4.1. Therapeutic indications

OCTIM Injection is indicated as follows:1. 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.2. To test for fibrinolytic response

4.2. Posology and method of administration

Mild to Moderate Haemophilia and von Willebrand's Disease:

By subcutaneous or intravenous administration.The dose for adults, children and infants is 0.3 micrograms per kilogram body weight, administered by subcutaneous injection or 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.For intravenous infusion, 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. Fibrinolytic Response Testing:

By subcutaneous or intravenous administration.The dose for adults and children is 0.3 micrograms per kilogram body weight, administered by subcutaneous injection or intravenous infusion.For 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 administration. 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

OCTIM Injection is contraindicated in cases of:- habitual and psychogenic polydipsia- 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 abnormal clotting factors which cause platelet aggregation. Fibrinolytic Response Testing should not be carried out in patients with hypertension, heart disease, cardiac insufficiency and other conditions requiring treatment with diuretic agents.

4.4. Special warnings and precautions for use

Precautions 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 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 OCTIM Injection interrupted.During administration of OCTIM Injection, it is recommended that the patient's blood pressure is monitored continuously.OCTIM 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 300 micrograms desmopressin 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.During intravenous infusion of OCTIM Injection, vasodilation may occur, resulting in decreased blood pressure and tachycardia with facial flushing. This side effect is normally avoided by infusing the product over 20 minutes.

4.9. Overdose

An overdose of OCTIM 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.