Nourem^® Express (Tablets) Instructions for Use

Marketing Authorization Holder

Canonpharma Production, CJS (Russia)

ATC Code

H01BA02 (Desmopressin)

Active Substance

Desmopressin

Dosage Forms

	Nourem® Express	Sublingual tablets 120 mcg
		Sublingual tablets 60 mcg
		Sublingual tablets 240 mcg

Dosage Form, Packaging, and Composition

Sublingual tablets

10 pcs. – blister packs – cardboard packs (10 pcs.) – By prescription
10 pcs. – blister packs (3 pcs.) – cardboard packs (30 pcs.) – By prescription
30 pcs. – blister packs – cardboard packs (30 pcs.) – By prescription
30 pcs. – blister packs (3 pcs.) – cardboard packs (90 pcs.) – By prescription

Sublingual tablets

0.060 mg (60 mcg) desmopressin, equivalent to 0.0675 mg desmopressin acetate (as trihydrate).

10 pcs. – blister packs – cardboard packs (10 pcs.) – By prescription
10 pcs. – blister packs (3 pcs.) – cardboard packs (30 pcs.) – By prescription
30 pcs. – blister packs – cardboard packs (30 pcs.) – By prescription
30 pcs. – blister packs (3 pcs.) – cardboard packs (90 pcs.) – By prescription

Sublingual tablets

10 pcs. – blister packs – cardboard packs (10 pcs.) – By prescription
10 pcs. – blister packs (3 pcs.) – cardboard packs (30 pcs.) – By prescription
30 pcs. – blister packs – cardboard packs (30 pcs.) – By prescription
30 pcs. – blister packs (3 pcs.) – cardboard packs (90 pcs.) – By prescription

Clinical-Pharmacological Group

Vasopressin analog. Antidiuretic

Pharmacotherapeutic Group

Pituitary and hypothalamic hormones and their analogues; posterior pituitary lobe hormones; vasopressin and its analogues

Pharmacological Action

A structural analog of the natural peptide hormone arginine-vasopressin, obtained by modifications in the vasopressin molecule structure. The differences consist of deamination of cysteine (at position 1) and replacement of L-arginine (at position 8) with D-arginine. This leads to a significant prolongation of the antidiuretic action and a less pronounced effect on the smooth muscles of blood vessels and internal organs compared to native arginine-vasopressin.

Desmopressin increases the permeability of the epithelium of the distal convoluted tubules and increases water reabsorption, which leads to a decrease in the volume of urine excreted, an increase in urine osmolality with a simultaneous decrease in blood plasma osmolality, a decrease in the frequency of urination, and a reduction in nocturia (nocturnal polyuria). The antidiuretic effect after oral administration at a dose of 0.1 mg lasts up to 8 hours.

Pharmacokinetics

Rapidly absorbed from the gastrointestinal tract. C_max is reached approximately 2 hours after administration. Concurrent food intake may reduce the degree of absorption from the gastrointestinal tract by 40%. With oral administration, the absolute bioavailability of desmopressin is 0.08-0.16%. Bioavailability may vary among different patients.

V_d is 0.2-0.3 L/kg. Desmopressin does not cross the blood-brain barrier.

In vitro studies of liver microsomes established that a small portion of desmopressin is metabolized in the liver. Based on the data obtained, it was concluded that the metabolism of desmopressin in the liver in vivo is not significant.

Desmopressin is excreted by the kidneys at a slower rate compared to arginine-vasopressin. T_1/2 after oral administration is 2-3.2 hours. Approximately 65% of desmopressin that enters the systemic circulation is excreted by the kidneys within 24 hours.

Indications

Treatment of central diabetes insipidus; polyuria/polydipsia after hypophysectomy or operations in the sella turcica region; primary nocturnal enuresis in children over 5 years of age; nocturia in adults associated with nocturnal polyuria (increased urine production at night exceeding bladder capacity and causing the need to get up more than once at night to empty the bladder), as symptomatic therapy.

ICD codes

Dosage Regimen

Administer sublingually. Place the tablet under the tongue and allow it to dissolve completely. Do not chew or swallow the tablet whole.

For central diabetes insipidus, initiate therapy with a dose of 60 mcg three times daily. Titrate the dose individually based on diuresis control and patient response. The typical maintenance dose ranges from 120 mcg to 240 mcg administered in two or three divided doses daily. The maximum total daily dose should not exceed 720 mcg.

For primary nocturnal enuresis in children over 5 years, the recommended initial dose is 120 mcg immediately before bedtime. If necessary, the dose may be increased to 240 mcg based on clinical response. Ensure fluid restriction for at least 1 hour before and 8 hours after administration to mitigate the risk of hyponatremia.

For nocturia in adults associated with nocturnal polyuria, the recommended dose is 60 mcg to 240 mcg as a single dose at bedtime. Initiate therapy at the lower end of the dosing range. The use for symptomatic therapy of nocturia is contraindicated in patients aged 65 years and older.

Perform dose titration cautiously. Monitor for signs of fluid retention or hyponatremia, especially during the first week of therapy and after any dose increase. In patients over 65 years, determine plasma sodium concentration before initiation and within 3 days after starting or increasing the dose.

