DESMOSPRAY Nasal spray, solution Ref.[49934] Active ingredients: Desmopressin

Special warnings

Use of the product should be under specialist supervision with appropriate facilities available for monitoring and interpretation of responses.

Desmospray should be used with caution in:

• Very young and elderly patients,
• Conditions characterised by fluid and/or electrolyte imbalance,
• Patients at risk for increased intracranial pressure

Desmospray should only be used in patients where orally administered formulations are not feasible.

When Desmospray is prescribed it is recommended

• To start at the lowest dose
• To ensure compliance with fluid restriction instructions
• To increase dose progressively, with caution
• To ensure that in children, administration is under adult supervision in order to control the dose intake.

When used for the treatment of nocturia associated with multiple sclerosis, fluid intake must be limited to a minimum from 1 hour before until 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).

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

Patients should be warned to avoid ingesting water while swimming.

When Desmospray is used in the treatment of nocturia associated with multiple sclerosis, periodic assessments should be made of blood pressure and weight to monitor the possibility of fluid overload.

All patients and, when applicable, their guardians should be carefully instructed to adhere to the fluid restrictions.

When used for diagnostic purposes the fluid intake must be limited to a maximum of 0.5 L to quench thirst from 1 hour before until 8 hours after administration. Renal concentration capacity testing in children below the age of 1 year should only be performed in hospital and under careful supervision.

Precautions

Severe bladder dysfunction and outlet obstruction should be considered before starting treatment with desmopressin.

Precautions to avoid hyponatraemia, including careful attention to fluid restriction and more frequent monitoring of serum sodium, must be taken in case of concomitant treatment with drugs, which are suspected to induce SIADH e.g. tricyclic antidepressants, selective serotonine reuptake inhibitors, chlorpromazine, carbamazepine, and some antidiabetics of the sulfonylurea group particularly chlorpropamide, and in case of concomitant treatment with NSAIDs.

Infants, elderly and patients with serum sodium levels in the lower range of normal may have an increased risk of hyponatraemia. Treatment with desmopressin should be interrupted or carefully adjusted during acute intercurrent illness characterised by fluid and/or electrolyte imbalance (such as systemic infections, fever, and gastroenteritis).

Precautions must be taken in patients at risk for increased intracranial pressure.

Desmopressin should be used with caution in patients with conditions characterised by fluid and/or electrolyte imbalance.

There is some evidence from post-marketing data for the occurrence of severe hyponatraemia in association with the nasal spray formulation of desmopressin when it is used in the treatment of central diabetes insipidus.

Due to the presence of benzalkonium chloride this product may cause bronchospasm.

Substances, which are known to induce SIADH, e.g., tricyclic antidepressants, selective serotonine 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 fluid retention/hyponatraemia (see section 4.4).

NSAIDs may induce fluid retention/hyponatraemia (see section 4.4).

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.

Pregnancy

Published data on a limited number of exposed pregnancies in women with diabetes insipidus (n=53) and in women with known bleeding complications (n=216) indicate no adverse effects of desmopressin on pregnancy or on the health of the foetus/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, embryonal/foetal development, parturition or postnatal development.

Caution should be exercised when prescribing to pregnant women.

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.

Breast-feeding

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

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

Summary of the safety profile

The most serious adverse reaction with desmopressin is hyponatraemia, which may cause headache, nausea, vomiting, decreased serum sodium, weight increase, malaise, abdominal pain, muscle cramps, dizziness, confusion, decreased consciousness and in severe cases convulsions and coma.

The majority of other events are reported as non-serious.

The most commonly reported adverse reactions during treatment were nasal congestion (27%), high body temperature (15%), and rhinitis (12%). Other common adverse reactions were headache (9%), upper respiratory tract infection (9%), gastroenteritis (7%), abdominal pain (5%). Anaphylactic reactions have not been seen in clinical trials but spontaneous reports have been received.

Tabulated summary of adverse reactions

The below table is based on the frequency of adverse drug reactions reported in clinical trials with nasal desmopressin, conducted in children and adults for treatment of CDI, PNE and RCCT (N=745), combined with the post-marketing experience for all indications. Reactions only seen in post-marketing or in other desmopressin formulations have been added in the ‘Not known’ frequency column.

^* Reported in connection with hyponatraemia
^** Reported primarily in children and adolescents
^*** Reported in the CDI indication

Description of selected adverse reactions

The most serious adverse reaction with desmopressin is hyponatraemia, and in severe cases its complications, i.e. convulsions and coma. The cause of the potential hyponatraemia is the anticipated antidiuretic effect.

Paediatric population

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 children special attention should be paid to the precautions addressed in section 4.4.

Other special populations

Infants, 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).

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517; Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

Not applicable.