Consumer medicine information

Minirin Tablets

Desmopressin

BRAND INFORMATION

Brand name

Minirin Tablets

Active ingredient

Desmopressin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Minirin Tablets.

SUMMARY CMI

MINIRIN® Tablets

Consumer Medicine Information (CMI) summary

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

1. Why am I taking MINIRIN Tablets?

MINIRIN Tablets 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 conditions including primary nocturnal enuresis (bedwetting) in patients over 6 years of age and cranial diabetes insipidus.

For more information, see Section 1. Why am I taking MINIRIN Tablets? in the full CMI.

2. What should I know before I take MINIRIN Tablets?

Do not take if you have ever had an allergic reaction to desmopressin acetate or any of the ingredients listed at the end of the 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 I take MINIRIN Tablets? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with MINIRIN Tablets 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 do I take MINIRIN Tablets?

  • Bedwetting (primary nocturnal enuresis) - the usual starting dose is one tablet (200 micrograms) at bedtime. If it does not resolve, the doctor may recommend increasing the dose up to two tablets (400 micrograms) at bedtime.
  • Cranial diabetes insipidus - doses of up to 200 micrograms three times daily are often used

More instructions can be found in Section 4. How do I take MINIRIN Tablets? in the full CMI.

5. What should I know while taking MINIRIN Tablets?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are taking MINIRIN Tablets.
  • 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.
Things you should not do
  • Do not take MINIRIN Tablets to treat any other complaints unless your doctor tells you to.
  • Do not stop taking your medicine or lower the dosage without checking with your doctor.
  • If you stop taking it suddenly, your condition may worsen.
Driving or using machines
  • This medicine is not expected to affect your ability to drive a car or operate machinery.
Looking after your medicine
  • Keep MINIRIN Tablets in the original container to protect from moisture and light until it is time to take it.
  • Store it in a cool dry place, where the temperature stays below 25°C, away from moisture, heat or sunlight.

For more information, see Section 5. What should I know while taking MINIRIN Tablets? 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 MINIRIN Tablets. 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

MINIRIN® Tablets

Active ingredient(s): desmopressin acetate


Consumer Medicine Information (CMI)

This leaflet provides important information about taking MINIRIN Tablets. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about taking MINIRIN Tablets.

Where to find information in this leaflet:

1. Why am I taking MINIRIN Tablets?
2. What should I know before I take MINIRIN Tablets?
3. What if I am taking other medicines?
4. How do I take MINIRIN Tablets?
5. What should I know while taking MINIRIN Tablets?
6. Are there any side effects?
7. Product details

1. Why am I taking MINIRIN Tablets?

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

MINIRIN Tablets has several different actions on the body including on the kidney to reduce the amount of urine produced. It is used for several different conditions including:

  • primary nocturnal enuresis (bedwetting) in patients over 6 years of age who have a normal ability to concentrate urine and who have not responded to treatment with an enuresis alarm or in whom an enuresis alarm is contraindicated or inappropriate
  • cranial diabetes insipidus (large amounts of urine being produced day and night and constant thirst).

2. What should I know before I take MINIRIN Tablets?

Warnings

Do not take MINIRIN Tablets if:

  • you are allergic to desmopressin, or any of the ingredients listed at the end of this leaflet
  • you are in the habit of drinking large amounts of fluid
  • you have cardiac insufficiency (shortness of breath, swelling of feet or legs due to fluid build-up)
  • you have kidney disease where you pass little or no urine
  • you have low levels of sodium in your bloodstream
  • you have a disease which causes excessive release of anti-diuretic hormone
  • you are breast-feeding
  • you are a child under the age of 6 years. Safety and effectiveness in children younger than 6 years have not been established
  • 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 take this medicine.

Check with your doctor if you:

  • have any other medical conditions especially the following:
    - a known allergy to anti-diuretic hormone
    - too little or too much fluid in the body
    - heart or blood vessel disease or any other disease for which you take diuretics
    - 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
    - galactose intolerance
    - raised pressure within your head (increased intracranial pressure)
  • 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.

MINIRIN Tablets should only be used in a pregnant woman if necessary. Your doctor can discuss with you the risks and benefits involved.

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

It is recommended that you do not breastfeed while you are taking MINIRIN Tablets.

