Pharmacological properties
Pharmacodynamics. Desmopressin is a structural analogue of the natural hormone l-arginine-vasopressin. The drug increases the permeability of the epithelium of the distal convoluted tubules of the kidneys for water and its reabsorption. Reduces the volume of urine excreted and simultaneously increases its osmolarity, reduces the osmolarity of blood plasma. This leads to a decrease in the frequency of urination and a decrease in nocturia. The antidiuretic effect after intranasal administration of 10-20 μg of desmopressin lasts for 8-12 hours.
Pharmacokinetics. The bioavailability of the drug after intranasal administration is 3-5%. A noticeable concentration of the active substance in the blood plasma occurs 15-30 minutes after application, C max is reached after 1 hour and depends on the dose administered. The volume of distribution is 0.2-0.3 l/kg. Desmopressin does not penetrate the blood-brain barrier. T ½ after intranasal administration is on average 2-3 hours. A small amount of desmopressin is metabolized in the liver.
Indication
As an antidiuretic agent: treatment of diabetes insipidus of central genesis; in post-traumatic polyuria and polydipsia in the presence of a transient deficiency or absence of antidiuretic hormone after hypophysectomy, surgery in the pituitary gland or traumatic brain injury.
As a diagnostic tool: for a rapid test to determine the concentrating ability of the kidneys; for differential diagnosis of diabetes insipidus.
Application
The drug is used intranasally. Before use, the nose should be cleaned.
Uropres, drops. 1 drop contains 5 mcg of the medicinal substance.
Uropres, spray. 1 drop contains 5 mcg of the drug substance and corresponds to one press.
Diabetes insipidus, post-traumatic polyuria and polydipsia of central genesis. The dose is selected individually, however, the optimal dose for adults is 10-20 mcg (2-4 drops for the drug in the form of drops or 2-4 presses for the drug in the form of a spray) 1-2 times a day. For children aged 1 year and older, the dose is 10 mcg (2 drops for the drug in the form of drops or 2 presses for the drug in the form of a spray) 1-2 times a day. In case of symptoms of fluid retention and / or hyponatremia, treatment should be discontinued and the dose adjusted.
Express test for determining the concentration capacity of the kidneys and for differential diagnosis of diabetes insipidus. To assess the concentration capacity of the kidneys, the following doses are used: for adults - 40 mcg (8 drops for the drug in the form of drops or 8 presses for the drug in the form of a spray), for children under 1 year old - 10 mcg (2 drops for the drug in the form of drops or 2 presses for the drug in the form of a spray), for children over 1 year old - 20 mcg (4 drops for the drug in the form of drops or 4 presses for the drug in the form of a spray).
The rapid test is used for differential diagnosis between diabetes insipidus and polyuric syndrome of other genesis, as well as for determination of reduced concentrating ability of kidneys associated with urinary tract infection (cystitis, pyelonephritis). The test is also used for early diagnosis of tubulointerstitial lesions, for example caused by lithium drugs, analgesics, chemotherapeutic drugs and immunosuppressants.
The rapid test is best performed in the morning. Fluid intake should be limited for the first 12 hours after administration. Children under 5 years of age and patients with heart disease or hypertension should have their fluid intake halved.
Before the test, urine osmolality should be determined. After the administration of desmopressin, 2 urine samples are taken (preferably after 2 and 4 hours). The urine obtained during the first hour should be collected separately and discarded. Osmolality is determined in both urine samples. To determine the concentrating ability of the kidneys, the highest achieved osmolality value is compared with the value before the study or with the reference value corresponding to the patient's age (for adults 800-1000 mOsm / kg). Low values, no increase or a slight increase in urine osmolality indicate a violation of the concentrating ability of the kidneys. If urine osmolality increases significantly and urine volume decreases significantly, this means that polyuria is associated with diabetes insipidus of central genesis.
Contraindication
Hypersensitivity to desmopressin or any component of the drug; primary or psychogenic polydipsia, polydipsia in patients with alcoholism; severe forms of von Willebrand disease (type IIb), decreased factor VIII activity to 5% and the presence of antibodies to factor VIII; heart failure or other conditions requiring the appointment of diuretics; moderate or severe renal failure (creatinine clearance 50 ml/min); hyponatremia; syndrome of inappropriate secretion of antidiuretic hormone.
Side effects
Excessive fluid intake can lead to hyperhydration, which is manifested by the following symptoms: weight gain, hyponatremia, in severe cases - the occurrence of seizures, sometimes with impaired consciousness, up to prolonged loss of consciousness. This is most often observed in children under 1 year of age and in elderly patients, depending on their general condition.
