Minirin

0.1 mg tablet: White, oval, convex tablet with a single score and marked "0.1" on one side.
Each tablet contains desmopressin acetate 0.1 mg, corresponding to desmopressin (free base) 0.089 mg.
0.2 mg tablet: White, round, convex tablet with a single score and marked "0.2" on one side.
Each tablet contains desmopressin acetate 0.2 mg, corresponding to desmopressin (free base) 0.178 mg.
The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.
60 mcg melt oral lyophilisate: White, round, oral lyophilisate marked with a drop shaped figure on one side.
Each oral lyophilisate contains 60 mcg desmopressin (free base), as desmopressin acetate.
120 mcg melt oral lyophilisate: White, round, oral lyophilisate marked with two drop shaped figures on one side.
Each oral lyophilisate contains 120 mcg desmopressin (free base), as desmopressin acetate.
Solution for injection: Each ml of solution contains desmopressin acetate 4 µg, sodium chloride q.s., hydrochloric acid (to adjust pH to 4) and water for injection to 1 ml.
Excipients/Inactive Ingredients: Tablet: Lactose monohydrate, potato starch, povidone, magnesium stearate.
Melt oral lyophilisate: Gelatin (from fish), mannitol (E421) and anhydrous citric acid (E330).

Pharmacotherapeutic group: vasopressin and analogues. ATC code: H01B A02.
Solution for injection: Properties: MINIRIN contains desmopressin, a structural analogue of the natural hormone arginine vasopressin. Two chemical changes have been made to the natural hormone, namely desamination of 1-cysteine and substitution of 8-L-arginine by 8-D-arginine. These structural changes result in a compound with significantly increased antidiuretic potency, very little activity on smooth muscle, hence the avoidance of undesirable pressor side effects. The duration of the antidiuretic effect is about 8-12 hours.
MINIRIN in a high dosage, 0.3 µg/kg body weight intravenously or subcutaneously, leads to a two-to-four-fold increase in plasma of factor VIII coagulant activity (VIII:C). Also the content of von Willebrand factor-antigen (vWF:Ag) increases, but to a lesser extent. At the same time there is a release of the plasminogen activator (t-PA).
Maximum plasma concentration following a dose of 0.3 µg/kg body weight, is reached after approximately 60 minutes and amounts to an average of 600 pg/ml. Plasma half life ranges between 3 and 4 hours. The duration of the haemostatic effect depends on the plasma half life for VIII:C which is about 8-12 hours.
Administration of desmopressin has also been shown to lead to a shortening or normalization of the bleeding time in patients with prolonged bleeding time as in uraemia, liver cirrhosis, congenital or drug-induced thrombocyte dysfunction and in patients with prolonged bleeding time of unknown aetiology.
The risk of transmission of HIV-infection and hepatitis virus as seen for factor VIII concentrates is avoided by administration of desmopressin.
pH of the solution is about 4.
Pharmacology: Pharmacodynamics: Tablet/Melt oral lyophilisate: MINIRIN contains desmopressin, a structural analogue of the natural pituitary hormone arginine vasopressin. The difference lies in that the amino group in cysteine has been removed and L-arginine has been substituted by D-arginine. This results in a considerably longer duration of action and a complete lack of pressor effect in the dosages used clinically. After oral administration of desmopressin (tablet), the antidiuretic effect could be expected to last 6-14 hours or more.
Clinical trials with desmopressin tablets in the treatment of nocturia showed the following: A reduction of at least 50% in the mean number of nocturnal voids was obtained in 39% of patients with desmopressin compared to 5% of patients with placebo (p<0.0001).
The mean number of voids per night decreased by 44% with desmopressin compared to 15% with placebo (p<0.0001).
The median duration of first undisturbed sleep period increased by 64% with desmopressin compared to 20% with placebo (p<0.0001).
The mean duration of first undisturbed sleep period increased by 2 hours with desmopressin compared to 31 minutes with placebo (p<0.0001).
Pharmacokinetics: Tablet: Absorption: The absolute bioavailability after perorally administered desmopressin is 0.16% (SD=0.17%). Desmopressin exhibits a moderate to high variability in bioavailability, both within and between subjects. Concomitant food intake decreases the rate and extent of absorption by about 40%.
The maximum plasma concentration is reached after 1-1.5 hours. C_max and AUC do not increase in proportion to the administered dose.
Distribution: The distribution volume is 0.2-0.3 l/kg. Desmopressin does not cross the blood-brain barrier.
Metabolism: In vitro studies with human liver microsomes have shown that no significant amount of desmopressin is metabolized in the liver. It is therefore unlikely that desmopressin is metabolized in the liver in human beings.
Elimination: The mean half-life for desmopressin in the elimination phase is 2-3 hours.
52% (44%-60%) of the amount of administered desmopressin is found in the urine.
Paediatric Population: The population pharmacokinetics has been studied in children with PNE and is comparable to that in adults.
Melt oral lyophilisate: Absorption: The plasma concentration of desmopressin has been shown to be equivalent after administration of MINIRIN tablets 2x0.2 mg (0.4 mg) and MINIRIN Melt 240 mcg respectively.
The mean bioavailability of desmopressin administered sublingually as MINIRIN Melt is approximately 0.25%. Concomitant intake of food has not been investigated with MINIRIN Melt but concomitant food intake with MINIRIN tablets decreases the rate and extent of absorption by 40%. Desmopressin exhibits a moderate to high variability in bioavailability, both within and between subjects. The plasma concentration of desmopressin increases proportionally to administered doses and after administration of 200, 400 and 800 mcg C_max was 14, 30 and 65 pg/mL respectively. T_max was reached after 0.5 - 2 hours. The terminal half-life is estimated to 2.8 hours.
Distribution: The distribution volume of desmopressin after intravenous administration is 33 L (0.41 L/kg). Desmopressin does not cross the blood-brain barrier.
Metabolism: In vitro studies with human liver microsomes have shown that no significant amount of desmopressin is metabolized in the liver. It is therefore unlikely that desmopressin is metabolized in the liver in human beings.
Elimination: 52% (44% - 60%) of the amount of administered desmopressin is found in the urine.
Paediatric Population: The population pharmacokinetics has been studied in children with PNE and is comparable to that in adults.

