Instructions Minirin tablets 0.1 mg bottle No. 30
Composition
active ingredient: desmopressin;
1 tablet contains desmopressin acetate 0.1 mg, corresponding to desmopressin base 0.089 mg or desmopressin acetate 0.2 mg, corresponding to desmopressin base 0.178 mg;
Excipients: lactose monohydrate; potato starch; povidone; magnesium stearate.
Dosage form
Pills.
Main physicochemical properties:
white oval biconvex tablets with a score on one side and embossed "0.1" on the other.
Pharmacotherapeutic group
Hormone preparations for systemic use, except sex hormones and insulins. Posterior pituitary hormones. ATC code H01B A02.
Pharmacological properties
Pharmacodynamics
The drug contains desmopressin - a structural analogue of the natural pituitary hormone - arginine vasopressin. The difference between them is the deamination of cysteine and the replacement of L-arginine with D-arginine. This leads to a significant increase in the duration of action and the complete absence of a pressor effect in clinically used doses. EC50 (half-maximal effective concentration) of desmopressin, which causes an antidiuretic effect, is 1.6 pg/ml. After oral administration, the effect lasts from 6 to 14 hours.
Pharmacokinetics
The absolute bioavailability of Minirin, tablets, is 0.16% with a 95% confidence interval of 0.17%. Peak plasma concentrations are achieved within 2 hours. Concomitant food intake reduces the rate and extent of absorption by 40%.
Distribution.
The distribution of desmopressin is best described by a biphasic 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, hepatic metabolism of desmopressin in vivo is unlikely.
The effect of desmopressin on the plasma concentrations of other drugs is likely to be minimal due to the lack of effect on the cytochrome P450 system.
Selection.
The total clearance of desmopressin is 7.6 l/h. The terminal half-life of desmopressin is 2.8 hours, and in healthy volunteers the proportion of the drug excreted unchanged was 52% (44%-60%).
Linearity/nonlinearity.
There is no evidence of nonlinearity in any pharmacokinetic parameter of desmopressin.
Indication
Central diabetes insipidus; primary nocturnal enuresis in children over 5 years of age with normal renal concentrating function; symptomatic treatment of nocturia associated with nocturnal polyuria in adults.
Contraindication
normal or psychogenic polydipsia (urine output greater than 40 ml/kg/24 h); heart failure or other conditions requiring diuretics; moderate to severe renal failure (creatinine clearance less than 50 ml/min); hyponatremia; syndrome of inappropriate antidiuretic hormone secretion; hypersensitivity to desmopressin or to any of the excipients; alcohol abuse; severe classical von Willebrand-Jürgens syndrome (type IIb), in patients with 5% factor VIII activity, factor VIII antibodies.
Interaction with other medicinal products and other types of interactions
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 concomitantly 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 plasma desmopressin levels by 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.
Interactions of desmopressin with drugs that affect hepatic metabolism are unlikely, as in vitro microsomal metabolism studies in human liver cells have not revealed significant metabolism of desmopressin. However, formal in vivo interaction studies have not been conducted.
Concomitant food intake reduces the rate and extent of absorption of Minirin tablets by 40%. No significant effects were observed on pharmacodynamic properties (urine formation or osmolality).
Food intake may reduce the intensity and duration of the antidiuretic effect when using low doses of Minirin tablets.
Application features
When taking Minirin, tablets for the treatment of nocturnal enuresis, as a precautionary measure, fluid intake should be restricted 1 hour before and for up to 8 hours after taking Minirin, limiting fluid intake to only quenching thirst. Treatment without simultaneous fluid restriction may lead to fluid retention and/or hyponatremia with symptoms such as headache, nausea, vomiting, weight gain and, in severe cases, cerebral edema, seizures, and coma. The safety of long-term use of the drug for the treatment of nocturnal enuresis has not been established.
Cerebral edema and seizures have been reported in healthy children and young adults receiving desmopressin for the treatment of nocturnal enuresis. This risk is considered to be particularly high during the first week of treatment.
Elderly patients (>65 years) and patients with serum sodium levels at the lower limit are at increased risk of hyponatremia.
The duration of action of the drug increases with increasing dose, and therefore the risk of hyponatremia also increases. The dosage should be titrated upward with caution.
Desmopressin should be used with extreme caution in patients with cystic fibrosis, coronary heart disease, hypertension, a tendency to thrombosis, chronic kidney disease, preeclampsia, increased intracranial pressure, or fluid and electrolyte imbalance.
Patients with hypertension and chronic kidney disease may experience an increase in the symptoms listed in the "Side effects" section. In very young or elderly patients, or in the presence of risk factors that may lead to increased intracranial pressure, Minirin should be used with caution to avoid fluid retention in the body.
In the absence of concomitant fluid restriction, desmopressin treatment may lead to fluid retention and hyponatremia.
Patients or their parents (in the case of children) should be informed that excessive fluid intake should be avoided and that in the event of vomiting, diarrhoea, systemic infections and fever, desmopressin should be discontinued until normal fluid balance is restored.
To reduce the risk of hyponatremia or water intoxication, it is especially important to limit fluid intake:
when using drugs known as inducers of the syndrome of inappropriate ADH secretion (SIADH) (tricyclic antidepressants, selective serotonin reuptake inhibitors, chlorpromazine, chlorpropamide and carbamazepine); during concomitant treatment with NSAIDs.
During treatment, it is important to control body weight.
In patients aged 65 years and over, serum sodium levels should be determined before starting treatment and 3 days after starting treatment or after each dose increase. If headache and/or nausea occur, treatment should be discontinued.
Organic causes of polyuria or increased urinary frequency or nocturia, such as benign prostatic hyperplasia (BPH), urinary tract infections, bladder stones or tumors, bladder sphincter disorders, polydipsia, or inadequately treated diabetes mellitus, should be excluded or appropriately treated. Any adrenal or thyroid insufficiency should be treated before starting desmopressin therapy.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Minirin tablets.
Ability to influence reaction speed when driving vehicles or other mechanisms
The drug has no or negligible influence on the ability to drive and use machines, which should be taken into account by drivers and professionals whose work requires increased alertness. It is necessary to take into account the possible risk of dizziness or drowsiness when using the drug.
Use during pregnancy or breastfeeding
Fertility.
Fertility studies have not been conducted.
Pregnancy.
The drug should be used with caution in pregnant women and blood pressure monitoring is recommended.
Available data on a limited number of pregnant women (n=53) with diabetes insipidus and pregnant women (n=54) with von Willebrand disease indicate that desmopressin has no adverse effects on pregnancy or on the health of the fetus or newborn. No relevant epidemiological data are available to date. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.
Minirin should be prescribed to pregnant women only after careful assessment of the benefits and risks of treatment.
Breastfeeding period.
Analysis of breast milk from mothers who received 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.
Method of administration and doses
If after 4 weeks of treatment and dose adjustment there is no adequate clinical effect, continuing to take the drug is not recommended.
In case of symptoms of fluid retention and/or hyponatremia (headache, edema, nausea/vomiting, weight gain and in severe cases, convulsions), treatment should be discontinued immediately until the patient recovers. When treatment is resumed, patients should be more closely monitored for fluid restriction.
The recommended doses for children are the same as for adults.
Diabetes insipidus of central genesis.
Dosage is individual, but clinical experience has shown that the total daily dose usually lies in the range of 0.2 to 1.2 mg. An appropriate initial dose in adults and children is 0.1 mg 3 times a day. This dosage regimen should be adjusted according to the patient's response. For most patients, the maintenance dose is 0.1 mg to 0.2 mg 3 times a day.
Primary nocturnal enuresis.
The recommended initial dose is 0.2 mg at bedtime. If this dose is not effective enough, the dose may be increased to 0.4 mg. During treatment, fluid intake should be limited.
The course of treatment is 3 months. The question of the need for continued 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 that exceeds the volume of the bladder or exceeds ⅓ of the daily diuresis.
The recommended initial dose is 0.1 mg at night. If this dose is not effective enough within 1 week, the dose is increased to 0.2 mg and then with a weekly increase to 0.4 mg. During treatment, it is necessary to limit fluid intake.
It is not recommended to prescribe treatment to patients over 65 years of age. If treatment has been prescribed, it is necessary to monitor the sodium level in the blood before starting treatment and three days after starting treatment or increasing the dose, as well as at any time as prescribed by the doctor.
Children
Use in children aged 5 years and older with normal renal concentrating function for the treatment of primary nocturnal enuresis.
Overdose
In case of acute overdose with Minirin, side effects may increase.
Overdosage of the drug results in a prolonged duration of action with an increased risk of fluid retention and hyponatremia. Although the treatment of hyponatremia depends on the individual patient, the following general recommendations should be tried:
In case of asymptomatic hyponatremia, treatment with the drug should be discontinued and fluid intake should be restricted; in case of severe symptomatic hyponatremia, infusions of isotonic or hypertonic sodium chloride solution may be additionally administered. In case of cerebral edema, the patient should be immediately transferred to the intensive care unit. Convulsions in children also require intensive care measures.
Adverse reactions
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, fainting, and in severe cases, seizures and coma.
In most adults treated for nocturia who developed hyponatremia, a decrease in serum sodium was observed after 3 days of treatment. In adults, the risk of hyponatremia increases with increasing desmopressin dose and is more pronounced in women.
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%), diarrhoea (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 trials, but there are isolated reports.
In children, the most frequent adverse reaction during treatment was headache (1%), rarely observed psychiatric disorders (tendency 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 during clinical studies, however, there are isolated manifestations.
Adults
The following adverse reactions have been reported in clinical trials of oral desmopressin in adults for the treatment of nocturia (N=1557) combined with post-marketing studies in adults across all indications (including central diabetes insipidus). The frequencies of reactions reported in the post-marketing period are listed as “Frequency unknown”.
Adverse reactions are classified by frequency as follows: very common (> 10%), common (1-10%), uncommon (0.1-1%), rare (0.1-0.01%), frequency unknown.
On the part of the immune system: frequency unknown - anaphylactic reactions.
Metabolism: often - hyponatremia*; frequency unknown - dehydration**, hypernatremia*.
Nervous system disorders: very common – headache*; common – dizziness*; uncommon – drowsiness, paresthesia; frequency unknown – convulsions*, asthenia*, coma*.
On the part of the organs of vision: infrequently - visual impairment.
Hearing and vestibular disorders: uncommon – vertigo*.
Cardiac: infrequently - palpitations.
Vascular disorders: often - arterial hypertension; infrequently - orthostatic hypotension.
On the part of the respiratory system: infrequently - shortness of breath.
Gastrointestinal: often - nausea*, abdominal pain*, diarrhea, constipation, vomiting*; infrequently - dyspepsia, (TVR1) flatulence, bloating.
Skin and subcutaneous tissue disorders: infrequently - sweating, itching, rash, urticaria; rarely - allergic dermatitis.
Musculoskeletal and connective tissue disorders: uncommon – muscle cramps, myalgia.
Renal and urinary disorders: common – (TVR1) bladder symptoms and urethral symptoms.
General disorders: often – (TVR1) edema, fatigue; infrequently – discomfort*, chest pain, influenza-like illness.
Investigations: uncommon – weight gain*, increased liver enzymes, hypokalemia.
* Hyponatremia can cause headache, abdominal pain, nausea, vomiting, weight gain, dizziness, confusion, general malaise, memory impairment, vertigo, fainting, seizures, and coma.
** Only for diabetes insipidus.
1 High-level term.
Children and adolescents
The following adverse reactions were reported during clinical trials of oral desmopressin in children and adolescents for the treatment of primary nocturnal enuresis (N=1923). The frequency of reactions reported during post-marketing experience is listed as “Frequency unknown”.
Adverse reactions are classified by frequency as follows: very common (> 10%), common (1-10%), uncommon (0.1-1%), rare (0.1-0.01%), frequency unknown.
On the part of the immune system: frequency unknown - anaphylactic reactions.
Metabolism: frequency unknown – hyponatremia****.
Psychiatric disorders: infrequently - mood lability**, aggression***; rare - (TVR1) anxiety symptoms, nightmares*, mood changes*; frequency unknown - abnormal behavior, emotional disorders, depression, hallucinations, insomnia.
Nervous system: often - headache; rarely - drowsiness; frequency unknown - impaired attention, psychomotor hyperactivity, convulsions*.
Vascular disorders: rare – arterial hypertension.
Respiratory system: frequency unknown - nosebleed.
Gastrointestinal: infrequently - abdominal pain, nausea, vomiting, diarrhea.
Skin and subcutaneous tissue disorders: frequency unknown - rash, allergic dermatitis, sweating, urticaria.
Renal and urinary disorders: uncommon – (TVR1) bladder symptoms and urethral symptoms.
General disorders: infrequently - peripheral edema, increased fatigue; rare - increased excitability.
*Hyponatremia can cause headache, abdominal pain, nausea, vomiting, weight gain, dizziness, confusion, general malaise, memory impairment, vertigo, fainting, seizures, and coma.
** In post-marketing studies, it was observed equally frequently in children and adolescents (<18 years).
*** In post-marketing studies, observed exclusively in children and adolescents (<18 years).
**** In post-marketing studies, primarily observed in children (<12 years).
Expiration date
3 years.
Storage conditions
Store in a dry place, out of reach of children, at a temperature not exceeding 25 °C.
Packaging
30 tablets in a bottle, 1 bottle in a cardboard box.
Vacation category
According to the recipe.
Producer
Ferring GmbH.
Location of the manufacturer and its business address
Witland 11, 24109 Kiel, Germany.
