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MELT AWAY THE MISERY OF BEDWETTING

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120mcg and 240mcg oral lyophilisate

desmopressin (as acetate)



MELT AWAY THE MISERY OF BEDWETTING





Prescribing information is available on the last page. This item is intended for Healthcare Professionals only.

Date of preparation: June 2011. DN/379/2011/UK

Children who wet the bed frequently (twice a week or more)

are more likely to continue through childhood.1



The ALSPAC questionnaire-based observational longitudinal study

(large UK population study) showed that:

– at age 7.5 years, while 15.5% of children wet the bed,

only 2.6% wet twice per week or more*3

– children (aged 5 years and older) wetting at least twice per week

were more likely to continue than those wetting infrequently 1









*It is estimated that, at any time, there could be around 140 -150,000 5-19 year olds who wet the bed at least twice per week

(based on a 15% spontaneous remission rate).3-6 This equates to about 3-4 children per GP in the UK.









Prescribing information is available on the last page. This item is intended for Healthcare Professionals only.

Date of preparation: June 2011. DN/379/2011/UK

A questionnaire-based observational study by Yeung et al showed 2:

– The proportion of enuretic children with severe bedwetting

increases with age

– 82% of adolescents (over 10 years) with PNE wet the bed

3 or more times per week



Severity of PNE versus age 2

<3 wet nights/week



3-6 wet nights/week



7 wet nights/week

14.3%



10.3%





30% 55.7%

48.3% 41.4%









n=70 n=29



Age 5 Age 19

Adapted from Yeung et al, 20062





The findings suggest that enuretic children with more severe

symptoms (≥3 episodes per week) probably have a significantly

greater chance of persistent PNE in adult life 2









It is important that

children suffering with

PNE are identified early,

and are offered an

appropriate treatment

intervention 1,2,7









Prescribing information is available on the last page. This item is intended for Healthcare Professionals only.

Date of preparation: June 2011. DN/379/2011/UK

8-12

PNE – A DISTRESSING CONDITION

PNE can be distressing for children8-12



Children may suffer low self esteem, anxiety, sadness or

depression, avoid socialisation and become withdrawn 8 -10



If low self esteem persists over years, psychological and/or

psychiatric dysfunction is more likely to occur 8



Research has suggested that bedwetting children experience

more light sleep associated with frequent cortical arousal but

an inability to awake completely 12



Children may not be able to, or choose not to, express how

they feel 10



PNE can be distressing for parents9,13,14



Parents endure extra workload and expense13,14



Parents may become irritable and intolerant,13,14 and may

respond inappropriately to their child 9,14









Prescribing information is available on the last page. This item is intended for Healthcare Professionals only.

Date of preparation: June 2011. DN/379/2011/UK

DESMOPRESSIN IN PNE

It is important to acknowledge that PNE is multi-factorial 15



Treating early may help to minimise the negative psychological

impact of unresolved PNE 1,8



Better treatment outcomes are achieved when both the child

and the parents have been involved in the decision about

treatment choice 16



PNE can occur when the night time increase in plasma

vasopressin levels is insufficient 17



Plasma vasopressin levels Urinary excretion rates



3.5 Non-enuretic 80 Non-enuretic

* Enuretic Enuretic

Plasma vasopressin levels (pg/ml)









3.0 70

*p<0.025

Urinary excretion rate (ml/hr)









*p<0.001

2.5 non-enuretic vs enuretic 60

enuretic vs non-enuretic

subjects at night

subjects at night

2.0

50 *

40

1.5

30

1.0

20



0.5

10



0.0 0

DAY NIGHT DAY NIGHT







Rittig S. et al. 1989 17







Desmopressin mimics the natural nocturnal anti-diuretic

effect of vasopressin – helping to normalise urinary output

at night 5,18



Long term treatment does not affect the

child’s own vasopressin secretion 19





Desmopressin

is suitable for use

in children of

5 years and over









Prescribing information is available on the last page. This item is intended for Healthcare Professionals only.