Tablet: Central diabetes insipidus: The use of MINIRIN in patients with an established diagnosis will result in a reduction in urinary output with concomitant increase in urine osmolality and decrease in plasma osmolality. This will result in decreased urinary frequency and decreased nocturia.
Primary nocturnal enuresis in children aged 5 years or more.
Symptomatic treatment of nocturia in adults, associated with nocturnal polyuria, i.e. nocturnal urine production exceeding bladder capacity.
Melt oral lyophilisate: Central diabetes insipidus.
Primary nocturnal enuresis (from 6 years of age) in patients with normal ability to concentrate urine.
Symptomatic treatment of nocturia in adults, associated with nocturnal polyuria, i.e. nocturnal urine production exceeding bladder capacity.
Solution for injection: Central diabetes insipidus: The use of MINIRIN in patients with an established diagnosis will result in a reduction in urinary output with concomitant increase in urine osmolality and decrease in plasma osmolality. This will result in decreased urinary frequency and decreased nocturia.
Renal concentrating capacity test: MINIRIN can be used to test the capacity of the kidneys to concentrate urine; as a diagnostic aid in the examination of the kidney function. This is especially useful in the differential diagnosis between level of urinary tract infections. Cystitis will opposite to pyelonephritis not cause a subnormal ability to concentrate urine.
Hemophilia A and von Willebrand's disease: For the therapeutic control of bleeding and bleeding prophylaxis in connection with minor surgical procedures in patients with mild haemophilia A and von Willebrand's disease who respond positively to the test dose. In exceptional cases, even moderate forms of the disease can be treated. MINIRIN must not be used in patients with von Willebrand's disease type II B.

