Consumer medicine information

Octostim

Desmopressin acetate

BRAND INFORMATION

Brand name

Minirin/ Octostim Injections

Active ingredient

Desmopressin acetate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Octostim.

SUMMARY CMI

OCTOSTIM® Injection

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about being given this medicine, speak to your doctor or pharmacist.

1. Why am I being given OCTOSTIM Injection?

OCTOSTIM Injection contains the active ingredient desmopressin acetate, which is a synthetic version of a naturally occurring substance produced in the brain called vasopressin. It is used for several different conditions including to increase the blood clotting factor VIII levels in patients with mild and moderate haemophilia A and von Willebrand's disease (but not type IIB) prior to dental or other surgery and to treat excessive bleeding in patients with certain defects of the blood clotting cells (platelets).
For more information, see Section 1. Why am I being given OCTOSTIM Injection? in the full CMI.

2. What should I know before being given OCTOSTIM Injection?

Do not use OCTOSTIM Injection if you have ever had an allergic reaction to desmopressin acetate or to any of the ingredients listed at the end of the CMI. (see Section 7. Product details in the full CMI.)
Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding. For more information, see Section 2. What should I know before being given OCTOSTIM Injection? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with OCTOSTIM Injection and affect how it works. A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How will I be given OCTOSTIM Injection?

OCTOSTIM Injection is given by injection into a vein (intravenously). It is never given by injection into your muscle (intramuscularly) and is not intended for self-administration.

  • For use prior to dental or other surgery of patients with mild and moderate haemophilia A and von Willebrand's disease (but not type IIB) - it is usually given 30 minutes before the procedure or surgery. For cardiac (heart) surgery, it will be given towards the end of the operation.

More instructions can be found in Section 4. How will I be given OCTOSTIM Injection? in the full CMI.

5. What should I know while being given OCTOSTIM Injection?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are being given OCTOSTIM Injection.
  • If you are going to have surgery, tell the surgeon or anaesthetist that you are being given this medicine.
Things you should not do
  • OCTOSTIM Injection should not be given to you to treat any other complaints unless your doctor tells you to do so.
Looking after your medicine
  • Keep OCTOSTIM Injection in a refrigerator at a temperature between 2°C and 8°C. Do not freeze. Keep it in its original packaging and protect it from light.
  • Store it in a cool dry place away from moisture, heat or sunlight.

For more information, see Section 5. What should I know while being given OCTOSTIM Injection? in the full CMI.

6. Are there any side effects?

All medicines can have side effects. Most of them are minor and temporary but some may need medical attention. Tell your doctor if you experience any side effects, including headache, stomach pain, nausea or vomiting, rapid weight gain, confusion or drowsiness. These are signs and symptoms of hyponatraemia (low sodium levels in the blood), a rare, but serious possible side effect of OCTOSTIM Injection. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

OCTOSTIM® Injection

Active ingredient(s): desmopressin acetate


Consumer Medicine Information (CMI)

This leaflet provides important information about being given OCTOSTIM Injection. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about being given OCTOSTIM Injection.

Where to find information in this leaflet:

1. Why am I being given OCTOSTIM Injection?
2. What should I know before being given OCTOSTIM Injection?
3. What if I am taking other medicines?
4. How will I be given OCTOSTIM Injection?
5. What should I know while being given OCTOSTIM Injection?
6. Are there any side effects?
7. Product details

1. Why am I being given OCTOSTIM Injection?

OCTOSTIM Injection contains the active ingredient desmopressin acetate. OCTOSTIM Injection is a synthetic version of a naturally occurring substance produced in the brain called vasopressin.

OCTOSTIM Injection has several different actions on the body including:

  • to increase the levels of the blood clotting factor VIII in patients with mild and moderate haemophilia A and von Willebrand's disease (but not type IIB) prior to dental or other surgery
  • to treat excessive bleeding in patients with certain defects of the blood clotting cells (platelets). OCTOSTIM can reduce spontaneous bleeds or bleeding after heart or other surgery in these patients.

