperinsulinism (1.2%), the difference was not significant (p = 0.088).
CONCLUSION
The rate of SAEs associated with (not necessarily caused by) diazoxide has been demonstrated. The rate of SAE in newborns with perinatal stress hyperinsulinism is significantly higher than that of otherwise healthy babies with genetic forms of hyperinsulinism, suggesting that caution should be used when prescribing diazoxide to this population. This information should help balance the risk benefit of treatment and provide guidance on screening for these complications in the population of treated patients.
Topics: Diazoxide; Female; Humans; Hyperinsulinism; Hypertension, Pulmonary; Infant; Infant, Newborn; Male; Neutropenia; Retrospective Studies; Risk Factors
PubMed: 30889588
DOI: 10.1159/000497458 -
American Journal of Perinatology May 2024This study aimed to evaluate the prevalence of adverse outcomes, specifically pulmonary hypertension (PH) and suspected or confirmed necrotizing enterocolitis (NEC),...
OBJECTIVE
This study aimed to evaluate the prevalence of adverse outcomes, specifically pulmonary hypertension (PH) and suspected or confirmed necrotizing enterocolitis (NEC), and their associated risk factors, in neonates treated with diazoxide.
STUDY DESIGN
A retrospective study in infants born ≥ 31 weeks and admitted between January 2014 and June 2020. Combined adverse outcomes possibly associated to diazoxide were PH (systolic pulmonary pressure of ≥40 mm Hg or an eccentricity index ≥1.3) and suspected or confirmed NEC (suspected: stop feeds and antibiotics and confirmed: modified Bell stage ≥2). Echocardiography data extractors were masked to infants' characteristics.
RESULTS
A total of 63 infants were included; 7 (11%) with suspected and 1 (2%) with confirmed NEC. Of the 36 infants with an available echocardiography after initiation of diazoxide treatment, 12 (33%) had PH. All infants with suspected or confirmed NEC were males ( = 0.01), whereas PH occurred mostly in females (75%, = 0.02). The combined adverse outcome occurred in 14/26 (54%) infants exposed to >10 mg/kg/day, compared to 6/37 (16%) exposed to ≤10 mg/kg/day ( = 0.006). This association remained significant after adjustment for sex, small for gestational age status, and gestational age at birth (odds ratio: 6.1, 95% confidence interval: 1.7-21.7, = 0.005). Left ventricular dysfunction was found in 19 infants (30%) but was not discriminative for the combined outcome.
CONCLUSION
PH and suspected or confirmed NEC were identified frequently in neonates treated with diazoxide. A total dose >10 mg/kg/day was associated with an increased occurrence of these complications.
KEY POINTS
· PH and suspected or confirmed NEC were frequently found in neonates treated with diazoxide.. · A total dose >10 mg/kg/day was associated with an increased occurrence of these complications.. · Echocardiography screening should be considered in neonates exposed to diazoxide..
Topics: Humans; Diazoxide; Female; Infant, Newborn; Male; Enterocolitis, Necrotizing; Retrospective Studies; Hypertension, Pulmonary; Echocardiography; Risk Factors; Infant, Premature; Vasodilator Agents
PubMed: 36882098
DOI: 10.1055/s-0043-1764385 -
Clinical Pharmacology and Therapeutics Jul 1975The effect of uremia on the binding of diazoxide to plasma proteins was studied. An equilibrium dialysis technique, using diazoxide-minus14C at approximately 30 and 300...