Tablet/Melt oral lyophilisate: General: The dose of MINIRIN is individually adapted. MINIRIN Melt 60 mcg is calculated to correspond to MINIRIN tablet 0.1 mg, and 120 mcg corresponds to 0.2 mg (see also Pharmacology: Pharmacokinetics under Actions).
Desmopressin should always be taken at the same time in relation to food intake, since food intake causes decreased absorption and by that also might influence the effect of desmopressin, see Interactions.
In the event of signs of water retention/hyponatraemia (headache, nausea/vomiting, weight gain, and in serious cases convulsions) the treatment should be temporarily interrupted until the patient has completely recovered. When the treatment is resumed strict fluid restriction is necessary, see Precautions.
Special Populations: Paediatric Population: MINIRIN is indicated in Central Diabetes Insipidus and Primary Nocturnal Enuresis (see indication specific information as follows and Pharmacology: Pharmacodynamics under Actions). Dose recommendations are the same as in adults.
Elderly: Treatment of nocturia should not be initiated in patients >65 years (see as follows).
Renal Impairment: see Contraindications.
Hepatic Impairment: see Interactions.
Tablet: Indication specific: Central diabetes insipidus: A suitable initial dose for children and adults is 0.1 mg 3 times daily. The dosage regimen is then adjusted in accordance with the patient's response. Clinical experience has shown, that the daily dose varies between 0.2 mg and 1.2 mg. For most patients, the maintenance dose is 0.1-0.2 mg 3 times daily. In the event of signs of water retention/hyponatraemia treatment should be temporarily interrupted and the dose should be adjusted.
Primary nocturnal enuresis: A suitable initial dose is 0.2 mg at bedtime. The dose may be increased up to 0.4 mg if the lower dose is not sufficiently effective. Fluid restriction shall be enforced. Evaluation of continued need of treatment should be carried out after three months by means of at least one treatment-free week.
Nocturia: In nocturic patients, a frequency/volume chart should be used to diagnose nocturnal polyuria for at least 2 days and nights before starting treatment. A night-time urine production exceeding the functional bladder capacity or exceeding 1/3 of the 24-hour urine production is regarded as nocturnal polyuria.
The recommended initial dose is 0.1 mg at bedtime. If this dose is not sufficiently effective after one week, the dose may be increased up to 0.2 mg and subsequently 0.4 mg by weekly dose escalations. Fluid restriction should be enforced.
Treatment should not be initiated in the elderly (65 years of age and over). Should treatment of these patients be considered, serum sodium should be measured before beginning of treatment and after 3 days of treatment. The same applies at increase in dosage and other occasions during treatment as deemed necessary by the treating physician, see Precautions.
If adequate clinical effect is not achieved within 4 weeks following appropriate dose titration the treatment should be discontinued.
Melt oral lyophilisate: Indication specific: Central diabetes insipidus: A suitable initial dose for children and adults is 60 mcg 3 times daily, administered sublingually. The dosage regimen is then adjusted in accordance with the patient's response. Clinical experience has shown, that the daily dose varies between 120 mcg and 720 mcg sublingually. For most patients, the maintenance dose is 60 mcg to 120 mcg sublingually 3 times daily. In the event of signs of water retention/hyponatraemia treatment should be temporarily interrupted and the dose should be adjusted.
Primary nocturnal enuresis: A suitable initial dose is 120 mcg at bedtime, administered sublingually. The dose may be increased up to 240 mcg sublingually if the lower dose is not sufficiently effective. Fluid restriction shall be enforced. Evaluation of continued need of treatment should be carried out after three months by means of at least one treatment-free week.
Nocturia: In nocturic patients, a frequency/volume chart should be used to diagnose nocturnal polyuria for at least 2 days and nights before starting treatment. A night-time urine production exceeding the functional bladder capacity or exceeding 1/3 of the 24-hour urine production is regarded as nocturnal polyuria.
The recommended initial dose is 60 mcg at bedtime, administered sublingually. If this dose is not sufficiently effective after one week, the dose may be increased up to 120 mcg sublingually and subsequently 240 mcg sublingually by weekly dose escalations. Fluid restriction should be enforced.
Treatment should not be initiated in the elderly (65 years of age and over). Should treatment of these patients be considered, serum sodium should be measured before beginning of treatment and after 3 days of treatment. The same applies at increase in dosage and other occasions during treatment as deemed necessary by the treating physician, see Precautions.
If adequate clinical effect is not achieved within 4 weeks following appropriate dose titration the treatment should be discontinued.
Administration: MINIRIN Melt is placed under the tongue where it is dissolved without water.
Solution for injection: Central diabetes insipidus: The injection may be used when the intranasal administration is considered unsuitable. Individual dosage is determined after testing of the effect on urine osmolality and diuresis at dose levels. In the event of signs of water retention/hyponatremia treatment should be interrupted and the dose should be adjusted.
Normal dosage, intravenous injection: Adults 1-4 µg (0,25-1 ml) 1-2 times daily. Children above the age of 1 year 0,4-1 µg (0,1-0,25ml) 1-2 times daily. Children below the age of 1 year 0,2-0,4 µg (0,05-0,1 ml) 1-2 times daily.
For patients who have been controlled on intranasal MINIRIN and who must be switched to the injection form, either because of poor intranasal absorption, or because of the need for surgery, the comparable antidiuretic dose of the injection is about 10% of the intranasal dose.
Renal concentrating capacity test: Normal adult dose by intramuscular or subcutaneous injection is 4 µg (1ml). For children over 12 months of age the dose is 1 to 2 µg (0,25 to 0,5ml). For children under 12 months the dose is 0,4 µg (0,1 ml). For children it is recommended to use primarily the intranasal presentation.
After administration of MINIRIN, possible urine within 1 hour is discarded. During the next 8 hours 2 portions of urine are collected for measurement of osmolality. A restricted water intake must be observed, see also under Precautions.
The reference level for normal urine osmolality after MINIRIN administration is 800 mOsm/kg for most patients. With values under this level, the test should be repeated. A repeated low result indicates an impaired ability to concentrate urine and the patient should be referred for further examination into the underlying cause of the malfunction.
Haemophilia A and von Willebrand's Disease: MINIRIN injection is administered as an intravenous infusion at a dose of 0,3 µg/kg bodyweight diluted in sterile physiological saline and infused slowly over 15-30 minutes. In adults and children weighing 10 kg or more, 50 ml of diluent is used; in children weighing 10 kg or less, 10 ml of diluent is used.
If a positive effect is obtained, the initial MINIRIN dose may be repeated 1-2 times with intervals of 6-12 hours. Further repetition of the dose may result in a reduced effect.
In patients with haemophilia the desired increase of VIII:C is appraised by the same criterion as in the treatment with factor VIII-concentrate. The VIII:C-concentration must be followed up regularly since in a few cases the effect has been seen to decrease with repeated doses. If the MINIRIN-infusion does not lead to the desired increase of the VIII:C-concentration in plasma, the treatment may be complemented with a supply of factor VIII-concentrate. The treatment of patients with haemophilia should be conducted in consultation with each patient's coagulation laboratory.
Determination of the coagulation factor and bleeding time before MINIRIN-treatment.
Plasma levels of VIII:C and vWF:Ag increase substantially after desmopressin administration. However, it has not been possible to establish any correlation between the plasma concentration of these factors and the bleeding time, either before or after desmopressin. The effect of desmopressin on the bleeding time should therefore, if possible, be tested in the individual patient.
The bleeding time test should be as standardized as possible, e.g. with the use of Simplate II. Determination of bleeding time and plasma levels of the coagulation factors should be conducted in cooperation or consultation with a coagulation laboratory.

Tablet/Melt oral lyophilisate: Toxicity: Overdosage leads to prolonged duration of action with an increased risk of fluid retention and hyponatraemia. Even normal doses may in combination with considerable fluid intake cause water intoxication. Doses from 0.3 mcg/kg i.v. and 2.4 mcg/kg intranasally have caused hyponatraemia and convulsions in children and adults. On the other hand, 40 mcg intranasally administered to a 5-month-old baby and 80 mcg intranasally to a 5-year-old gave no symptoms. 4 mcg administered parenterally to a newborn caused oliguria and weight gain.
Symptoms: The same symptoms as for water intoxication. Headache, nausea. Fluid retention, hyponatraemia, hypoosmolality, oliguria, CNS depression, convulsions, pulmonary oedema. See also Adverse Reactions described in the text.
Treatment: The treatment of hyponatraemia should be individual but the following general recommendations may be given: Hyponatraemia is treated by interrupting the desmopressin treatment and fluid restriction. If the patient has symptoms an infusion of isotonic or hypertonic sodium chloride may be given. When the fluid retention is serious (convulsions and loss of consciousness) furosomide treatment is given.
Solution for injection: Overdose of MINIRIN solution for injection can lead to water retention and hyponatremia.
Treatment: Although the treatment of hyponatremia should be individualized, the following general recommendations can be given. Asymptomatic hyponatremia is treated with discontinuation of desmopressin treatment and fluid restriction. Infusion of isotonic or hypertonic sodium chloride may be added in cases with symptoms. When the fluid retention is severe (convulsions and unconsciousness) treatment with furosemide should be added.

