MINIRIN ®

Tablets 0.1 and 0.2 mg

Declaration
Tablets 0.1 mg. Each tablet contains desmopressin acetate 0.1 mg and excipients q.s
Tablets 0.2 mg. Each tablet contains desmopressin acetate 0.2 mg and excipients q.s

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. Oral administration
of 0.1-0.2 mg desmopressin provides an antidiuretic effect lasting in most patients for 8-12 hours.
Relative to intranasal administration the bioavailability is about 5 per cent.

Pharmacokinetic properties
The absolute bioavailability after perorally administered desmopressin varies between 0.08 and
0.16%. Desmopressin exhibits a moderate to high variability in bioavailabilty, both within and
between subjects. Concomitant use of food decreases the rate and extent of absorption by about
40%.
The maximal plasma concentration is reached after 1-1.5 hours. C max and AUC do not increase
in proportion to the administered dose. The distribution volume is 0.2-0.3 l/kg. Desmopressin
does not cross the blood-brain barrier. The mean half-life for desmopressin in the elimination
phase is 2-3 hours on average.

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.

After i.v injection 45% of the amount of desmopressin is found in the urine within 24 hours.

Indications

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.

Contraindications
MINIRIN ® tablet are contraindicated in cases of:
- Habitual or psychogenic polydipsia (resulting in a urine production exceeding 40 ml/kg/24
hours);
- A history of known or suspected cardiac insufficiency and other conditions that require treatment
with diuretics;
- Moderate to severe renal insufficiency (creatinine clearance below 50 ml/min);
- Syndrome of inappropriate ADH secretion;
- Known hyponatraemia;
- Hypersensitivity to desmopressin or to any of the excipients.

Special warnings and special precautions for use

In the treatment of primary nocturnal enuresis and nocturia fluid intake shall be limited to the least
possible during the period of one hour before and 8 hours after administration. Treatment without
concomitant reduction in fluid intake can lead water retention and/or hyponatraemia
(headache,nausea/vomiting,weight gain and in serious cases convulsions).

In patients with urgency/urge incontinence, organic causes for increased micturition frequency or
nocturia (e.g. benign prostate hyperplasia (BPH), urinary tract infection, bladder stones/tumors),
polydipsia and poorly adjusted diabetes mellitus, the specific cause should be treated.

In clinical trials, higher occurence of hyponatraemia was found in patients over 65 years.
Therefore, initiation of treatment in the elderly is not recommended, especially not in those
patient suffering from other conditions that may increase the likelihood of fluid or electrolyte
imbalance.

Elderly patients, patient with low serum sodium levels and patients with a high 24-hour urine
volume (above 2.8 to 3 litres) may 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 in:

case of concomitant treatment with drugs, which are known to induce SIADH, e.g. tricyclic
antidepressants, selective serotonin reuptake inhibitors, chlorpromazine and
carbamazepine.
case of concomitant treatment with NSAIDs.

Treatment with desmopressin should be interrupted during acute intercurrent illnesses,

characterized by fluid and/or electrolyte imbalance such as systemic infections, fever,
gastroenteritis.

Pregnancy
Data on a limited number (n=53) of exposed pregnancies in women with diabetes insipidus
indicate no adverse effects of desmopressin on pregnancy or on the health of the foetus/newborn
child. To date, no other relevant epidemiological data area 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.

Lactation
Results from analyses of milk from nursing mothers receiving high dose desmopressin (300 µg
intranasally), indicate 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.

Effects on ability to drive and use machines

None

Undesirable effects
Treatment without concomitant reduction of fluid intake may lead to water retention/hyponatremia
with or without accompanying warning signs and symptoms (headache, nausea/vomiting,
decreased serum sodium, weight gain, and in serious cases, convulsions).

Primary nocturnal enuresis and diabetes insipidus.

Common (>1/100) General: Headache
GI: Abdominal pain, nausea

Post marketing experience:

- Very rare cases of emotional disturbances in children have been reported
- Isolated cases of allergic skin reactions and more severe general allergic reactions have been
reported.

Nocturia:
Common:
Hyponatraemia (low serum sodium levels), headache, dizzines, peripheral oedema, more
frequent need of urinating during daytime, stomach pain, nausea, dry mouth and weight gain.

Interactions with other medicaments and other forms of interaction

Concomitant treatment with some medicines against depression (tricyclic antidepressant,
selective serotonin re-uptake inhibitors), chlorpromazine (against psychosis), carbamazepine
(against epilepsy), loperamide (against diarrhoea), medicines that slow down intestinal passage
and some pain-relieving and anti-inflammatory medicines (NSAID-preparations) may reinforce
the effect of MINIRIN ® , with an increased risk for abnormal accumulation of fluid in the body.

Concomitant treatment with dimeticone (against meteorism) may result in a decreased absorption
of MINIRIN ® .

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 interactions studies in vivo have been
carried out.

A standardised meal with 27% fat taken together with or 1.5 h prior to desmopressin decreased
the extent and rate of absorption of desmopressin by about 40%. No significant effect was
observed with respect to pharmacodynamics (urine production or osmolality). However, it can not
be excluded that some patients may have altered effect at concomitant food intake.

Dosage and administration

Optimal dose of MINIRIN ® tablets is individually adjusted. 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.

Central diabetes insipidus: A suitable initial dose for children and adults is 0.1 mg three times
daily. The dose is then adjusted according to the response of the patient. According to clinical
experience gained so far, the daily dose lies in the range of 0.2 mg and 1.2 mg. For most
patients, 0.1-0.2 mg three times daily is the optimal dose regimen.
In the event of signs of water retention/hyponatraemia, treatment should be 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. The need for continued
treatment should be reassessed after 3 months by means of a period of at least 1 week without
MINIRIN ® treatment. Fluid restriction should be observed, see also under Special warning and
special precautions for use. In the event of signs of water retention, treatment should be
interrupted.

Nocturia: The recommended initial dose is 0.1 mg at bedtime.If this dose is not sufficiently
effective after one week, it can be increased to 0.2 mg and then to 0.4 mg by means of weekly
increases. Fluid restriction is to be enforced.

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
functional bladder capacity or exceeding 1/3 of the 24-hour urine production is regarded as
nocturnal polyuria.

The initiation of treatment in the elderly (65 years of age and over) is not recommended. Should
treatment of these patient be considered, serum sodium should be measured before beginning
the treatment and 3 days after initiation or increase in dosage and other times during treatment as
deemed necessary by the treating physician.

Should there be signs or symptoms of water retention and/or hyponatremia (headache,

nausea/vomiting, weight gain, and in serious cases convulsions) the treatment should be
interrupted until the patient has completely recovered. When the treatment is resumed strict fluid
restriction is necessary.

If adequate clinical effect is not achieved within 4 weeks following appropriate dose titration the
medication should be discontinued.

Overdose
Overdose of MINIRIN ® tablets can lead to water retention and hyponatraemia.
Treatment
Although the treatment of hyponatraemia should be individualized, the following general
recommendations can be given. Asymptomatic hyponatraemia is treated with discontinuing the
desmopressin treatment and fluid restriction. Infusion of isotonic or hypertonic sodium chloride
may be added in cases with symptoms. When the water retention is severe (convulsions, and
unconsciousness) treatment with furosemide should be added.

Stability and storage

MINIRIN ® tablets should be stored below 30oC.

In areas where temperature is higher than the one suggested, the bottles should be stored in a
refrigerator. The top cap of the bottle should be firmly closed and the desiccant capsule should
not be removed from the cap.

Legal category
Prescription only medicine.

Package quantities
0.1 mg: 30 tablets
0.2 mg: 30 tablets

Manufacturer
FERRING International Center SA
St. Prex, Switzerland

Revision: June 2009

HARUS DENGAN RESEP DOKTER

Reg No:

Imported by:
PT. DKSH TUNGGAL
Jakarta - Indonesia