Minirin Melt, 120 mcg 30 pcs

Pharmacodynamics:

Minirin® Melt contains desmopressin, a structural analog of the natural peptide hormone of the hypothalamus, arginine vasopressin, derived from changes in the structure of the vasopressin molecule. The difference consists in the deamination of cysteine (in the 1st position) and replacement of L-arginine (in the 8th position) by D-arginine. This leads to a significant prolongation of antidiuretic action and complete absence of action on vascular and internal smooth muscle compared to native arginine vasopressin.

Desmopressin increases permeability of distal tubule epithelium and increases water reabsorption, resulting in decrease of urine output, increase of urine osmolarity with simultaneous decrease of blood plasma osmolarity, decrease of frequency of urination and decrease of nocturia (nocturnal polyuria).

Clinical studies

Clinical studies of Minirin® Melt, lyophilizate tablets, for the treatment of nocturia showed the following results:

There was a 50% reduction in nocturnal urinary frequency in 39% of patients taking desmopressin compared with 5% of patients in the placebo group (p&p<0.0001) ;

– the mean number of urges to urinate at night was reduced by 44% in the desmopressin group and by 15% in the placebo group (p&p<0.0001);

the mean duration of the first period of sleep was increased by 64% in the patients taking desmopressin compared to 20% in the placebo group (p<0.0001);

The mean initial sleep time increased by 2 hours in the desmopressin group and by 31 minutes in the placebo group (p<0.0001).

Pharmacokinetics:

Absorption and distribution

The maximum plasma concentration (Cmax) of desmopressin is reached within 0.5-2 h (Tmax) after sublingual administration of the drug and is directly proportional to the dose taken: After administration of 200, 400, and 800 mcg, the Tmax was 14 pg/mL, 30 pg/mL, and 65 pg/mL, respectively. Simultaneous intake of food may reduce the degree and rate of absorption by 40%. The bioavailability of desmopressin in sublingual form in doses of 200, 400 and 800 mcg is about 0.25%. Bioavailability may vary from patient to patient.

Desmopressin does not penetrate the blood-brain barrier.

Metabolism and excretion

In an in vitro liver microsome study, it was found that a small portion of desmopressin is metabolized in the liver. Based on the findings, it was concluded that the metabolism of desmopressin in the liver in vivo is not significant. Desmopressin is excreted by the kidneys with a half-life of 2.8 h.

Indications

– Central diabetes mellitus;

Polyuria/polydipsia after pituitaryectomy or turkey saddle surgery;

Primary nocturnal enuresis in adults and children over 5 years old;

– Nocturia in adults associated with nocturnal polyuria (increased urination at night, which exceeds bladder capacity and causes the need to get up at night more than once to empty the bladder) – as symptomatic therapy.

Active ingredient

Composition

How to take, the dosage

The method of administration is strictly under the tongue. DO NOT PASS THE TABLE WITH LIQUID!

The optimal dose of the drug Minirin® Melt is selected individually. Dose ratios between the two dosage forms of the drug are shown in the table:

tablets

lyophilisate tablets

0.1 mg

60 µg

0.2 mg

120 µg

0.4 mg

240 µg

Minirin® Melt should be taken some time after meals because eating reduces the absorption of desmopressin and its effectiveness.

Central diabetes mellitus and polyuria/polydipsia after pituitaryectomy

At the beginning of treatment, the optimal dose of the drug is determined by the physician individually, taking into account osmolarity and urine volume. During treatment duration of sleep and water-electrolyte balance should be monitored.

The recommended starting dose for children and adults of Minirin® Melt is 60 mcg sublingually (under the tongue) 3 times a day. Subsequently the dose is changed depending on the therapeutic effect. The recommended daily dose is between 120 and 720 mcg. The optimal maintenance dose is 60-120 mcg 3 times daily sublingually.

In case of signs of fluid retention/hyponatremia, treatment should be stopped and the drug dose taken adjusted.

Primary nocturnal enuresis

The optimal therapeutic dose is determined individually and adjusted according to the patient’s response to treatment.

