{"id":3408150,"date":"2022-01-30T20:06:00","date_gmt":"2022-01-31T01:06:00","guid":{"rendered":"https:\/\/myendoconsult.com\/learn\/?p=3408150"},"modified":"2023-03-16T05:53:20","modified_gmt":"2023-03-16T10:53:20","slug":"diazoxide-mechanism-of-action","status":"publish","type":"post","link":"https:\/\/myendoconsult.com\/learn\/diazoxide-mechanism-of-action\/","title":{"rendered":"Diazoxide Mechanism of Action"},"content":{"rendered":"

Diazoxide works by blocking the release of insulin from the pancreas, thus allowing recovery from hypoglycemia in, most commonly, pediatric patients with congenital hyperinsulinemic hypoglycemia.\u00a0 This is a medication that is not likely to be required often, but is effective when it is called upon.<\/p>\n

Of note, there was recently an FDA-issued warning in September 2015 regarding findings of pulmonary hypertension and respiratory distress in infants and children (especially those with other factors that may contribute to either of these).\u00a0 This has been found to be reversible upon discontinuation of diazoxide.<\/p>\n

Regarding cost, one bottle contains multiple doses, as each 30mL bottle contains 1500mg of diazoxide.\u00a0 Depending on the age and weight of the child, a bottle would likely contain 15-30 days\u2019 worth of medication.\u00a0 The question that next needs to be answered is regarding the number of days of therapy.<\/p>\n

This is addressed in the article, \u201cManagement strategies for neonatal hypoglycemia,\u201d published in The Journal of Pediatric Pharmacology and\u00a0 Therpeutics <\/em>in 2013.\u00a0 According to the authors, the typical time it takes for these patients to see normal blood glucose levels is roughly 2-4 days, but a trial of 5-8 days is recommended before stopping the dose.2<\/sup> That being said, and per the above cost calculations, consider a patient who is one year old and weighs 11kg, and the plan is to trial diazoxide for a full eight days.\u00a0 The total cost would be approximately $140, and the total dose over those eight days would be 17.6mL (just over half of one bottle).\u00a0 Overall, diazoxide has been considered a first-line agent for congenital hyperinsulinemic hypoglycemia, and has been found to be especially effective for the treatment of this disorder in infants.<\/p>\n\n\n\n\n\n\n\n\n
Generic (Trade) Name:<\/td>\ndiazoxide (Proglycem)<\/td>\n<\/tr>\n
Drug Class:<\/td>\nhyperglycemic agent<\/td>\n<\/tr>\n
Formulation:<\/td>\noral suspension (for pediatric population)<\/td>\n<\/tr>\n
FDA-Approved Indications:<\/td>\nhypoglycemia, due to (usually congenital) hyperinsulinism<\/td>\n<\/tr>\n
Off-Label Usage:<\/td>\nnone at this time<\/td>\n<\/tr>\n
Mechanism of Action:<\/td>\nincrease in blood glucose via inhibition of insulin release from pancreas via opening of the \u03b2-cell KATP <\/sub>channels2<\/sup><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

\u00a0<\/strong><\/p>\n

Adverse Drug Reactions<\/h2>\n
    \n
  • sodium and fluid retention<\/strong> (esp. young infants and adults)<\/li>\n
  • hirsutism <\/strong><\/li>\n
  • pulmonary hypertension\/respiratory distress (neonates, infants, children)<\/strong><\/li>\n
  • GI intolerance<\/li>\n
  • hyperglycemia\/glycosuria, diabetic ketoacidosis<\/li>\n
  • hyperosmolar non-ketoacidotic coma<\/li>\n
  • rarely: hypotension, eosinophilia, decreased hemoglobin\/hematocrit, increased liver enzymes, decreased CrCl, decreased urinary output, anxiety, dizziness, insomnia, pruritis, extrapyramidal signs, blurred vision, diplopia, lacrimation, fever, lymphadenopathy, gout, thrombocytopenia<\/li>\n<\/ul>\n

    Monitoring<\/h2>\n
      \n
    • blood glucose<\/li>\n
    • serum electrolytes and uric acid<\/li>\n
    • BUN, SCr, CrCl<\/li>\n
    • CBC with differential<\/li>\n
    • LFTs, especially bilirubin<\/li>\n
    • urine glucose and ketones<\/li>\n
    • respiratory distress (especially in neonates and infants)<\/strong><\/li>\n<\/ul>\n