Date of preparation: June 2011. DN/379/2011/UK

DESMOMELT – SPECIFICALLY

DESIGNED WITH CHILDREN IN MIND

Children may find tablets difficult to swallow 11



A randomised crossover study in 221 children and

adolescents with PNE compared the Melt with the tablet

formulation of oral desmopressin, and concluded that: 11



Significantly more children aged 5-11 years preferred the

Melt formulation to the tablet (p=0.0089)



Encourages compliance11



Compliance was numerically greater in patients receiving

DesmoMelt than those receiving the tablet formulation





Non-compliance with therapy (<80%, safety population)11

10 9.5







8

% of subjects









6

4.6



4





2 p=NS

Melt

0 Tablet

Melt (n=219) Tablet (n=220)



Persson B-E et al. 200611 All randomised patients (n=221) with available data.









Prescribing information is available on the last page. This item is intended for Healthcare Professionals only.

Date of preparation: June 2011. DN/379/2011/UK

DESMOMELT 120MCG – EQUIVALENT ®



EFFICACY TO DESMOTABS 0.2MG 11,20

WITH LOWER DOSES

Clinically equivalent



A recent study involving over 200 patients compared

DesmoMelt with Desmotabs, and showed efficacy was similar

for the two formulations 11



During a 6 month study, 70 -76% of children taking

Desmopressin improved 21



Desmopressin efficacy continued or improved throughout

the treatment period 22









DesmoMelt is

preferred to tablets,

particularly by younger

children, and is the

11







most widely prescribed

form of desmopressin

23

in new patients









120mcg and 240mcg oral lyophilisate

desmopressin (as acetate)



MELT AWAY THE MISERY OF BEDWETTING





Prescribing information is available on the last page. This item is intended for Healthcare Professionals only.

Date of preparation: June 2011. DN/379/2011/UK

DESMOMELT – SAFETY IS 5

MAINTAINED LONG-TERM

Greater bioavailabilty means DesmoMelt provides equivalent

efficacy and safety to Desmotabs at a lower dose 20



In a review of 9 trials, patients did not develop a tolerance

to desmopressin5



Long term treatment with desmopressin did not cause any

clinically significant changes in haematology, biochemistry,

blood pressure or endogenous ADH secretion5



Incidence of adverse events considered to be treatment-

related in 1,083 patients treated for six months or more

with oral or nasal desmopressin5





Headache 2% Other 3%

None 95% n=1,083









Van Kerrebroeck PEV. 2002 5









Prescribing information is available on the last page. This item is intended for Healthcare Professionals only.

Date of preparation: June 2011. DN/379/2011/UK

DESMOMELT – MAY BE USED

LONG-TERM

DesmoMelt may be used for as long as symptoms persist



The need for continued treatment should be assessed at

three monthly intervals, with at least one week off treatment

to see if symptoms return. Recommence if necessary



DesmoMelt dosing 24







INCREASING

ONLY IF OR

NECESSARY TO





1 x 120mcg 1 x 240mcg

at bedtime



2 x 120mcg

at bedtime





No unpleasant taste



Dissolves under the tongue



Rapidly dissolving formulation makes it difficult to spit out



DesmoMelt avoids the need for additional water

intake just before bedtime



DesmoMelt can be

used for as long as

symptoms persist –

reassess every

3 months (minimum

one week off treatment

to see if symptoms

24

return)









Prescribing information is available on the last page. This item is intended for Healthcare Professionals only.

Date of preparation: June 2011. DN/379/2011/UK

IMPORTANT SAFETY INFORMATION

Desmopressin Nasal Spray: Removal of the Primary Nocturnal Enuresis Indication



The indication for the treatment of primary nocturnal enuresis (PNE) was removed in 2006

from all spray products. Desmospray remains available for the treatment of patients with

cranial diabetes insipidus or nocturia associated with multiple sclerosis. In comparison

with oral formulations of desmopressin, nasal forms were associated with the majority of

serious adverse drug reactions (ADRs) reported in patients with PNE. Rare, serious ADRs

included hyponatraemia, water intoxication and convulsions. As the risk benefit profile of

the oral formulations is more favourable than the nasal spray, the nasal form should no

longer be used for the treatment of PNE in adults and children.



Prescribing Advice

Patients may complete their current course of treatment with desmopressin nasal spray.