Discontinue therapy temporarily during episodes of acute illness that may affect fluid and electrolyte balance, such as fever, vomiting, or diarrhea. Do not resume administration until the condition has resolved and electrolyte balance is normalized.

Adverse Reactions

Use of desmopressin without concomitant fluid intake restriction can lead to fluid retention and/or hyponatremia, which may be asymptomatic or accompanied by the following symptoms: headache, nausea or vomiting, weight gain; in severe cases – seizures, which are combined with impaired consciousness up to prolonged loss of consciousness.

Immune system disorders frequency unknown – anaphylactic reactions.

Metabolism and nutrition disorders common – hyponatremia; uncommon – weight gain, hypokalemia; frequency unknown – dehydration, hypernatremia.

Psychiatric disorders uncommon – insomnia; rare – confusion.

Nervous system disorders: very common – headache; common – dizziness; uncommon – somnolence, paresthesia; frequency unknown – seizures, asthenia, coma.

Eye disorders uncommon – decreased visual acuity.

Ear and labyrinth disorders uncommon – vertigo.

Cardiac disorders uncommon – “sensation of palpitations”.

Vascular disorders common – arterial hypertension; uncommon – orthostatic hypotension.

Respiratory, thoracic and mediastinal disorders uncommon – dyspnea.

Gastrointestinal disorders common – nausea, abdominal pain, diarrhea, constipation, vomiting; uncommon – dyspepsia, flatulence, abdominal distension, increased liver enzyme activity.

Skin and subcutaneous tissue disorders uncommon – increased sweating, pruritus, skin rash, urticaria; rare – allergic dermatitis.

Musculoskeletal and connective tissue disorders uncommon – muscle spasms, myalgia.

Renal and urinary disorders common – bladder dysfunction, impaired micturition.

General disorders and administration site conditions common – peripheral edema, feeling of fatigue; uncommon – feeling of discomfort, chest pain, flu-like syndrome.

Hyponatremia can cause headache, abdominal pain, nausea, vomiting, weight gain, dizziness, confusion, feeling of discomfort, memory impairment, vertigo, falls, seizures, and coma. The risk of developing hyponatremia is increased in elderly patients (over 65 years) and patients with sodium concentration at the lower limit of normal.

Adverse reactions such as dehydration and asthenia were observed only in patients with diabetes insipidus.

Children

Immune system disorders frequency unknown – anaphylactic reactions.

Metabolism and nutrition disorders frequency unknown – hyponatremia.

Psychiatric disorders uncommon – emotional lability, aggressive behavior; rare – anxiety, nightmares, abrupt mood changes; frequency unknown – emotional disorders, behavior changes, depression, hallucinations, insomnia.

Nervous system disorders common – headache; rare – somnolence; frequency unknown – attention disturbance, psychomotor hyperactivity, seizures.

Vascular disorders rare – arterial hypertension.

Respiratory, thoracic and mediastinal disorders frequency unknown – epistaxis.

Gastrointestinal disorders: uncommon – stomach pain, nausea, vomiting, diarrhea.

Skin and subcutaneous tissue disorders frequency unknown – skin rash, allergic dermatitis, increased sweating, urticaria.

Renal and urinary disorders uncommon – bladder dysfunction, impaired micturition.

General disorders and administration site conditions uncommon – peripheral edema, feeling of fatigue; rare – irritability.

Contraindications

Hypersensitivity to desmopressin; habitual or psychogenic polydipsia (with urine output of 40 ml/kg/24 hours); polydipsia in chronic alcoholism; known or suspected chronic heart failure and other conditions requiring the prescription of diuretics; hyponatremia, including history; moderate and severe renal failure (creatinine clearance less than 50 ml/min); syndrome of inappropriate antidiuretic hormone secretion; children under 4 years of age (for the treatment of diabetes insipidus) and under 5 years of age (for the treatment of primary nocturnal enuresis); age 65 years and older (when using the drug for symptomatic therapy of nocturia).

With caution

In chronic renal failure (creatinine clearance more than 50 ml/min), bladder fibrosis, cystic fibrosis, coronary heart disease, arterial hypertension, risk of thrombosis, in case of water-electrolyte balance disorders, potential risk of increased intracranial pressure, during pregnancy, including with potential risk of increased intracranial pressure in pregnancy complications (severe late gestosis – preeclampsia), as well as in elderly patients (over 65 years).

Use in Pregnancy and Lactation

No negative effects on the course of pregnancy, the health of the pregnant woman, the fetus, and the newborn were observed when using desmopressin in pregnant women with diabetes insipidus.

Desmopressin is prescribed only when the expected benefit to the mother outweighs the potential risk to the fetus. The use of desmopressin during pregnancy requires careful medical supervision; the dosage regimen should be adjusted according to the patient’s condition. Regular blood pressure monitoring is recommended.

Desmopressin passes into breast milk in insignificant amounts. The amount of desmopressin ingested by the newborn with the breast milk of a woman taking high doses of desmopressin is significantly less than that which could affect his diuresis.