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 MINIRIN Tablets and affect how it works.

Medicines that may increase the effect of MINIRIN Tablets include:

  • loperamide, a medicine used to stop diarrhoea
  • medications which are known to release antidiuretic hormone (e.g. tricyclic antidepressants, selective serotonin reuptake inhibitors, chlorpromazine or carbamazepine) or some medications which are known to treat high blood sugar (diabetes), as they can increase the risk of fluid buildup in the body
  • non-steroidal anti-inflammatory drugs (NSAIDs), medicines used to relieve pain and inflammation.
    NSAIDs may induce water retention/low sodium levels in the blood (hyponatraemia).

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

Food intake may reduce the effect of MINIRIN Tablets

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

4. How do I take MINIRIN Tablets?

How much to take

Some of the details for MINIRIN Tablets will vary depending on the purpose for which it is used.

Bedwetting (primary nocturnal enuresis)

  • the usual starting dose is one tablet (200 micrograms) at bedtime. If this dose does not adequately resolve the bedwetting, your doctor may recommend that you increase the dose up to two tablets (400 micrograms) at bedtime.
  • if after four weeks of MINIRIN Tablet treatment there has been no resolution of the bedwetting, treatment should be stopped.
  • fluid intake should be limited in preparation for your dose of MINIRIN Tablets (see 'Things to be careful of').

Cranial diabetes insipidus

  • the dose you need will be adjusted to suit your personal requirements
  • doses of up to 200 micrograms three times daily are often used
  • your doctor will advise you about the dose that is most suitable for you.

Follow the instructions provided and take MINIRIN Tablets until your doctor tells you to stop.

When to take MINIRIN Tablets

Bedwetting (primary nocturnal enuresis)

  • take MINIRIN Tablets at bedtime.

Cranial diabetes insipidus

  • take MINIRIN Tablets at times specified by your doctor.

How long to take MINIRIN Tablets

Continue taking your medicine for as long as your doctor tells you.

This medicine helps to control your condition but does not cure it. It is important to keep taking your medicine even if you feel well.

Bedwetting (primary nocturnal enuresis)

  • MINIRIN Tablets for bedwetting is usually taken for periods up to 3 months.
  • After this period, you should have at least one week without MINIRIN Tablets to check if your bedwetting has stopped.

Cranial diabetes insipidus

  • Your doctor will advise you.

If you forget to take MINIRIN Tablets

MINIRIN Tablets should be used regularly at the same time each day.

Bedwetting (primary nocturnal enuresis)

If you miss your dose at the usual time, skip the missed dose and take the next dose when you are meant to.

Cranial diabetes insipidus

Take the next dose as soon as you remember. You will then have to adjust the time of the following dose.

When this is done, go back to taking your medicine as you would normally. You should talk to your doctor about this situation.

Do not take a double dose to make up for the dose you missed.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much MINIRIN Tablets

If you think that you have taken too much MINIRIN Tablets, you may need urgent medical attention.

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.

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

5. What should I know while taking MINIRIN Tablets?

Things you should do

If you are about to be started on any new medicine, remind any doctor, dentist, or pharmacist you visit that you are taking MINIRIN Tablets.

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.

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

It may interfere with the results of some tests.

Keep all 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

  • Do not take MINIRIN Tablets to treat any other complaints unless your doctor tells you to.
  • Do not give your medicine to anyone else, even if they have the same condition as you.
  • Do not stop taking your medicine or lower the dosage without checking with your doctor.
  • If you stop taking it suddenly, your condition may worsen.

Things to be careful of

Bedwetting (primary nocturnal enuresis)

  • You must avoid drinking fluids from one hour before taking MINIRIN Tablets until the next morning (at least eight hours).
  • Over this period, drink no more than a few sips of water or other fluids. This is because a high fluid intake during this period can increase the chance that you will feel unwell (e.g. headache, nausea, dizziness).
  • Remember to drink normally throughout the day.
  • This is very important to prevent dehydration during daytime.

Cranial diabetes insipidus

  • Carefully follow your doctor's instruction about fluid intake.
  • It is very important to keep your body water in balance.

Driving or using machines

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

Looking after your medicine

Keep MINIRIN Tablets in the original container to protect from moisture and light until it is time to take it.

If you take the tablets out of the bottle they will not keep well.

