Each mL of Octostim solution contains desmopressin acetate 15 mcg, sodium chloride 9 mg, hydrochloric acid and water for injection to make 1 mL.
Pharmacology: Desmopressin is a structural analogue of the natural hormone arginine vasopressin. Two chemical changes have been made to the natural hormone namely, desamination of 1-cysteine and substitution of 8-L-arginine by 8-D-arginine. Desmopressin in a high dosage 0.3 mcg/kg body weight IV or SC leads to a 2- to 4-fold increase in plasma of factor VIII coagulant activity (VIII:C). Also the content of von Willebrand factor antigen (vWF:Ag) increases, but to a lesser extent. At the same time, there is a release of the plasminogen activator (t-PA).
Pharmacokinetics: The bioavailability following SC injection compared with IV administration is about 85%. Maximum plasma concentration following a dose of 0.3 mcg/kg body weight is reached after approximately 60 min and amounts to an average of 600 pg/mL. Plasma half-life ranges between 3 and 4 hrs. The duration of the haemostatic effect depends on the plasma half-life for VIII:C which is about 8-12 hrs.
Administration of desmopressin at high dose has also been shown to lead to a shortening or normalization of the bleeding time in patients with prolonged bleeding time as in uraemia, liver cirrhosis, congenital or drug-induced thrombocyte dysfunction and in patients with prolonged bleeding time of unknown aetiology.
In patients with von Willebrand's disease of type II B, the factor VIII is abnormal and desmopressin may then cause thrombocyte aggregation and thrombocytopenia.
The risk of transmission of HIV-infection and hepatitis virus as seen for factor VIII concentrates is avoided by administration of desmopressin.
The pH of the solution is about 4.
Shortening or normalization of prolonged bleeding time prior to an invasive therapeutic or diagnostic operation, or for the therapeutic control of bleeding in patients with prolonged bleeding time as a consequence of congenital or drug-induced thrombocyte dysfunction, uraemia, cirrhosis of the liver or in patients with prolonged bleeding time of unknown aetiology.
For the therapeutic control of bleeding and bleeding prophylaxis in connection with minor surgical procedures in patients with mild haemophilia A and von Willebrand's disease who respond positively to the test dose. In exceptional cases, even moderate forms of the disease can be treated. Octostim must not be used in patients with von Willebrand's disease type II B.
Therapeutic Control of Bleeding or Bleeding Prophylaxis Prior to an Invasive Operation: 0.3 mcg/kg body weight SC or diluted in physiological saline to 50-100 mL and given as an IV infusion over 15-30 min. If a positive effect is obtained, the initial Octostim dose may be repeated 1-2 times with intervals of 6-12 hrs. Further repetition of the dose may result in a reduced effect.
In patients with haemophilia, the desired increase of VIII:C is appraised by the same criterion as in the treatment with factor VIII-concentrate. The VIII:C-concentration must be followed up regularly since in a few cases the effect has been seen to decrease with repeated doses. If the Octostim infusion does not lead to the desired increase of the VIII:C concentration in plasma, the treatment may be complemented with a supply of factor VIII-concentrate. The treatment of patients with haemophilia should be conducted in consultation with each patient's coagulation laboratory.
Determination of the coagulation factor and bleeding time before Octostim treatment. Plasma levels of VIII:C and vWF:Ag increase substantially after desmopressin administration. However, it has not been possible to establish any correlation between the plasma concentration of these factors and the bleeding time, either before or after desmopressin. The effect of desmopressin on the bleeding time should therefore, if possible, be tested in the individual patient.
The bleeding time test should be as standardized as possible eg, with the use of Simplate II. Determination of bleeding time and plasma levels of the coagulation factors should be conducted in cooperation or consultation with a coagulation laboratory.
Octostim must not be used in cases of habitual or psychogenic polydipsia, unstable angina pectoris, decompensated cardiac insufficiency, von Willebrand's disease type II B.
Octostim must be taken with caution in very young and elderly patients, conditions characterized by fluid and/or electrolye imbalance and in patients at risk for increased intracranial pressure.
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/hyponatremia. Fluid intake should be restricted to the least possible, and the body weight should be checked regularly. If there is gradual increase of the body weight, decrease of serum sodium to below 130 mmol/L or plasma osmolality to below 270 mOsm/kg body weight, the fluid intake must be reduced drastically and the administration of Octostim interrupted. Octostim does not reduce prolonged bleeding time in thrombocytopenia.
A few percent of treated patients can be expected to experience side effects eg, fatigue, headache, nausea and stomach pain. Other effects may include a transient fall in blood pressure with a reflex tachycardia and facial flushing at the time of administration and dizziness (rare).
Treatment without concomitant reduction of water intake may lead to water retention/hyponatremia with accompanying signs and symptoms (headache, nausea/vomiting, reduced serum sodium, weight gain and, in serious cases, convulsions).
Isolated cases of allergic skin reactions and more severe general allergic reactions have been reported.
Substances which are known to release antidiuretic hormone eg, tricyclic
antidepressants, chlorpromazine and carbamazepine, may cause an additive
antidiuretic effect leading to an increased risk of water retention/hyponatremia.
Indomethacin increases the urine concentrating effect of desmopressin without
influencing the duration. The effect is probably without any clinical significance.
H01BA02 - desmopressin ; Belongs to the class of vasopressin and analogues. Used in posterior pituitary lobe hormone preparations.