2. What should I know before being given OCTOSTIM Injection?

Warnings

OCTOSTIM Injection should not be used if:

  • you are allergic to desmopressin, or any of the ingredients listed at the end of this leaflet.
  • you suffer from polydipsia (have excessive thirst and requiring increased fluid intake) or psychogenic polydipsia (psychologically-caused are in the habit of drinking large amounts of fluid
  • you have cardiac insufficiency (heart failure in which the heart is not able to pump enough blood throughout the body resulting in shortness of breath, swelling of feet or legs due to fluid build-up)
  • you have low levels of sodium in your bloodstream
  • you have SIADH (hormone secretion disorder where there is an overproduction of a hormone causing fluid retention, resulting in weakness, tiredness or confusion)
  • you have a history of a condition marked by severe pain in the chest, often also spreading to the shoulders, arms and neck, owing to an inadequate supply to the heart (angina pectoris).
  • you have von Willebrand's disease type IIB (a Bleeding disorder)
  • the expiry date printed on the pack has passed
  • the packaging is torn or shows signs of tampering.

Always check the ingredients to make sure you can use this medicine.

Check with your doctor if you:

  • have any other medical conditions especially the following:
    - a known allergy to anti-diuretic hormone (ADH)
    - too little or too much fluid in the body
    - heart or blood vessel disease or any other disease for which you take diuretics (fluid tablets)
    - low blood pressure
    - cystic fibrosis or any other disease which causes fluid or salt imbalance
    - any disease of the blood clotting cells (platelets)
    - serious problems with bladder function or with passing urine
    - raised pressure within your head (increased intracranial pressure)
    - moderate to severe renal insufficiency
  • take any medicines for any other condition.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

OCTOSTIM Injection should only be given to a pregnant woman if it is needed. Your doctor can discuss with you the risks and benefits involved.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

OCTOSTIM Injection is not recommended while you are breast-feeding.

3. What if I am taking other medicines?

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

Some medicines may interfere with OCTOSTIM Injection and affect how it works.

Medicines that may increase the effect of OCTOSTIM Injection include:

  • medications which are known to release antidiuretic hormone, which can increase the risk of fluid buildup in the body such as:
    - tricyclic antidepressants
    - selective serotonin reuptake inhibitors (SSRIs) (antidepressants)
    - chlorpromazine (anti-psychotic)
    - carbamazepine (bipolar disorder and epilepsy medication)
    - opioids (pain relief medications)
    - medications which are known to treat high blood sugar (diabetes) (e.g. medicines in the sulfonylurea group)
    - non-steroidal anti-inflammatory drugs (NSAIDs), which are medicinal products used for the treatment of pain and inflammation (e.g. aspirin and ibuprofen).
    - NSAIDs may induce water retention/low sodium levels in the blood (hyponatraemia).

These medicines may affect how well OCTOSTIM Injection works. You may need different amounts of your medicines, or you may need to take different medicines.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect OCTOSTIM Injection.

4. How will I be given OCTOSTIM Injection?

OCTOSTIM Injection is given by injection into a vein (intravenously). It is never given by injection into your muscle (intramuscularly).

OCTOSTIM Injection is not intended for self-administration.

How much OCTOSTIM Injection is given

The dose of OCTOSTIM Injection prescribed by your doctor will vary depending on the condition being treated and your response to the treatment.

The dose of OCTOSTIM Injection you will be given will be calculated based on your body weight.

When OCTOSTIM Injection is given

Patients with mild and moderate haemophilia A and von Willebrand's disease (but not type IIB) prior to dental or other surgery

  • if it is used for dental or minor surgery, OCTOSTIM Injection is usually given 30 minutes before the procedure or surgery
  • if you are undergoing cardiac (heart) surgery, OCTOSTIM Injection will be given towards the end of the operation
  • if you have responded to treatment with OCTOSTIM Injection and require more doses, further doses may be given every 12 hours for as long as it is needed.

How long OCTOSTIM Injection is given

This will depend on your condition and on your response to treatment with OCTOSTIM Injection.

If you are being treated with OCTOSTIM Injection to prevent or control bleeding, it will be given for as long as necessary to stop excessive bleeding.

You doctor will decide when treatment with OCTOSTIM Injection should be stopped.

What to expect

Individuals will vary greatly in their response to OCTOSTIM Injection and you may not feel any effect. You will receive regular monitoring to check on your body's response to OCTOSTIM.

If you have a defect in your blood clotting cells, your skin bleeding time will be monitored before surgery to determine whether you are at high risk of blood loss.

If you are given too much OCTOSTIM Injection

It is unlikely that you will be given too much OCTOSTIM Injection.