Keep the container tightly closed and do not remove the desiccant capsule from the cap.

Store it in a cool dry place, where the temperature stays below 25°C, 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 take this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not take 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.

If you are over 65 years of age, commencing MINIRIN Tablet treatment is not recommended.

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.
Uncommon side effects (affect less than 1 in 100 users):
  • fatigue
  • diarrhoea.
Rare side effects (affect less than 1 in 1000 users):
  • sleepiness
Side effects (unknown frequency):
  • sweating
  • nosebleed.
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 blood pressure
  • bladder problems
  • emotional or behavioural disturbances
  • hallucinations.
*Hypersensitivity or allergic reactions (uncommon side effects - affect less than 1 in 100 users):
  • 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 taking MINIRIN Tablets.

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 MINIRIN Tablets contains

Active ingredient
(main ingredient)
desmopressin acetate
Other ingredients
(inactive ingredients)
  • povidone
  • lactose monohydrate
  • potato starch
  • magnesium stearate
Potential allergenscontains sugars as lactose

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

What MINIRIN Tablets looks like

MINIRIN Tablets are supplied in bottles of 30 tablets.

MINIRIN Tablets 200 micrograms are white, round and convex tablets with a single score and marked '0.2' on one side. (AUST R 93731).

Who distributes MINIRIN Tablets

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 August 2023.

AU-MN-2300002_v.2.0

Published by MIMS October 2023

BRAND INFORMATION

Brand name

Minirin Tablets

Active ingredient

Desmopressin

Schedule

S4

 

1 Name of Medicine

Desmopressin acetate.

2 Qualitative and Quantitative Composition

Minirin Tablets contain desmopressin (present as the hydrated acetate with variable amounts of acetic acid and water), a synthetic structural analogue of the natural pituitary hormone arginine vasopressin. The difference lies in the desamination of cysteine and substitution of L-arginine by D-arginine.
Desmopressin free base represents 89% of the desmopressin acetate content. This is due to the difference in molecular weight as well as the presence of acetic acid/ acetate, water and impurities.
Desmopressin acetate is a white, fluffy powder, soluble in water, in alcohol and in glacial acetic acid.

Excipient with known effect.

Contains sugars as lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Minirin Tablets 100 microgram desmopressin (as desmopressin acetate). White, oval and convex tablets with a single score and marked "0.1" on one side.
Minirin Tablets 200 microgram desmopressin (as desmopressin acetate). White, round and convex tablets with a single score and marked "0.2" on one side.

4 Clinical Particulars

4.1 Therapeutic Indications

Minirin Tablets are indicated for the treatment of:
cranial diabetes insipidus;
primary nocturnal enuresis in patients from 6 years of age with normal ability to concentrate urine, who are refractory to an enuresis alarm or in whom an enuresis alarm is contraindicated or inappropriate.

4.2 Dose and Method of Administration

There is no predictable dose equivalence between intranasal and oral dosing, so individual dose titration is needed. If adequate clinical effect is not achieved within 4 weeks following appropriate dose titration, the medication should be discontinued.

For ADH sensitive cranial diabetes insipidus.

Dosage is individualised in diabetes insipidus but clinical experience has shown that the total daily dose normally lies in the range of 200 microgram to 1,200 microgram. A suitable starting dose in adults and children is 100 microgram three times daily. The dosage regimen should then be adjusted in accordance with the patient's response. For the majority of patients, the maintenance dose is 100 microgram to 200 microgram three times daily.
In the event of signs of water retention/ hyponatraemia, treatment should be interrupted and the dose should be adjusted (see Section 4.4 Special Warnings and Precautions for Use).

Primary nocturnal enuresis.

The recommended initial dose is 200 microgram at bedtime. If this dose is not sufficiently effective, the dose may be increased up to 400 microgram. Fluid intake must be limited to a minimum from 1 hour before until 8 hours after administration.
In the event of signs or symptoms of water retention and/or hyponatraemia (headache, nausea/ vomiting, weight gain and, in severe cases, convulsions) treatment should be interrupted until the patient has fully recovered. When restarting treatment, strict fluid restriction should be enforced (see Section 4.4 Special Warnings and Precautions for Use).
Minirin Tablets are intended for treatment periods of up to 3 months. The need for continued treatment should be reassessed by means of a period of at least one week without Minirin Tablets.