The recommended starting dose is 120 mcg sublingually at night. If there is no effect, the dose may be increased to 240 mcg. Evening fluid restriction should be monitored.

If there are any signs of fluid retention/hyponatremia, treatment should be discontinued and the dose taken adjusted.

The recommended course of continuous treatment is 3 months. The decision to continue treatment is made on the basis of clinical findings after 1 week of withdrawal.

Nockuria

The recommended starting dose is 60 mcg at night sublingually. If there is no effect within 1 week, the dose is increased to 120 mcg and thereafter to 240 mcg with increasing doses at a frequency of no more than once a week.

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

Control of fluid restriction is necessary.

Patient special groups

Patients of advanced age

The drug is contraindicated in patients aged 65 years and older for symptomatic therapy of nocturia. Caution should be exercised when using the drug in patients 65 years of age or older for treatment of nonsanguineous diabetes.

When prescribing desmopressin in elderly patients, plasma sodium should be monitored before starting treatment, 3 days after starting treatment or when increasing the dose, and if necessary during the course of the drug.

Interaction

When used concomitantly, clofibrate, indomethacin and other nonsteroidal anti-inflammatory drugs (NSAIDs), tricyclic antidepressants, selective serotonin reuptake inhibitors, chlorpromazine, chlorpropamide, carbamazepine and other drugs that can cause syndrome of inadequate secretion of antidiuretic hormone, may increase antidiuretic effect of desmopressin and lead to increased risk of fluid retention and hyponatremia. When concomitant use of desmopressin with the above drugs, blood pressure, plasma sodium concentration and urine volume should be monitored closely.

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

It is possible that other drugs that decrease intestinal smooth muscle tone and motility may have a similar effect.

Simultaneous administration with oxytocin may increase the antidiuretic effect of desmopressin and decrease uterine perfusion.

When Minirin® Melt is used concomitantly with the above drugs to prevent hyponatremia, blood pressure, plasma sodium concentration, and urine volume should be monitored carefully.

The administration of glibenclamide and lithium drugs may decrease the antidiuretic effect of desmopressin.

Interaction with drugs metabolized in the liver is unlikely because desmopressin has no significant effect on hepatic metabolism according to in vitro studies of liver microsomes. No in vivo studies have been performed.

Special Instructions

In order to avoid the development of side effects, it is mandatory to limit fluid intake to a minimum 1 h before and within 8 h after administration of the drug in patients with primary nocturnal enuresis.

Incompliance with the rules of taking the drug may cause fluid retention in the body and/or hyponatremia, which may be manifested by the following symptoms: headache, dizziness, nausea, vomiting, weight gain, in severe cases – cerebral edema, seizures and coma.

The safety of the drug with long-term use in cases of nocturnal enuresis has not been studied.

To diagnose nocturnal polyuria in patients with nocturia, the frequency and volume of urination should be monitored 2 days before treatment. Increased urine output at night, exceeding bladder capacity or exceeding 1/3 of daily urine volume, is considered as nocturnal polyuria.

When using desmopressin to treat nocturnal enuresis, cases of cerebral edema and seizures in healthy children and adolescents have been observed. Based on the available information, we can conclude that the risk of cerebral edema and seizures is highest in the first week of treatment.

Hyponatremia most often occurs in elderly patients (>65 years) and in patients with baseline low sodium concentration.

The duration of action of the drug increases with increasing dose, leading to increased risk of hyponatremia. Increasing the dose should be done with great caution.

Minirin® Melt 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; in patients with electrolyte and water disorders; in patients at risk of thrombosis; in pregnancy, including preeclampsia; in elderly patients (over 65 years) when used for treatment of diabetes mellitus.

Before starting the drug (and 3 days after starting or increasing the dose), plasma sodium levels should be determined in patients over 65 years of age.

If headache and/or nausea occur, the drug should be discontinued.

In patients with arterial hypertension or chronic kidney disease, the symptoms listed under “Side effects” may develop.

Particular caution should be exercised when using Minirin® Melt in children and elderly patients or patients who are at risk of increased intracranial pressure, taking care to prevent fluid retention.

Patients and, if using in children, their parents should be informed to limit fluid intake and discontinue desmopressin if there is vomiting, diarrhea, systemic infection, and fever, and not resume until water-electrolyte balance is normalized.

To reduce the risk of hyponatremia or fluid retention, fluid intake should be reduced in the following cases:

– when taking medications that lead to inadequate antidiuretic hormone production syndrome (tricyclic antidepressants, selective serotonin reuptake inhibitors, chlorpromazine, chlorpropamide and carbamazepine);

– when concomitant use of NSAIDs.

Body weight changes should be monitored during treatment.

Before using the drug, organic causes of polyuria, increased urine volume, or nocturia, including prostatic hyperplasia, urinary tract infections, nephrolithiasis, bladder tumors, impaired bladder sphincter function, polydipsia, or glycemic control disorders in diabetes, should be excluded, and appropriate treatment should be given if the above conditions exist.

Inadequate adrenal or thyroid function should be treated before starting treatment.

Influence on ability to drive vehicles and machines:
There are currently no data on possible effects of Minirin® Melt on ability to drive and operate machinery. Nevertheless, the use of the drug may lead to the development of such adverse reactions as dizziness, headache which may adversely affect the ability to drive vehicles and perform potentially dangerous activities requiring high concentration and quick psychomotor reactions.

We advise caution when driving vehicles or operating machinery.

Contraindications

High sensitivity to desmopressin or other drug components;

– habitual or psychogenic polydipsia (with a urine output of 40 ml/kg/24 hours);

– known or suspected chronic heart failure and other conditions requiring the prescription of diuretics;

– hyponatremia;

p>- moderate to severe renal impairment (creatinine clearance (CK) less than 50 ml/min);

children under 5 years of age;

– age 65 years and older when used for symptomatic treatment of nocturia;

– inadequate antidiuretic hormone production syndrome;

polydipsia in chronic alcoholism.

With caution:
Renal insufficiency (CK more than 50 ml/min), bladder fibrosis, cystic fibrosis, coronary heart disease, arterial hypertension, water-electrolyte balance disorders, potential risk of increased intracranial pressure, risk of thrombosis, pregnancy, including preeclampsia.including preeclampsia, advanced age (65 years and older) when used for the treatment of non-sugar diabetes.

Side effects

The use of the drug without concomitant fluid restriction may lead to fluid retention and/or hyponatremia, which may be asymptomatic or accompanied by the following symptoms: headache, nausea and/or vomiting, weight gain; in severe cases – convulsions, which are combined with impaired consciousness up to long-term loss of consciousness. These symptoms are particularly common in children under one year of age or the elderly, depending on their general condition.

Frequency of side effects: Very common (≥ 1/10), common (≥ 1/100 to < 1/10), infrequent (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1 /10000), frequency not determined (no data on the incidence of adverse reactions currently available, identified during post-registration use of Minirin® Melt).

Adults:

The table shows adverse reactions and their frequency based on data from a clinical trial in patients with nocturia (N=1557) and post-registration use of the drug for all indications of use (including nonsanguineous diabetes).

System-organ class

Very frequently

Frequently

Infrequently

Rarely

.Frequency Not Established

Immune System Disorders

Anaphylactic reactions

Metabolic and nutritional disorders

Hyponatremia

Hyponatremia*, hypernatremia*

Psychiatric disordersMental disorders

Lack of sleep

Consciousness confusion

Nervous system disorders

Headache

Dizziness

Sleepiness, paresthesia

Convulsions, asthenia*, coma

Visual disturbances

Decreased visual acuity

Hearing and labyrinth disturbances

Vertigo

Heart disorders

Perception of palpitations

Vascular disorders

Arterial

Hypertension

Orthostatic hypotension

Respiratory, chest, and mediastinal disorders

Dyspnea

HypertensionGastrointestinal disorders

Nausea, abdominal pain, diarrhea, constipation, vomiting

Dyspepsia, flatulence, bloating

Skin and subcutaneous tissue disorders

Intensified sweating, itching, skin rash, urticaria

Periodic dermatitis.Allergic dermatitis

Muscular and connective tissue disorders

Muscular cramps, myalgia

Muscle spasmsRenal and urinary tract disorders

Peripheral edema, fatigue

Bladder function, urinary disorders

General disorders and disorders at the site of administration

Peripheral edema, feeling tired

discomfort, chest pain, flu-like syndrome

Laboratory and instrumental findings

Elevated body weight, increased liver enzyme activity, hypokalemia

* Adverse reactions were observed only in patients with non-sugar diabetes.

Children

The table shows the adverse reactions and their frequency of occurrence, based on data from a clinical study (n=1923) and post-registration use of minirin® melt for treatment of primary nocturnal enuresis in children.

System-organ class

very often

frequently

infrequently

frequently

frequently not determined

disorders of the immune system

anaphylactic reactions

metabolic and nutritional disorders

hyponatremia

psychiatric disorders

emotional lability, display of aggression

anxiety, nightmares, violent mood swings

behavioral changes, emotional disturbances, depression, hallucinations, insomnia

/p>

Nervous system disorders

headache

sleepiness

disorders of attention, psychomotor hyperactivity, convulsions

vascular disorders

harterial hypertension

disorders of the respiratory system, chest and mediastinum

nasal bleeding

gastrointestinal disorders

stomach pain, nausea, vomiting, diarrhea

dermal and subcutaneous disorders

p>allergic dermatitis, skin rash, increased sweating, urticaria

disorders of the kidneys and urinary tract

disorders of bladder function, disorders of urinary excretion

general disorders and disorders at the site of administration

peripheral edema, feeling of fatigue

irritability

warnings! Desmopressin may have an antidiuretic effect. administration of minirin® melt, lyophilisate tablets without simultaneous fluid restriction can cause fluid retention accompanied by hyponatremia which leads to headache, abdominal pain, nausea, vomiting, weight gain, dizziness, confusion, malaise, and, in severe cases, can lead to seizures, cerebral edema and coma.

In particular, the risk of developing the above complications is highest in children under 1 year of age or in older patients (over 65), depending on general health. when treating nocturia in adults, hyponatremia is more common at the start of treatment or when the dose is increased. hyponatremia is reversible. the water-electrolyte balance should be monitored when taking minirin® melt.

The treatment may result in arterial hypertension due to fluid retention. patients with coronary heart disease may have angina.

If any of the adverse reactions listed in the instructions worsen, or if you notice any other adverse reactions not listed in the instructions, tell your doctor.

Overdose

Symptoms of overdose

Symptoms of overdose may occur if desmopressin is used at too high a dose or if excessive fluid intake occurs simultaneously or soon after taking desmopressin.

The symptoms of overdose are weight gain due to fluid retention, headache, nausea, and in severe cases, hyperhydration (water intoxication) accompanied by seizures, confusion, or loss of consciousness.

Overdose may be seen in children at an early age due to poorly controlled dosing.

Treatment

In case of overdose, depending on the severity of overdose, the dose should be reduced, the time between doses of the drug increased during the day, or the drug stopped.

If cerebral edema is suspected, immediate admission to the intensive care unit is necessary.

In case of seizures, immediate intensive care is required.

There is no known specific antidote for desmopressin.

Diuretics such as furosemide may be used to induce diuresis, with simultaneous monitoring of plasma electrolytes.

Pregnancy use

Pregnancy

While there are limited data on the use of desmopressin in pregnant women with nonsanguineous diabetes (n=53), no adverse effects on pregnancy or on the health of the pregnant woman, fetus, or newborn have been reported. Preclinical animal studies showed no direct or indirect effects on pregnancy, fetal development, delivery, or postpartum development. However, the drug is prescribed only when the expected benefits to the mother exceed the potential risk to the fetus. The dosing regimen of the drug during pregnancy should be adjusted to the patient’s condition. Taking into account the increased risk of preeclampsia, it is recommended to control blood pressure.

Breastfeeding period

A study of the breast milk of women who received desmopressin at a dose of 300 mcg intranasally showed that the amount of desmopressin that could be ingested by the baby was too small to affect his diuresis.