If you think that you or anyone else have been given too much OCTOSTIM Injection, you should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

Symptoms of an overdose may include confusion, drowsiness, continuing headache, nausea or vomiting, rapid weight gain due to a build-up of water in the body, or, in severe cases, convulsions.

The signs of overdosage can be treated by restoring your body's fluid balance, lowering the dose or giving OCTOSTIM Injection less often or it may be stopped completely.

5. What should I know while being given OCTOSTIM Injection?

Things you should do

If you are about to be started on any new medicine, remind your doctor, dentist, or pharmacist you visit that you are being given OCTOSTIM Injection.

If you are going to have surgery, tell the surgeon or anaesthetist that you are being given this medicine.

It may affect other medicines used during surgery.

If you become pregnant while being given OCTOSTIM Injection, tell your doctor immediately.

Your doctor can discuss with you the risks of being given it while you are pregnant.

If you are about to have any blood tests, tell your doctor that you are being given this medicine.

It may interfere with the results of some tests.

Keep all of your doctor's appointments so that your progress can be checked.

Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

Things you should not do

OCTOSTIM Injection should not be given to you to treat any other complaints unless your doctor tells you to do so.

Driving or using machines

This medicine is not expected to affect your ability to drive a car or operate machinery.

Looking after your medicine

OCTOSTIM Injection is usually stored in the hospital pharmacy or in the ward.

Keep OCTOSTIM Injection in a refrigerator at a temperature between 2°C and 8°C. Do not freeze. Keep it in its original packaging and protect it from light.

If you store the medicine out of its original packaging it may not keep well.

Store it away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Heat and dampness can destroy some medicines.

Follow the instructions in the carton on how to take care of your medicine properly.

Keep it where young children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date. The expiry date refers to the last day of that month.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

The elderly may be at an increased risk of some side effects.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Side effects

Side effectsWhat to do
Hyponatraemia or low sodium levels in the blood may have the following signs or symptoms:
  • headache
  • stomach pain
  • nausea.
Hyponatraemia can potentially become a serious side effect, see below.
Common side effects (affects between 1 to 10 in 100 users):
  • fatigue (tiredness)
Rare side effects (affect less than 1 in 1000 users):
  • dizziness (feeling lightheaded)
Side effects (unknown frequency):
  • generalised or local swelling (limbs, face)
  • chills
These side effects are not usually serious but can become serious.
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • high or low blood pressure
  • fast heart rate
  • emotional or behavioural disturbances
*Hypersensitivity or allergic reactions (unknown frequency):
  • 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.
*Hyponatraemia or low sodium levels in the blood may have the following serious signs or symptoms:
  • confusion or drowsiness
  • continuing headache
  • nausea or vomiting
  • rapid weight gain, which may be due to a build-up of water in the body
  • convulsions, fitting and blackouts (including coma)
*These side effects are rare
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are being given OCTOSTIM Injection.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What OCTOSTIM Injection contains

Active ingredient
(main ingredient)
desmopressin acetate
Other ingredients
(inactive ingredients)
  • sodium chloride
  • hydrochloric acid (to adjust the pH)
  • water for injections

Do not take this medicine if you are allergic to any of these ingredients.

What OCTOSTIM Injection looks like

OCTOSTIM Injection are supplied in 1 mL ampoules and are available in boxes of 10.

OCTOSTIM desmopressin acetate 15 micrograms/1 mL injection ampoule is a clear colourless solution for injection packed in 1 mL ampoules (AUST R 46758).

Who distributes OCTOSTIM Injection

Ferring Pharmaceuticals Pty Ltd
Suite 2, Level 1, Building 1
20 Bridge Street
Pymble, NSW 2073
Toll free: 1800 337 746

This leaflet was prepared in July 2023.

AU-OM-2300001_v.2.0

OCTOSTIM and FERRING are registered trademarks of Ferring B.V.

Published by MIMS September 2023

BRAND INFORMATION

Brand name

Minirin/ Octostim Injections

Active ingredient

Desmopressin acetate

Schedule

S4

 

1 Name of Medicine

Desmopressin acetate.

2 Qualitative and Quantitative Composition

Minirin Injection contains desmopressin 4 microgram/mL. Octostim Injection contains desmopressin 15 microgram/mL.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for Injection.
Clear colourless solution.

4 Clinical Particulars

4.1 Therapeutic Indications

Diabetes insipidus (Minirin Injection).

