Ddavp Ns 0.1 mg / 1ml Nasal Spray

a) Diagnosis of central diabetes insipidus: Adult patients should be given a 1 litre oral water load initially and urine flow rate stabilised by giving oral fluids equivalent in volume to the volume of urine passed. Then 20 uf06d g DDAVPu00ae is administered intranasally. This will be followed by a sharp decrease in urine flow rate and an increase in urine osmolality within 2 hours if the patient has vasopressin sensitive diabetes insipidus.

b) DDAVPu00ae is indicated for the treatment of vasopressin sensitive central diabetes insipidus or in the treatment of post hypophysectomy polyuria and polydipsia.

c) Renal function testing: Adults and children with normal renal function can be expected to achieve concentrations above 800 mOsm/kg in the period of 5 u2013 9 hours following intranasal administration of 40 uf06d g and 20 uf06d g DDAVPu00ae , respectively. It is recommended that the bladder should be emptied at the time of DDAVPu00ae administration. A restricted water intake must be observed (see SPECIAL WARNINGS). In normal infants a urine concentration of 600 mOsm/kg should be achieved in the 5-hour period following administration. Infants should be given a 10 uf06d g intranasal dose of DDAVPu00ae and the fluid intake at the two meals after administration restricted to 50 % of the ordinary intake in order to avoid water overload.

d) DDAVPu00ae is indicated for the symptomatic short term (4 u2013 8 weeks) treatment of primary nocturnal enuresis in both young and adult patients (children older than 5 years) who have normal ability to concentrate urine. Safety in the elderly has not been established.

One dose of the spray provides 0,1 ml, which corresponds to 10 u03bcg desmopressin acetate.

To institute therapy with DDAVPu00ae , patients should be withdrawn from previous medication and allowed to establish a baseline polyuria and polydipsia. The stable polyuria is used as a baseline to determine the magnitude and duration of the response to medication. In less severe cases, prior water loading may be desirable to establish a vigorous flow of urine. When the urine osmolality reaches a plateau at the low level (in most cases, less than 100 mOsm per kilogram), the first dose of DDAVPu00ae is administered intranasally. A urine sample is obtained after two hours and hourly thereafter following DDAVPu00ae administration. Samples are measured for volume and osmolality. When the patient has reached the previous baseline urine osmolality and urine flow, the medication effect has ceased and the next dose of DDAVPu00ae is administered. The cycle is then repeated until the patient has reached a stable condition.

DDAVPu00ae is dosed individually after testing the effect of different doses on urine osmolality and diuresis (according to the procedure described in the above paragraph).

A summary of the therapeutic results in patients who have hitherto been treated with DDAVPu00ae makes the following suggestion of an average dosage possible. Central diabetes insipidus Dosage is individual. A proposal for normal dosage is : Children: 0,05 u2013 0,1 ml (5 u2013 10 uf06d g) 1 u2013 2 times daily, intranasally. Adults: 0,1 u2013 0,2 ml (10 u2013 20 uf06d g) 1 u2013 2 times daily, intranasally.

Renal concentrating capacity test: To establish renal concentration capacity, the following single doses are recommended: the normal dose for adults is 40 u03bcg; for children over 1 year 20 u03bcg; for children under 1 year 10 u03bcg. After administration of DDAVPu00ae , any urine collected within one hour is discarded. During the next 8 hours two portions of urine are collected for osmolality testing. A restricted water intake must be observed (see also under SPECIAL WARNINGS).

DDAVPu00ae in nocturnal enuresis: The clinical effective intranasal dose varies between patients and ranges between 10 and 20 uf06d g given at the hour of sleep. The posology should be established progressively beginning with 10 u03bcg dose. In case of non response the daily dose should be increased to 20 u03bcg with a minimal duration of one week. The maximal dose should not exceed 20 u03bcg. A short term treatment period of four to eight weeks is recommended. The recommended dosage may only be administered once in every 24 hours.

A restricted water intake must be observed (see SPECIAL WARNINGS). In the event of signs of fluid retention/hyponatraemia, treatment should be interrupted.

DDAVPu00ae must not be used in cases of:

• 1. Renal diabetes insipidus
• 2. Hypersensitivity to DDAVPu00ae .
• 3. Peripheral vascular disease.
• 4. History of known or suspected cardiac insufficiency and other conditions requiring treatment with diuretic agents
• 5. Hypersensitivity to the preservative.
• 6. Habitual and psychogenic polydipsia.
• 7. Cirrhosis.
• 8. Syndrome of inappropriate ADH secretion (SIADH)
• 9. Hypertension.
• 10. Cerebral vascular disease.
• 11. Moderate or severe renal insufficiency (creatinine clearance below 50 ml/min).
• 12. Known hyponatraemia.

