Ferring International Center
Composition of the medicinal product:
| desmopressin acetate | 0.1 mg |
| desmopressin acetate | 0.2 mg |
| desmopressin acetate | 0.1 mg/ml |
Pharmacological properties
Pharmacodynamics. The drug Minirin contains desmopressin - a synthetic analogue of the natural hormone of the posterior pituitary - L-arginine-vasopressin. The difference between them is that the cysteine amino group in position 1 is absent, and 8-L-arginine is replaced by 8-D-arginine. These changes mean that the molecule has largely lost its vasopressor effect, while the antidiuretic effect and its duration have increased.
Desmopressin increases the permeability of the epithelium of the distal convoluted tubules to water and increases its reabsorption from primary urine.
After oral administration of Minirin, the effect lasts from 6 to 14 hours.
With intranasal administration of desmopressin, the dose required to control diabetes insipidus varies considerably among individuals. On average, 20 mcg of intranasal desmopressin is effective for 10 hours or more.
Pharmacokinetics
The absolute bioavailability of Minirin, tablets, is 0.16% with a 95% confidence interval of 0.17%. C max in blood plasma is achieved within 2 hours. Food intake reduces the rate and extent of absorption by 40%.
After intranasal administration, the bioavailability of desmopressin is about 10%. C max in blood plasma is achieved approximately 50 minutes after intranasal administration of desmopressin.
distribution
The distribution of desmopressin is best described by a two-phase model with a volume of distribution in the elimination phase of 0.3-0.5 l/kg.
Biotransformation
The metabolism of desmopressin in vivo has not been studied. In vitro studies of microsomal metabolism in human liver cells have shown that no significant amounts of desmopressin are metabolized by the cytochrome P450 system.
Thus, metabolism of desmopressin in the liver in vivo is unlikely.
The effect of desmopressin on the plasma concentrations of other drugs is probably minimal due to the lack of effect on the cytochrome P450 system.
allocation
The total clearance of desmopressin is 7.6 l / h. The final T ½ of desmopressin is 2.8 h, in healthy volunteers the proportion of the drug excreted unchanged was 52% (44-60%). Desmopressin is excreted by the kidneys.
Linearity / nonlinearity
There are no data on the nonlinearity of any pharmacokinetic parameter of desmopressin.
Indication
Minirin tablets
Diabetes insipidus of central genesis; primary nocturnal enuresis in children over 5 years of age with normal concentrating kidney function; symptomatic treatment of nocturia associated with nocturnal polyuria in adults.
Minirin spray
As an antidiuretic agent:
for the treatment of diabetes insipidus of central genesis; in post-traumatic polyuria and polydipsia in the presence of a transient deficiency or absence of antidiuretic hormone after hypophysectomy, surgery in the pituitary gland or in case of craniocerebral trauma.
As a diagnostic tool for:
rapid test to determine the concentrating ability of the kidneys; differential diagnosis of diabetes insipidus.
Minirin tablets. The optimal dose of Minirin is selected individually. The drug is taken with meals.
Central diabetes insipidus
The initial dose for adults and children 5 years and older is 0.1 or 0.2 mg of desmopressin 3 times a day. Then the dose is selected depending on the body's response. The daily dose varies from 0.2 to 1.2 mg/day. For most patients, the optimal dose is 0.1-0.2 mg of desmopressin 3 times a day. In case of fluid retention (hyponatremia), treatment should be discontinued and the dosage adjusted.
Primary nocturnal enuresis
The dosage for adults and children 5 years and older is 0.2 mg of desmopressin before bedtime. In case of insufficient effect, the dose can be increased to 0.4 mg. During treatment, it is necessary to limit fluid intake. The course of treatment is 3 months. The question of the need to continue therapy should be decided after a week's break in taking Minirin.
nocturia
In order to diagnose nocturnal polyuria, data on the volume and frequency of urination in patients with nocturia should be available no later than 2 days before the start of therapy. Nocturnal polyuria is the excretion of urine, the volume of which exceeds the volume of the bladder or 1/3 of the daily diuresis.
The initial dose is 0.1 mg of desmopressin. If this dose is not effective enough within 1 week, it is increased to 0.2 mg and then with weekly increases to 0.4 mg.
It is not recommended to prescribe treatment to elderly patients (65 years and older). If treatment is prescribed, it is necessary to monitor the sodium level in the blood before starting treatment, after 3 doses of the drug and after increasing the dose.
If symptoms of fluid retention and/or hyponatremia develop (headache, nausea/vomiting, weight gain and, in severe cases, convulsions), treatment should be discontinued immediately until the patient has fully recovered. If treatment is continued, patients should be more closely monitored for fluid restriction.
If after 4 weeks of treatment and dose adjustment there is no adequate clinical effect, continued therapy is not recommended.
Minirin nasal spray. The drug is used intranasally.
Before use, clean your nose. Insert the nasal applicator exactly into the nasal passage and press once. One spray provides a dose of 10 mcg.
If a larger dose is required, the drug should be administered into another nasal passage. Breathe calmly through the nose during injection. After use, the protective cap should be put on the bottle with the applicator.
Diabetes insipidus and post-traumatic polyuria and polydipsia of central genesis
The dose should be selected individually, but the optimal dose for adults is 10-20 mcg 1-2 times a day. For children, the dose is 10 mcg 1-2 times a day.
If signs of fluid retention and/or hyponatremia appear, treatment should be temporarily discontinued and the dose adjusted.
Urine volume and osmolality should be determined to titrate the dose to the optimal level. If ineffective, the dose should be increased.
Intranasal administration (daily dose administered in 1-2 doses)
Daily dose (mcg) Administration via
| adults | 10-20 mcg | 1-2 injections |
| Children aged 1 year and older | 10 mcg | 1 injection |
|
Therapy should be focused on adequate sleep duration and adequate water balance.
Rapid test for determining the concentrating ability of the kidneys and for differential diagnosis of diabetes insipidus
Intranasal administration (daily dose administered in 1-2 doses)
Daily dose (mcg) Administration via
| adults | 1 × 40 mcg | 4 injections |
| Children aged 1 year and older | 1 × 20 mcg | 2 injections |
| Children under 1 year old | 1 × 10 μg | 1 injection |
|
The rapid test is used for the differential diagnosis between diabetes insipidus and polyuric syndrome of other genesis, as well as for the determination of reduced concentrating ability of the kidneys associated with urinary tract infection (cystitis, pyelonephritis). It is also used for the early diagnosis of tubulointerstitial lesions, for example, caused by lithium drugs, analgesics, chemotherapeutic drugs and immunosuppressants.
The rapid test is best performed in the morning. Fluid intake should be limited for the first 12 hours after administration. Children under 5 years of age and patients with heart disease or hypertension should have their fluid intake halved.
Before the test, urine osmolality should be determined. After the administration of desmopressin, 2 urine samples are taken (preferably after 2 and 4 hours). Urine obtained during the 1st hour should be collected separately and discarded. Osmolality is determined in both urine samples. To determine the concentrating ability of the kidneys, the highest achieved osmolality value is compared with the value before the study or with the reference value corresponding to the patient's age (for adults 800-1000 mOsm / kg). Low values, no increase or a slight increase in urine osmolality indicate a violation of the concentrating ability of the kidneys. If urine osmolality increases significantly and urine volume decreases significantly, this means that polyuria is associated with diabetes insipidus of central genesis.
Contraindication:
habitual or psychogenic polydipsia, polydipsia in patients with alcoholism (urine production exceeds 40 ml/kg/24 h); severe forms of classical von Willebrand disease (type IIb), a decrease in factor VIII activity to 5% and the presence of antibodies to factor VIII; heart failure or other conditions requiring the appointment of diuretics; moderate to severe renal failure (creatinine clearance below 50 ml/min); hyponatremia; syndrome of inappropriate antidiuretic hormone secretion; hypersensitivity to desmopressin or other components of the drug; alcohol abuse.
SIDE EFFECTS:
Minirin tablets. The most serious adverse reaction associated with the use of desmopressin is hyponatremia, which can cause headache, abdominal pain, nausea, vomiting, weight gain, dizziness, confusion, general malaise, memory impairment, vertigo, and in severe cases, seizures and coma.
Most adults treated for nocturia who develop hyponatremia have had a decrease in serum sodium after 3 days of treatment. In adults, the risk of hyponatremia increases with increasing desmopressin dose and is more pronounced in women.
Cerebral edema and fever are possible; angina attacks may occur in patients with ischemic heart disease.
In adults, the most common adverse reaction during treatment was headache (12%). Other common adverse reactions were hyponatremia (6%), dizziness (3%), hypertension (2%) and gastrointestinal disorders (nausea - 4%, vomiting -1%, abdominal pain - 3%, diarrhea - 2% and constipation -1%). Effects on sleep/level of consciousness were less common, namely: insomnia (0.96%), somnolence (0.4%), asthenia (0.06%). Anaphylactic reactions were not observed in clinical studies, but there are isolated observations.
In children, the most common adverse reaction during treatment was headache (1%), rarely observed mental disorders (proneness to affect - 0.1%, aggression - 0.1%, anxiety - 0.05%, mood swings - 0.05%, nightmares - 0.05%), which decreased after the end of treatment, and gastrointestinal disorders (abdominal pain - 0.65%, nausea - 0.35%, vomiting - 0.2%, diarrhea - 0.15%). Anaphylactic reactions were not observed in clinical studies, however, there are isolated manifestations.
Table 1
Adverse reactions in adults
Classification by organ system Very common (> 10%) Common (1-10%) Uncommon (0.1-1%) Very rare (0.1-0.01%) unknown
| Immune system disorders | | | | | anaphylactic reaction |
| Metabolic disorders | | hyponatremia * | | | Dehydration**, hypernatremia** |
| mental disorders | | | insomnia | Confusion of consciousness * | |
| Nervous system disorders | Headache* | dizziness * | drowsiness,
paresthesias | | Convulsions*, asthenia*, coma* |
| Visual impairment | | | visual impairment | | |
| Hearing and vestibular disorders | | | vertigo * | | |
| Cardiac disorders | | | feeling of heartbeat | | |
| vascular disorders | | AG | orthostatic hypotension | | |
| Respiratory system disorders | | | dyspnea | | |
| Gastrointestinal disorders | | Nausea*, abdominal pain*, diarrhea, constipation, vomiting* | Dyspepsia, flatulence, bloating | | |
| Skin and subcutaneous tissue disorders | | | Increased sweating, itching, rash, hives | allergic dermatitis | |
| Musculoskeletal and connective tissue disorders | | | Muscle cramps, muscle pain | | |
| Renal and urinary disorders | | Bladder and urethral symptoms | | | |
| general disorders | | Edema, increased fatigue | Discomfort*, chest pain, flu-like illness | | |
| research | | | Weight gain*, increased liver enzymes, hypokalemia | | |
|
* Hyponatremia can cause headache, abdominal pain, nausea, vomiting, weight gain, dizziness, confusion, general malaise, memory impairment, and in severe cases, seizures and coma.
** Only for diabetes insipidus.
Table 2
Adverse reactions in children
Classification by organ system Very common (> 10%) Common (1-10%) Uncommon (0.1-1%) Very rare (0.1-0.01%) unknown
| Immune system disorders | | | | | anaphylactic reaction |
| Metabolic disorders | | | | | hyponatremia **** |
| mental disorders | | | Mood lability **, aggression *** | Anxiety symptoms, nightmares*, mood swings* | Abnormal behavior, emotional disturbances, depression, hallucinations, insomnia |
| Nervous system disorders | | Headache | | drowsiness | Attention deficit, psychomotor hyperactivity, seizures * |
| Cardiovascular system disorders | | | AG | | |
Respiratory system disorders | | | | | Nosebleed | | Gastrointestinal disorders | | | Nausea*, abdominal pain*, diarrhea, vomiting* | | |
| Skin and subcutaneous tissue disorders | | | | | Allergic dermatitis, increased sweating, rash, urticaria |
| Renal and urinary disorders | | | Bladder and urethral symptoms | | |
| general disorders | | | Peripheral edema, increased fatigue | increased excitability | |
|
* Hyponatremia can cause headache, abdominal pain, nausea, vomiting, weight gain, dizziness, confusion, general malaise, memory impairment, and in severe cases, seizures and coma.
** In post-marketing studies, it was observed equally frequently in children of different age groups (<18 years).
*** Observed exclusively in children (<18 years) during post-marketing studies.
**** In post-marketing studies, it was primarily observed in children (<12 years).
Minirin nasal spray. Excessive fluid intake can lead to hyperhydration, which is manifested by the following symptoms: weight gain, hyponatremia, and in severe cases - convulsions, which are combined with impaired consciousness up to prolonged loss of consciousness. This is more often observed in children under 1 year of age and in elderly patients, depending on their general condition.
System organ class Common (> 1/100 to <1/10) Rare (> 1/10,000 to <1/1,000) Very rare (<1/10,000)
| Respiratory system, chest organs, mediastinum | Nosebleed, nasal congestion, rhinitis | | |
| Gastrointestinal tract | Nausea, vomiting, abdominal pain | | |
| From the CNS | | Cerebral edema, impaired consciousness, and seizures associated with hyponatremia | |
| Skin/general reactions, injection site reactions | | | Allergic reactions, hypersensitivity reactions (e.g. itching, skin rash, fever, bronchospasm, anaphylaxis) |
| metabolic disorders | | | hyponatremia |
|
Cardiovascular disorders
Due to increased water reabsorption, blood pressure may increase, and in some cases (persistent) hypertension may develop. Patients with coronary heart disease may experience angina attacks.
Headaches and emotional disorders are possible in children.
When the dose is reduced, all these side effects, with the exception of allergic reactions, disappear.
It is mandatory to limit fluid intake to a minimum 1 hour before and within 8 hours after the use of the drug in patients with primary nocturnal enuresis and nocturia. Treatment without a concomitant reduction in fluid intake may lead to fluid retention and/or hyponatremia with/without concomitant symptoms and signs (headache, nausea, vomiting, edema, weight gain, and in severe cases - cerebral edema, convulsions and coma). All patients and their caregivers should be carefully instructed on the need to adhere to the water regimen.
The drug contains lactose. It should not be used in patients with hereditary galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Bladder dysfunction and ductal obstruction should be assessed before initiating treatment.
Elderly patients and patients with low serum sodium levels are at increased risk of hyponatremia.
Treatment with the drug should be discontinued in the event of an acute intercurrent illness characterized by water and/or salt imbalance (systemic infections, fever, gastroenteritis).
The drug should be used with caution in patients at risk of increased intracranial pressure, as well as water and/or salt imbalance.
Use with caution in patients at risk of developing thrombosis.
Before starting treatment, the patient's agreement to limit fluid intake should be sought. Patients should be advised to avoid fluid overload (including swimming) and to discontinue desmopressin in the event of vomiting or diarrhea until fluid balance is restored.
The risk of hyponatremic seizures caused by hyponatremia can be minimized by maintaining the recommended starting dose and avoiding concomitant use of drugs that increase vasopressin secretion.
Minirin nasal spray should only be used when oral administration of desmopressin is not possible. Treatment should be started with the lowest doses, increasing the dose gradually, and with caution.
When conducting a concentration test, the volume of fluid should be limited to 0.5 l, especially 1 hour before and within 8 hours after taking the drug.
Minirin nasal spray should be used with caution in: young and elderly patients; in conditions characterized by water and/or salt imbalance; in patients at risk of increased intracranial pressure; in patients at risk of developing thrombosis.
In the treatment of central diabetes insipidus, severe hyponatremia may be associated with the use of Minirin nasal spray.
In the presence of damage to the nasal mucosa (e.g. scarring, edema), intranasal administration may alter drug absorption. In these cases, desmopressin should not be used intranasally.
The drug should be used with extreme caution in patients with cystic fibrosis.
Benzalkonium chloride, which is contained in the drug as an excipient, may cause swelling of the nasal mucosa, especially with prolonged use. If such a reaction is suspected (in chronic nasal congestion), the patient should be switched to a nasal form of the drug without preservative, if possible. If such preparations are not available, the possibility of using the drug in another dosage form should be considered.
Use during pregnancy or breastfeeding
Minirin tablets
It is prescribed with caution during pregnancy only if the expected benefit to the expectant mother outweighs the potential risk to the fetus.
Analysis of breast milk from mothers taking high doses of desmopressin (300 mcg intranasally) indicates that the amount of desmopressin that can be passed to the infant is significantly less than that required to affect diuresis.
Minirin nasal spray
Clinical studies of the use of the nasal form of the drug desmopressin during pregnancy and breastfeeding have not revealed any signs of adverse effects on the mother or child. Minirin nasal spray can be used during pregnancy for replacement treatment of antidiuretic hormone deficiency.
Only small amounts of Minirin nasal spray pass into breast milk. Results of analysis of milk from mothers who breastfed their infants and took high doses of desmopressin (300 mcg intranasally) indicate that the amount of desmopressin that can be transferred to the infant is significantly less than that required to affect diuresis.
children
Minirin tablets
It is used in children from 5 years of age with normal concentrating kidney function for the treatment of primary nocturnal enuresis and diabetes insipidus of central genesis.
Minirin nasal spray
Use in children - under adult supervision to control the dose of the drug.
The concentration test in children under 1 year of age is performed exclusively in a hospital setting with follow-up observation.
The ability to influence the reaction speed when driving or working with other mechanisms
Minirin tablets. The drug does not affect or has a negligible effect on the ability to drive vehicles and work with other mechanisms, which should be taken into account by drivers and specialists whose work requires increased attention. The possible risk of dizziness or drowsiness when using the drug should be taken into account.
Minirin nasal spray. Has no effect.
The use of drugs that can cause the syndrome of inappropriate antidiuretic hormone secretion, such as tricyclic antidepressants, selective serotonin reuptake inhibitors, chlorpromazine and carbamazepine, as well as some antidiabetic agents from the sulfonylurea group, especially chlorpropamide, may enhance the antidiuretic effect of the drug and lead to an increased risk of fluid retention and hyponatremia.
Concomitant use with nonsteroidal anti-inflammatory drugs may cause fluid retention/hyponatremia.
When used simultaneously with oxytocin, an increase in the antidiuretic effect and a decrease in uterine perfusion should be taken into account.
Clofibrate, indomethacin may enhance the antidiuretic effect of desmopressin, while glibenclamide and lithium salts may reduce it.
Concomitant use with loperamide may increase desmopressin plasma levels 3-fold and increase the risk of side effects (fluid retention and hyponatremia). Although similar studies have not been conducted, it is likely that other drugs that reduce the tone and motility of intestinal smooth muscle may have a similar effect.
Food intake may reduce the intensity and duration of the antidiuretic effect when using low doses of the drug.
If all of the above drugs are used simultaneously, blood pressure, plasma sodium levels, and diuresis should be monitored.
Conditions and shelf life
Overdose symptoms may occur when taking too high a dose of the drug, excessive fluid intake during or shortly after taking desmopressin, or under inadequate conditions for the preparation of the drug during intranasal administration.
Symptoms: weight gain (water retention), headache, nausea, mild hypertension, tachycardia, "hot flashes", and in severe cases - hyperhydration and seizures.
Overdose may occur in children at an early age due to insufficiently careful dose selection.
In case of overdose, the dose of the drug should be reduced, the interval between individual doses should be increased, or the drug should be discontinued. The presence of cerebral edema requires immediate hospitalization of the patient in the intensive care unit. Convulsions in children also require intensive care. There is no specific antidote. If there are indications for diuretic therapy, saluretics such as furosemide may be used.
STORAGE CONDITIONS:
in a place protected from light at a temperature not exceeding 25 °C.