The following symptoms may appear:
from the nervous system: headache, cerebral edema, impaired consciousness, convulsions associated with hyponatremia;
from the respiratory system: nasal congestion, rhinitis, nosebleeds, dry throat;
from the digestive tract: nausea/vomiting, abdominal pain;
others: increased sweating.
Allergic reactions, hypersensitivity reactions (e.g. itching, skin rash, fever, bronchospasm, anaphylaxis) are also possible.
In very rare cases, emotional disorders are possible in children.
When the dose is reduced, all these side effects, with the exception of allergic reactions, disappear.
Special instructions
Treatment should begin with the lowest doses, increasing the dose gradually and with caution.
Uropres, nasal drops, are prescribed only to patients for whom oral administration of desmopressin in tablet form is contraindicated.
Benzalkonium chloride, which is contained in the drug as an excipient, can cause bronchospasm. Uropres, nasal drops, should not be used if the mucous membrane is altered: scars, edema or other disorders.
When performing a test for renal concentration capacity, fluid intake should be limited to 0.5 L, especially 1 hour before and 8 hours after administration of the drug.
The drug should be used with caution in young and elderly patients; in conditions characterized by water and/or salt imbalance; in patients at risk of increased intracranial pressure, as well as at risk of developing thrombosis.
The drug should be used with extreme caution in patients with cystic fibrosis.
Desmopressin therapy without concomitant fluid restriction may lead to water retention and hyponatremia, which are accompanied by symptoms such as weight gain, headache, nausea and edema. In severe cases, cerebral edema, seizures and coma may develop.
Before treatment, ensure that the patient agrees to limit fluid intake. Patients should be advised to avoid fluid overload (including swimming) and to discontinue desmopressin if vomiting or diarrhea occurs until fluid balance is restored.
The risk of hyponatremic seizures can be minimized by maintaining the recommended starting dose and avoiding concomitant use of drugs that increase vasopressin secretion.
The presence of fluid retention can be determined by monitoring the patient's body weight, plasma sodium concentration, or osmolality.
Weight gain may be associated with drug overdose or, more commonly, hyperhydration.
Desmopressin treatment should be discontinued in the event of acute intercurrent illnesses that may lead to electrolyte and fluid imbalance, such as systemic infections, gastroenteritis, and fever.
The ability to influence the reaction speed when driving vehicles or working with other mechanisms. Does not affect.
Use during pregnancy or breastfeeding. Clinical studies of the use of nasal desmopressin during pregnancy or breastfeeding have not revealed any signs of adverse effects on the mother or child. Uropress can be used during pregnancy for replacement therapy of antidiuretic hormone deficiency.
Only small amounts of the drug are excreted in breast milk. Results from analyses of milk from breast-feeding mothers who received high doses of desmopressin (300 mcg intranasally) indicate that the amount of desmopressin that can be transferred to the infant is significantly less than that required to produce diuresis.
Children: Use in children under adult supervision to control the dose of the drug.
A test for the concentrating ability of the kidneys in children under 1 year of age is performed exclusively in a hospital setting and with subsequent observation.
Interactions
When used simultaneously with oxytocin, an increase in the antidiuretic effect and a decrease in uterine perfusion should be taken into account.
Clofibrate, indomethacin and carbamazepine may enhance the antidiuretic effect of desmopressin, while glibenclamide and lithium salts may reduce it.
Chlorpromazine, tricyclic antidepressants, selective serotonin reuptake inhibitors and nonsteroidal anti-inflammatory drugs may enhance the antidiuretic effect and increase the risk of fluid retention.
If all of the above drugs are used simultaneously, blood pressure, plasma sodium levels, and diuresis should be monitored.
Overdose
Symptoms: weight gain (water retention), headache, nausea, mild ag, tachycardia, hot flashes, and in severe cases - hyperhydration and convulsions. Overdose may occur in young children due to insufficiently careful selection of the dose.
Treatment. In case of overdose, the dose of the drug should be reduced, the interval between individual doses should be increased, or the drug should be discontinued. The presence of cerebral edema requires immediate hospitalization of the patient in the intensive care unit. Convulsions in children also require intensive therapy.
There is no specific antidote. If diuretic therapy is indicated, saluretics such as furosemide may be used.
Storage conditions
In a place protected from light at a temperature of 2-8 ° C. Shelf life after opening the bottle is 50 days.