Tablet/Melt oral lyophilisate: Habitual or psychogenic polydipsia (urine production exceeding 40 mL/kg/24 hours).
Known or suspected cardiac insufficiency and other conditions that require treatment with diuretics.
Moderate and severe renal insufficiency (creatinine clearance below 50 ml/min).
Syndrome of inappropriate ADH secretion (SIADH).
Known hyponatraemia.
Hypersensitivity to the active substances or to any of the excipients (Melt oral lyophilisate contains fish gelatine).
Solution for injection: MINIRIN solution for injection is contraindicated in cases of: In general: habitual and psychogenic polydipsia.
If used for renal concentration capacity testing: cardiac insufficiency and other conditions requiring treatment with diuretics.
If used for haemostatic indications: unstable angina pectoris; decompensated cardiac insufficiency; von Willebrand's disease type IIB.

Tablet/Melt oral lyophilisate: In patients with urgency/urge incontinence, organic causes for increased micturition frequency or nocturia (e.g. benign prostate hyperplasia, urinary tract infection, bladder stone/tumor), polydipsia and poorly adjusted diabetes mellitus, the specific cause should be treated primarily.
At treatment of primary nocturnal enuresis and nocturia, fluid intake should be limited to the least possible during the period of 1 hour before evening dose until at least 8 hours after administration. Treatment without concomitant reduction in fluid intake may lead to water retention and/or hyponatraemia (headache, nausea/vomiting, weight gain and in serious cases convulsions).
All patients and, when applicable, their guardians should be carefully instructed to adhere to the fluid restrictions.
In clinical trials, higher occurrence of hyponatraemia was found in patients over 65 years. Therefore, treatment should not be initiated in the elderly, especially not in patients suffering from other conditions that may increase the likelihood of fluid or electrolyte imbalance.
Elderly patients, patients with low serum sodium levels and patients with a high 24-hour urine volumes (above 2.8 to 3 litres) have an increased risk for hyponatraemia.
Precautions to avoid hyponatraemia including careful attention to fluid restriction and more frequent monitoring of serum sodium must be taken at: concomitant treatment with drugs known to induce syndrome of inappropriate ADH secretion (SIADH), e.g. tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRI), chlorpromazine and carbamazepine, concomitant treatment with NSAIDs.
Precautions must be taken in patients at risk for increased intracranial pressure.
Treatment with desmopressin should be interrupted during acute illnesses characterised by fluid and/or electrolyte imbalance such as systemic infections, fever, gastroenteritis.
MINIRIN tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Solution for injection: For all indications, MINIRIN solution for injection should be used with caution in: very young and elderly patients; conditions characterized by fluid and/or electrolyte imbalance; patients at risk for increased intracranial pressure.
In addition for renal concentration capacity testing: The fluid intake must be limited to a maximum of 0,5 l to quench thirst from 1 hour before until 8 hours after administration. Renal concentration capacity testing in children below the age of 1 year should only be performed in hospital and under careful supervision.
In addition for haemostatic use: Measures to prevent fluid overload must be taken in patients requiring treatment with diuretic agents.
Special attention must be paid to the risk of water retention/hyponatremia. The fluid intake should be restricted to the least possible and the body weight should be checked regularly. Should there be a gradual increase of the body weight, decrease of serum sodium to below 130 mmol/l or plasma osmolality to below 270 mOsm/kg body weight, the fluid intake must be reduced drastically and the administration of MINIRIN interrupted.
MINIRIN does not reduce prolonged bleeding time in thrombocytopenia.
Effects on Ability to Drive and Use Machines: MINIRIN has no or negligible effect on the ability to drive vehicles and use machines.

Tablet/Melt oral lyophilisate: Fertility: Fertility studies have not been carried out. In vitro analysis of human cotyledon models have shown that there is no transplacental transport of desmopressin when administered at therapeutic concentrations corresponding to recommended dose.
Pregnancy: Data on a limited number (n = 53) of exposed pregnancies in women with diabetes insipidus as well as data on a limited number (n = 54) of exposed pregnancies in women with von Willebrand disease indicate no adverse effects of desmopressin on pregnancy or on the health of the foetus/newborn child. No other relevant epidemiological data are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.
Caution should be exercised when giving MINIRIN Melt/tablets to pregnant women.
Lactation: Results from analyses of milk from nursing mothers receiving high dose desmopressin (300 mcg intranasally), show that desmopressin is transferred to the milk but that the amount of desmopressin that can be transferred to the child is low and probably less than the amounts required to influence diuresis. Whether desmopressin will accumulate in breast milk upon repeated doses has not been studied.
Solution for injection: Pregnancy: Reproduction studies performed in rats and rabbits with doses more that 100 times the human dose have revealed no evidence of a harmful action of desmopressin on the foetus. One investigator has reported 3 cases of malformations in children to mothers suffering from diabetes insipidus and receiving desmopressin during pregnancy. However, several other published reports comprising more than 120 cases show that women treated with desmopressin during pregnancy have given birth to normal children. Furthermore a review of a very large data set identifying 29 children who have been exposed to desmopressin during the full pregnancy shows no increase in the malformation rate in the children born.
Lactation: Results from analyses of milk from nursing mothers receiving high dose desmopressin (300 µg intranasally), indicate that the amounts of desmopressin that may be transferred to the child are considerably less than the amounts required to influence diuresis or hemostasis.

Tablet/Melt oral lyophilisate: Summary of the safety profile: The most serious adverse reaction with desmopressin is hyponatraemia, see under "Description of selected adverse reactions" as follows.
In adults the most commonly reported adverse reaction during treatment was headache (12%). Other common adverse reactions were hyponatraemia (6%), dizziness (3%), hypertension (2%) and gastrointestinal disorders (<10%). Anaphylactic reactions have not been seen in clinical trials but spontaneous reports have been received.
In children the most commonly reported adverse reaction was headache (1%). Less common were psychiatric disorders (<1%), which generally abated after treatment discontinuation and gastrointestinal disorders (<1%). Anaphylactic reactions have not been seen in clinical trials but spontaneous reports have been received.
Tabulated summary of adverse reactions: Adults: The frequency of adverse drug reactions reported in clinical trials with oral desmopressin conducted in adults for treatment of nocturia (N=1557) combined with the post marketing experience for all adult indications (incl. central diabetes insipidus). Reactions only seen post marketing have been added in the 'Not known'-frequency column. (See Table 1.)

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Paediatric Population: The frequency of adverse drug reactions reported in clinical trials with oral desmopressin conducted in children and adolescents for treatment of primary nocturnal enuresis (N = 1923). Events only seen in post marketing have been added in the 'Not known' frequency column. (See Table 2.)

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Special populations: Elderly patients and patients with low serum sodium levels may have an increased risk of developing hyponatraemia (see Precautions).
Description of selected adverse reactions: The most serious adverse reaction with desmopressin is hyponatraemia, which may cause headache, abdominal pain, nausea, vomiting, weight increase, dizziness, confusion, malaise, vertigo and in serious cases convulsions and coma. The cause of the potential hyponatraemia is the anticipated antidiuretic effect. Hyponatraemia is reversible and in children it is often seen to occur in relation to changes in daily routines affecting fluid intake and/or perspiration. In adult study subjects treated for nocturia, the majority of those developing low serum sodium, developed this after 3 days of treatment or after dose increase. Special precautions should be observed in adults as well as in children, see Precautions.
Solution for injection: A few percent of treated patients can be expected to experience side such as fatigue, headache, nausea and stomach pain. (See Table 3.)

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Treatment without concomitant restriction of fluid intake may lead to water retention/hyponatremia with accompanying signs and symptoms (headache, nausea/vomiting, decreased serum sodium, weight gain, and in serious cases, convulsions).
Post marketing experience: Isolated cases of allergic skin reactions and more severe general allergic reactions have been reported.

Tablet/Melt oral lyophilisate: Substances that are known to induce disturbed ADH-secretion, e.g. tricyclic antidepressants, SSRI, chlorpromazine and carbamazepine as well as some antidiabetics of the sulfonylurea group, especially chlorpropamide, may cause an additive antidiuretic effect with an increased risk of fluid retention (see Precautions).
NSAID preparations may induce water retention/hyponatraemia (see Precautions).
Concomitant treatment with loperamide may result in a three-fold increase in desmopressin plasma concentration, which may lead to an increased risk of water retention and/or hyponatraemia.
Other drugs slowing intestinal transport might have the same effect. However, this has not been investigated.
Concomitant treatment with dimeticone may result in a decreased absorption of desmopressin.
It is unlikely that desmopressin interacts with pharmaceuticals affecting hepatic metabolism, since desmopressin has not been shown to undergo any significant liver metabolism in in vitro studies with human microsomes. However, no formal interaction studies in vivo have been carried out.
Concomitant food intake has not been investigated with MINIRIN Melt. A standardised meal with 27% fat taken together with or 1.5 h prior to MINIRIN tablet decreased the extent and rate of absorption of desmopressin by 40%. No significant effect was observed with respect to pharmacodynamics (urine production or osmolality). It cannot be excluded that some patients may have decreased antidiuretic effect at concomitant food intake.
Solution for injection: Substances which are known to release antidiuretic hormone, eg. tricyclic antidepressants, chlorpromazine and carbamazepine, may cause an additive antidiuretic effect leading to an increased risk of water retention/hyponatremia.
Indomethacin increases the urine concentrating effect of desmopressin without influencing the duration. The effect is probably without any clinical significance.

Special Precautions for Disposal and Other Handling: The oral lyophilisates are brittle and could not be pressed through the foil since they may break. The oral lyophilisates should be taken out from the blisters by removing the aluminium cover.
Opening instructions for MINIRIN Melt Blister Pack: 1. Remove the end tab completely starting from the corner where a hand symbol is printed.
2. Tear off the blister unit along the vertical perforation.
3. Peel off the foil starting at the corner with the printed arrow. The product can then be removed from the pack.
4. To access the next tablet, tear off the blister unit along the horizontal perforation.
Tablet/Melt oral lyophilisate: Incompatibilities: Not applicable.

Tablet: Do not store above 25°C. Keep the container tight closed and do not remove the desiccant capsule from the cap.
Melt oral lyophilisate: Do not store above 25°C. Store in the original package in order to protect from moisture and light.
Solution for injection: Keep refrigerated at 2-8°C.
Tablet/Melt oral lyophilisate: Shelf Life: 36 months.

Antidiuretics / Haemostatics

H01BA02 - desmopressin ; Belongs to the class of vasopressin and analogues. Used in posterior pituitary lobe hormone preparations.

P₁S₁S₃