At their next routine review, patients needing continued treatment should only be prescribed

an oral form of desmopressin. Regardless of the dose of spray they have been taking, all

patients starting treatment with oral desmopressin should start at the lower recommended

dose, which should only be increased if necessary to achieve control of symptoms.



Further Information

Desmopressin is a synthetic analogue of vasopressin with increased antidiuretic activity

and a prolonged duration of action in comparison with the natural peptide. The nasal spray

has greater bioavailability than the oral formulations. Both forms produce a sustained

decrease in urine output and a decrease in plasma osmolality which can result in

hyponatraemia and water intoxication in the presence of an inappropriate fluid intake.

Hyponatraemia is a rare but serious ADR. Symptoms have been reported at a rate of

approximately 15 cases per 100,000 patient years of exposure for nasal formulations

and 6 cases per 100,000 patient years for oral formulations, and has been predominantly

associated with overdose, excessive fluid intake or inappropriate use. It is not known

whether these adverse effects are dose-related but there is strong evidence of a

relationship to the formulation. Since the majority of cases of hyponatraemia occurred

with the nasal formulation in the PNE indication, only oral formulations should be used

in PNE. The risk of hyponatraemia occurring with oral desmopressin can be further reduced

by closely following the advice in the Summary of Product Characteristics (SPC) and the

Patient Information Leaflet (PIL).









Prescribing information is available on the last page. This item is intended for Healthcare Professionals only.

Date of preparation: June 2011. DN/379/2011/UK

Prescribing information is available on the last page. This item is intended for Healthcare Professionals only.

Date of preparation: June 2011. DN/379/2011/UK

Summary



It is important that children suffering with PNE are identified early, and are

offered treatment intervention1,2,7



Children who wet the bed at least twice a week or more at age 5 are more

likely to continue through childhood 1



Bedwetting children may suffer low self esteem, anxiety, sadness or

depression, avoid socialisation and become withdrawn8 -10



DesmoMelt is preferred to tablets, particularly by younger children11



DesmoMelt is suitable for use in patients of 5 years and over and can be

used for as long as symptoms persist – reassess every 3 months (minimum

one week off treatment to see if symptoms return). Recommence if necessary



Prescribing Information: DesmoMelt® 120 and 240 micrograms oral lyophilisate; Desmotabs® References: 1. Butler RJ & Heron J. Scan J Urol Neph 2008; 42: 257-64.

0.2mg. Please consult the full Summaries of Product Characteristics before prescribing. 2. Yeung CK et al. BJU Int 2006; 97: 1069-1073. 3. Butler RJ et al. BJU Int 2005;

Name of Product: DesmoMelt 120 micrograms oral lyophilisate; DesmoMelt 240 micrograms 96: 404-410. 4. Government Actuary’s Department, Population Projections 2006,

oral lyophilisate; Desmotabs 0.2mg; Composition: DesmoMelt: 120 or 240 micrograms of http://www.gad.gov.uk/Demography_Data/Population/2006/uk/wuk06singyear.xls (Accessed

desmopressin (as acetate). Desmotabs: 0.2mg desmopressin acetate. Indications: Treatment 2nd February 2009). 5. van Kerrerbroeck PEV. BJU Int 2002; 89: 420-425. 6. Forsythe WI,

of primary nocturnal enuresis (5 to 65 years of age). Dosage: Children and adults (5–65 years Redmond A. Arch Dis Child 1974; 49: 259-63. 7. Hjälmås K. Acta Paediatr 1997; 86: 919-22.

of age) with normal urine concentrating ability: DesmoMelt: Initial dose of 120 micrograms 8. Hägglöf B et al. Scand J Urol Nephrol 1997; 183: 79-82. 9. Warzak WJ. Clinical Pediatrics

sublingually at bedtime and only if needed should the dose be increased to 240 micrograms 1993; 38-40. 10. Joinson C et al. J Paed Psychol 2007; 32(5): 605-616. 11. Persson B-E et al.

sublingually. Desmotabs: Initial dose of one tablet (0.2mg) at bedtime and only if needed should 15th European Urology Winter Forum, Davos, Switzerland, February 11-15, 2006. Poster 13.

the dose be increased to two tablets (a total of 0.4mg). Fluid restriction should be observed. The 12. Yeung CK et al. NEJM 2008: 358; 2414-5. 13. Läckgren G et al. Acta Pediatr 1999; 88:

need for continued treatment should be reassessed after 3 months by means of a period of at 679-90. 14. Dobson P Nocturnal enuresis. Family Medicine; 2000; December: 15-17.

least 1 week without desmopressin. Contraindications: Cardiac insufficiency and other conditions .