The effect of uremia on the binding of diazoxide to plasma proteins was studied. An equilibrium dialysis technique, using diazoxide-minus14C at approximately 30 and 300 mug/ml in the plasma phase, was used to measure diazoxide binding to plasma. Serum albumin concentration (Alb) and serum creatinine (Cr) or blood urea nitrogen (BUN) were negatively correlated. By single regression analysis, per cent free diazoxide (%FD) correlated negatively with Alb and positively with Cr or BUN. When %FD was regressed simultaneously against Alb and Cr or BUN, Alb emerged as the sole determinant of %FD (p less than 0.001), indicating that creatinine or BUN correlated with %FD by their inverse correlation to Alb rather than by an effect on drug protein binding. At the levels of Alb studied, %FD varied over a 2-fold range. In a retrospective study of the influence of uremia on diazoxide effect in hypertensive patients, a relatively low correlation (r, 0.59) was found between BUN and hypotensive effect. Prospective studies involving correlations of drug effect with renal function and %FD are required to assess the clinical importance of decreased binding of diazoxide to uremic plasma.
Topics: Adult; Blood Proteins; Blood Urea Nitrogen; Creatinine; Diazoxide; Female; Humans; Hypertension; Male; Middle Aged; Protein Binding; Serum Albumin; Uremia
PubMed: 1149362
DOI: 10.1002/cpt197518153 -
Diabetes Dec 1975In two studies for toxicity, cataracts occurred in beagle dogs given diazoxide daily in high doses. Two of eighteen dogs given diazoxide intravenously at doses of 30.0...
In two studies for toxicity, cataracts occurred in beagle dogs given diazoxide daily in high doses. Two of eighteen dogs given diazoxide intravenously at doses of 30.0 mg. per kilogram twice a day for fourteen days had reversible lenticular changes. These changes were not observed in dogs given 22.5 or 10.0 mg. per kilogram twice a day. By fifty-eight days after the last treatment, the cataracts had regressed or disappeared completely. In a study of diazoxide given orally for a maximum of seventy-eight weeks, cataracts developed in six of forty-two dogs given doses ranging from 50 to 200 mg. per kilogram daily, but none occurred in dogs receiving 15 or 30 mg. per kilogram daily. Hyperglycemia was observed at doses of 50 mg. per kilogram or higher. In five of the six dogs that had cataracts and hyperglycemia, vacuolation or absence of islet cells was seen on histologic examination of pancreatic tissue at necropsy. Ocular changes were attributed to the hyperglycemic effect of high doses of diazoxide given daily for prolonged periods. The daily doses given dogs in which cataracts developed were from ten to forty times that suggested in man (5 mg./kg.).
Topics: Administration, Oral; Alloxan; Animals; Blood Glucose; Cataract; Diazoxide; Dogs; Dose-Response Relationship, Drug; Female; Hyperglycemia; Injections, Intravenous; Lens, Crystalline; Male; Pancreas
PubMed: 1193308
DOI: 10.2337/diab.24.12.1041 -
The Medical Letter on Drugs and... Dec 1978
Topics: Administration, Oral; Animals; Diazoxide; Female; Humans; Hypoglycemia; Infant; Pregnancy
PubMed: 732751
DOI: No ID Found -
Lancet (London, England) Dec 1979
Comparative Study
Topics: Diazoxide; Heart Rate; Humans; Hypertension; Infusions, Parenteral; Injections, Intravenous; Propranolol
PubMed: 93203
DOI: 10.1016/s0140-6736(79)92302-x -
Lancet (London, England) Mar 1973
Topics: Animals; Blood Pressure; Diazoxide; Female; Haplorhini; Humans; Hypertension; Pregnancy
PubMed: 4120534
DOI: 10.1016/s0140-6736(73)91526-2 -
Annals of the New York Academy of... Apr 1968
Topics: Adenoma, Islet Cell; Adrenal Glands; Adult; Aged; Benzothiadiazines; Blood Glucose; Diabetes Mellitus; Diazoxide; Female; Humans; Hypertrichosis; Hypoglycemia; Male; Metabolic Diseases; Nephrotic Syndrome; Uric Acid
PubMed: 4299225
DOI: 10.1111/j.1749-6632.1968.tb19063.x -
The New England Journal of Medicine Dec 1971
Topics: Coma; Diazoxide; Furosemide; Humans; Hyperglycemia; Injections, Intravenous; Tolbutamide
PubMed: 5122901
DOI: No ID Found