Overhydration: The risk of overhydration including cardiac failure should be borne in mind, especially in children or the elderly and when DDAVPu00ae is being used to test renal concentrating capacity or the patient is on fluid supplements either orally or parenterally. Children should be closely observed to avoid over-ingestion of fluid. Excessive water intake can produce hyponatraemia with associated effects, including convulsions.

DDAVPu00ae NASAL SPRAY should be used with caution in:

• uf0b7 Very young and elderly patients
• uf0b7 Conditions characterised by fluid and/or electrolyte imbalance.
• uf0b7 Patients at risk for increased intracranial pressure.

Special Warnings: DDAVPu00ae NASAL SPRAY should only be used in patients where orally administered formulations are not feasible. When DDAVPu00ae nasal spray is prescribed it is recommended:

• uf0b7 To start at the lowest dose.
• uf0b7 To ensure compliance with fluid restriction instructions.
• uf0b7 To increase dose progressively, with caution.
• uf0b7 To ensure that in children administration is under adult supervision in order to control the dose intake.

In case of treatment of enuresis the fluid intake must be limited to a minimum and only to satisfy 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. When used for diagnostic purposes the fluid intake must be limited and not exceed 0,5 litre from 1 hour before until 8 hours after administration. Due to the presence of benzalkonium chloride this product may cause bronchospasm.

Substances which are known to release antidiuretic hormone, e.g. tricyclic antidepressants, selective serotonin reuptake inhibitors, chlorpromazine and carbamazepine, may cause an additive antidiuretic effect and increase the risk of water retention and dilutional hyponatraemia. This may lead to convulsions. NSAIDs may induce fluid retention/hyponatraemia (see SIDE EFFECTS AND SPECIAL PRECAUTIONS). Indomethacin in combination with DDAVPu00ae increases the magnitude but not the duration, of the response to DDAVPu00ae. Glibenclamide: A few cases, where the antidiuretic response induced by DDAVPu00ae was reduced, were reported. Carbamazepine may also prolong the action of DDAVPu00ae . Pressor agents u2013 Large doses of DDAVPu00ae together with other pressor agents should only be given with careful monitoring.

Pregnancy: Safety in pregnancy and lactation has not been established.

Lactation: Results from analysis of milk from nursing mothers receiving high doses of desmopressin (300 uf06d g intranasally), indicate that the amounts of desmopressin that may be transferred to the child are considerably less than the amounts required to influence diuresis.

Not stated in the provided text.

Side-effects: Treatment without concomitant restriction of water intake may lead to water retention/ hyponatraemia with or without accompanying warning signs and symptoms (headache, nausea/ vomiting, reduced serum sodium, weight gain and, in serious cases, convulsions and coma).

Metabolism and nutrition disorders: Very rare ( u2264 1/10 000): Hyponatraemia.

Psychiatric disorders: Isolated cases of emotional disturbances in children have been reported but the frequency is unknown.

Respiratory, thoracic and mediastinal disorders: Common(> 1/ 100 u2264 1/ 10): Nasal congestion/ rhinitis, epistaxis.

Gastrointestinal disorders: Common (> 1/ 100 u2264 1/ 10): Abdominal pain, nausea.

General disorders: Common (> 1/ 100 u2264 1/ 10): Headache.

Isolated cases of allergic skin reactions and more severe general allergic reactions have been reported, but the frequency is unknown.

Excessive doses may cause tachycardia, headaches, mild abdominal cramps, nausea, vomiting, facial flushing, vulva pain and water intoxication from overhydration. In such cases the dosage should be reduced, frequency of administration decreased, or the drug withdrawn according to severity of the condition.

At high doses, a transient fall in blood pressure with a reflex tachycardia and facial flushing may occur at the time of administration. There is no known specific antidote for DDAVPu00ae . Treatment is symptomatic and supportive. Overdosage increases the risk of fluid retention and hyponatraemia. Although the treatment of hyponatraemia should be individualised, the following general recommendations can be given. Asymptomatic hyponatraemia is treated with discontinuation of desmopressin treatment and fluid restriction. Infusion of isotonic or hypertonic sodium chloride may be added in cases with symptoms. When the fluid retention is severe (convulsions and unconsciousness) treatment with furosemide should be added.