Uropress

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT UROPRES® (UROPRES)

Composition:

active substance: desmopressin;

1 ml of solution contains desmopressin acetate equivalent to 0.1 mg of desmopressin 100% substance;

excipients: benzalkonium chloride, sodium chloride, glycine, betaine hydrochloride, purified water.

Pharmaceutical form. Nasal spray.

Main physicochemical properties: clear, colorless liquid. Forms a layer of foam when shaken, which disappears within 30 minutes.

Pharmacotherapeutic group. Hormones for systemic use, excluding sex hormones and insulin. Posterior pituitary hormones. Vasopressin and analogues. ATC code H01BA02.

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 to water and enhances its reabsorption. It reduces the volume of excreted urine and simultaneously increases its osmolarity while decreasing plasma osmolarity. This leads to a reduction in the frequency of urination and a decrease in nocturia. The antidiuretic effect after intranasal administration of 10–20 mcg of desmopressin lasts 8–12 hours.

Pharmacokinetics.

The bioavailability of the drug after intranasal administration ranges from 3% to 5%. A noticeable concentration of the active substance in blood plasma occurs within 15–30 minutes after administration, with peak concentration reached after 1 hour and dependent on the administered dose. The volume of distribution is 0.2–0.3 L/kg. Desmopressin does not cross the blood-brain barrier. The elimination half-life after intranasal administration averages 2–3 hours. A small amount of desmopressin is metabolized in the liver.

Clinical characteristics.

Indications.

As an antidiuretic agent: treatment of central diabetes insipidus; for post-traumatic polyuria and polydipsia in the presence of transient deficiency or absence of antidiuretic hormone following hypophysectomy, surgery in the pituitary region, or traumatic brain injury.

As a diagnostic agent: for rapid testing to determine renal concentrating ability; for differential diagnosis of diabetes insipidus.

Contraindications.

• Hypersensitivity to desmopressin or to any of the excipients;
• Primary or psychogenic polydipsia, polydipsia in patients with alcoholism;
• Severe forms of von Willebrand's disease (type IIb); factor VIII activity below 5% and presence of inhibitors to factor VIII;
• Heart failure or other conditions requiring diuretic therapy;
• Moderate or severe renal impairment (creatinine clearance below 50 ml/min);
• Hyponatremia;
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Interaction with other medicinal products and other forms of interaction.

Medicinal products that may cause syndrome of inappropriate antidiuretic hormone secretion, such as tricyclic antidepressants, selective serotonin reuptake inhibitors, chlorpromazine, carbamazepine, and certain oral hypoglycemic agents of the sulfonylurea class (particularly chlorpropamide), may enhance the antidiuretic effect and increase the risk of fluid retention or hyponatremia.

NSAIDs may cause fluid retention or hyponatremia.

When used concomitantly with oxytocin, increased antidiuretic effect and reduced uterine perfusion should be considered.

Clofibrate and indometacin may enhance the antidiuretic effect of desmopressin, while glibenclamide and lithium salts may reduce it.

When all the above-mentioned medicinal products are used concomitantly, arterial pressure, plasma sodium levels, and diuresis should be monitored.

Interaction of desmopressin with medicinal products affecting hepatic metabolism is unlikely, as in vitro studies of microsomal metabolism in human liver cells have shown no significant metabolism of desmopressin. However, formal in vivo interaction studies have not been conducted.

Special precautions for use.

Treatment should be initiated at the lowest possible dose, with gradual and cautious dose titration. URINEX® nasal spray should only be prescribed to patients for whom oral administration of desmopressin in tablet form is contraindicated.

Desmopressin therapy without concomitant fluid restriction may lead to water retention and hyponatremia, which may manifest as weight gain, headache, nausea, vomiting, and edema. In severe cases, cerebral edema, seizures, and coma may occur. To prevent water overload, fluid balance must be carefully maintained.

In the treatment of central diabetes insipidus, severe hyponatremia may be associated with the use of this medicinal product.

The drug should be used with caution in: young and elderly patients; patients with conditions characterized by water and/or electrolyte imbalance; patients at risk of increased intracranial pressure; patients at risk of thrombosis.