The treatment of ADH sensitive cranial diabetes insipidus, including treatment of posthypophysectomy polydipsia and polyuria.

Renal concentrating capacity (Minirin Injection).

By intramuscular administration to adults only, as a diagnostic test to establish renal concentrating capacity.

Mild and moderate haemophilia A and von Willebrand's disease (Minirin and Octostim Injections).

By intravenous infusion only, for the increase of factor VIII levels in patients undergoing dental or minor surgery. Not to be used in type IIB von Willebrand's disease, since platelet aggregation may be induced.

Bleeding in patients with platelet dysfunction (Minirin and Octostim Injections).

Treatment of excessive bleeding in patients with congenital or acquired clinical conditions associated with platelet dysfunction which is characterised by a prolonged bleeding time, except Glanzmann's thrombasthenia or platelet cyclooxygenase deficiency.
Examples are patients with uraemia, congenital or drug induced platelet dysfunction, and patients undergoing cardiac surgery with cardiopulmonary bypass for prosthetic valve replacement or aortocoronary bypass grafting, especially when it is complicated by platelet function defects sufficient to prolong bleeding time despite relatively normal platelet cover. Desmopressin acetate offers no benefit as routine therapy in patients having an uncomplicated (simple) cardiopulmonary bypass procedure.
There is no definite evidence of efficacy in bleeding associated with cirrhosis of the liver and such use is not recommended.

4.2 Dose and Method of Administration

Minirin Injection is normally administered intravenously but may, if needed, be given intramuscularly. Octostim Injection is recommended for intravenous use only.

a. For ADH-sensitive cranial diabetes insipidus (Minirin Injection).

Adult.

The average daily dose is 1 to 4 micrograms by injection.

Paediatric.

Up to 0.4 micrograms (400 nanograms) daily.
The daily dose is usually given as two divided doses. The dosage must be determined for each individual patient and adjusted according to the diurnal pattern of response. Response should be estimated by two parameters: adequate duration of sleep and adequate, but not excessive, water turnover. In the event of signs of water retention/ hyponatraemia, treatment should be interrupted and the dose adjusted. A single daily dose may be appropriate if it is tolerated and also satisfactorily controls the diabetes insipidus. About one-third of patients may be controlled on a small daily dose. For immediate postoperative polyuria and polydipsia, the dose should be controlled by measurement of the urine osmolality. Monitoring in a high dependency setting is recommended. If there is doubt that a dose has been administered, a second dose should not be given until diuresis has occurred.

Mode of administration.

Minirin Injection may be administered intramuscularly or intravenously when the intranasal route is inconvenient.
When using doses of less than 4 micrograms the dose should be drawn up from the ampoule as a fraction of a millilitre using a diabetic syringe and not prepared by dilution or given by infusion. This is necessary because of the tendency of peptides to adhere to glass surfaces when in very dilute solutions.
The parenteral daily doses are usually given as 2 divided doses separately adjusted if necessary. A single daily dose may be appropriate if it is tolerated and also satisfactorily controls the diabetes insipidus.

b. As a diagnostic test of renal concentrating capacity (Minirin Injection).

(See Section 4.4 Special Warnings and Precautions for Use, In addition for renal concentrating capacity testing).

Adults.

Single dose of up to 4 micrograms by intramuscular injection.

Paediatric.

Due to lack of safety data, paediatric use is not recommended.

c. Mild to moderate haemophilia A and von Willebrand's disease (Minirin and Octostim Injections).

VIII: C assays should be undertaken regularly during treatment. Within ½ hour before surgery 0.4 microgram desmopressin acetate/kg diluted to 10-100 mL in isotonic saline is given as slow intravenous infusion over 15-20 min. Before and 20 min after the infusion, VIII: C assays and in the case of von Willebrand's disease determination of VIIIR: Ag and bleeding time should also be carried out unless the patient's response is known from pretesting.
The critical haemostatic level for dentistry or surgery should be judged by the same criteria as if the patient were being managed with blood products, except that the level may be expected to continue to rise for one to two hours after the infusion rather than beginning to fall immediately.
If a sufficient response was obtained with the initial dose of desmopressin acetate, further doses may be given at 12 hourly intervals so long as cover is required. VIII: C levels must be monitored regularly since some patients have shown a diminishing response to successive infusions.
If a sufficient level has not been reached to cover the intended surgical procedure, a supplementary dose of factor VIII concentrate should be given to make up the deficit.

d. Treatment of bleeding in subjects with inherited and acquired platelet function defects (Minirin and Octostim Injections).

