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Diazoxide: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on Oct 19, 2020.

1. How it works

  • Diazoxide may be used to increase blood sugar levels in people with low blood sugar levels caused by excessive production of insulin (this is called hyperinsulinism) due to certain types of cancer or some medical conditions. It is only used when surgery or other medications are not successful.
  • Diazoxide raises blood sugar by slowing the release of insulin from the pancreas. It does this by opening potassium channels on pancreatic beta cells (these are unique cells in the pancreas that produce, store and release the hormone insulin), which hyperpolarizes the cell, inhibiting insulin release, and reducing blood sugar levels.
  • Diazoxide belongs to the class of medicines known as glucose-elevating agents. It may also be used for hypertensive emergencies and is a direct-acting vasodilator.

2. Upsides

  • May be used to increase blood sugar levels in people with hypoglycemia other specific medical therapy or surgical management has been unsuccessful or is unfeasible.
  • Conditions where diazoxide may be used include hyperinsulinemia caused by specific types of cancer (such as an inoperable islet cell adenoma or carcinoma, or an extrapancreatic malignancy) in adults. In infants and children, it may be caused by several different conditions, such as leucine sensitivity, islet cell hyperplasia, nesidioblastosis, extrapancreatic malignancy, islet cell adenoma, or adenomatosis.
  • Diazoxide may also be used pre and postoperatively in certain situations.
  • Diazoxide may be used in combination with a diuretic (such as a thiazide diuretic), especially in people who have developed the diazoxide side effects of fluid retention, edema, or congestive heart failure.
  • Diazoxide is available as a generic and under the brand name Proglycem.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Fluid retention is a significant side effect of diazoxide and can lead to swelling and puffiness of the lower arms and legs (this is called edema) and congestive heart failure if not managed properly. Patients need to be monitored for this side effect and may be treated with thiazide diuretics such as chlorothiazide and hydrochlorothiazide.
  • Other side effects include low blood pressure, dizziness, headache, a fast heartbeat, a skin rash, itchiness, and gastrointestinal side effects.
  • The development of abnormal facial features has been reported in children treated for more than 4 years for hypoglycemia hyperinsulinism. Nonketotic hyperosmolar coma and ketoacidosis have also occurred during treatment; usually in patients with a concomitant illness.
  • Reversible pulmonary hypertension has also been reported in newborns and young infants. Discontinue if this occurs. Diazoxide may also displace bilirubin from albumin and diazoxide should be used with caution in newborns with hyperbilirubinemia.
  • The addition of a thiazide diuretic may make diazoxide more effective at increasing blood sugar levels, which may require a dosage adjustment of diazoxide.
  • While on diazoxide, symptoms, and signs of fluid retention need to be regularly evaluated.
  • Dosage is based on weight for both adults and children (initial dose in adults 3mg/kg/day and children 5mg/kg/day). This total daily dose should be split and given in three divided doses every eight hours. The dosage should be titrated every few days if needed. If no response is seen after two to three weeks consider discontinuing diazoxide.
  • People prescribed diazoxide need to be closely monitored for side effects such as fluid retention and to ensure that it is effective. Laboratory monitoring should include blood glucose, serum uric acid, BUN, creatinine clearance, CBC with differential, AST; urine glucose, and ketones (especially during infection, stress, or with prolonged treatment); serum electrolytes and uric acid; and respiratory distress (in neonates and infants).
  • Diazoxide may not be suitable for people with a history of gout, preexisting heart failure, or poor cardiac function. If diazoxide is started in these people then they will need intensive monitoring.
  • Diazoxide should NOT be used to treat occasional low blood sugar caused by diet.
  • Diazoxide may interfere with laboratory tests and cause an increase in serum renin concentrations and IgG concentrations. It may decrease serum cortisol concentrations and cause a false-negative insulin response to glucagon.
  • The dosage of diazoxide may need reducing in people with kidney disease.
  • Some dosage forms may contain sodium benzoate/benzoic acid or propylene glycol. Large amounts are potentially toxic and these preparations should be avoided or used with caution in newborns.
  • Diazoxide should only be used during pregnancy if the benefits outweigh the risks. Altered carbohydrate metabolism, hyperbilirubinemia, and thrombocytopenia have been reported in the fetus or neonate. Alopecia (hair loss) and hypertrichosis lanuginosa (excessive lanugo hair present at birth) have also been reported in newborns following the use of diazoxide during the last 19 to 60 days of pregnancy.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

  • Diazoxide raises blood sugar levels by slowing the release of insulin from the pancreas. It is only used when other medications or surgery are ineffective. Side effects of diazoxide may include fluid retention, edema, heart failure, pulmonary hypertension (in children), and gastrointestinal effects. If diazoxide has not been effective after two to three weeks it should be discontinued.

5. Tips

  • Shake diazoxide suspension well before use. Administer exactly as directed by your doctor. Diazoxide is usually given three times a day and you must follow the schedule your doctor has given you.
  • If the person or child taking diazoxide gains weight or develops swelling around their ankles or legs, then tell your doctor as soon as possible. Diazoxide can cause fluid retention and other medication, such as a thiazide diuretic, may need to be started to counteract this side effect.
  • Tell your doctor straight away if you develop any severe side effects, such as severe abdominal pain, severe nausea or vomiting, shortness of breath, severe constipation, fast or abnormal heartbeat, bruising, urinary problems, vision changes, hair growth, tremors, movement disorders, bleeding, or signs of an allergic reaction.
  • If you are caring for a child taking diazoxide, seek urgent medical attention if they develop a blue/gray skin discoloration, fast breathing, flaring of the nostrils, abnormal chest movements, trouble eating, or grunting.
  • Keep your diazoxide at room temperature (around 77°F [25°C]). Do not place in the refrigerator or expose to extreme heat. Protect from light.
  • Monitor your blood sugar levels. Tell your doctor if your blood sugar levels remain low or go too high and seek urgent medical help if you develop symptoms such as confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit.

6. Response and Effectiveness

  • Diazoxide exerts its effect within an hour of administration and lasts for up to 8 hours in people with normal kidney function. In people with kidney disease, the duration of the effect of diazoxide may be delayed.
  • May take several days to assess the dose-response of diazoxide because of its long half-life (9.5 to 24 hours in children; 24 to 36 hours in adults).
  • In some conditions, the onset of effect may be delayed. If there is no effect within two to three weeks, the manufacturer recommends discontinuing diazoxide.

7. Interactions

Medicines that interact with diazoxide may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with diazoxide. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with diazoxide include:

  • antidiabetic agents, such as metformin, glyburide, or glipizide (diazoxide may diminish their effect)
  • antiepileptics, such as fosphenytoin and phenytoin (diazoxide may decrease serum concentrations of epileptics; total concentrations may be affected more than free concentrations)
  • antipsychotics, such as clozapine, chlorpromazine, or quetiapine
  • benzodiazepines, such as clobazam or diazepam
  • blood pressure-lowering agents or any medication that may lower blood pressure, such as atenolol, ACE inhibitors, or ARBs (diazoxide may enhance the blood pressure-lowering effect)
  • bupropion
  • cannabis
  • corticosteroids, such as betamethasone or budesonide
  • insulin
  • lithium
  • licorice
  • selegiline
  • sildenafil
  • thiopental (may enhance the blood pressure-lowering effect)
  • tizanidine (may enhance the blood pressure-lowering effect)
  • zolpidem.

Thiazide diuretics are often added to diazoxide treatment to manage side effects such as fluid retention and edema. However, thiazides can also enhance the blood pressure-lowering effect of diazoxide, so the dosage of diazoxide may need to be reduced.

Note that this list is not all-inclusive and includes only common medications that may interact with diazoxide. You should refer to the prescribing information for diazoxide for a complete list of interactions.

References

Diazoxide. Revised 07/2020. Drugs.com. https://www.drugs.com/ppa/diazoxide.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use diazoxide only for the indication prescribed.

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