Minirin^® (Tablets) Instructions for Use

Marketing Authorization Holder

Ferring International Center, S.A. (Switzerland)

Manufactured By

Ferring International Center, S.A. (Switzerland)

Primary Packaging

FERRING INTERNATIONAL CENTER, S.A. (Switzerland)

Secondary Packaging

FERRING INTERNATIONAL CENTER, S.A. (Switzerland)

Or

IZVARINO PHARMA, LLC (Russia)

Quality Control Release

FERRING INTERNATIONAL CENTER, S.A. (Switzerland)

Or

IZVARINO PHARMA, LLC (Russia)

Contact Information

FERRING PHARMACEUTICALS B.V. (Netherlands)

ATC Code

H01BA02 (Desmopressin)

Active Substance

Desmopressin (Rec.INN registered by WHO)

Dosage Forms

	Minirin®	Tablets 0.1 mg: 15, 30 or 90 pcs.
		Tablets 0.2 mg: 15, 30 or 90 pcs.

Dosage Form, Packaging, and Composition

Tablets white, oval, biconvex, with a score on one side and an engraving “0.1” on the other.

Excipients : lactose monohydrate – 123.7 mg, potato starch – 73.4 mg, povidone – 1.9 mg, magnesium stearate – 0.51 mg.

15 pcs. – polyethylene bottles (1) – cardboard packs^×.
30 pcs. – polyethylene bottles (1) – cardboard packs^×.
90 pcs. – polyethylene bottles (1) – cardboard packs^×.

^× the cardboard pack may be perforated or have sticker(s) applied for first-opening control.

Tablets white, round, biconvex, with a score on one side and an engraving “0.2” on the other.

Excipients : lactose monohydrate – 123.7 mg, potato starch – 73.4 mg, povidone – 1.9 mg, magnesium stearate – 0.51 mg.

15 pcs. – polyethylene bottles (1) – cardboard packs^×.
30 pcs. – polyethylene bottles (1) – cardboard packs^×.
90 pcs. – polyethylene bottles (1) – cardboard packs^×.

^× the cardboard pack may be perforated or have sticker(s) applied for first-opening control.

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

Vasopressin analog. Antidiuretic.

Desmopressin is a structural analog of the natural hormone arginine vasopressin. Desmopressin is obtained by modifications in the structure of the vasopressin molecule – deamination of 1-cysteine and substitution of 8-L-arginine with 8-D-arginine. The structural changes, combined with a significantly enhanced antidiuretic ability, result in a less pronounced effect on the smooth muscles of blood vessels and internal organs compared to vasopressin, which eliminates undesirable spastic side effects.

The drug increases the permeability of the epithelium of the distal parts of the convoluted tubules to water and increases its reabsorption.

Use of Minirin^® in central diabetes insipidus leads to a decrease in the volume of urine excreted and a simultaneous increase in urine osmolality and a decrease in plasma osmolality. This leads to a decrease in the frequency of urination and a reduction in nocturnal polyuria.

In most cases, taking 0.1-0.2 mg of desmopressin provides an antidiuretic effect for 8-12 hours.

Pharmacokinetics

Absorption and Distribution

Concomitant food intake may reduce the degree of absorption from the gastrointestinal tract by 40%. C_max in plasma is reached within 2 hours. V_d is 0.2-0.3 l/kg.

The bioavailability of desmopressin ranges from 0.08% to 0.16% and is highly variable. Desmopressin does not cross the blood-brain barrier.

Elimination

Excreted in urine. T_1/2 when taken orally is 2-3 hours.

Indications

• Central diabetes insipidus;
• Primary nocturnal enuresis in children over 5 years of age;
• Nocturnal polyuria in adults (as symptomatic therapy).

ICD codes

Dosage Regimen

The optimal dose of Minirin^® should be selected individually. The drug should be taken after meals, as food intake may affect the absorption of the drug and its effectiveness.

For central diabetes insipidus the recommended initial dose for children and adults is 100 mcg 1-3 times/day. Subsequently, the dose is adjusted depending on the response to treatment. The usual daily dose is within the range of 0.2-1.2 mg. For most patients, the optimal maintenance dose is 100-200 mcg 1-3 times/day.

For primary nocturnal enuresis the recommended initial dose is 200 mcg at night. If there is no effect, the dose may be increased to 400 mcg. Control of compliance with fluid intake restriction in the evening is necessary. The recommended course of continuous treatment is 3 months. The decision to continue treatment should be made based on clinical data observed after drug withdrawal for 1 week.

For nocturnal polyuria inadults the recommended initial dose is 100 mcg at night. If there is no effect within 1 week, the dose is increased to 200 mcg and subsequently to 400 mcg, with dose increases no more than once a week. The danger of fluid retention in the body should be kept in mind.