Use in Renal Impairment

Contraindicated in patients with moderate and severe renal failure (creatinine clearance less than 50 ml/min); use with caution in chronic mild renal failure (creatinine clearance more than 50 ml/min).

Pediatric Use

Contraindicated in children under 4 years of age (for the treatment of diabetes insipidus) and under 5 years of age (for the treatment of primary nocturnal enuresis).

Geriatric Use

Use with caution in elderly patients (≥65 years); the use of desmopressin for symptomatic therapy of nocturia in this category of patients is contraindicated.

Special Precautions

Patients with primary nocturnal enuresis must minimize fluid intake for 1 hour before and for 8 hours after desmopressin administration. Failure to follow the administration rules may cause fluid retention in the body and/or hyponatremia, which may manifest with the following symptoms: headache, dizziness, nausea, vomiting, weight gain, in severe cases – cerebral edema, seizures, and coma. The safety of desmopressin with long-term use in cases of nocturnal enuresis has not been studied.

Cases of cerebral edema and seizures have been observed in healthy children and adolescents taking desmopressin for the treatment of nocturnal enuresis. The risk of developing cerebral edema and seizures is highest during the first week of desmopressin use. The risk of developing hyponatremia is increased in elderly patients (over 65 years) and in patients with initially low sodium concentration.

The duration of action of desmopressin increases with increasing dose, leading to an increased risk of hyponatremia. Dose increases should be performed with great caution. Desmopressin should be used with caution in patients with chronic renal failure, bladder fibrosis, cystic fibrosis, coronary heart disease, arterial hypertension, with potential risk of increased intracranial pressure; water-electrolyte balance disorders; in patients at risk of thrombosis; during pregnancy, including with preeclampsia; in elderly patients (over 65 years). Before starting the drug (and 3 days after starting or increasing the dose), plasma sodium concentration should be determined in patients over 65 years. If headache and/or nausea occur, administration should be discontinued. Adverse reactions develop more frequently in patients with arterial hypertension or chronic kidney disease.

Particular caution should be exercised when using Desmopressin in children and elderly patients, or patients at risk of increased intracranial pressure, trying to prevent fluid retention in the body.

Patients and parents of children taking Desmopressin should be informed about the need to restrict fluid intake and to discontinue desmopressin in case of vomiting, diarrhea, systemic infectious diseases, and fever, and not to resume administration until the water-electrolyte balance has normalized.

To reduce the risk of developing hyponatremia or fluid retention, fluid intake should be reduced in the following cases: when using drugs that lead to the syndrome of inappropriate antidiuretic hormone secretion (tricyclic antidepressants, selective serotonin reuptake inhibitors, chlorpromazine, chlorpropamide and carbamazepine); with concomitant use of NSAIDs.

Changes in body weight should be monitored during treatment.

Before starting desmopressin, organic causes of polyuria, increased urine volume, or nocturia should be excluded, including prostatic hyperplasia, urinary tract infections, nephrolithiasis, bladder tumors, bladder sphincter dysfunction, polydipsia or impaired glycemic control in diabetes mellitus, and if the above diseases are present, appropriate treatment should be carried out.

Before starting treatment, therapy for adrenal cortex insufficiency or thyroid insufficiency should be performed.

A standard diet containing 27% fat leads to a decrease in the absorption of desmopressin when taken orally. No significant effect on pharmacodynamics was identified; Desmopressin can be taken with food. However, a decrease in the severity and duration of the antidiuretic effect is possible when taking desmopressin at a low dose simultaneously with food.

Influence on the ability to drive vehicles and mechanisms

There are no data on the possible influence of desmopressin on the ability to drive vehicles and mechanisms. Considering that Desmopressin can lead to the development of such side effects as dizziness, headache, etc., which may negatively affect the ability to drive vehicles and perform potentially hazardous activities requiring increased concentration and speed of psychomotor reactions, it is recommended to exercise caution when driving vehicles and mechanisms.

Drug Interactions

Clofibrate, indomethacin and NSAIDs, tricyclic antidepressants, selective serotonin reuptake inhibitors, chlorpromazine, chlorpropamide, carbamazepine and other drugs capable of causing the syndrome of inappropriate antidiuretic hormone secretion, when used concomitantly with desmopressin, may enhance the antidiuretic effect of desmopressin and lead to an increased risk of fluid retention and hyponatremia. When desmopressin is taken concomitantly with the above drugs, blood pressure, plasma sodium concentration, and urine volume should be carefully monitored.

When desmopressin is used with loperamide, a threefold increase in the plasma concentration of desmopressin is possible, which significantly increases the risk of fluid retention and the occurrence of hyponatremia.

It is possible that other drugs that reduce the tone and motility of the intestinal smooth muscles may have a similar effect.

Concomitant use with oxytocin may enhance the antidiuretic effect of desmopressin and reduce uterine perfusion.

Use of glibenclamide and lithium preparations may reduce the antidiuretic effect of desmopressin.

Interaction with drugs metabolized in the liver is unlikely, since, according to the results of in vitro liver microsome studies, Desmopressin does not have a significant effect on hepatic metabolism. In vivo studies have not been conducted.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.