Desmopressin acetate is given at a dose of 0.3 microgram/kg diluted to 50 mL in isotonic saline as a slow intravenous infusion over 30 minutes. Further doses may be given at 12 hourly intervals as long as cover is required. In some patients, a 12 hourly injection for 3-4 days may result in clinically significant fluid retention. In some studies, combined therapy consisting of desmopressin acetate and a fibrinolytic inhibitor was used.

General surgery (except cardiac surgery).

Half an hour prior to surgery, desmopressin acetate is given as a slow intravenous infusion over 30 minutes.

Cardiac surgery.

Desmopressin acetate is to be administered in patients with a prolonged bleeding time when cardiopulmonary bypass has been completed and immediately after protamine has been given to neutralise the effect of heparin or at any time thereafter.

Nonsurgical use.

In patients with epistaxis, menorrhagia or other bleeding episodes, desmopressin acetate is given as a slow intravenous infusion over 30 minutes. Red blood cell transfusion is of value in improving haemostasis in uraemic patients.

Instructions to be given to patients.

Parenteral.

Desmopressin acetate is not intended for self administration.

4.3 Contraindications

Hypersensitivity to desmopressin acetate or any of the excipients.
Habitual and psychogenic polydipsia (resulting in a urine production exceeding 40 mL/kg/24 hours).
A history of unstable angina pectoris and/or known or suspected cardiac insufficiency and other conditions requiring treatment with diuretics.
Known hyponatraemia.
Syndrome of inappropriate ADH secretion (SIADH).
von Willebrand's disease type IIB.

4.4 Special Warnings and Precautions for Use

Desmopressin acetate is ineffective for the treatment of nephrogenic diabetes insipidus.
a. Minirin/ Octostim Injections should be used with caution in patients at risk for increased intracranial pressure.
b. Minirin/ Octostim Injections should be used with caution in patients with conditions characterised by fluid and/or electrolyte imbalance.
Desmopressin acetate should not be administered to dehydrated or overhydrated patients until water balance has been adequately restored. In haemophilia, where high doses are given, extreme care must be paid to the water balance. Fluid intake should be restricted as much as possible and the patient should be weighed regularly.
Treatment with Minirin/ Octostim Injections should be interrupted or carefully adjusted during acute intercurrent illnesses characterised by fluid and/or electrolyte imbalance (such as systemic infections, fever, gastroenteritis) as well as in excessive bleeding, and the fluid and electrolyte balance should be carefully monitored.

c. Hyponatraemia and hydration.

Hyponatraemia in the context of the use of desmopressin is generally due to fluid overload, thus careful attention to fluid balance is needed. Other causes of hyponatraemia which may need excluding depending on the clinical situation include renal salt wasting due to central lesions, renal disorders or adrenal disorders.
Infants, elderly and patients with serum sodium levels in the lower range of normal may have an increased risk of hyponatraemia.

Central diabetes insipidus.

The aim of fluid therapy is to replace urinary fluid loss.
Children, patients with cognitive impairment, and patients with inadequate thirst sensation need close monitoring of fluid intake.
Regular monitoring of serum and urinary sodium and osmolality is recommended at the discretion of the clinician.

In addition for renal concentrating capacity testing.

When used for diagnostic purposes the fluid intake must be limited to a maximum of 0.5 L to satisfy thirst from 1 hour before until at least 8 hours after administration. Renal concentrating capacity testing in children below the age of 1 year should only be performed under carefully supervised conditions in hospital.

In addition for haemostatic use.

Measures to prevent fluid overload must be taken in patients requiring treatment with diuretic agents.
d. Special attention must be paid to the risk of fluid retention/hyponatraemia. The fluid intake should be restricted to the least possible and the body weight should be checked regularly. Should there be a gradual increase of the body weight, decrease of serum sodium to below 130 mmol/L or plasma osmolality to below 270 mOsm/kg body weight, the fluid intake must be reduced drastically and the administration of Minirin/ Octostim Injections interrupted.

e. Risks of thrombosis and cardiovascular events.

The benefits of desmopressin versus other haemostatic therapies should be carefully assessed in situations where prolonged haemostasis is required including active postoperative bleeding and variceal bleeding in patients with cirrhosis.

Myocardial ischaemia.

