Vazomirin (Spray) Instructions for Use

Marketing Authorization Holder

Genfamedica S.A. (Switzerland)

Manufactured By

Apotex, Inc. (Canada)

ATC Code

H01BA02 (Desmopressin)

Active Substance

Desmopressin

Dosage Form

Vazomirin

Metered-dose nasal spray 10 mcg/1 dose: 25 or 50 dose bottle with dosing device

Dosage Form, Packaging, and Composition

* Desmopressin is the non-proprietary international name recommended by WHO.

25 doses – dark glass bottles (1) with a dosing device – cardboard packs.
50 doses – dark glass bottles (1) with a dosing device – cardboard packs.

Clinical-Pharmacological Group

Vasopressin analog

Pharmacotherapeutic Group

Remedy for diabetes insipidus

Pharmacological Action

Desmopressin is a synthetic analog of the natural antidiuretic hormone arginine vasopressin.

Structural changes in the arginine vasopressin molecule (deamination of cysteine at position 1 and replacement of L-arginine with D-arginine at position 8) cause a decrease in the vasopressor activity and an enhancement of the antidiuretic action of desmopressin.

The drug increases the permeability of the epithelium of the distal parts of the convoluted tubules of the kidneys to water and increases its reabsorption. The use of desmopressin leads to a decrease in the volume of urine excreted and a simultaneous increase in urine osmolality and a decrease in blood plasma osmolality. This leads to a decrease in the frequency of urination and a decrease in nocturnal polyuria.

The antidiuretic activity appears 15-30 minutes after administration of the dose, reaches a clinically significant level within 1 hour and remains high for 8 hours after administration of the dose.

Pharmacokinetics

The bioavailability of desmopressin with intranasal administration is about 10%.

After administration of 20 mcg, Desmopressin is detected in plasma after 15 minutes. C_max after intranasal administration is reached after 1 hour. Desmopressin binds to proteins to a very insignificant extent. It is excreted in human breast milk in low concentration.

Desmopressin, like vasopressin, is metabolized mainly in the liver and kidneys. However, deamination of cysteine-1 gives it resistance to enzymatic breakdown, which is expressed in a significantly longer T_1/2 of desmopressin. T_1/2 is about 4 hours. There is no information on enterohepatic circulation and on the pharmacological activity of its metabolites.

Indications

• Central diabetes insipidus;
• Primary nocturnal enuresis in children 5 years and older;
• Diagnostic test for renal concentrating capacity.

ICD codes

Dosage Regimen

The drug is intended for intranasal administration.

Primary nocturnal enuresis

The initial dose for children (starting from 5 years) and for adults (up to 65 years) who have primary nocturnal enuresis but with normal renal concentrating capacity is 20 mcg – one press on the dosing device (10 mcg) into each nostril at night before going to bed.

If necessary, the dose should be increased to 40 mcg – two presses on the dosing device (20 mcg) into each nostril.

The decision to continue treatment is made after 3 months of continuous therapy based on clinical data that will be observed after discontinuation of the drug for one week.

In the case of enuresis treatment, fluid intake should be limited to a minimum – only to quench thirst for 1 hour before and for 8 hours after drug administration.

Central diabetes insipidus

The dose is selected individually; however, as clinical experience shows, the average daily dose for adults is 10-40 mcg, for children – 10-20 mcg (one or two presses on the dosing device (10-20 mcg) 1 or 2 times a day. This daily dose can be given once or can be divided into 2-3 doses.

Test for renal concentrating capacity

The following average doses are used to determine renal concentrating capacity: for adults – 40 mcg; children over 1 year – 10-20 mcg, children under 1 year of age – 10 mcg.

Immediately after drug administration, the patient must empty the bladder and for the duration of the test and 4 hours after its completion (a total of 8 hours), 2 portions of urine are collected to measure its osmolality. During the test, it is necessary to limit fluid intake (the volume of fluid that entered the body 1 hour before the study and within 8 hours after should not exceed 0.5 l).

For most patients, a normal urine osmolality after Vazomirin administration is 800 mOsm/kg. In children, a urine concentration of 600 mOsm/kg should be achieved within 5 hours after drug administration. If an osmolality value below this is detected, the study should be repeated. Repeated detection of a low value indicates a violation of the renal concentrating capacity, and in this case, the patient needs additional examination.

Adverse Reactions

The following may be observed: headache, abdominal pain, nausea, swelling of the nasal mucosa, rhinitis and nosebleed. In rare cases, allergic reactions to the components of the drug in the form of skin manifestations are observed.

In isolated cases – dizziness, increased blood pressure, algodysmenorrhea, conjunctivitis, decreased lacrimation.

Treatment with desmopressin without a simultaneous reduction in fluid intake may be accompanied by fluid retention in the body, accompanied by hyponatremia, weight gain, edema and in severe cases – transient neurological disorders, mainly generalized convulsions.

Contraindications

• Anuria;
• Edema syndrome of various origins;
• Syndrome of inappropriate antidiuretic hormone secretion;
• Hypo-osmolality of plasma;
• Decompensated heart failure (including history);
• Need for diuretic therapy;
• Hyponatremia;
• Habitual polydipsia (congenital or psychogenic);
• Predisposition to thrombosis;
• Allergic rhinitis;
• Nasal congestion;
• Edema and cicatricial changes of the nasal mucosa;
• Upper respiratory tract infections;
• Impaired consciousness;
• Hypersensitivity to the components of the drug.

With caution the drug should be used in renal failure, bladder fibrosis, children under 1 year and the elderly, with water-electrolyte balance disorders, potential risk of increased intracranial pressure, during pregnancy.

Use in Pregnancy and Lactation

Vazomirin should be prescribed with caution to pregnant patients, despite the very low activity of desmopressin in stimulating labor. No harmful effects of desmopressin on the fetus have been identified.

The amount of desmopressin that can be passed to the newborn with mother’s milk is significantly less than that necessary to affect diuresis. However, caution is recommended when prescribing treatment to women who are breastfeeding.

Use in Renal Impairment

Contraindicated in anuria. With caution the drug should be used in renal failure.

Pediatric Use

The drug should be used with caution in children under 1 year of age.

Geriatric Use

The drug should be used with caution in elderly patients.

Special Precautions

Particular caution should be exercised in relation to patients at risk of intracranial hypertension; patients with impaired water and/or electrolyte balance and patients with conditions in which hyperhydration of the body may be dangerous, for example, impaired renal function, heart failure, cystic fibrosis or anesthesia.

Before prescribing Vazomirin, diagnoses of psychogenic polydipsia and alcoholism should be excluded.

The test for renal concentrating capacity in children under 1 year of age should be performed only in a hospital setting.

Patients receiving treatment for primary nocturnal enuresis should be warned about the need to avoid excessive fluid intake and the need to discontinue Vazomirin in case of vomiting and/or diarrhea until their normal fluid balance is restored.

To prevent fluid retention, caution should be exercised after diagnostic tests to detect diabetes insipidus or to study renal concentrating capacity. Fluid administration should not be forced either orally or parenterally, and patients should take as much fluid as they need to quench their thirst.

Vazomirin should not be used for mucosal changes such as scars, edema or other diseases, as this may lead to uneven and unreliable absorption.

In patients with nasal disorders, including colds, there is a risk of unstable and/or reduced effectiveness of the drug. This may also be observed in patients engaged in activities where the drug may be removed from the nasal cavity before its absorption, for example, when swimming.

Vazomirin should not be prescribed to children who require doses of less than 10 mcg of desmopressin (in the form of acetate hydrate).

Effect on ability to drive vehicles and operate machinery

Taking the drug does not have a negative impact on the ability to drive a car and other mechanisms.

Overdose

Overdose increases the risk of fluid retention and leads to convulsions.

In case of hyponatremia, treatment with Vazomirin must be immediately discontinued and fluid intake restricted until the serum sodium level normalizes, in severe cases – slow intravenous infusion of concentrated saline solutions simultaneously with furosemide.

Drug Interactions

Indomethacin may enhance, but not increase the duration of action of desmopressin.

Oral hypoglycemic agents, for example, glibenclamide, may reduce the duration of action of desmopressin.

Therapy in combination with drugs that cause the release of antidiuretic hormone and enhance antidiuretic activity or disrupt water-electrolyte balance, for example, tricyclic antidepressants (chlorpromazine and carbamazepine), clofibrate and chlorpropamide, enhances the antidiuretic effect and increases the risk of fluid retention in the body.

Glybutide, tetracycline, lithium, norepinephrine weaken the antidiuretic effect. Desmopressin enhances the effect of hypertensive agents.

Storage Conditions

The drug should be stored in a dry, light-protected place, out of the reach of children, at a temperature from 15°C (59°F) to 30°C (86°F). Do not freeze.

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

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.