4.3 Contraindications

Habitual or psychogenic polydipsia (resulting in a urine production exceeding 40 mL/kg/24 hours).
A history of known or suspected cardiac insufficiency and other conditions requiring treatment with diuretics.
Moderate and severe renal insufficiency (creatinine clearance below 50 mL/min).
Known hyponatraemia.
Syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Hypersensitivity to desmopressin acetate or any of the excipients of Minirin Tablets.

4.4 Special Warnings and Precautions for Use

When used for primary nocturnal enuresis, the fluid intake must be limited to a minimum from 1 hour before administration, until the next morning (at least 8 hours) after administration. Treatment without concomitant reduction of fluid intake may lead to water retention and/or hyponatraemia with or without accompanying warning signs and symptoms (headache, nausea/ vomiting, weight gain and, in severe cases, convulsions). In the event of signs or symptoms of water retention and/or hyponatraemia (headache, nausea/ vomiting, weight gain, and, in severe cases, convulsions) treatment should be interrupted until the patient has fully recovered. When restarting treatment, strict fluid restriction should be enforced. All patients and, when applicable, their guardians, should be carefully instructed to adhere to the fluid restrictions. In the event of signs of water retention/ hyponatraemia in cranial diabetes insipidus patients, treatment should be interrupted and the dose should be adjusted.
This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Severe bladder dysfunction and outlet obstruction should be considered before starting treatment for primary nocturnal enuresis.
Caution should be exercised in patients with other causes of urinary frequency (e.g. multiple sclerosis or urge incontinence), and in diabetes mellitus and renal impairment, since the use of desmopressin has not been well studied in these populations.
Elderly patients and patients with low serum sodium levels may have an increased risk of hyponatraemia (see Use in the elderly).
Precautions to avoid hyponatraemia must be taken in:
conditions characterised by fluid and/or electrolyte imbalances (such as systemic infections, fever and syndrome of inappropriate ADH secretion (SIADH)) (see Section 4.3 Contraindications);
conditions requiring concomitant treatment with diuretic agents;
concomitant treatment with drugs known to induce SIADH (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.3 Contraindications) including careful attention to fluid restrictions and more frequent monitoring of serum sodium;
concomitant treatment with NSAIDs (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Treatment with desmopressin should be interrupted during acute intercurrent illness characterised by fluid and/or electrolyte imbalance (such as systemic infections, fever, gastroenteritis).
Precautions must be taken in patients at risk of increased intracranial pressure.
For each approved indication the lowest effective dose should be used. Patient dosage should be reassessed periodically.
Minirin Tablets should be used with caution in patients with cardiovascular disease and the elderly.
Minirin Tablets should not be administered to dehydrated or overhydrated patients until water balance has been adequately restored.
The risk of overhydration including cardiac failure should be borne in mind, especially in children or the elderly or in chronic use.
Minirin Tablets should be used with caution in patients with cystic fibrosis because of impaired water handling and increased risk of hyponatraemia.

Use in the elderly.

The initiation of treatment in patients over 65 years of age is not recommended. Should physicians decide to initiate Minirin treatment in these patients then serum sodium should be measured before beginning the treatment and 3 days after initiation or dosage increase, and at other times during treatment as deemed necessary by the treating physician.

Paediatric use.

Dose recommendations are the same as in adults. Children should be closely observed to avoid overingestion of fluid and to ensure that only the recommended dose of Minirin Tablet is taken.

