Натива®

General characteristics. Structure:

Active ingredient: 0,1 mg or 0,2 mg of desmopressin of acetate that there correspond 0,089 mg and 0,178 mg of desmopressin.

Excipients: lactoses monohydrate, кросповидон XL, magnesium stearate, лудипресс.

Pharmacological properties:

Pharmacodynamics. Desmopressin – a structural analog of natural hormone arginine-vasopressin, with the expressed antidiuretic action. Desmopressin is received as a result of changes in a vasopressin molecule structure – deamination of L-cysteine and substitution of 8-L-arginine with 8-D-arginine.

Desmopressin increases permeability of an epithelium of distal departments of gyrose tubules of nephron for water and raises its reabsorption. Structural changes in a combination with considerably the increased antidiuretic ability lead to less expressed effect of desmopressin on smooth muscles of vessels and internals in comparison with vasopressin that causes lack of undesirable spastic side effects. Unlike vasopressin works is longer and does not cause increase in the arterial pressure (AP).

Use of desmopressin at not diabetes mellitus of the central genesis leads to reduction of volume of the emitted urine and simultaneous increase in osmolarity of urine and decrease in osmolarity of a blood plasma. It leads to decrease in frequency of an urination and reduction of a night polyuria.

The maximum antidiuretic effect at intake occurs in 4 – 7 hours. Antidiuretic action at intake in a dose of 0,1 - 0,2 mg – till 8 o'clock, in a dose  of 0,4 mg – till 12 o'clock.

Pharmacokinetics. Absorption. At intake the maximum concentration in plasma (Cmax) is reached within  0,9 hours. The volume of distribution (Vd) makes 0,2 – 0,3 l/kg. The concomitant use of food can lower extent of absorption from the digestive tract (DT) by 40%.

Distribution. Absorption at intake – 5%. Desmopressin does not get through a blood-brain barrier.

Removal. It is removed by kidneys. An elimination half-life (T1/2) at intake 1,5 – 2,5 hours.

Indications to use:

- Not diabetes mellitus of the central genesis;
- Primary night enuresis at children is more senior than 5 years;
- A night polyuria at adults (as symptomatic therapy).

Route of administration and doses:

Inside. The optimum dose of drug is selected individually. Drug should be accepted after a while after meal as meal can influence absorption of drug and its efficiency.

Central not diabetes mellitus: the recommended initial dose for children is more senior than 4 years and adults are made by 0,1 mg of 1 - 3 time a day. In the subsequent the dose is selected depending on response to treatment. Usually day dose makes from 0,2 to 1,2 mg. For most of patients an optimum maintenance dose are 0,1 – 0,2 mg of 1 - 3 time a day.

Primary night enuresis: the recommended initial dose for children is more senior than 5 years and adults are made by 0,2 mg for the night. In the absence of effect the dose can be increased to 0,4 mg. The recommended course of continuous treatment makes 3 months. The decision on continuation of treatment should be made on the basis of clinical data which will be observed after drug withdrawal within 1 week. Control of liquid reception restriction observance is necessary in the evening.

Night polyuria at adults: the recommended initial dose makes 0,1 mg for the night. In the absence of effect within 7 days the dose is increased to 0,2 mg and in the subsequent to 0,4 mg at increase in a dose with frequency no more than 1 once a week. It is necessary to remember danger of a delay of liquid in an organism. If after 4 weeks of treatment and correction of a dose of adequate clinical effect it is not observed, it is not recommended to continue drug use.

Features of use:

Use at pregnancy and during breastfeeding. According to the known data, at use of desmopressin for pregnant women with not diabetes mellitus side effect on the course of pregnancy, on the state of health of the pregnant woman, a fruit and the newborn was not noted.

However it is necessary to correlate estimated advantage for mother and potential risk for a fruit. As showed researches, amount of the desmopressin getting to the newborn's organism with breast milk of the woman accepting high doses of desmopressin it is much less than that which is capable to affect a diuresis.

Most often the hyponatremia arises at patients of advanced age (65 years are more senior). Control at treatment of children, teenagers, patients with risk of increase in intracranial pressure is necessary. In order to avoid development of side effects it is necessary to limit without fail to a minimum reception of liquid in 1 hour prior to use and within 8 hours after administration of drug at patients with primary night enuresis.

Drug Nativa should not be used when there are other additional reasons for a delay of liquid and electrolytic frustration. Patients of advanced age with initially low concentration of sodium in a blood plasma and a polyuria from 2,8 to 3 l have high risk of development of side effects.

Prevention of development of a hyponatremia consists in increase in frequency of definition of sodium in a blood plasma, especially at simultaneous use with the drugs causing a syndrome of inadequate secretion of antidiuretic hormone (tricyclic antidepressants, selective serotonin reuptake inhibitors, narcotic analgetics, ламотриджин, Chlorpromazinum and carbamazepine) and NPVP. At emergence of an acute incontience of urine, a dysuria and/or nocturia, an infection of urinary tract, suspicion of a tumor of a bladder or a prostate, existence of a polydipsia and dekompensirovanny diabetes mellitus diagnosis and treatment of the specified states and diseases should be carried out prior to treatment by drug Nativa.

At development against the background of treatment of system infections, fever, a gastroenteritis it is necessary to stop use of drug.

Possible influence of medicine on ability to manage vehicles, mechanisms. Now data on possible influence of drug Nativa on ability to drive the car and to manage mechanisms is absent. Nevertheless, use of drug can lead to development of such side effects as dizziness, a headache which can negatively influence ability to drive the car and to carry out potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions. It is recommended to be careful during the driving of the car or work with mechanisms.

Side effects:

The listed below undesirable phenomena noted at desmopressin use are distributed on emergence frequency according to the following gradation: very often (≥ 1/10), it is frequent (≥ 1/100 to <1/10), infrequently (≥ 1/1000 to <1/100), is rare (≥ 1/10000 to <1/1000), is very rare (<1/10000), not specified frequency (it cannot be counted according to the available data).

Disturbances from a nervous system: often - a headache, dizziness, not specified frequency – spasms.

Disturbances from the alimentary system: often - nausea, vomiting, dryness in a mouth.

Disturbances from cardiovascular system: infrequently - a tranzitorny tachyarrhythmia.

Disturbances from an organ of sight: infrequently – conjunctivitis.

General disturbances: often - peripheral hypostases, increase in body weight.

Nativa without restriction of reception of liquid can lead administration of drug to a liquid delay in an organism and/or a hyponatremia which can be asymptomatic or be followed by a headache, nausea, vomiting, hypostases, increase in body weight, and in hard cases – spasms.

Interaction with other medicines:

At simultaneous use desmopressin strengthens action of hypertensive means.

At simultaneous use Buforminum, tetracycline, lithium drugs, Norepinephrinum weaken antidiuretic effect of desmopressin.

At simultaneous use of desmopressin with non-steroidal anti-inflammatory drugs (NPVP) increase in risk of emergence of side effects is possible. At simultaneous use indometacin strengthens, but does not increase duration of effect of desmopressin.

At simultaneous use tricyclic antidepressants, selective serotonin reuptake inhibitors, narcotic analgetics, NPVP, ламотриджин, Chlorpromazinum and carbamazepine capable to cause a syndrome of inadequate secretion of antidiuretic hormone can strengthen antidiuretic effect of desmopressin and lead to increase in risk of a delay of liquid and a hyponatremia.

At use of desmopressin with loperamide perhaps triple increase in concentration of desmopressin in plasma that significantly increases risk of a delay of liquid and emergence of a hyponatremia. Perhaps, other medicines which are slowing down a peristaltics can cause similar effect.

At simultaneous use of desmopressin with dimetikony desmopressin absorption reduction is possible.

Contraindications:

- hypersensitivity to desmopressin or other components of drug;
- usual or psychogenic polydipsia;
- the heart failure and other states demanding purpose of diuretic drugs;
- a hyponatremia, including in the anamnesis (concentration of ions of sodium in a blood plasma is lower than 135 mmol/l);
- a renal failure of average and heavy degree (the clearance of creatinine is lower than 50 ml/min.);
- children's age up to 4 years (for treatment of not diabetes mellitus) and 5 years (for treatment of primary night enuresis);
- syndrome of inadequate products of antidiuretic hormone;
- deficit of lactase, lactose intolerance, glyukozo-galaktozny malabsorption.

With care use drug at a renal failure, bladder fibrosis, at disturbances of water and electrolytic balance, potential risk of increase in intracranial pressure, during pregnancy.

With extra care use drug at patients of advanced age (65 years are more senior) in connection with high risk of development of side effects (a liquid delay, a hyponatremia). At purpose of therapy Nativa in 3 days after the beginning of reception and at each increase in a dose it is necessary to determine by drug concentration of sodium in a blood plasma and to control a condition of the patient.

Overdose:

The overdose leads to increase in duration of effect of desmopressin and increase in risk of emergence of a delay of liquid (a headache, nausea, vomiting, peripheral hypostases, spasms) and hyponatremias at which concentration of ions of sodium in a blood plasma is lower than 135 mmol/l.

Treatment: at a hyponatremia – drug phase-out, cancellation of restriction on liquid reception, is possible performing infusion of 0,9% or hypertonic salt solution of sodium of chloride. At the expressed liquid delay (spasms and a loss of consciousness) - it is necessary to attach furosemide to above-mentioned therapy.

Storage conditions:

To store in the place protected from light at a temperature not above 25 °C. Drug should be stored in the place, unavailable to children. A period of validity - 2 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, 0,1 mg, 0,2 mg. On 30 tablets in bottles polymeric, corked by plastic covers (with a dehumidifier and with control of the first opening). On 1 bottle together with the instruction on a medical use in a cardboard pack.