Desmopressin acetate should be used with caution in patients with cardiovascular disease and the elderly.
There have been post-marketing reports of deep vein thrombosis, cerebrovascular accident and disorder (stroke), cerebral thrombosis, myocardial infarction, angina pectoris and chest pain, in patients using Minirin/ Octostim Injections, mainly for haemostasis. An individualised risk based approach is recommended for the control of haemostasis in patients with other risk factors for thrombosis.
Special attention should be given when desmopressin is co-administered with other drugs affecting water and/or sodium homeostasis (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). In patients with chronic therapy with drug(s) affecting water and/or sodium homeostasis, Minirin/ Octostim Injections should be administered after confirmation of normal baseline sodium.

f. Postoperative use.

In a context of the management of diabetes insipidus, the use of desmopressin in a postoperative setting should only occur after the diagnosis of diabetes insipidus has been confirmed. Small doses should be administered with strict fluid balance and regular clinical assessment.

g. In patients with platelet dysfunction.

Skin bleeding time should be monitored i) before surgery, with marked prolongation indicating high risk of increased blood loss, ii) during treatment with desmopressin acetate.
h. Minirin/ Octostim Injections do not reduce prolonged bleeding time in thrombocytopenia.
i. Minirin/ Octostim Injections should be used with caution in patients with cystic fibrosis because of impaired water handling and increased risk of hyponatraemia.
j. Severe bladder dysfunction and outlet obstruction should be considered before starting treatment for central diabetes insipidus.

Paediatrics use.

Minirin/ Octostim injections should be used with caution in very young patients.

Use in the elderly.

Minirin/ Octostim Injections should be used with caution in elderly patients, particularly those with other risk factor for thrombotic disease.

Use in renal impairment.

Minirin/ Octostim Injections should be used with caution in patients with moderate and severe renal insufficiency (creatinine clearance below 50 mL/min) (see Section 5.2 Pharmacokinetic Properties).

Use in hepatic impairment.

No dose adjustment is needed for patients with hepatic impairment (see Section 5.2 Pharmacokinetic Properties).

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Special attention should be given when desmopressin is co-administered with other drugs affecting water and/or sodium homeostasis, e.g. opioids, selective serotonin reuptake inhibitors, tricyclic antidepressants, nonsteroidal anti-inflammatory drugs, chlorpromazine, carbamazepine and some antidiabetics of the sulfonylurea group since concurrent use can lead to an increased risk of fluid retention/hyponatraemia (see Section 4.4 Special Warnings and Precautions for Use).
It is unlikely that desmopressin will interact with drugs affecting hepatic metabolism, since desmopressin has been shown not to undergo significant liver metabolism in in vitro studies with human microsomes. However, formal in vivo interaction studies have not been performed.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Studies with desmopressin in animals have shown no impairment of fertility in male and female rats.
(Category B1)
Caution should be exercised when prescribing to pregnant women.
Data on a limited number (n = 53) of exposed pregnancies in women with diabetes insipidus as well as data on a limited number of exposed pregnancies in women with bleeding complications (n = 216) indicate no adverse effects of desmopressin on pregnancy or on the health of the fetus/ newborn child. To date, no other relevant epidemiological data are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/ fetal development, parturition or postnatal development.
Embryofetal development studies performed with desmopressin in rats and rabbits given subcutaneous doses up to 50 nanogram/kg/day and 200 microgram/kg/day, respectively, and in rats given intravenous doses up to 241 microgram/kg/day, revealed no evidence for a harmful effect on the fetus.
Animal reproduction studies have shown no clinically relevant effects on parents and offspring. In vitro analysis of human cotyledon models have shown that there is no transplacental transport of desmopressin when administered at therapeutic concentration corresponding to recommended dose.
Subtherapeutic levels of desmopressin acetate have been detected in the breast milk of lactating women. Until further evidence of its safe use during lactation is available, it is not to be administered to lactating women.

4.7 Effects on Ability to Drive and Use Machines

Minirin and Octostim Injections have no or negligible influence on the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

Summary of the safety profile.

The most frequently reported adverse reaction with Minirin Injection during post-marketing is hyponatraemia. Hyponatraemia may cause headache, nausea, vomiting, water intoxication, weight increase, malaise, abdominal pain, muscle cramps, dizziness, confusion, decreased consciousness, generalised or local oedemas (peripheral, face), and in severe cases brain oedema, hyponatraemic encephalopathy, convulsions, and coma (see Section 4.4 Special Warnings and Precautions for Use).
Rare cases of serious hypersensitivity reactions including anaphylactoid shock and reaction have been reported in association with Minirin/ Octostim Injections (see Section 4.4 Special Warnings and Precautions for Use).

