Each ml of solution contains desmopressin acetate 4 μg, sodium chloride q.s., hydrochloric acid (to adjust pH to 4) and water for injection to 1ml.
pH of the solution is about 4.
MINIRIN contains desmopressin, 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. These structural changes result in a compound with significantly increased antidiuretic potency, very little activity on smooth muscle, hence the avoidance of undesirable pressor side effects. The duration of the antidiuretic effect is about 8-12 hours.
MINIRIN in a high dosage, 0.3 μg/kg body weight intravenously or subcutaneously, leads to a two-to-four-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).
Maximum plasma concentration following a dose of 0.3 μg/kg body weight, is reached after approximately 60 minutes and amounts to an average of 600 μg/ml. Plasma half life ranges between 3 and 4 hours. The duration of the haemostatic effect depends on the plasma half life for VIII:C which is about 8-12 hours.
Administration of desmopressin 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.
The risk of transmission of HIV-infection and hepatitis virus as seen for factor VIII concentrates is avoided by administration of desmopressin.
Central diabetes insipidus: The use of MINIRIN in patients with an established diagnosis will result in a reduction in urinary output with concomitant increase in urine osmolality and decrease in plasma osmolality. This will result in decreased urinary frequency and decreased nocturia.
Renal concentrating capacity test: MINIRIN can be used to test the capacity of the kidneys to concentrate urine; as a diagnostic aid in the examination of the kidney function. This is especially useful in the differential diagnosis between level of urinary tract infections. Cystitis will opposite to pyelonephritis not cause a subnormal ability to concentrate urine.
Hemophilia A and von Willebrand's disease: 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. MINIRIN must not be used in patients with von Willebrand's disease type II B.
Other bleeding disorders: Shortening or normalization of prolonged bleeding time prior to an invasive therapeutic or diagnostic operation, or for 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.
Central diabetes insipidus: The injection may be used when the intranasal administration is considered unsuitable. Individual dosage is determined after testing of the effect on urine osmolality and diuresis at different dose levels. In the event of signs of water retention/hyponatremia treatment should be interrupted and the dose should be adjusted.
Normal dosage, intravenous injection: Adults 1-4 μg (0.25-1 ml) 1-2 times daily. Children above the age of 1 year 0.4-1 μg (0.1-0.25 ml) 1-2 times daily. Children below the age of 1 year 0.2-0.4 μg (0.05-0.1 ml) 1-2 times daily.
For patients who have been controlled on intranasal MINIRIN and who must be switched to the injection form, either because of poor intranasal absorption, or because of the need for surgery, the comparable antidiuretic dose of the injection is about 10% of the intranasal dose.
Renal concentrating capacity test: Normal adult dose by intramuscular or subcutaneous injection is 4 μg (1ml). For children over 12 months of age the dose is 1 to 2 μg (0.25 to 0.5ml). For children under 12 months the dose is 0.4 μg (0.1 ml). For children it is recommended to use primarily the intranasal presentation.
After administration of MINIRIN possible urine within 1 hour is discarded. During the next 8 hours 2 portions of urine are collected for measurement of osmolality. A restricted water intake must be observed, see also Precautions.
The reference level for normal urine osmolality after MINIRIN administration is 800 mOsm/kg for most patients. With values under this level, the test should be repeated. A repeated low result indicates an impaired ability to concentrate urine and the patient should be referred for further examination into the underlying cause of the malfunction.
Therapeutic control of bleeding or bleeding prophylaxis prior to an invasive operation: 0.3μg/kg bodyweight diluted in physiological saline to 50-100ml and given as an intravenous infusion over 15-30 minutes. If a positive effect is obtained, the initial MINIRIN dose may be repeated 1-2 times with intervals of 6-12 hours. 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 MINIRIN-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 MINIRIN-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, e.g. 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.
Overdose of MINIRIN solution for injection can lead to water retention and hyponatremia.
Treatment: Although the treatment of hyponatremia should be individualized, the following general recommendations can be given. Asymptomatic hyponatremia 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.
MINIRIN solution for injection is contraindicated in cases of: In general: habitual and psychogenic polydipsia.
If used for renal concentration capacity testing: cardiac insufficiency and other conditions requiring treatment with diuretics.
If used for haemostatic indications: unstable angina pectoris; decompensated cardiac insufficiency; von Willebrand's disease type IIB.
For all indications MINIRIN solution for injection should be used with caution in: very young and elderly patients; conditions characterized by fluid and/or electrolyte imbalance; patients at risk for increased intracranial pressure.
In addition for renal concentration capacity testing: 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.
In addition for haemostatic use: Measures to prevent fluid overload must be taken in patients requiring treatment with diuretic agents.
Special attention must be paid to the risk of water retention/hyponatremia. The fluid intake should be restricted to the least possible and the body weight should be checked regularly.
Should there be a 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 MINIRIN interrupted.
MINIRIN does not reduce prolonged bleeding time in thrombocytopenia.
Effects on ability to drive and use machines: None.
Pregnancy: Reproduction studies performed in rats and rabbits with doses more than 100 times the human dose have revealed no evidence of a harmful action of desmopressin on the foetus. One investigator has reported 3 cases of malformations in children to mothers suffering from diabetes insipidus and receiving desmopressin during pregnancy. However, several other published reports comprising more than 120 cases show that women treated with desmopressin during pregnancy have given birth to normal children.
Furthermore a review of a very large data set identifying 29 children who have been exposed to desmopressin during the full pregnancy shows no increase in the malformation rate in the children bom.
Lactation: 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 or hemostasis.
A few per cent of treated patients can be expected to experience side effects such as fatigue, headache, nausea and stomach pain. (See table.)
Click on icon to see table/diagram/image
Treatment without concomitant restriction of fluid intake may lead to water retention/hyponatremia with accompanying signs and symptoms (headache, nausea/vomiting, decreased serum sodium, weight gain, and in serious cases, convulsions).
Post marketing experience:
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.
Keep refrigerated at 2-8°C.
H01BA02 - desmopressin ; Belongs to the class of vasopressin and analogues. Used in posterior pituitary lobe hormone preparations.
Inj (amp) 4 mcg/mL x 10's.