15. Butler RJ & Holland P Scan J Urol Nephrol 2000; 34: 270-7. 16. Monda JM et al. J Urol

requiring treatment with diuretics, moderate and severe renal insufficiency. DesmoMelt and 1995; 154: 745-78. 17. Rittig S et al. Am J Physiol 1989; 256 (Renal fluid Electrolyte Physiol 25):

Desmotabs should only be used in patients with normal blood pressure and they should not F664-F671. 18. Lawless MR. Pediatrics in Review 2001; 22(12): 399-406. 19. Rew D, Rundle JSH.

be used in patients over the age of 65. Exclude diagnosis of psychogenic polydipsia or alcohol Br J Urol 1989; 63:352-353. 20. DOF. Source: Pharmacokinetic study. Ferring Pharmaceuticals.

abuse. Special Warnings and Precautions: Take care in patients with reduced renal function 21. Stenberg A, Läckgren G. Pediatrics 1994; 94(6): 841-846. 22. Lottmann H et al. Int J Clin

and/or cardiovascular disease or cystic fibrosis. Fluid intake must be limited to a minimum from Prac 2009: 63; 1, 35–45. 23. CSD Patient Data. Cegedim Strategic Data UK Ltd, 06/2007.

1 hour before until 8 hours after administration. Care should be taken to avoid ingesting water 24. DesmoMelt SmPC, January 2006. Ferring Pharmaceuticals Ltd. Further information

while swimming. Treatment with desmopressin should be interrupted during an episode of is available from: Ferring Pharmaceuticals Ltd., Drayton Hall, Church Road, West Drayton, UB7 7PS.

vomiting and/or diarrhoea until their fluid balance is once again normal. Precautions to prevent Main switchboard: 0844 931 0050. Main fax: 0844 931 0051. *DesmoMelt and Desmotabs are

fluid overload must be taken in: illnesses characterized by fluid and/or electrolyte imbalance; trademarks of Ferring BV.

patients at risk for increased intracranial pressure. Side Effects: Headache, stomach pain and

nausea. Isolated cases of allergic skin reactions and more severe general allergic reactions.

Very rare cases of emotional disturbances in children. Treatment with desmopressin without

concomitant reduction of fluid intake may lead to water retention/hyponatraemia with or without Adverse events should be reported. Reporting forms and information can be

accompanying warning symptoms of headache, nausea/vomiting, decreased serum sodium, found at www.yellowcard.gov.uk. Adverse events should also be reported to:

weight gain and in serious cases convulsions. Please consult the full Summaries of Product Medical Information, Ferring Pharmaceuticals Ltd., Drayton Hall, Church Road,

Characteristics for further information about side effects. Basic NHS Prices: DesmoMelt: West Drayton, UB7 7PS. Tel: 0844 931 0050. Email: medical@ferring.com

Carton containing 30 oral lyophilisates in blister strips. 30 x 120 micrograms £30.34.

30 x 240 micrograms £60.68. Desmotabs: Polyethylene bottle containing 30 tablets.

£29.43. Marketing Authorisation Number: DesmoMelt: 120 micrograms 03194/0094. 240

micrograms 03194/0095. Desmotabs: 03194/0046. Marketing Authorisation Holder: Ferring

Pharmaceuticals Ltd., Drayton Hall, Church Road, West Drayton, UB7 7PS. Legal Category: POM

Date of Preparation of Prescribing Information: May 2011. All trademarks registered to Ferring. www.urinecontrol.co.uk









120mcg and 240mcg oral lyophilisate

desmopressin (as acetate)



MELT AWAY THE MISERY OF BEDWETTING





Prescribing information is available on the last page. This item is intended for Healthcare Professionals only.

Date of preparation: June 2011. DN/379/2011/UK



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