Consumer medicine information

DBL Diazoxide Injection BP

Diazoxide

BRAND INFORMATION

Brand name

DBL Diazoxide Injection BP

Active ingredient

Diazoxide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using DBL Diazoxide Injection BP.

What is in this leaflet

This leaflet answers some common questions about DBL™ Diazoxide Injection. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given diazoxide against the benefits they expect it will have for you.

If you have any concerns about being given this medicine, ask your doctor or pharmacist.

Keep this leaflet. You may need to read it again.

What DBL™ Diazoxide Injection is used for

This medicines is used to :

  • quickly lower very high blood pressure in emergency situations
  • prevent bleeding during diagnostic procedures if you have high blood pressure.

This medicine belongs to a group of medicines called vasodilators.

It works by widening blood vessels, which causes a decrease in blood pressure.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is not addictive. It is only available with a doctor’s prescription.

Before you are given DBL™Diazoxide Injection

When you must not be given it

You must not be given DBL™ Diazoxide Injection if you have an allergy to:

  • diazoxide
  • any of the ingredients listed at the end of this leaflet
  • other thiazides, such as hydrochlorthiazide.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

You must not be given this medicine if you have any of the following medical conditions:

  • hypertension due to mechanical abnormalities of the heart (such as an AV shunt).

If you are not sure whether you should be given this medicine, talk to your doctor.

Before you are given it

Tell your doctor or pharmacist if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any medical conditions:

  • kidney problems
  • diabetes
  • circulation problems
  • gout
  • leucopenia (low numbers of white blood cells)or thrombocytopenia (low numbers of platelets)

Tell your doctor if you are pregnant or intend to become pregnant or are breast-feeding. Your doctor can discuss the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you are given DBL™Diazoxide Injection.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and diazoxide may interfere with each other. These include:

  • diuretics (fluid tablets)
  • other medications used to treat high blood pressure.

These medicines may be affected by diazoxide, or may affect how well it works. You may need different amounts of your medicine, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while using this medicine.

How DBL™ Diazoxide Injection is given

How much is given

Your doctor will decide what dose will receive. This depends on your condition and other factors, such as your weight.

How it is given

DBL™Diazoxide Injection is given as an injection into a vein (intravenously). It must only be given by a nurse or doctor.

If you receive too much (overdose)

As DBL™ Diazoxide Injection is given to you under the supervision of your doctor, it is very unlikely that you will receive an overdose.

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26 in Australia, or call 0800 764 766 in New Zealand) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much DBL™ Diazoxide Injection. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of an overdose may include the side effects listed below in the ‘Side Effects’ section, but are usually of a more severe nature.

Ask your doctor or pharmacist if you have any concerns.

While you are being given it

Things you must do

Stay lying down for at least 30 minutes after receiving this medicine. You may feel light-headed or dizzy.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are being given DBL™ Diazoxide Injection.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine. It may affect other medicines used during surgery.

If you become pregnant while taking this medicine, tell your doctor immediately.

Keep all of your doctor’s appointments so that your progress can be checked. Your doctor may do some tests, such as glucose monitoring tests, from time to time to make sure the medicine is working and to prevent unwanted side effects.

Things to be careful of

Be careful driving or operating machinery until you know how diazoxide affects you. This medicine may cause dizziness, light-headedness or tiredness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Children should be careful when riding bicycles or climbing trees.

Be careful when drinking alcohol while you are taking this medicine. If you drink alcohol, symptoms as dizziness or light-headedness may be worse.

Side effects

Tell your doctor or nurse as soon as possible if you do not feel well while you are being given DBL™ Diazoxide Injection. This medicine may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor, nurse or pharmacist if you notice any of the following and they worry you:

  • oedema (swelling of the hands feet or ankles)
  • weight gain
  • flushing
  • feeling of warmth
  • burning or itching
  • headache
  • sweating
  • weakness
  • pain along the vein where the injection was given
  • nausea, vomiting
  • abdominal discomfort.

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

If any of the following happen, tell your doctor or nurse immediately:

  • signs of high blood sugar levels such as lethargy or tiredness, headache, thirst, passing large amounts of urine, blurred vision
  • signs of heart failure such as shortness of breath, swelling of the feet or legs due to fluid build-up
  • dizziness, light-headedness or fainting which may be due to very low blood pressure
  • signs of an allergic reaction such as those listed at the start of this leaflet.

The above list includes very serious side effects. You may need urgent medical attention.

Tell your doctor, nurse or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may occur in some patients.

After using DBL™ Diazoxide Injection

Storage

DBL™Diazoxide Injection will be stored in the pharmacy or on the ward. The injection is kept in a cool dry place, protected from light, where the temperature stays below 25°C.

Product description

What it looks like

DBL™Diazoxide Injection is a clear, colourless solution in a glass ampoule. It is available in packs of one ampoule.

Ingredients

DBL™Diazoxide Injection contains diazoxide as the active ingredient.

It also contains:

  • sodium hydroxide
  • water for injections

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Sponsor

DBL™ Diazoxide Injection is supplied by:

Australian Sponsor:

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number : 1800 675 229
www.pfizer.com.au

DBL™ Diazoxide Injection is available in the following strength:

  • 300 mg/20mL amp AUST R 16377

This leaflet was prepared in
June 2019.

Published by MIMS September 2019

BRAND INFORMATION

Brand name

DBL Diazoxide Injection BP

Active ingredient

Diazoxide

Schedule

S4

 

1 Name of Medicine

Diazoxide.

2 Qualitative and Quantitative Composition

DBL Diazoxide Injection BP is a sterile solution of Diazoxide BP in Water for Injections BP. Each 20 mL ampoule contains 300 mg of diazoxide.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

DBL Diazoxide Injection BP is a clear colourless solution for intravenous injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Diazoxide is a non-diuretic antihypertensive agent. It is administered by rapid IV injection for emergency reduction of blood pressure in patients with malignant hypertension when prompt and urgent decrease in diastolic pressure is required. DBL Diazoxide Injection BP is recommended in the treatment of hypertensive crises associated with acute glomerular nephritis, acute hypertensive encephalopathy, cerebral haemorrhage or congestive heart failure.
Diazoxide is usually effective in patients with refractory hypertension not responsive to other agents. It has also been used in the treatment of chronic hypertension to control elevated blood pressure before commencement of therapy with oral antihypertensive agents.
In order to reduce the danger of haemorrhage due to elevated blood pressure, DBL Diazoxide Injection BP may be used in hypertensive patients undergoing diagnostic procedures such as renal biopsy or arteriography.

4.2 Dose and Method of Administration

Dosage.

The usual adult dose of diazoxide for the treatment of hypertension is 300 mg administered undiluted by rapid intravenous (IV) injection over a period of 30 seconds or less. Children and unusually large or small adults may be given 5 mg/kg bodyweight. Recent studies have shown that minibolus IV administration of diazoxide in doses of 1 to 3 mg/kg every 5 to 15 minutes may be as effective as the administration of a single 300 mg intravenous dose and may be associated with fewer adverse effects.

Method of administration.

Following intravenous administration of diazoxide, blood pressure should be closely monitored until it has stabilised, and hourly thereafter. Further reduction in blood pressure 30 minutes or more after injection should be investigated for causes other than the effects of the drug. The patient should remain recumbent for at least 30 minutes after injection. In ambulatory patients, final blood pressure measurements should be made while the patient is standing.
Repeated administration of DBL Diazoxide Injection BP at 4 to 24 hourly intervals is generally sufficient to maintain blood pressure below pretreatment levels. Administration of DBL Diazoxide Injection BP for more than 5 days is seldom necessary and oral antihypertensive agents should replace diazoxide therapy as soon as adequate blood pressure control has been achieved.

4.3 Contraindications

Diazoxide is contraindicated in patients who are hypersensitive to it or other thiazide derivatives. Diazoxide is not recommended for use in hypertension due to mechanical abnormality, e.g. aortic coarctation or arteriovenous shunt.

4.4 Special Warnings and Precautions for Use

DBL Diazoxide Injection BP is for intravenous administration only. Due to the high alkalinity of the injection, it should not be administered intramuscularly, subcutaneously, or into body cavities. Care should be taken to avoid extravascular injection or leakage.
Patients receiving diazoxide should be carefully observed for possible development of severe hyperglycaemia. This is especially important in patients with renal insufficiency or impaired carbohydrate metabolism. During intravenous therapy with diazoxide, blood glucose levels should be monitored daily.
Diazoxide should be administered with caution in patients in whom retention of sodium and water or abrupt reductions in blood pressure may be hazardous, e.g. those with impaired cardiac or cerebral circulation.
Caution should be exercised when administering diazoxide to uremic patients as they may experience a greater hypotensive effect. Haematological monitoring for signs of leucopenia and thrombocytopenia may be advisable in patients on prolonged diazoxide therapy.
Serum uric acid should be monitored in patients with hyperuricaemia or a history of gout.

Use in the elderly.

No data available.

Paediatric use.

In children, it is recommended that bone and psychological maturation and growth should be regularly assessed.

Reports of pulmonary hypertension in neonates and infants treated for hyperinsulinaemic hypoglycaemia.

There have been post-marketing reports of pulmonary hypertension occurring in infants and neonates treated with diazoxide for hyperinsulinaemic hypoglycaemia. The cases were reversible upon discontinuation of the drug. Patients under treatment, especially those with risk factors for pulmonary hypertension, should be monitored for respiratory distress. Diazoxide should be discontinued if pulmonary hypertension is suspected.

Note.

DBL Diazoxide Injection BP is not indicated for the treatment of hyperinsulinaemic.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Concomitant administration of diuretics may result in potentiation of the hyperglycaemic, hyperuricaemic or hypotensive effect of diazoxide. Diazoxide may potentiate the hypotensive effect of other antihypertensive agents; this effect is usually used to therapeutic advantage, but careful adjustment of dosage is necessary when these drugs are used concomitantly.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effect on the human fetus or neonate without causing malformations. These effects may be reversible.
Safe use of diazoxide in pregnancy has not been established. It is a powerful relaxant of uterine smooth muscle and may arrest labour. Uterine contractions can, however, be re-established with oxytocic agents. Diazoxide crosses the placenta and although hypertensive crises of eclampsia have been treated fairly successfully with diazoxide, the possibility of adverse effects on the foetus cannot be excluded. Hyperglycaemia has been observed in the newborn.
No data available.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Although numerous adverse effects may occur in patients receiving prolonged diazoxide therapy, serious adverse effects rarely occur when the drug is administered intravenously for short periods of time.
Hyperglycaemia frequently occurs in patients on intravenous diazoxide therapy. Although this is usually mild and subsides without treatment, administration of oral hypoglycaemic agents or insulin may be required, especially in diabetic patients or those receiving repeated doses of diazoxide. Hyperglycaemic effects of diazoxide are potentiated in the presence of hypokalaemia.
Sodium and water retention occur frequently and may result in oedema, weight gain, congestive heart failure and refractoriness to the hypotensive effects of the drug. However, these may be prevented by appropriate diuretic therapy.
Severe hypotension occurs infrequently and can be treated if necessary with sympathomimetic agents such as noradrenaline.
Other adverse effects resulting from the vasodilatory action of intravenous diazoxide include flushing, generalised or localised sensations of warmth, burning or itching, headache, sweating, lightheadedness and transient weakness.
Transient myocardial or cerebral ischaemia may occur. When diazoxide is administered intravenously, pain or a feeling of warmth frequently occurs along the injected vein.
Gastrointestinal upsets including nausea, vomiting and abdominal discomfort are frequent, but usually transient.
Hypersensitivity reactions such as rash, leucopenia, fever and thrombocytopenia occur infrequently.
Pulmonary hypertension has been reported in neonates and young infants treated with diazoxide for hyperinsulinaemic hypoglycaemia. (See Section 4.4 Special Warnings and Precautions for Use).

Note.

DBL Diazoxide Injection BP is not indicated for the treatment of hyperinsulinaemic hypoglycaemia.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Overdosage of diazoxide produces hyperglycaemia and possibly ketoacidosis which should be treated promptly with insulin and restoration of fluid and electrolyte balance. Severe hypotension can be controlled with sympathomimetic agents if necessary. Diazoxide has a long half-life and, therefore, prolonged surveillance of overdose patients is recommended.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Diazoxide reduces peripheral vascular resistance and blood pressure through a direct vasodilatory effect on smooth muscle in peripheral arterioles. Although the precise mechanism of its hypotensive effect is not yet understood, it has been postulated that antagonism of calcium may be involved. Diazoxide-induced decreases in blood pressure are accompanied by reflex increases in heart rate and cardiac output.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Following rapid intravenous administration diazoxide produces a prompt reduction in blood pressure; maximum hypotensive effects generally occur within less than 5 minutes. Blood pressure usually rises rapidly over the next 10 to 20 minutes, followed by a more gradual increase as pretreatment levels are approached. The duration of the antihypertensive effect of diazoxide varies greatly - generally 3 to 12 hours, but may be much longer in some cases. The hypotensive response may be greater and more prolonged with subsequent intravenous doses.

Distribution.

Diazoxide crosses the placenta and blood-brain barrier. In plasma, approximately 90% of diazoxide is protein-bound. However, the extent of protein-binding may be reduced in uremic patients. The high degree of protein-binding is responsible for the prolonged half-life of diazoxide which averages approximately 28 hours in adults, but may be shorter in children or prolonged in patients with renal impairment.

Metabolism.

Diazoxide is partly metabolised in the liver.

Excretion.

Diazoxide is excreted in the urine both unchanged and in the form of metabolites. Only small amounts are recovered from the faeces.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium hydroxide, water for injections.

6.2 Incompatibilities

Diazoxide has been found to be incompatible with hydralazine hydrochloride, lignocaine hydrochloride and propranolol hydrochloride. Do not dilute. Diazoxide is to be administered undiluted rapidly for maximum effect. Slower administration may reduce the antihypertensive response.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light. Avoid excessive heat and freezing.

6.5 Nature and Contents of Container

See Table 1.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

The pH of the solution is adjusted to approximately 11.5 with Sodium Hydroxide BP.

Chemical structure.


CAS number.

364-98-7.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes