Central diabetes insipidus, polyuria, polydipsia post-hypophysectomy or surgery in the pituitary region.

Nocturnal enuresis in patients aged 5 years and older with normal renal concentration capacity, after failure of
usual measures, only in patients with normal blood pressure and after exclusion of organic cause, for shortterm
treatment. The nasal forms of Minirin (nasal drops and nasal spray) must not be used for the treatment of
nocturnal enuresis.
Testing of renal concentration capacity (diagnosis of diabetes insipidus).

Central diabetes insipidus, polyuria, polydipsia post-hypophysectomy or surgery in the pituitary region
At the start of treatment, the optimal dosage must be individually established by the physician by determining
urine volume and urine osmolality. Treatment should be aligned to two parameters: an adequate duration of
sleep and an equilibrated water balance.
Intranasal use
Adults: daily dose 10–40 μg, equivalent to 1–4 nasal spray actuations, divided into 1 – 2 single doses.
Children: daily dose 5–20 μg, equivalent to 1–2 nasal spray actuations, divided into 1–2 single doses. Minirin
nasal spray is unsuitable for the treatment of children requiring a dose of 5 μg, as dosages below 10 μg cannot
be administered with the nasal spray.
Testing of renal concentration capacity
Testing of renal concentration capacity with Minirin in infants below 1 year of age should be performed only
under hospital conditions.
The short test should preferably be performed in the morning. The amount of ingested fluids should be
restricted during the first 12 hours after application. Children below 5 years of age and patients with heart
disease or high blood pressure should reduce their fluid intake by one-half.
Urine osmolality should be determined before the start of the test. Following administration of desmopressin,
2 urine samples are taken (preferably after about 2 and 4 hours). Within the first hour, urine should be taken
and discarded. Osmolality is determined in both urine samples. To determine renal concentration capacity, the
higher value is compared with the baseline value before the start of the test or with the age-specific reference
value (adults: 800-1000 mOsm/kg). Low values and no or only minimal increase in urine osmolality indicate
impaired renal concentration capacity. Polyuria related to central diabetes insipidus is present when there is a
significant increase in urine osmolality and a significant decrease in urine volume.
Intranasal use
Adults: 40 μg (4 nasal spray actuations).
Children aged 10-16 years: 20 μg (2 nasal spray actuations).
Infants and toddlers: 10 μg (1 nasal spray actuation).

Desmopressin must not be used in the following cases: - primary or psychogenic polydipsia; - heart failure and other diseases requiring treatment with diuretics; - in patients with hyponatraemia; - mild or severe renal insufficiency (creatinine clearance below 50 ml/min); - syndrome of inappropriate ADH secretion (SIADH); - severe classic von Willebrand-Jürgen’s syndrome (type IIb), patients with 5% factor VIII activity, factor VIII antibodies; hypersensitivity to the active substance or to any of the excipients.

When administering Minirin tablets or sublingual tablets for nocturnal enuresis, fluid intake should be
restricted as a precaution 1 hour before and up to 8 hours after administration of Minirin and reduced to
quenching the thirst only. Treatment without concomitant reduction in fluid intake can lead to water retention
and/or hyponatraemia with symptoms of headache, nausea, vomiting, weight gain and, in severe cases, cerebral
oedema, seizures and coma. The safety of long-term use in nocturnal enuresis has not been established.
There have been repeated reports of cerebral oedema and seizures occurring in otherwise healthy children and
young adults treated with desmopressin for nocturnal enuresis. This risk seems to be particularly high in the
first week of treatment.
Elderly patients (>65 years of age) and patients with low sodium levels may be at increased risk of
hyponatraemia.
The duration of action increases at higher dosages and hence also the risk of hyponatraemia. The dosage should
be titrated upwards accordingly.
Desmopressin should be used with particular caution in patients with cystic fibrosis, coronary heart disease,
hypertension, thrombotic tendency, chronic renal disease, pre-eclampsia, increased intracranial pressure or
with fluid and electrolyte imbalances.
In patients with hypertension and chronic renal disease, the symptoms mentioned under “Undesirable effects”
may be accentuated. In very young and elderly patients, or if risk factors exist that may lead to increased
intracranial pressure, care must be taken whilst using Minirin to ensure that no water retention occurs.
Without concomitant restriction of fluid intake, treatment with desmopressin can lead to water retention and
hyponatraemia.
Patients and, in the case of children, their parents should be informed that excessive fluid intake must be
avoided and that, in the event of vomiting, diarrhoea, systemic infections and fever, desmopressin use should
be suspended until the fluid balance has returned to normal.
To reduce the risk of hyponatraemia or water intoxication, a reduction in fluid intake is particularly important:
- when using medicinal products known to induce SIADH (tricyclic antidepressants, selective serotonin
reuptake inhibitors, chlorpromazine, chlorpropamide and carbamazepine);
- during concomitant treatment with NSAIDs.
It is important to monitor body weight during treatment.
In patients over 65 years of age, serum sodium should be determined before the start of therapy and 3 days
after the start of therapy or dose escalations. Treatment must be discontinued at the onset of headache and/or
nausea.
Organic causes for polyuria or increased urination rate or nocturia, such as benign prostatic hyperplasia (BPH),
urinary tract infections, bladder stones or tumours, bladder sphincter disorders, polydipsia or poorly treated
diabetes mellitus, should be excluded or treated accordingly. Any adrenal or thyroid insufficiency must be
treated before the start of desmopressin therapy.
With intranasal use, changes in - or diseases of - the nasal mucosa may lead to altered absorption. In these
cases, desmopressin should not be used. The preservative contained in Minirin nasal spray (benzalkonium
chloride) may lead to bronchospasms and, especially in prolonged use, may cause swelling of the nasal
mucosa. If such a reaction is suspected (persistent blocked nose), a medicinal product for nasal use without
preservatives should - as far as possible - be used. If such medicines are not available, a different formulation
should be considered.
Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose
malabsorption should not take Minirin tablets.

If oxytocin is co-administered, an increase in the antidiuretic effect is possible and a reduction in uterine
perfusion is likely. Glibenclamide and lithium can reduce the antidiuretic effect of Minirin.
Clofibrate, indometacin and other NSAIDs, chlorpromazine, carbamazepine, antidepressants, selective
serotonin reuptake inhibitors and all medicinal products that affect the fluid/electrolyte balance can potentiate
the antidiuretic effect of Minirin and thus increase the risk of water retention/hyponatraemia. Blood pressure,
plasma sodium levels and urine output should be monitored during concomitant use of the above medications.
Concomitant treatment with loperamide can result in an up to 3-fold increase in desmopressin plasma
concentrations which, in turn, can lead to an increased risk of water retention/hyponatraemia.
Desmopressin is unlikely to interact with substances that affect hepatic metabolism, as desmopressin shows no
significant hepatic metabolism in in vitro studies on human microsomes. To date, no in vivo studies on
potential interactions have been performed.
A standardised diet with 27% fat significantly reduces the absorption (amount and duration) of orally
administered desmopressin. With regard to pharmacodynamic properties (urine production or osmolality), no
significant effect has been observed. Thus, desmopressin can, if desired, be taken with a meal. However, at a
low oral desmopressin dosage, food intake can reduce the intensity and duration of the antidiuretic effect.

The available data in a limited number (n=53) of pregnant women with diabetes insipidus show that
desmopressin has no negative effects on pregnancy or the state of health of the foetus or neonate. To date, 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 prescribing to pregnant women.
When treating diabetes insipidus in pregnancy, the dose must be adjusted to individual requirements, as these
may change during the pregnancy. Blood pressure monitoring is recommended.
Tests on the breast milk of women, who were given a high dosage of 300 μg desmopressin (intranasally),
showed the amounts of desmopressin that might be transferred to the infant are too low to influence diuresis.

No corresponding studies have been performed.

The undesirable effects are classified according to organ classes and degrees of frequency, taking into account
the following definition: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100);
rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).
Immune system disorders:
Very rare: allergic reactions and hypersensitivity reactions (e.g. pruritus, exanthema, fever, bronchospasm,
anaphylaxis)
Metabolism disorders:
Very rare: hyponatraemia, water intoxication
Psychiatric disorders:
Very rare: emotional disturbances (in children)
Nervous system disorders:
Common: headache
Rare: cerebral oedema, hyponatraemic seizures
Respiratory, thoracic and mediastinal disorders
Common: (nasal drops, nasal spray) nasal congestion, epistaxis, rhinitis
Gastrointestinal disorders:
Common: abdominal pain, cramps, nausea, diarrhoea, vomiting
Vascular disorders:
Common: transient hypotension, increased pulse rate, flushing
Not known: thrombotic complications (cerebral and coronary arteries)
General disorders and administration site conditions:
Common: fatigue
If fluid intake is excessive or if excessively high dosages are used, weight gain, hyponatraemia, seizures,
cerebral oedema and coma may occur as a result of water retention. This particularly applies to children up to
1 year of age or elderly patients, depending on their general state of health. To avoid water intoxication, an
equilibrated water balance should be ensured.
Blood pressure may rise due to increased water reabsorption and hypertension may develop in some cases.
Angina pectoris may occur in patients with coronary heart disease.

In the event of acute overdose with Minirin, the above-mentioned undesirable effects may be accentuated.
Overdose may occur particularly when the dose is carelessly titrated in infants.
There is an increased risk of fluid retention and hyponatraemia in the event of overdose. Although treatment of
hyponatraemia should be individualised, the following general recommendations have been tried and tested:
In the case of asymptomatic hyponatraemia, treatment with desmopressin is discontinued and fluid intake
restricted. If hyponatraemia is symptomatic, infusions of isotonic or hypertonic saline solution can additionally
be given. For cerebral oedema, immediate admission for intensive care therapy is necessary. Childhood
seizures also require intensive care measures.

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Absorption
The systemic availability of intravenously administered desmopressin is virtually complete; that of
subcutaneously administered desmopressin is approximately 90% compared with intravenous administration.
tmax is less than 20 minutes with IV injection and about 1 hour with subcutaneous injection.
Minirin, intranasally and orally administered, is rapidly but incompletely absorbed, whereby bioavailability
after intranasal administration is about 3–5% compared with IV administration. Following intranasal
administration of desmopressin, the peak plasma concentration is reached after about 50 min.
The plasma half-life is between 2 and 3 hours.
The absolute bioavailability of desmopressin after oral administration is between 0.08 and 0.16%. The mean
peak plasma concentration is reached after about 2 hours.
The mean systemic bioavailability of sublingually administered desmopressin such as Minirin Melt at doses of
200, 400 and 800 μg is 0.25% with a 95% confidence interval of 0.21–0.31%. Cmax was 14, 30 and 65 pg/ml
after administration of 200, 400 and 800 μg, respectively. tmax was observed 0.5–2.0 hours post-dose. The
geometric mean half-life is 2.8 (CV = 24%) hours.
Desmopressin exhibits high variability in bioavailability both inter- and intraindividually.
Distribution
The volume of distribution is 0.2–0.3 l/kg. Desmopressin does not cross the blood/brain barrier. Desmopressin
passes into breast milk in very small amounts.
Metabolism
With human liver microsomes, it was shown in vitro that only a small fraction of desmopressin is metabolised
in the liver. Thus, the hepatic metabolism of desmopressin in vivo is of little importance.
Elimination
The elimination of desmopressin follows first-order kinetics, but runs somewhat more slowly than the
elimination of native vasopressin. The plasma half-life of desmopressin is between 2.5 and 4.5 hours after
parenteral and intranasal administration and between 2.0 and 3.2 hours after oral administration.
Approximately 65% of desmopressin absorbed after oral administration (after IV injection: 45%) is excreted
within 24 hours via the urine.
Kinetics of special patient groups
There are no gender-specific differences in the pharmacokinetic behaviour of desmopressin.

From chronic toxicity studies, there are no data to suggest that hitherto unknown side effects might occur in
humans.
There was no indication of mutagenic potential in an Ames test. No long-term studies have been performed to
investigate carcinogenic potential.
Embryotoxicity studies, after subcutaneous administration of no more than 10 μg/kg desmopressin on Days 6-
18 post conception in rabbits, revealed a higher post-implantation loss of 10.6% in the high-dose group
compared with controls (1.2%) and a lower number of living foetuses. No teratogenic effects were observed.

sodium chloride, citric acid monohydrate, disodium phosphate dihydrate, preservatives: benzalkonium chloride
0.1 mg, purified water q.s. 1 ml

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This medicinal product must not be used after the date, which is stated on the pack after “Exp”. After opening, the nasal spray has a shelf life of 2 months at 25°C max.

To be kept at room temperature (below 30°C). Do not freeze. After opening the bottle, Minirin Nasal Spray can
be stored for 8 weeks at room temperature. Store Minirin in the original packaging protected from light and
moisture.

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