Effects of laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

NSAIDs may induce water retention/ hyponatraemia (see Section 4.4 Special Warnings and Precautions for Use).
Substances which are known to release antidiuretic hormone, e.g. tricyclic antidepressants, selective serotonin reuptake inhibitors, chlorpromazine and carbamazepine, as well as some antidiabetics of the sulfonylurea group particularly chlorpropamide may cause an additive antidiuretic effect leading to an increased risk of water retention/ hyponatraemia.
Concomitant treatment with loperamide may result in a 3-fold increase of desmopressin plasma concentrations, which may lead to an increased risk of water retention/ hyponatraemia. Although not investigated, other drugs slowing intestinal transport might have the same effect.
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.
A standardised 27% fat meal significantly decreased absorption (rate and extent) of oral desmopressin. No significant effect was observed with respect to pharmacodynamics (urine production or osmolality). Food intake may reduce the intensity and duration of the antidiuretic effect at low oral doses of desmopressin.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Fertility studies have not been done. 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.
(Category B2)
Data on a limited number (n = 53) of exposed pregnancies in women with diabetes insipidus as well as data on a limited number (n = 54) of exposed pregnancies in women with von Willebrand disease 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.
However, these findings are based on case report data and should be interpreted with caution. No reproduction study has been conducted in animals using oral administration. Studies performed in rats and rabbits with cutaneous doses up to 50 nanogram/kg/day and 10 microgram/kg/day, respectively, revealed no evidence for a harmful effect on the fetus.
Caution should be exercised when prescribing to pregnant women.
No study has been conducted in animals to examine the effects of desmopressin on postnatal development.
There have been no controlled studies in nursing mothers. In a single dose study in 6 lactating women administered 300 microgram desmopressin intranasally, the concentration of desmopressin was less in breast milk than in plasma. However, until further evidence is available for its safe use during lactation, desmopressin should not be used in breastfeeding mothers.

4.7 Effects on Ability to Drive and Use Machines

Minirin Tablets has no or negligible influence on the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

Treatment with and without concomitant reduction of fluid intake may lead to water retention/ hyponatraemia with or without accompanying warning signs and symptoms (headache, nausea/ vomiting, weight gain, and in severe cases, convulsions). The risk appears to be dose related and the elderly (> 60 years) are at increased risk.
The most serious adverse reaction with desmopressin is hyponatraemia, which may cause headache, abdominal pain, nausea, vomiting, weight increase, dizziness, confusion, malaise, memory impairment, vertigo, falls and in severe cases convulsions and coma. The cause of the potential hyponatraemia is the anticipated antidiuretic effect. The hyponatraemia is reversible and in children it is often seen to occur in relation to changes in daily routines affecting fluid intake and/or perspiration. In both adults and children special attention should be paid to the precautions addressed, see Section 4.4 Special Warnings and Precautions for Use.

Clinical trials.

Cranial diabetes insipidus.

During clinical trials with desmopressin in diabetes insipidus the following adverse events have been reported more than once: headache, cold, weight gain, dizziness, sore throat and depressed mood.

Primary nocturnal enuresis.

Adverse events experienced by at least 2% of exposed patients in CESE (clinical study of Minirin Tablets for PNE) (see Table 1).
Based on the frequency of adverse drug reactions reported in clinical trials with oral desmopressin conducted in children and adolescents for treatment of primary nocturnal enuresis (N = 1923), the following adverse events have been listed, see Table 2.

Post marketing experience.

Table 3 lists additional adverse drug reactions reported in the post marketing period in children, adolescents and adults treated with oral desmopressin, distributed by organ class. The frequency of adverse drug reactions occurring in the post marketing period is regarded as unknown.

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 http://www.tga.gov.au/reporting-problems.

4.9 Overdose

Overdose of Minirin Tablets leads to a prolonged duration of action with an increased risk of water retention and hyponatraemia.
Although the treatment of hyponatraemia should be individualised, the following general recommendations can be given. Hyponatraemia is treated by discontinuing the desmopressin treatment, fluid restriction and symptomatic treatment if needed.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Pharmacotherapeutic group: vasopressin and analogues.
Compared to vasopressin, desmopressin has a considerably longer duration of action and a complete lack of pressor effect in the dosages clinically used.

Clinical trials.

Cranial diabetes insipidus.

Results of 9 published studies in 163 patients demonstrated that diabetes insipidus patients can successfully switch from intranasal to oral treatment. No data are available to suggest that there is an advantage for the oral route over the intranasal dose form although there is a patient preference for the oral form. There is no predictable dose equivalence between intranasal and oral dosing, so individual dose titration is needed (see Section 4.2 Dose and Method of Administration).

Primary nocturnal enuresis.

