What are the primary uses of diazoxide and chlorothiazide. How are these medications administered to patients. What are the potential side effects and interactions of diazoxide and chlorothiazide.

Understanding Diazoxide and Chlorothiazide: A Comprehensive Overview

Diazoxide and chlorothiazide are two medications often prescribed together to manage specific medical conditions. Diazoxide is primarily used to treat persistently low blood sugar levels (hypoglycemia) caused by excessive insulin production (hyperinsulinism). Chlorothiazide, on the other hand, is a diuretic that increases urine production by the kidneys. This combination is particularly effective in managing certain health issues, but it’s crucial to understand their uses, administration, and potential side effects.

The Mechanism of Action: How Diazoxide and Chlorothiazide Work

Diazoxide functions by inhibiting the body’s insulin release. This mechanism is particularly useful in cases of hyperinsulinism, where the body produces too much insulin, leading to dangerously low blood sugar levels. Chlorothiazide, as a diuretic, helps the body eliminate excess fluid. It’s often prescribed alongside diazoxide to counteract one of its common side effects: fluid retention.

Why are these medications prescribed together?

The combination of diazoxide and chlorothiazide is strategic. While diazoxide effectively manages blood sugar levels, it can cause fluid retention. Chlorothiazide helps mitigate this side effect by promoting fluid elimination, thus creating a balanced treatment approach.

Administration and Dosage: How to Take Diazoxide and Chlorothiazide

Both medications are typically administered orally. Diazoxide is usually given two to three times a day, while chlorothiazide is generally prescribed twice daily. They are available as liquid suspensions, making them suitable for pediatric patients or those who have difficulty swallowing tablets.

• Diazoxide suspension: 50mg of active ingredient per 1ml (equivalent to 250mg in 5ml)
• Chlorothiazide suspension: 250mg of active ingredient per 5ml

It’s important to note that these medications, especially in suspension form, may not be readily available at local pharmacies. They often need to be imported, which can lead to longer wait times for supplies.

Can older children take these medications in different forms?

Yes, older children may prefer to take diazoxide and chlorothiazide in tablet or capsule form. This option should be discussed with the prescribing doctor to ensure it’s appropriate for the individual patient.

Contraindications: Who Should Avoid These Medications?

While diazoxide and chlorothiazide can be highly effective, they’re not suitable for everyone. Certain conditions may preclude their use or require careful consideration before prescription:

• Hypersensitivity to diazoxide, chlorothiazide, or any of their ingredients
• Pregnancy, potential pregnancy, or breastfeeding
• Pre-existing heart or lung problems, including:
  • Pulmonary hypertension
  • Meconium aspiration
  • Respiratory distress
  • Transient tachypnea
  • Pneumonia
  • Sepsis
  • Congenital diaphragmatic hernia
  • Congenital heart disease

Is it safe to take these medications during pregnancy or while breastfeeding?

Pregnant women, those who could become pregnant, or those who are breastfeeding should consult their doctor before taking diazoxide or chlorothiazide. These medications may pose risks to fetal development or pass through breast milk, potentially affecting the infant.

Side Effects: Potential Reactions to Diazoxide and Chlorothiazide

As with any medication, diazoxide and chlorothiazide can cause side effects. It’s crucial to be aware of these potential reactions and to report any severe or persistent symptoms to a healthcare provider.

Diazoxide Side Effects

• Loss of appetite, nausea, and vomiting
• Elevated uric acid levels in the blood
• Salt and fluid retention, leading to puffiness (edema)
• High blood sugar levels
• Low blood pressure
• Irregular or rapid heart rate
• Increased hair growth

Chlorothiazide Side Effects

• Weakness and low blood pressure
• Mild gastrointestinal discomfort
• Changes in blood count

Are there any severe side effects to watch out for?

Yes, patients should be vigilant for signs of breathing difficulties, which may include:

• Flaring nostrils
• Unusual chest movements
• Rapid breathing
• Feeding difficulties
• Blue tinge to lips or skin

If any of these symptoms occur, immediate medical attention is necessary. Patients or caregivers should contact their doctor or visit the nearest emergency department.

Drug Interactions: Medications to Avoid While Taking Diazoxide and Chlorothiazide

Both diazoxide and chlorothiazide can interact with other medications, potentially altering their effectiveness or causing adverse reactions. It’s crucial to inform healthcare providers about all medications, including over-the-counter drugs, herbal supplements, and vitamins.

Diazoxide Interactions

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

Chlorothiazide Interactions

• Anti-diabetic medications
• Anti-hypertension medications (as mentioned for diazoxide)
• Cholestyramine and colestipol resins
• Corticosteroids
• Lithium
• Non-steroidal anti-inflammatory drugs (NSAIDs)

How can patients ensure their medication regimen is safe?

Patients should maintain an up-to-date list of all medications they’re taking and share this information with their healthcare providers. Regular check-ups and open communication with doctors and pharmacists can help identify and prevent potential drug interactions.

Proper Storage and Handling of Diazoxide and Chlorothiazide

Proper storage and handling of these medications are crucial for maintaining their effectiveness and ensuring patient safety. Here are some important guidelines:

• Keep all medicines out of reach of children
• Store suspensions, tablets, or capsules at room temperature
• Protect medications from bright light, direct sunlight, and heat
• Avoid storing in bathrooms or other humid environments
• Check expiration dates regularly and dispose of expired medications properly

How long can these medications be stored?

The shelf life of diazoxide and chlorothiazide can vary depending on the formulation and storage conditions. Generally, these medications can be stored for up to one year when kept at room temperature and protected from light and moisture. However, it’s always best to check the expiration date on the packaging and consult with a pharmacist if there are any doubts about the medication’s viability.

Monitoring and Follow-up: Ensuring Safe and Effective Treatment

Regular monitoring is essential when taking diazoxide and chlorothiazide to ensure the treatment is effective and to catch any potential side effects early. This typically involves:

1. Regular blood tests to check blood sugar levels, electrolyte balance, and kidney function
2. Blood pressure checks
3. Periodic physical examinations to assess for fluid retention or other side effects
4. In pediatric patients, monitoring of growth and development

How often should patients have follow-up appointments?

The frequency of follow-up appointments can vary depending on the individual patient’s condition and response to treatment. Initially, appointments may be more frequent, possibly every few weeks. As the treatment stabilizes, visits may be spaced out to every few months. However, patients should always contact their healthcare provider if they experience any new or worsening symptoms between scheduled appointments.

Diazoxide and chlorothiazide, when used appropriately and under close medical supervision, can be highly effective in managing specific medical conditions. However, as with any medication regimen, it’s crucial for patients and caregivers to be well-informed about proper usage, potential side effects, and the importance of regular monitoring. By maintaining open communication with healthcare providers and following prescribed guidelines, patients can maximize the benefits of these medications while minimizing potential risks.

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)

Share this page

Read more about

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 – Cardiologist – a site about diseases of the heart and blood vessels

Pharmacological action

Diazoxide is a peripheral vasodilator. Expands predominantly resistive vessels (arterioles), reducing peripheral vascular resistance, has no effect on capacitive vessels (veins). According to the mechanism of action, it belongs to the group of potassium channel activators. The opening of potassium channels causes the release of potassium ions and hyperpolarization of the membrane of vascular smooth muscle cells, which disrupts the function of voltage-dependent calcium channels and reduces the entry of calcium ions into the cells.

Intravenous administration of the drug to patients with arterial hypertension causes a rapid drop in systolic and diastolic pressure, an increase in cardiac output and tachycardia. Orthostatic hypotension does not develop. The maximum hypotensive effect occurs 2-5 minutes after intravenous administration of the drug and lasts 2-12 hours, in most cases – 3 hours. Diazoxide causes sodium and water retention in the body, reduces the glomerular filtration rate and excretion of uric acid in the tubules. Edema may occur in patients with heart failure. Diazoxide is a strong uterine relaxant. As a result of inhibition of the release of insulin from the pancreas, diazoxide can cause a hyperglycemic effect.

Pharmacokinetics

Plasma diazoxide is highly protein bound (90%), so intravenous administration must be rapid. The hypotensive effect depends on the dose administered intravenously. About 60% of diazoxide is metabolized, the rest is excreted in the urine in an unchanged state. T _1/2 – 28 hours

Indications

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

Dosing mode

Intravenous bolus: at a dose of 1 to 3 mg/kg of body weight over 30 seconds, the maximum single dose should not exceed 150 mg.

Intravenous infusion: 10-30 mg/min up to a total dose of 5 mg/kg or reduction in blood pressure, if necessary, repeat the infusion after 4-24 hours.

Avoid getting the drug into the subcutaneous tissues. Urgent therapy of hypertensive conditions should be limited to a few days with the fastest possible transition to oral antihypertensive drugs.

Side effects

Headache, dizziness, skin flushing, Na+ and water retention in the body, hyperglycemia, hyperuricemia, decreased blood pressure, collapse, tachycardia, ischemia of the heart and/or brain, confusion, allergic reactions.

Contraindications

Hypersensitivity, compensatory hypertension, disorders of cerebral and coronary circulation.

Special instructions

Rarely used due to unpredictable decrease in blood pressure.

Causes hyperglycemia by suppressing insulin secretion and reducing glucose utilization by tissues. In diabetes mellitus, correction of hypoglycemic therapy is required.

May cause cerebral and myocardial ischemia.

Repeated administration causes significant sodium and water retention.

Used by mouth for chronic hypoglycemia due to insulin-secreting tumors.

When administered intravenously, treatment is continued for no more than 10 days.

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

Drug interactions

Use with caution in patients taking hydralazine, papaverine-like substances, methyldopa or reserpine and other rauwolfia derivatives. Concurrent administration of diazoxide and diuretics, especially thiazides, may enhance the hyperglycemic, hyperuremic and hypotensive effects of the drug.