Diazoxide and chlorothiazide suspensions | Great Ormond Street Hospital

Diazoxide is used to treat persistently low blood sugar levels (hypoglycaemia) caused by the body producing too much insulin (hyperinsulinism). Chlorothiazide is a diuretic, that is, a medicine that increases the amount of urine produced by the kidneys. This page from Great Ormond Street Hospital (GOSH) describes diazoxide and chlorothiazide, which are usually prescribed together. It explains how they are given and some of their side effects. Each person reacts differently to medicines so your child will not necessarily suffer every side effect mentioned.Diazoxide works by blocking the release of insulin by the body. Chlorothiazide is used in conditions where the body retains too much fluid, causing puffiness (oedema) especially around the eyes or affecting the hands or feet. Chlorothiazide is commonly prescribed alongside diazoxide, as a side effect of this medicine is fluid retention.

How are they given?

Diazoxide is given by mouth two or three times a day. Chlorothiazide is usually given twice a day.

Both are available as a suspension (liquid medicine). For guidance on how to give your child liquid medicines, please read our information sheet or watch our video podcast available on our websiteor the GOSH YouTube™ channel.

Diazoxide and chlorothiazide suspensions are not readily available from your community pharmacy. Neither medicine is available in the UK and so has to be imported from abroad by a licensed pharmaceutical import company. Supplies of these medicines may take longer than usual to obtain, usually several days.

Currently, the Pharmacy department at GOSH obtains diazoxide suspension under the brand name of Proglycem®. The packaging gives the strength of the medicine as 50mg of active ingredient in 1ml of suspension, which is equivalent to 250mg in 5ml. It also contains preservatives, colouring, flavourings and sweetener.

There have been incidents when the wrong strength of other types of medicine have been prescribed so please check the label before giving it your child. If you are given the wrong strength of diazoxide, please inform the team immediately and do not give to your child.

Chlorothiazide suspension is supplied at GOSH in the strength of 250mg of active ingredient in 5ml of suspension. It also contains preservatives, colouring, flavourings and sweetener.

Older children may prefer to take diazoxide and chlorothiazide in tablet or capsule form. Talk to your doctor about this.

Who should not take these medicines?

People with the following conditions should discuss taking these medicines with their doctor.

• Hypersensitivy to diazoxide, chlorothiazide or any of their ingredients
• Pregnant, could be pregnant, trying to become pregnant or breastfeeding
• Existing heart or lung problems, such as pulmonary hypertension, meconium aspiration, respiratory distress, transient tachypnoea, pneumonia, sepsis, congenital diaphragmatic hernia or congenital heart disease.

What are the side effects?

Note: If your child shows any signs of breathing difficulties, such as flaring nostrils, unusual chest movements, rapid breathing, feeding difficulties or a blue tinge to their lips or skin, please see your doctor or take your child to your nearest Accident and Emergency (A&E) department.

If any of the side effects described below are severe or carry on for a long time, please tell your doctor.

Diazoxide

• Loss of appetite, nausea and vomiting
• Raised levels of uric acid in the blood, retention of salts and fluid, puffiness (oedema)
• High blood sugar levels
• Low blood pressure
• Irregular or fast heart rate
• Increased hair growth

Chlorothiazide

• Weakness and low blood pressure
• Mild upset stomach
• Changes in blood count

Interactions with other medicines

Some medicines can react with diazoxide and/or chlorothiazide, altering how well they work. Always check with your doctor or pharmacist before giving your child any other medicines, including herbal or complementary medicines. The following are known to react with diazoxide and/or chlorothiazide so your child will require regular careful monitoring.

