4.1. Therapeutic indications

DDAVP® /Desmopressin Injection is indicated as follows :1) Diagnosis and treatment of cranial diabetes insipidus.2) To increase Factor VIII:C and Factor VIII:Ag in patients with mild to moderate haemophilia or von Willebrand's disease undergoing surgery or following trauma.3) To establish renal concentration capacity.4) To treat headache resulting from a lumbar puncture.5) To test for fibrinolytic response.

4.2. Posology and method of administration

Treatment of Cranial Diabetes Insipidus:

By subcutaneous, intramuscular or intravenous injection.Adults:The usual dose is 1 to 4 micrograms given once daily.Children and infants:Doses from 0.4 micrograms (0.1ml) may be used. Diagnosis of Cranial Diabetes Insipidus:

The diagnostic dose in adults and children is 2 micrograms given by subcutaneous or intramuscular injection. Failure to elaborate a concentrated urine after water deprivation, followed by the ability to do so after the administration of Desmopressin confirms a diagnosis of cranial diabetes insipidus. Failure to concentrate after the administration suggests nephrogenic diabetes insipidus. Mild to moderate haemophilia and von Willebrand's disease:

By intravenous administration.The dose for adults, children and infants is 0.4 micrograms per kilogram body weight administered by intravenous infusion. Further doses may be administered at 12 hourly intervals so long as cover is required. As some patients have shown a diminishing response to successive doses, it is recommended that monitoring of Factor VIII levels should continue. The dose should be diluted in 50ml of 0.9% sodium chloride for injection and given over 20 minutes. This dose should be given immediately prior to surgery or following trauma. During administration of intravenous Desmopressin, vasodilation may occur resulting in decreased blood pressure and tachycardia with facial flushing in some patients.Increase of Factor VIII levels are dependent on basal levels and are normally between 2 and 5 times the pre-treatment levels. If results from a previous administration of Desmopressin are not available then blood should be taken pre-dose and 20 minutes post-dose for assay of Factor VIII levels in order to monitor response.Unless contraindicated, when surgery is undertaken, tranexamic acid may be given orally at the recommended dose from 24 hours beforehand until healing is complete. Renal Function Testing:

By subcutaneous or intramuscular injection.Adults and children can be expected to achieve urine concentrations above 700mOsm/kg in the period of 5 to 9 hours following a dose of 2 micrograms DDAVP® /Desmopressin Injection. 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 five hour period following a dose of 0.4 micrograms DDAVP® /Desmopressin Injection. The fluid intake at the two meals following the administration should be restricted to 50% of the ordinary intake to avoid water overload. Post Lumbar Puncture Headache:

By subcutaneous or intramuscular injection.Where a headache is thought to be due to a lumbar puncture, an adult patient can be given a dose of 4 micrograms DDAVP® /Desmopressin Injection which may be repeated 24 hours later if necessary. Alternatively, a prophylactic dose of 4 micrograms can be given immediately prior to the lumbar puncture and repeated 24 hours later. Fibrinolytic Response Testing:

By intravenous administration.The dose for adults and children is 0.4 micrograms per kilogram body weight administered by intravenous infusion. The dose should be diluted in 50ml of 0.9% sodium chloride for injection and given over 20 minutes.A sample of venous blood should be taken 20 minutes after the infusion. In patients with a normal response the sample should show fibrinolytic activity of euglobulin clot precipitate on fibrin plates of at least 240mm2.

4.3. Contraindications

DDAVP® /Desmopressin Injection is contraindicated in cases of :GENERAL:- habitual and psychogenic polydipsiaRENAL FUNCTION TESTING, TREATMENT OF LUMBAR PUNCTURE HEADACHE OR FIBRINOLYTIC RESPONSE TESTING:- should not be carried out in patients with hypertension, heart disease, cardiac insufficiency and other conditions requiring treatment with diuretic agentsFOR HAEMOSTATIC USE- unstable angina pectoris- decompensated cardiac insufficiency- von Willebrand's Disease Type IIB where the administration of Desmopressin may result in pseudothrombocytopenia due to the release of clotting factors which cause platelet aggregation.

4.4. Special warnings and precautions for use

GENERALPrecautions to prevent fluid overload must be taken in:- conditions characterised by fluid and/or electrolyte imbalance- patients at risk for increased intracranial pressureCare should be taken with patients who have reduced renal function and/or cardiovascular disease.When DDAVP® /Desmopressin Injection is used for diagnostic purposes, fluid intake must be limited and not exceed 0.5 litres 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 under carefully supervised conditions in hospital.FOR HAEMOSTATIC USEWhen repeated doses are used to control bleeding in haemophilia or von Willebrand's disease, 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. Intravenous infusions should not be left up as a routine after surgery. Fluid accumulation can be readily monitored by weighing the patient or by determining plasma sodium or osmolality.Measures to prevent fluid overload must be taken in patients with conditions requiring treatment with diuretic agents.Special attention must be paid to the risk of water retention. The fluid intake should be restricted to the least possible and the body weight should be checked regularly.If there is a gradual increase of the body weight, decrease of serum sodium to below 130mmol/l or plasma osmolality to below 270mOsm/kg, the fluid intake must be reduced drastically and the administration of DDAVP® /Desmopressin Injection interrupted.During infusion of DDAVP® /Desmopressin Injection for haemostatic use, it is recommended that the patient's blood pressure is monitored continuously.DDAVP® /Desmopressin Injection does not reduce prolonged bleeding time in thrombocytopenia.

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 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 or haemostasis.

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.

4.9. Overdose

An overdose of DDAVP® /Desmopressin injection 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.