      Contraindications\/Warnings<\/h2>\n

      Contraindications<\/em><\/p>\n

        \n
      • functional hypoglycemia (also called reactive hypoglycemia \u2013 low blood sugar in the four hours after eating, often accompanied by shakiness, sleepiness, lightheadedness, hunger)<\/li>\n
      • hypersensitivity to diazoxide or other thiazide<\/li>\n<\/ul>\n

        Precautions<\/em><\/p>\n

          \n
        • treatment under close monitoring only<\/u><\/strong> with regular assessment of clinical response<\/li>\n
        • prolonged use requires increased monitoring for glucosuria and ketones in the urine<\/li>\n
        • take care when administering concomitantly with other medications that also have antihypertensive effects<\/li>\n
        • may displace bilirubin from albumin (keep in mind if treating newborn with bilirubinemia)<\/strong><\/li>\n<\/ul>\n

          Drug Interactions<\/h2>\n
            \n
          • diuretics \u2013 potentiation of hyperglycemic and hyperuricemic effects<\/li>\n
          • warfarin \u2013 potentiation of hypoprothrombin effects<\/li>\n
          • diphenylhydantoin \u2013 may lead to loss of seizure control<\/li>\n
          • chlorpromazine \u2013 may enhance hyperglycemic action of diazoxide<\/li>\n<\/ul>\n

            How supplied, preparation, administration, and stability\/storage<\/p>\n

            How supplied:<\/em><\/p>\n

              \n
            • 50mg\/mL suspension<\/li>\n
            • 30 mL bottle<\/li>\n<\/ul>\n

              Dosing<\/em><\/p>\n

                \n
              • adults, children, adolescents<\/u><\/strong>\u00a0 3 mg\/kg\/day divided into every 8 hour dosingusual range: 3-8 mg\/kg\/day divided into every 8 or 12 hour dosing<\/li>\n
              • neonates and infants<\/u><\/strong>\u00a0 10 mg\/kg\/day divided every 8 hoursusual range: 8-12 mg\/kg\/day divided into every 8 or 12 hour dosing*range of 5-20 mg\/kg\/day divided every 8 hours has been used<\/li>\n<\/ul>\n

                Administration<\/em><\/p>\n

                  \n
                • shake suspension well prior to administration<\/li>\n<\/ul>\n

                  Stability\/Storage<\/em><\/p>\n

                    \n
                  • store at room temperature-\u00a0 25 \u00b0C (77\u00b0F)<\/li>\n
                  • may have \u201cexcursions\u201d\u00a0 between 15\u00b0C and 30\u00b0C (59\u00b0F and 86\u00b0F)<\/li>\n
                  • store in box until use and protect from light<\/li>\n<\/ul>\n

                    Pharmacokinetics and Pharmacodynamics<\/h2>\n
                      \n
                    • onset of action = 1 hour<\/li>\n
                    • duration = 8 hours (normal renal function)<\/li>\n
                    • >90% bound to serum proteins, renal excretion<\/li>\n
                    • half-life = pediatrics 9-24 hours<\/strong><\/li>\n<\/ul>\n

                      adults 24-36 hours<\/p>\n

                        \n
                      • per package insert, if no effect is seen within 2-3 weeks, diazoxide should be discontinued<\/strong><\/li>\n<\/ul>\n

                        Hazardous\/Cytotoxic<\/h2>\n

                        Animal studies were inconclusive regarding risks, primarily risks that were found were related to the embryonic stage of development<\/p>\n","protected":false},"excerpt":{"rendered":"

                        Diazoxide works by blocking the release of insulin from the pancreas, thus allowing recovery from hypoglycemia in, most commonly, pediatric patients with congenital hyperinsulinemic hypoglycemia.\u00a0 This is a medication that is not likely to be required often, but is effective when it is called upon. Of note, there was recently an FDA-issued warning in September […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[235],"tags":[],"class_list":["post-3408150","post","type-post","status-publish","format-standard","hentry","category-pharmacology-monographs","post-wrapper","thrv_wrapper"],"_links":{"self":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/posts\/3408150","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/comments?post=3408150"}],"version-history":[{"count":21,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/posts\/3408150\/revisions"}],"predecessor-version":[{"id":4415930,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/posts\/3408150\/revisions\/4415930"}],"wp:attachment":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/media?parent=3408150"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/categories?post=3408150"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/tags?post=3408150"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}