Diazoxide

• Anti-hypertension medicines, including ACE inhibitors, angiotensin II receptor agonists, beta blockers, calcium channel blockers and some diuretics
• Alcohol
• Anti-depressants
• Anti-epileptics including phenytoin
• Anti-psychotics

Chlorothiazide

• Anti-diabetic medicines
• Anti-hypertension medicines as above
• Cholestyramine and colestipol resins
• Corticosteroids
• Lithium
• Non-steroidal anti-inflammatory drugs (NSAIDs)

Important

• Keep medicines in a safe place where children cannot reach them
• Keep the suspension, tablets or capsules at room temperature, away from bright light or direct sunlight and away from heat. Do not store in a fridge.
• If you forget to give your child a dose and it is within a few hours of when the dose was due, give it as soon as you remember. Otherwise, do not give this dose but take the next dose when it is due. Do not give a double dose.
• If your child vomits straight after taking the dose, inform your local doctor or nurse, as your child may need to take another one
• If your doctor decides that your child should stop taking these medicines or they pass the expiry date, return any remaining suspension to your pharmacist. Do not flush it down the toilet or throw it away.

Compiled by:

The Pharmacy and Endocrinology departments in collaboration with the Child and Family Information Group Please read this information in conjunction with any patient information leaflet provided by the manufacturer.

Last review date:

July 2020

Ref:

2020F0376

Diazoxide | VCA Animal Hospitals

What is diazoxide?

Diazoxide (brand names: Proglycem®, Eudemine®, Glicemin®, Hypertonalum®, Proglicem®, Sefulken®, Tensuril®) is a medication used to treat low blood sugar in pets with an insulinoma (a tumor of insulin producing cells in the pancreas).

Its use in cats, dogs, ferrets, and other small mammals to treat low blood sugar due to an insulinoma is ‘off label’ or ‘extra label’. Many drugs are commonly prescribed for off label use in veterinary medicine. In these instances, follow your veterinarian’s directions and cautions very carefully as their directions may be significantly different from those on the label.

How is diazoxide given?

Diazoxide is given by mouth in the form of a liquid suspension or compounded capsule. Give with food. Shake liquids well before dosing. Measure liquid forms carefully.

This medication should take effect within 1 to 2 hours; however, effects may not be visibly obvious and therefore laboratory tests may need to be done to evaluate how well this medication is working.

What if I miss giving my pet the medication?

If you miss a dose, give it when you remember, but if it is close to the time for the next dose, skip the dose you missed and give it at the next scheduled time, and return to the regular dosing schedule. Never give your pet two doses at once or give extra doses.

Are there any potential side effects?

The most common side effects include drooling, lack of appetite, vomiting, and diarrhea. Serious side effects include a fast heartbeat, fever, bleeding, bruising, drinking and urinating more, prolonged lack of appetite, muscle weakness, severe vomiting, muscle twitches, seizures, or collapse. In ferrets, side effects include lack of appetite, vomiting, diarrhea, tiredness, and bone marrow abnormalities.

This short-acting medication should stop working within 24 hours, although effects can be longer in pets with liver or kidney disease.

Are there any risk factors for this medication?

Diazoxide should not be used in pets that are allergic to it or thiazide diuretics. Do not use in pets with low blood sugar due to anything other than a tumor. Diazoxide should be used cautiously in pets with heart or kidney disease and very cautiously in pregnant or nursing pets as safety has not been established.

Are there any drug interactions I should be aware of?

The following medications should be used with caution when given with diazoxide: alpha-adrenergic agents, glucocorticoids, hypotensive agents, phenothiazines, phenytoin, or thiazide diuretics.

Be sure to tell your veterinarian about any medications (including vitamins, supplements, or herbal therapies) that your pet is taking.

Is

there any monitoring that needs to be done with this medication?

Blood sugar levels, blood cell counts, and physical examinations should be performed at regular intervals. Your veterinarian may monitor your pet to be sure that the medication is working. Monitor your pet at home for serious side effects.

How do I store diazoxide?

Store the capsules and liquid suspensions between 2°C and 30°C (36°F and 86°F) and protect from light and freezing. Do not use liquid suspensions that have darkened in color, as this may indicate that the medication is no longer effective.

What should I do in case of emergency?

If you suspect an overdose or an adverse reaction to the medication, call your veterinary office immediately. If they are not available, follow their directions in contacting an emergency facility.

