PRODUCT SUMMARY

1. NAME OF THE MEDICINAL PRODUCT DDAVP®/Desmopressin Intranasal Solution

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Desmopressin acetate 0.01% w/v

3.    PHARMACEUTICAL FORM

Aqueous solution for intranasal administration

4.    CLINICAL PARTICULARS

4.1.    Therapeutic Indications

DDAVP®/Desmopressin Intranasal Solution is indicated for :

1)    The diagnosis and treatment of vasopressin-sensitive cranial diabetes insipidus.

2)    The treatment of nocturia associated with multiple sclerosis where other treatments have failed.

3)    Establishing renal concentration capacity.

4.2.    Posology and Method of Administration

Treatment of Diabetes Insipidus:

Dosage is individual but clinical experience has shown that the average maintenance doses are as follows :

Adults: 10 to 20 micrograms once or twice daily.

Elderly: 10 to 20 micrograms once or twice daily.

Children: 5 to 20 micrograms daily, (a lower dose may be required for infants).

Diagnosis of Diabetes Insipidus:

The diagnostic dose in adults and children is 20 micrograms. Failure to elaborate a concentrated urine after water deprivation, followed by the ability to do so after the administration of Desmopressin confirms the diagnosis of cranial diabetes insipidus. Failure to concentrate after the administration suggests nephrogenic diabetes insipidus.

Treatment of nocturia:

For multiple sclerosis patients up to 65 years of age with normal renal function suffering from nocturia the dose is 10 to 20 micrograms at bed time. Not more than one dose should be used in any 24 hour period.

Renal Function Testing:

To establish renal concentration capacity, the following single doses are recommended:

Adults: 40 micrograms

Elderly: 40 micrograms

Children (1 - 15 years): 20 micrograms

Infants (to 1 year): 10 micrograms

Adults and children with normal renal function can be expected to achieve concentrations above 700mOsm/kg in the period of 5-9 hours following administration of DDAVP®/Desmopressin Intranasal Solution. It is recommended that the bladder should be emptied at the time of administration.

In normal infants a urine concentration of 600mOsm/kg should be achieved in the 5 hour period following the administration of DDAVP®/Desmopressin Intranasal Solution. The fluid intake at the two meals following the administration should be restricted to 50% of the ordinary intake in order to avoid water overload.

4.3. Contra-Indications

DDAVP®/Desmopressin Intranasal Solution is contraindicated in cases of:

-    cardiac insufficiency and other conditions requiring treatment with diuretic agents

-    hypersensitivity to the preservative

Before prescribing DDAVP^®/Desmopressin Intranasal the diagnoses of psychogenic polydipsia and alcohol abuse should be excluded.

When used to control nocturia in patients with multiple sclerosis, Desmopressin should not be used in patients with hypertension or cardiovascular disease.

Desmopressin should not be prescribed to patients over the age of 65 for the treatment of nocturia associated with multiple sclerosis.

4.4. Special Warnings and Special Precautions for Use

Care should be taken with patients who have reduced renal function and/or cardiovascular disease or cystic fibrosis.

When DDAVP^®/Desmopressin Intranasal Solution is used for the treatment of nocturia associated with multiple sclerosis, fluid intake must be limited from 1 hour before until 8 hours after administration. Periodic assessments should be made of blood pressure and weight to monitor the possibility of fluid overload.

When used for diagnostic purposes, fluid intake must be limited and not exceed 0.5 litres from 1 hour before until 8 hours after administration.

Following diagnostic testing for diabetes insipidus or renal concentration, care should be taken to prevent fluid overload. Fluid should not be forced, orally or parenterally, and patients should only take as much fluid as they require to satisfy thirst.

Precautions to prevent fluid overload must be taken in:

-    conditions characterised by fluid and/or electrolyte imbalance

-    patients at risk for increased intracranial pressure

Renal concentration capacity testing in children below the age of 1 year should only be performed under carefully supervised conditions in hospital.

4.5. Interaction with other Medicinal Products and other Forms of Interaction

Substances which are known to induce SIADH e.g. tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine and carbamazepine, may cause an additive antidiuretic effect leading to an increased risk of water retention and/or hyponatraemia.

NSAIDs may induce water retention and/or hyponatraemia.

4.6. Pregnancy and Lactation

Pregnancy:

Data on a limited number (n=53) of exposed pregnancies in women with diabetes insipidus indicate rare cases of malformations in children treated during pregnancy. To date, no other relevant epidemiological data are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development.

Caution should be exercised when prescribing to pregnant women. Blood pressure monitoring is recommended due to the increased risk of preeclampsia.

Lactation:

Results from analyses of milk from nursing mothers receiving high dose Desmopressin (300 micrograms intranasally) indicate that the amounts of Desmopressin that may be transferred to the child are considerably less than the amounts required to influence diuresis.

4.7. Effects on Ability to Drive and Use Machines

None.

4.8 Undesirable effects

Side-effects include headache, stomach pain, nausea, nasal congestion, rhinitis and epistaxis. Isolated cases of allergic skin reactions and more severe general allergic reactions have been reported. Very rare cases of emotional disorders including aggression in children have been reported. Treatment with Desmopressin without concomitant reduction of fluid intake may lead to water retention/hyponatraemia with accompanying symptoms of headache, nausea, vomiting, weight gain, decreased serum sodium and in serious cases, convulsions.

4.9. Overdose

An overdose of DDAVP®/Desmopressin Intranasal Solution leads to a prolonged duration of action with an increased risk of water retention and/or hyponatraemia.

Treatment:

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.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic Properties

Desmopressin is a structural analogue of vasopressin, with two chemical changes namely desamination of the N-terminal and replacement of the 8-L-Arginine by 8-D-Arginine. These changes have increased the antidiuretic activity and prolonged the duration of action. The pressor activity is reduced to less than 0.01% of the natural peptide as a result of which side-effects are rarely seen.

5.2. Pharmacokinetic Properties

Following intranasal administration, the bioavailability of Desmopressin is of the order of 10%.

Pharmacokinetic parameters following intravenous administration were reported as follows:

Total clearance : 2.6ml/min/kg body weight.

T/ : 55 mins

Plasma kinetics of DDAVP in man H .Vilhardt, S. Lundin, J. Falch.

Acta Pharmacol. ET. Toxicol. 1986, 58, 379-381

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.

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.

5.3. Pre-clinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to those already included in other sections of the SPC.

6. PHARMACEUTICAL PARTICULARS 6.1. List of Excipients

Sodium Chloride BP Chlorobutanol EP

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

28th April 1997

DATE OF REVISION OF THE TEXT

04/11/2015