If adequate clinical effect is not observed after 4 weeks of treatment and dose adjustment, it is not recommended to continue using the drug.

Adverse Reactions

Adverse effects are most often observed in cases where treatment is carried out without fluid restriction and result in fluid retention and/or hyponatremia, which may be asymptomatic or manifest with the following symptoms.

From the central and peripheral nervous system headache, dizziness; in severe cases – convulsions.

From the digestive system nausea, vomiting, dry mouth.

Other peripheral edema, weight gain.

Contraindications

• Habitual or psychogenic polydipsia;
• Heart failure and other conditions requiring the prescription of diuretics;
• Hyponatremia;
• Moderate and severe renal failure (CrCl<50 ml/min);
• Syndrome of inappropriate antidiuretic hormone secretion;
• Hypersensitivity to desmopressin or other components of the drug.

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

With special caution the drug is used in elderly patients (over 65 years of age) due to the high risk of adverse effects (including fluid retention, hyponatremia). If the decision to treat with Minirin^® is made: before prescribing the drug, 3 days after starting administration and with each dose increase, the plasma sodium level should be determined and the patient’s condition monitored.

Use in Pregnancy and Lactation

Results of the use of Minirin^® in 53 pregnant women with diabetes insipidus indicate no adverse effects on the course of pregnancy, on the health of the pregnant woman, the fetus and the newborn.

However, caution should be exercised when using the drug during pregnancy.

Studies have shown that the amount of desmopressin entering the body of a newborn with the breast milk of a woman taking high doses of desmopressin is significantly less than that which can affect diuresis.

Use in Renal Impairment

Contraindicated in moderate and severe renal failure (CrCl<50 ml/min).

With caution the drug should be used in renal failure, bladder fibrosis.

Geriatric Use

Clinical studies have shown that hyponatremia most often occurs in elderly patients (over 65 years of age).

Special Precautions

To avoid the development of adverse effects, it is mandatory to minimize fluid intake for 1 hour before administration and for 8 hours after administration of the drug in patients with primary nocturnal enuresis.

Clinical studies have shown that hyponatremia most often occurs in elderly patients (over 65 years of age).

Minirin^® should not be used when there are other additional causes for fluid retention and electrolyte disorders. There is a high risk of adverse effects in elderly patients with initially low plasma sodium levels and polyuria from 2.8 to 3 liters.

Prevention of the development of hyponatremia consists of increasing the frequency of determination of plasma sodium, especially when used concomitantly with drugs that cause the syndrome of inappropriate antidiuretic hormone secretion (including tricyclic antidepressants, selective serotonin inhibitors, chlorpromazine and carbamazepine) and NSAIDs.

In case of acute urinary incontinence, dysuria and/or nocturia, urinary tract infection, suspicion of a tumor of the bladder or prostate gland, presence of polydipsia and decompensated diabetes mellitus, diagnosis and treatment of these conditions and diseases should be carried out before starting treatment with Minirin^®.

If systemic infections, fever, gastroenteritis develop during treatment, the use of the drug should be discontinued.

Effect on ability to drive vehicles and machinery

No effect on the ability to drive vehicles and operate machinery.

Overdose

Symptoms overdose leads to an increase in the duration of action of the drug and an increased risk of fluid retention (including convulsions, loss of consciousness) and hyponatremia.

Treatment for hyponatremia – discontinue the drug, remove fluid intake restrictions, infusion of isotonic or hypertonic sodium chloride solution may be performed. In case of severe fluid retention – furosemide should be added to the above therapy.

In case of overdose, a doctor should be consulted.

Drug Interactions

Concomitant use of indomethacin may enhance, but not prolong, the action of Minirin^®.

Concomitant use of glybutide, tetracycline, lithium, norepinephrine weakens the antidiuretic effect of Minirin^®.

Concomitant use of Desmopressin enhances the effect of hypertensive agents.

Concomitant use of tricyclic antidepressants, selective serotonin inhibitors, chlorpromazine and carbamazepine, which can cause the syndrome of inappropriate antidiuretic hormone secretion, may enhance the antidiuretic effect of Minirin^® and lead to an increased risk of fluid retention and hyponatremia.

Concomitant use of Minirin^® with NSAIDs may increase the risk of adverse effects.

Concomitant use of Minirin^® with loperamide may lead to a threefold increase in the plasma level of desmopressin, which significantly increases the risk of fluid retention and the occurrence of hyponatremia. Presumably, other drugs that slow down peristalsis may cause a similar effect.

Concomitant use of Minirin^® with dimethicone may reduce the absorption of desmopressin.

Storage Conditions

The drug should be stored out of the reach of children, in a dry place at a temperature not exceeding 25°C (77°F); the desiccant capsule should not be removed from the cap.

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.