Diazoxide – instructions for use

Diazoxide

Instruction:

• Pharmacological action
• Pharmacokinetics
• Readings
• Contraindications
• With care
• Pregnancy and breastfeeding
• Dosage and Administration
• Side effects
• Overdose
• Interaction
• Special instructions
• Transport Management
• Classification

Pharmacological action

Diazoxide is a peripheral arteriolar vasodilator of myotropic action, has a rapid hypotensive (lowering blood pressure) effect due to peripheral vasodilation (expansion of the lumen of the vessels). Expands predominantly resistive vessels, activates potassium channels, causes the release of K ⁺ and hyperpolarization of the membrane of vascular smooth muscle cells, disrupts the function of voltage-dependent Ca2+ channels and reduces the entry of Ca ²⁺ into cells. When administered intravenously, it causes a rapid decrease in systolic and diastolic blood pressure, which is not accompanied by the phenomena of orthostatic hypotension. Leads to retention of Na ⁺ and water. It has a strong relaxing effect on the gastrointestinal tract and uterus. Reduces glomerular filtration and inhibits the excretion of uric acid in the tubules of the kidneys.

Pharmacokinetics

When administered intravenously, the maximum plasma concentration (C _max ) is reached after 2-5 hours.

Plasma protein binding is 90%.

Metabolized in the liver (up to 60%), excreted by the kidneys. The half-life is 2-28 hours.

Indications

Hypertensive crises, especially those associated with acute encephalopathy, acute glomerulonephritis and eclampsia.

Contraindications

• Hypersensitivity to diazoxide;
• acute cerebrovascular accident;
• acute stage of myocardial infarction;
• functional hypoglycemia;
• period of childbirth;
• lactation.

Precautions

• Ischemic heart disease;
• angina;
• heart failure;
• diabetes mellitus;
• pregnancy.

Pregnancy and breastfeeding

Use in pregnancy

FDA fetal category C.

Adequate and strictly controlled studies on the safety of the use of diazoxide during pregnancy have not been conducted. The potential risk to humans is unknown.

In experimental studies on animals, a decrease in the growth and survival of fetuses, an increase in the duration of labor was revealed.

The use of diazoxide during pregnancy is not recommended, except in cases of emergency, on the advice of a physician and if the potential benefit to the mother outweighs the possible risk to the fetus.

Childbirth

Due to the pronounced relaxing effect, the introduction of diazoxide in the first stage of labor can lead to the termination of independent labor.

Use during breastfeeding

Special studies on the safety of the use of diazoxide during breastfeeding have not been conducted.

It is not known if diazoxide passes into breast milk.

If necessary, breast-feeding should be avoided.

Dosage and Administration

Intravenous bolus, undiluted, 1–3 mg/kg. The maximum single dose is 150 mg. If there is no effect, re-introduction at the same dose after 5-15 minutes.

Side effects

Headache, dizziness, redness of the skin, edema, hyperglycemia, severe arterial hypotension (up to collapse), the appearance of signs of ischemia of the heart or brain, confusion, allergic reactions.

Overdose

Symptoms

Hyperglycemia, which may be combined with ketoacidosis, as well as glucosuria.

Treatment

Insulin administration and fluid and electrolyte rebalancing. Due to the long half-life of the drug (approximately 30 hours), overdose symptoms require long-term observation (up to 7 days) until the blood glucose concentration returns to normal. Successful reduction of blood diazoxide concentrations has been reported with peritoneal dialysis in one patient and hemodialysis in another.

Interactions

• Diuretics (diuretics) – the hyperglycemic and hyperuricemic effects of diazoxide may be enhanced by the simultaneous administration of thiazides or other commonly used diuretics;
• Anticoagulants (drugs that prevent blood clots) coumarin derivatives – the use of diazoxide in patients taking coumarin and its derivatives may lead to increased anticoagulant action and require a reduction in the dose of anticoagulant;
• Diphenylhydantoin (epilepsy medicine) – administration of diazoxide to patients taking diphenylhydantoin may cause loss of control of seizures;
• Chlorpromazine (antipsychotic drug) – the hyperglycemic effect of diazoxide may be enhanced by concomitant use of chlorpromazine;
• Insulin (blood glucose lowering drug) blocks the hyperglycemic action of diazoxide. In addition, diazoxide, by inhibiting glucagon-induced insulin release, may cause a false-negative glucagon test;
• alpha-blockers (expand blood vessels and reduce their tone, most often used in the treatment of arterial hypertension and prostate adenoma) – reduce the severity of the hyperglycemic action of diazoxide;
• Antihypertensive drugs (drugs that lower blood pressure) – Diazoxide may increase the effect of antihypertensive drugs.