The drug should be used with caution in patients with cystic fibrosis.

Before initiating treatment, the absence of bladder dysfunction and bladder outlet obstruction should be confirmed.

Prior to treatment, it is essential to ensure that the patient consents to fluid intake restriction. Patients, parents (if the patient is a child), and medical staff should be informed of the need to avoid fluid overload (including during swimming) and to discontinue desmopressin during episodes of vomiting and diarrhea until fluid balance is restored.

The risk of hyponatremic seizures can be minimized by adhering to the recommended starting dose and avoiding concomitant use of drugs that increase vasopressin secretion.

Fluid retention may be monitored by measuring patient body weight, plasma sodium concentration, or plasma osmolality.

Weight gain may be related to drug overdose, but more commonly results from water overload.

Desmopressin treatment should be temporarily discontinued during acute intercurrent illnesses that may disrupt fluid and electrolyte balance, such as systemic infections, gastroenteritis, or fever.

Precautions to prevent hyponatremia—including strict adherence to fluid restriction and more frequent monitoring of serum sodium—should be implemented when concomitant therapy includes drugs known to cause the syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as tricyclic antidepressants, selective serotonin reuptake inhibitors, chlorpromazine, carbamazepine, sulfonylurea derivatives, and NSAIDs.

When performing a kidney concentration test, fluid intake should be limited to 0.5 L, especially during the hour before and the 8 hours following drug administration.

After diagnostic testing for diabetes insipidus or kidney concentration capacity, care should be taken to avoid fluid overload. Fluid administration—either orally or parenterally—should not be forced, and patients should consume only the amount of fluid necessary to satisfy thirst.

Benzalkonium chloride, included in the formulation as an excipient, may cause nasal mucosal swelling, particularly with prolonged use. If such a reaction is suspected (e.g., chronic nasal congestion), the patient should be switched to a preservative-free nasal formulation.

Benzalkonium chloride, included in the formulation as an excipient, may cause bronchospasm. URINEX® nasal spray should not be used in the presence of nasal mucosal abnormalities such as scarring, swelling, or other disorders that may alter drug absorption.

Use during pregnancy or breastfeeding.

Use during pregnancy: desmopressin should be administered with caution during pregnancy. Reproductive studies in rats and rabbits using doses more than 100 times higher than the human dose did not reveal any evidence of fetal harm. Rare cases of congenital malformations have been reported in children born to mothers who received treatment for diabetes insipidus during pregnancy. However, a review of available data does not indicate an increased frequency of congenital malformations in infants exposed to desmopressin throughout pregnancy.

Use during lactation: analysis of breast milk from mothers who were breastfeeding and receiving high doses of desmopressin (300 mcg intranasally) indicates that the amount of desmopressin transferred to the infant is significantly below the level required to affect diuresis.

Effects on the ability to drive and use machines.

The medicinal product has no or negligible effect on the ability to drive or operate machinery.

Administration and Dosage

The medication should be administered intranasally. The nose should be cleared before use.

One spray dose contains 5 mcg of the active substance and corresponds to one spray pump actuation.

Diabetes insipidus, post-traumatic polyuria and central polydipsia.

Dosage should be individually adjusted. However, the optimal dose for adults is 10–20 mcg (2–4 sprays) once or twice daily. For children aged 1 year and older, the dose is 10 mcg (2 sprays) once or twice daily. If symptoms of fluid retention and/or hyponatremia occur, treatment should be discontinued and the dose adjusted.

Concentration test for assessing renal concentrating ability and for differential diagnosis of diabetes insipidus.

To evaluate renal concentrating ability, use the following dosages: for adults – 40 mcg (8 sprays); for children under 1 year of age – 10 mcg (2 sprays); for children aged 1 year and older – 20 mcg (4 sprays).

The concentration test is used for differential diagnosis between diabetes insipidus and polyuric syndrome of other etiologies, as well as for detecting reduced renal concentrating ability associated with urinary tract infections (cystitis, pyelonephritis). This test is also applied for early diagnosis of tubulointerstitial damage, for example, caused by lithium, analgesics, chemotherapeutic agents, and immunosuppressants.

The concentration test should preferably be performed in the first half of the day. Fluid intake should be restricted for the first 12 hours after administration of the medication. For children under 5 years of age and patients with heart disease or arterial hypertension, fluid intake should be reduced by half.

Before starting the test, urine osmolality should be measured. After administration of desmopressin, collect two urine samples (preferably at 2 and 4 hours). Urine collected during the first hour should be collected separately and discarded. Osmolality should be measured in both urine samples. To assess renal concentrating ability, the highest achieved osmolality value should be compared with the pre-test value or with the age-appropriate reference value (for adults, 800–1000 mOsm/kg). Low values, absence of increase, or only a slight increase in urine osmolality indicate impaired renal concentrating ability. If urine osmolality increases significantly and urine volume decreases markedly, this indicates that polyuria is due to central diabetes insipidus.

Instructions for using the nasal spray:

1. Remove the protective cap from the bottle.
2. Prime the spray pump by pressing (test spray).
3. While standing upright, insert the nozzle tip alternately into each nostril and press the pump.
4. After use, replace the protective cap on the bottle.

Children.

The medication should be administered to children under adult supervision to ensure correct dosing.

The renal concentrating ability test in children under 1 year of age should be performed exclusively in a hospital setting with subsequent monitoring.

Overdose.

Desmopressin overdose may lead to hyponatremia and seizures. Symptoms of overdose may occur with excessively high doses, excessive fluid intake during or immediately after desmopressin administration, or inadequate absorption conditions with intranasal administration. Overdose may manifest as: weight gain (water retention), headache, nausea, mild arterial hypertension, tachycardia, flushing; in severe cases – cerebral edema and seizures.

Overdose may occur in young children due to inadequate dose adjustment.

Treatment: In case of overdose, reduce the dose, increase the interval between doses, or discontinue the medication. Cerebral edema requires immediate hospitalization in an intensive care unit. Seizures in children require immediate intensive treatment. In case of hyponatremia, desmopressin treatment must be stopped immediately and fluid intake restricted until serum sodium normalizes. There is no specific antidote. If diuretic therapy is indicated, saluretic diuretics such as furosemide may be used.

Side effects.

Immune system disorders: hypersensitivity reactions, including fever, bronchospasm, anaphylaxis.

Metabolism and nutrition disorders: hyponatremia, dehydration.

Nervous system disorders: dizziness, headache, drowsiness, cerebral edema, hyponatremic seizures, seizures, confusion, decreased level of consciousness, coma.

Psychiatric disorders: insomnia, affective lability, nightmares, restlessness, aggression, emotional disturbances in children.

Cardiovascular disorders: arterial hypertension, flushing; in patients with ischemic heart disease, episodes of angina pectoris may occur.

Respiratory system disorders: nasal congestion, rhinitis, epistaxis, dryness of the throat, upper respiratory tract infection, dyspnea.

Gastrointestinal disorders: nausea, vomiting, abdominal pain, diarrhea, gastroenteritis.

Skin and subcutaneous tissue disorders: increased sweating, allergic reactions, including skin rash, pruritus, urticaria.

Musculoskeletal and connective tissue disorders: muscle spasms.

General disorders: increased fatigue, malaise, peripheral edema, chest pain, chills.

Laboratory and diagnostic findings: increased body temperature, weight gain.

Pediatric population: hyponatremia is a reversible condition, frequently observed in children due to changes in daily routine affecting water intake and/or sweating.

Other special patient groups: in young children and elderly patients with serum sodium concentration at the lower limit of normal, an increased risk of hyponatremia may be observed.

Shelf life. 2 years. Shelf life after opening the bottle – 50 days.

Do not use the medication after the expiry date stated on the packaging.

Storage conditions.

Store in a light-protected and child-inaccessible place at a temperature from 2 °C to 8 °C.

Incompatibility. Not established.

Packaging. 2.5 mL or 5 mL in a vial, placed in a carton.

Prescription status. Prescription only.

Manufacturer. JSC "Farmak".

Manufacturer's address and place of business.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.