Two double blind, randomised, placebo controlled studies (RG-84063-607 and RG-84063-609) were conducted in 340 patients, aged 5 to 17 years, with primary nocturnal enuresis. A total of 329 patients were evaluated for efficacy. Patients were evaluated over a two week baseline period followed by a fixed dose response phase during which patients were randomly assigned to receive 200, 400 or 600 microgram of Minirin or placebo for either two weeks (RG-84063-607) or six weeks (RG-84063-609). The primary efficacy variable for both studies was the mean reduction from baseline in the number of wet nights during the final two weeks of treatment (see Table 4 for results).
Study RG-84063-607 differed in that patients could subsequently enter an ascending dose titration period lasting up to 8 weeks in which patients were randomised to receive either 200 microgram of Minirin or placebo. Patients who were not completely dry at the end of two weeks had their study medication increased in increments of 1 (200 microgram) tablet. If required, this titration was repeated at 2 weekly intervals to a maximum of 3 tablets (see Table 5 for results). Whilst some patients treated with 200 microgram/day and 400 microgram/day of Minirin were completely dry after two weeks, the majority were not and required titration to 600 microgram/day.
An uncontrolled long-term study (45A06-62 CESE) was conducted in 294 patients, aged 6-18 years. Those patients (n = 256) with a minimum of 10 wet nights during a 28 day observation period were treated with 200 microgram/day Minirin for a period of 2 weeks. Those achieving a ≥ 90% reduction in the number of wet nights (full response) compared to the observation period were treated for 12 weeks at 200 microgram Minirin. The remaining patients were titrated to 400 microgram/day Minirin for a further 2 weeks and, if they achieved ≥ 50% reduction in the number of wet nights, were then treated for 12 weeks at this dose. The other patients were withdrawn from the study. 16 of 253 (6.3%) patients receiving 200 microgram Minirin achieved a ≥ 90% reduction in the number of wet nights (full response). 237 patients received 400 microgram Minirin of whom 107 achieved a ≥ 50% reduction in the number of wet nights.
Patients were treated for a year, treatment being stopped for 7 days every 12 week period to allow assessment of the patients for spontaneous remission.
During the 4 blocks of 12 weeks treatment, 24 to 34% of the patients achieved a > 90% reduction in the number of wet nights (full response) and 41-51% of the patients achieved a ≥ 50% reduction in the number of wet nights (responder).

5.2 Pharmacokinetic Properties

Absorption.

The absolute bioavailability of orally administered Minirin 200 microgram tablets is approximately 0.08% (range 0.029-0.115%). Mean maximum plasma concentration is reached within 2 hours. Desmopressin exhibits a moderate to high variability in bioavailability, both within and between subjects. The bioequivalence of the 200 and 400 microgram Minirin Tablets has not been established.
Concomitant intake of food decreases the rate and extent of absorption of Minirin 200 microgram tablets, administered at a dose of 400 microgram, by > 40%. No significant effect was observed with respect to pharmacodynamics (urine production or osmolality) (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Distribution.

The distribution volume is 0.2-0.37 L/kg. Desmopressin does not cross the blood brain barrier.

Metabolism.

The oral terminal half-life varies between 2.0 and 3.21 hours. In vitro in human liver microsome preparations, it has been shown that no significant amount of desmopressin is metabolised in the liver, and thus human liver metabolism in vivo is not likely to occur.

Elimination.

After iv injection 45% of the amount of desmopressin could be recovered in the urine within 24 hours.
No gender related differences in desmopressin pharmacokinetics have been observed.

5.3 Preclinical Safety Data

Genotoxicity.

The genotoxic potential of desmopressin has not been adequately investigated, although in vitro studies in bacterial and mammalian cells revealed no mutagenicity of the drug.

Carcinogenicity.

The carcinogenic and mutagenic potentials of desmopressin have not been investigated in preclinical studies.

6 Pharmaceutical Particulars

6.1 List of Excipients

Minirin Tablets contain lactose monohydrate, potato starch, povidone and magnesium stearate as excipients.

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 below 25°C. Keep the container tightly closed and do not remove the desiccant capsule from the pack.

6.5 Nature and Contents of Container

Minirin Tablets are available in bottles of 30 tablets. Not all strengths are being distributed in Australia.

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

Chemical structure.


Synonyms of desmopressin: DDAVP.
1-desamino-8-d-arginine vasopressin.
Desamino cys-1-d-arginine-8 vasopressin.

CAS number.

(Base): 16679-58-6.
Molecular weight (base): 1069.22.

7 Medicine Schedule (Poisons Standard)

(S4) Prescription Only Medicine.

Summary Table of Changes