Special instructions

Diabetes mellitus requires correction of hypoglycemic therapy.

Influence on the ability to drive vehicles and control mechanisms

It is recommended to refrain from driving and engaging in activities that require increased concentration and speed of psychomotor reactions.

Classification

• ATX

  C02DA01, V03AH01

• Pharmacological group

  Vasodilators

• ICD code 10

  I10 Essential (primary) hypertension

• FDA pregnancy category

  C
  (risk not excluded)

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Find out more about the active substance Diazoxide:

• INN
• Reviews
• Questions
• Latin name
• Chemical formula

Information about the active substance Diazoxide is intended for medical and pharmaceutical professionals, for reference purposes only. The instructions are not intended to replace professional medical advice, diagnosis or treatment. The information contained here may change over time. The most accurate information on the use of drugs containing the active substance Diazoxide is contained in the manufacturer’s instructions attached to the package.

Diazoxide: generic, uses, side effects, dosage, interactions, warnings

Medicines and vitamins

• Brand Name: , Proglycem
• Drug class: Glucose raising agents

• Medical Author: Divya Jacob, Pharm. D.
• Medical Reviewer: Sarfaroy Khan, BHMS, PGD Health Operations

• Usage
  • What is diazoxide and how does it work?
• Dosages
  • What are the doses of diazoxide?
• Side effects
  • What side effects are associated with the use of diazoxide?
• Drug Interactions
  • What other drugs interact with diazoxide?
• Warnings and Precautions
  • What are the warnings and precautions for diazoxide?

What is diazoxide and how does it work?

Diazoxide is a prescription drug used to treat hypoglycemia.

• Diazoxide is available under the following brand names: Proglycem

What are the doses of diazoxide?

Adult and pediatric dosage

Oral suspension

how much aspirin is in ibuprofen

• 50 mg/ml

hypoglycemia

Adult dosage

• 3 mg/kg/day orally every 8–12 hours initially; typical dose range 3-8 mg/kg/day

Pediatric dosage

• Neonate/infant: Initially 10 mg/kg/day orally every 8 hours; typical dose range is 8-15 mg/kg/day orally every 8-12 hours (see also Precautions Concerning Suspected Pulmonary Hypertension in Neonates and Infants)
• Children: initially 3 mg/kg/day orally every 8 hours; a typical dose range is 3-8 mg/kg/day orally, divided every 8-12 hours.

Dosage considerations – should be given as follows:

• See “Dosages”

What side effects are associated with the use of diazoxide?

Common side effects of diazoxide include:

• nausea,
• vomiting,
• loss of appetite,
• abdominal pain or disorder,
• diarrhea,
• changes in the sense of taste,
• temporary increase in body hair (especially in women and children),
• Headache,
• dizziness,
• anxiety,
• weakness or
• itching or skin rash.

Serious side effects of diazoxide include:

• blurred vision, tunnel vision, eye pain or visible halos around lights,
• breathing problems in infants or neonates treated with diazoxide,
• shortness of breath (even with mild exertion), edema, rapid weight gain,
• light feeling, or
• signs of high blood sugar (hyperglycemia) such as increased thirst, increased urination, hunger, dry mouth, fruity breath, drowsiness, dry skin, blurred vision and weight loss.

Rare side effects of diazoxide include:

• none

This is not a complete list of side effects and other serious side effects or health problems that may result from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You can report side effects or health concerns to the FDA at 1-800-FDA-1088.

What other drugs interact with diazoxide?

