Minirin^® Melt (Lyophilized tablets) Instructions for Use

Marketing Authorization Holder

Ferring, GmbH (Germany)

Manufactured By

Catalent UK Swindon Zydis, Ltd. (United Kingdom)

Secondary Packaging

FERRING INTERNATIONAL CENTER, S.A. (Switzerland)

Quality Control Release

FERRING, GmbH (Germany)

ATC Code

H01BA02 (Desmopressin)

Active Substance

Desmopressin (Rec.INN registered by WHO)

Dosage Forms

	Minirin® Melt	Lyophilized tablets 60 mcg: 30 or 100 pcs.
		Lyophilized tablets 120 mcg: 30 or 100 pcs.
		Lyophilized tablets 240 mcg: 30 or 100 pcs.

Dosage Form, Packaging, and Composition

Lyophilized tablets white, round, with an engraving of one drop on one side.

Excipients : gelatin – 12.5 mg, mannitol – 10.25 mg, citric acid – to pH 4.8 (0.12-0.35 mg).

10 pcs. – blisters (3) – cardboard packs^×.
10 pcs. – blisters (10) – cardboard packs^×.

^× first-opening control stickers may be applied to the cardboard pack.

Lyophilized tablets white, round, with an engraving of two drops on one side.

Excipients : gelatin – 12.5 mg, mannitol – 10.25 mg, citric acid – to pH 4.8 (0.12-0.35 mg).

10 pcs. – blisters (3) – cardboard packs^×.
10 pcs. – blisters (10) – cardboard packs^×.

^× first-opening control stickers may be applied to the cardboard pack.

Lyophilized tablets white, round, with an engraving of three drops on one side.

Excipients : gelatin – 12.5 mg, mannitol – 10.25 mg, citric acid – to pH 4.8 (0.12-0.35 mg).

10 pcs. – blisters (3) – cardboard packs^×.
10 pcs. – blisters (10) – cardboard packs^×.

^× first-opening control stickers may be applied to the cardboard pack.

Clinical-Pharmacological Group

Vasopressin analog. Antidiuretic

Pharmacotherapeutic Group

Vasopressin and its analogues

Pharmacological Action

Desmopressin is a structural analogue of the natural hypothalamic peptide hormone arginine vasopressin, obtained by modifications in the structure of the vasopressin molecule. 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 plasma osmolality, a decrease in the frequency of urination, and a reduction in nocturia (nocturnal polyuria).

The antidiuretic effect after oral administration of a 0.1 mg dose lasts up to 8 hours.

Pharmacokinetics

Desmopressin is rapidly absorbed from the gastrointestinal tract. C_max is reached in approximately 2 hours. 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 orally. Place the lyophilized tablet on the tongue; it dissolves instantly without water.

Individualize the dose and schedule based on indication and clinical response.

For central diabetes insipidus: The typical maintenance dose is 0.1-0.2 mg (60-120 mcg) three times daily. Titrate the dose if signs of fluid retention or hyponatremia occur. The total daily dose range is 0.2-1.2 mg.

For primary nocturnal enuresis in children over 5 years: Initiate therapy with 120 mcg at bedtime. Adjust the dose based on response; the maximum recommended dose is 240 mcg.

For adult nocturia: The recommended initial dose is 60 mcg at bedtime. Titrate as needed; the maximum recommended dose is 120 mcg.

In all cases, strictly limit fluid intake for at least 1 hour before and 8 hours after administration to reduce the risk of water intoxication and hyponatremia.

For pediatric patients, use the lowest effective dose. Do not use in children under 4 years for diabetes insipidus or under 5 years for enuresis.

In elderly patients (≥65 years), use with extreme caution; contraindicated for nocturia treatment. Monitor plasma sodium concentration before initiation and during therapy.

Discontinue treatment during episodes of acute illness that may cause fluid and/or electrolyte imbalance (e.g., fever, vomiting, diarrhea).

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 in history; moderate and severe renal failure (CrCl 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 (CrCl 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 (CrCl less than 50 ml/min); use with caution in chronic mild renal failure (CrCl 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 taking desmopressin. Failure to follow the rules of taking the drug 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 taking desmopressin. 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 a potential risk of increased intracranial pressure; water-electrolyte imbalance; in patients at risk of thrombosis; during pregnancy, including 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 limit fluid intake and to discontinue desmopressin in case of vomiting, diarrhea, systemic infectious diseases and fever, and not to resume administration until 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 cause 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.

Therapy for adrenal cortex insufficiency or thyroid insufficiency should be performed before starting treatment.

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

Effect on ability to drive vehicles and machinery

There are no data on the possible effect of desmopressin on the ability to drive vehicles and machinery. Considering that Desmopressin can lead to the development of side effects such 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 machinery.

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 increase the antidiuretic effect of desmopressin and reduce uterine perfusion.

Taking 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.