Tabulated list of adverse reactions.

Table 1 is based on the frequency of adverse drug reactions reported in clinical trials with Minirin Injection conducted in adults for treatment of central diabetes insipidus and haematological indications (N=53) and Octostim injections (n=76), combined with the post-marketing experience for Minirin/ Octostim Injections. Reactions only seen in post-marketing or in other desmopressin formulations have been added in the ‘Not known’ frequency column. The table below shows the frequencies of adverse reactions reported. Adverse reactions are classified according to frequency and system organ class. Frequency categories are defined according to the following convention: Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1,000 to < 1/100); Rare (≥ 1/10,000 to < 1/1,000); Very rare (< 1/10,000) and Not known (cannot be estimated from the available data).

Description of selected adverse reactions.

During post-marketing the most frequently reported adverse reaction with Minirin/ Octostim is hyponatraemia. Hyponatraemia may cause headache, nausea, vomiting, water intoxication, weight increase, malaise, abdominal pain, muscle cramps, dizziness, confusional state, decreased consciousness, generalised or local oedemas (peripheral, face), and in severe cases brain oedema, hyponatraemic encephalopathy, convulsions, and coma. Nausea, vomiting, headache and dizziness have been reported without registered hyponatraemia. The hyponatraemia is a result of the antidiuretic effect, arising from increased water reabsorption by the renal tubules and osmotic dilution of plasma. Special attention should be paid to the precautions addressed, see Section 4.4 Special Warnings and Precautions for Use.
Hyponatraemia is reversible. Treatment should be individualised and rapid overcorrection should be avoided to reduce the risk of further complications (see Section 4.4 Special Warnings and Precautions for Use).
Post-marketing hypersensitivity reactions including local allergic reactions such as dyspnoea, erythema, generalized or local oedemas (peripheral, face), pruritus, rash, rash macular, rash maculopapular, rash erythematous, skin plaque and urticaria, have been reported in association with Minirin/ Octostim Injections. More serious hypersensitivity reactions including anaphylactic shock and reaction, and anaphylactoid shock and reaction have also been reported in association with Minirin/ Octostim Injections. Allergic reactions usually occur rapidly after drug administration and may occur during first time usage or after repeated exposure of Minirin/ Octostim Injections.
Rare post-marketing cases of deep vein thrombosis, cerebrovascular accident/disorder (stroke), cerebral thrombosis, pulmonary embolism, myocardial infarction, angina pectoris and chest pain have been reported in patients treated with desmopressin. Due to confounding factors and/or missing information, a causal relationship with Minirin/ Octostim Injections has not been established/ confirmed.

Paediatric population.

Adverse reaction data from clinical trials in children is very limited.

Other special populations.

Elderly and patients with serum sodium levels in the lower range of normal may have an increased risk of developing hyponatraemia (see Section 4.4 Special Warnings and Precautions for Use).

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

Overdose of Minirin/ Octostim Injection leads to a prolonged duration of action with an increased risk of water retention and hyponatraemia.

Treatment.

The treatment of hyponatraemia should be individualised and can include discontinuation of Minirin treatment fluid restriction and symptomatic treatment.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: vasopressin and analogues.
ATC code: H01B A02.
Minirin Injection 4 microgram/mL and Octostim Injection 15 microgram/mL, contain desmopressin, a structural analogue of the natural pituitary hormone arginine vasopressin, also known as antidiuretic hormone (ADH). Early treatment of central diabetes insipidus used a more or less purified extract from bovine or porcine posterior pituitaries. These caused unpleasant complications of use. When vasopressin became known, two forms were found - arginine vasopressin (found in humans) and lysine vasopressin (found in pig pituitaries).
Two chemical changes have been made to the natural hormone to form desmopressin: a. desamination of the N-terminal of cysteine-1 b. substitution of 8-D-arginine for 8-L-arginine.
According to results from antidiuretic and pressor tests in rats these changes increase antidiuretic activity three to five fold, while pressor activity is reduced to 0.1% of that of ADH.

Mechanism of action.