If your doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and can monitor them. Do not start, stop, or change the dosage of any medicine without first talking to your doctor, health care provider, or pharmacist.

• Diazoxide has no serious interactions with any other drugs.
• Diazoxide has no serious interactions with any other drugs:
• Diazoxide has moderate interactions with the following drugs:
  • amifostine
  • atazanavir
  • benazepril
  • captopril
  • darunavir
  • fosamprenavir
  • hydrochlorothiazide
  • indinavir
  • insulin degludec
  • insulin degludec/ insulin aspart
  • inhaled insulin
  • lopinavir
  • metformin
  • nelfinavir
  • ritonavir
  • saquinavir
  • tesamorelin
  • tipranavir
• Diazoxide has minor interactions with the following drugs:
  • bendroflumethiazide
  • chlorothiazide
  • chlorthalidone
  • cyclopentiazide
  • etotoin
  • fosphenytoin
  • hydralazine
  • hydrochlorothiazide
  • indapamide
  • methiclothiazide
  • metolazone
  • phenytoin

This information does not contain all possible interactions or side effects. Visit the RxList Drug Interaction Checker to learn about any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Consult your healthcare provider or physician for further medical advice or if you have questions or health concerns.

What are the warnings and precautions for diazoxide?

Contraindications

• Hypersensitivity to diazoxide, thiazides or sulfonamide derivatives.

Consequences of drug abuse

• None

Short-term effects

• See “What side effects are associated with the use of diazoxide?”

Long-term effects

• See “What side effects are associated with the use of diazoxide?”

Precautions

• Use with caution in coronary or cerebral insufficiency, DM extravasation, heart failure (may increase fluid retention), cardiovascular insufficiency, gout, hypotension, hypokalemia, liver disease, renal dysfunction
• Pregnancy
• Compensatory hypertension (aortic coarctation, arteriovenous shunt)
• Not effective in pheochromocytoma
• nonketotic hyperosmolar coma may occur during treatment; transient cataract reported
• May displace bilirubin from albumin; use caution in neonates with hyperbilirubinemia
• The antidiuretic property of diazoxide can lead to significant fluid retention, which in patients with impaired cardiac reserve may be precipitated by chronic heart failure; fluid retention will respond to conventional diuretic therapy
• Simultaneous use of thiazides may enhance the hyperglycemic and hyperuricemic effects of diazoxide.
• Ketoacidosis and nonketotic hyperosmolar coma have been reported in patients receiving recommended doses, usually during intercurrent illness; rapid recognition and treatment essential long-term follow-up required after an acute episode due to the drug’s long half-life of approximately 30 hours; the occurrence of these serious events can be reduced by carefully informing patients about monitoring urine for sugar and ketones and reporting abnormal findings and unusual symptoms to a healthcare professional in a timely manner.
• The effect of diazoxide on the hematopoietic system and serum uric acid levels should be taken into account; the latter should be considered in particular in patients with hyperuricemia or a history of gout
• the antihypertensive effect of other drugs may be enhanced by diazoxide; this should be remembered when used simultaneously with antihypertensive agents.
• Due to protein binding, the administration of diazoxide with coumarin or its derivatives may require a reduction in the dose of anticoagulants.
• Pulmonary hypertension in neonates and infants
• July 16, 2015: FDA warns clinicians to monitor for signs of pulmonary hypertension in infants treated for hypoglycemia with diazoxide and discontinue the drug when symptoms appear.
• Since the approval of the drug (1973), 11 cases have been identified, and after the withdrawal of diazoxide, the symptoms disappeared.
• Signs of respiratory distress include flaring of the nostrils, grunting, abnormal chest movements, rapid breathing, difficulty feeding, or a bluish tint to the lips or skin.
• Monitoring is especially important for infants who have other risk factors for pulmonary hypertension (eg, meconium aspiration syndrome, respiratory distress syndrome, transient tachypnea of ​​the newborn, pneumonia, sepsis, congenital diaphragmatic hernia, and congenital heart disease)

Pregnancy and lactation

• Use with caution if benefit outweighs risk during pregnancy.