DESMOPRESSIN MELT 120 MICROGRAMS ORAL LYOPHILISATE - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Desmopressin Melt 120 micrograms oral lyophilisate

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each unit contains 120 micrograms desmopressin (as acetate).

For excipients, see 6.1

3 PHARMACEUTICAL FORM

Oral lyophilisate

White, round, oral lyophilisate marked with two drop shaped figures on one side.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Desmopressin Melt is indicated for the treatment of primary nocturnal enuresis.

4.2 Posology and method of administration

Desmopressin Melt is for sublingual use.

Children (from 5 years of age) and adults (up to 65 years of age) with normal urine concentrating ability who have primary nocturnal enuresis should take 120 micrograms at bedtime administered sublingually and only if needed should the dose be increased to 240 micrograms sublingually.

The need for continued treatment should be reassessed after 3 months by means of a period of at least 1 week without Desmopressin Melt.

4.3 Contraindications

Desmopressin Melt is contraindicated in cases of cardiac insufficiency and other conditions requiring treatment with diuretic agents. Desmopressin Melt should only be used in patients with normal blood pressure.

Before prescribing Desmopressin Melt, the diagnoses of psychogenic polydipsia and alcohol abuse should be excluded.

Desmopressin should not be prescribed to patients over the age of 65 for the treatment of primary nocturnal enuresis.

4.4 Special warnings and precautions for use

Care should be taken with patients who have reduced renal function and/or cardiovascular disease or cystic fibrosis. In chronic renal disease the antidiuretic effect of Desmopressin Melt would be less than normal.

When Desmopressin Melt is used for the treatment of enuresis, fluid intake must be limited from 1 hour before until 8 hours after administration.

Patients being treated for primary nocturnal enuresis should be warned to avoid ingesting water while swimming and to discontinue Desmopressin Melt during an episode of vomiting and/or diarrhoea until their fluid balance is once again normal.

Precautions to prevent fluid overload must be taken in:

– conditions characterised by fluid and/or electrolyte imbalance

– patients at risk for increased intracranial pressure

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.

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 and/or hyponatraemia. Although not investigated, other drugs slowing intestinal transport might have the same effect.

A standardised 27% fat meal significantly decreased the absorption (rate and extent) of a 0.4mg dose of oral desmopressin tablets. Although it did not significantly affect the pharmacodynamic effect (urine production and osmolality) there is the potential for this to occur at lower doses. If a diminution of effect is noted, then the effect of food should be considered before increasing the dose.

4.6 Fertility, 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 pre-eclampsia.

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 and nausea. 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.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard.

4.9 Overdose

An overdose of Desmopressin Melt 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

Pharmacotherapeutic group: vasopressin and analogues

ATC code: H01B A02

In its main biological effects, desmopressin does not differ qualitatively from vasopressin. However, desmopressin is characterised by a high antidiuretic activity whereas the uterotonic and vasopressor actions are extremely low.

5.2 Pharmacokinetic properties

The overall mean systemic bioavailability of desmopressin administered sublingually as Melts at doses of 200, 400 and 800 micrograms is 0.25% with a 95% confidence interval of 0.21% – 0.31%. The Cmax was 14, 30 and 65pg/ml after administration of 200, 400 and 800 micrograms respectively. tmax was observed at 0.5 – 2.0 hours after dosing. The geometric mean terminal half-life is 2.8 (CV= 24%) hours.

Correlation table between desmopressin in Tablet and Melt forms:

Tablet Tablet Melt Melt

Desmopressin acetate Desmopressin

free base Desmopressin free base Desmopressin acetate 0.1mg 89 micrograms 60 micrograms Approx. 67 micrograms * 0.2mg 178 micrograms120 microgramsApprox. 135 micrograms * 0.4mg 356 micrograms240 microgramsApprox. 270 micrograms * *calculated for comparative purposes

The distribution volume of desmopressin after intravenous administration is 33 L (0.41 L/kg). Desmopressin does not cross the blood-brain barrier. Desmopressin exhibits a moderate to high variability in bioavailability, both within and between subjects. Concomitant use of food decreases the rate and extent of absorption by 40%.

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 Preclinical safety data

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

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Gelatin

Mannitol

Citric acid, anhydrous

6.2 Incompatibilities

Not applicable

6.3 Shelf life

48 months

6.4 Special precautions for storage

Store in the original package in order to protect from moisture and light

6.5 Nature and contents of container

PVC/Polyamide/A­luminium/Poly­amide/PVC blisters. Top foil consists of Paper/Polyester teraphthalate/A­luminium/heat seal lacquer. Strips of 10 oral lyophilisates in packs of 10, 30 and 100 oral lyophilisates.

Not all pack sizes may be marketed.