The actions of desmopressin can be summarised as follows:

Antidiuretic action.

Desmopressin acts at a receptor site in the renal collecting tubule to increase permeability to water reabsorption.

Effect on factor-VIII.

High doses (0.3 microgram/kg intravenously) of desmopressin acetate produce marked and sustained increases of factor-VIII coagulant activity (VIII: C) as well as of the von Willebrand factor (vWF). At the same time plasminogen activator is released.

Effect on bleeding time.

At doses of 0.3-0.4 microgram/kg intravenously, desmopressin results in a normalisation of, or marked reduction in, the prolonged skin (template) bleeding time. The exact mechanism of this effect is not known. It is not known whether the effects of desmopressin are direct or act through a mediator or second messenger.
There is a temporal correlation between a reduction in bleeding time and the presence in plasma of high molecular weight monomers of the von Willebrand factor which are thought to be released from storage sites. It is thought likely that desmopressin exerts its effect through its V2-receptor agonist activity.

Other effects.

Oxytocic effect.

A slight in vitro oxytocic effect has been reported in animals. A slight stimulatory effect on uterine activity in non-pregnant women has been noted at doses of 15 and 20 micrograms intranasally (See Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).

Vasodilator effect.

At doses used to treat bleeding, desmopressin has a vasodilatory effect, causing a minor decrease in diastolic or systolic blood pressure.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Using i.v. doses, 100% of desmopressin is systematically available. The bioavailability following subcutaneous injection compared with intravenous administration is about 85%. Maximal plasma concentration after 0.3 microgram/kg given as a subcutaneous injection is achieved after approximately 60 minutes and in average it amounts to 600 nanogram/mL.

Distribution.

No information is available on protein binding. The distribution of desmopressin is best described by a two compartment distribution model, with a volume of distribution during the elimination phase of 0.3-0.5 L/kg.

Metabolism.

It is thought that the presence of the D-isomer in position eight prolongs the antidiuretic effect compared to ADH.
The in-vivo metabolism of desmopressin has not been studied. In vitro human liver microsome metabolism studies of desmopressin have shown that no significant amount is metabolised in the liver by the cytochrome P450 system, and thus human liver metabolism in vivo by the cytochrome P450 system is unlikely to occur. The effect of desmopressin on the pharmacokinetics of other drugs is likely to be minimal due to its lack of inhibition of the cytochrome P450 drug metabolising system.

Excretion.

The excretion of desmopressin is similar to that of ADH but considerably slower. The total clearance of desmopressin has been calculated to 7.6 L/hr. In healthy subjects the fraction excreted unchanged was 52% (44-60%). Plasma half- life varies between 3 and 4 hours. The duration of the haemostatic effect depends on the half-life for factor-VIII coagulant activity (VIII: C), which is about 8-12 hours.

Characteristics in specific groups of patients.

Renal impairment.

See Table 2.

Clinical implications of pharmacokinetic data.

Desmopressin is thought to be resistant to the inactivation that occurs with ADH. Intravenous or intramuscular doses should be about one tenth the intranasal dose for equivalent efficacy. In some patients, the duration of effect may be sufficiently long to permit once daily dosage if the single dose can be tolerated.

5.3 Preclinical Safety Data

Genotoxicity.

Non-clinical data reveal no special hazard for humans based on conventional studies of safety, pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction and development.

Carcinogenicity.

No studies of the carcinogenic potential have been performed.

6 Pharmaceutical Particulars

6.1 List of Excipients

Minirin and Octostim Injections also contain sodium chloride, hydrochloric acid and water for injections.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

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 at 2 to 8°C. Refrigerate. Do not freeze. Protect from light.

6.5 Nature and Contents of Container

Parenteral.
Minirin Injection 4 microgram/mL: Box of 10 ampoules of 1 mL.
Octostim Injection 15 microgram/mL (for intravenous administration only): Box of 10 ampoules of 1 mL.

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

Synonyms of desmopressin.

DDAVP.
1-desamino-8-D-Arginine vasopressin.
Desamino-cys-1-D-Arginine-8 vasopressin.

Molecular weights.

Desmopressin base: 1069.22.
Desmopressin acetate: 1183.34.
Desmopressin is a white, fluffy powder, soluble in water, alcohol and glacial acetic acid.

Chemical structure.


CAS number.

Desmopressin base: 16679-58-6.
Desmopressin acetate: 62288-83-9.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes