Minirin

/ Ferring Pharmaceuticals

Tablets administration. A suitable initial dose for children and adults is 0.1 mg three times daily. The dose is than adjusted according to the response of the patient. The average daily dose is between 0.2 and 1.2 mg with tablet administration. For most patients, 0.1 – 0.2 mg three times daily is the optimal dose regimen.
Nocturnal Enuresis:
Tablets administration. 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.
If treatment continues over the long-term, a treatment-free week should be introduced every three months, in order to ascertain whether the condition has resolved spontaneously.
If the desired clinical effect has not been achieved after 4 weeks of dose titration, treatment should be discontinued.
Nocturia:
The recommended initial dose is 0.1 mg at bedtime. If this does 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 the functional bladder capacity or exceeding 1/3 of the 24-hour urine production is regarded as nocturnal polyuria.
Serum sodium must be measured before beginning the treatment and 3 days after initiation or increase in dosage and other times during treatment as seemed necessary by the treating physician.
If adequate medical effect is not achieved within 4 weeks following appropriate dose titration the medication should be discontinued. Assessment of the necessity of continued treatment should be made after three months during one drugfree week. Fluid restriction should be observed. In the event of signs of water retention/hyponatraemia treatment should be interrupted.

Central diabetes insipidus.
Nocturnal Enuresis.
Treatment of nocturia in adults associated with nocturnal polyuria.

Patients with Habitual or psychogenic polydipsia (resulting in a urine production exceeding 40 ml/kg/24 hours).
Patients with syndrome of inappropriate ADH secretion.
Patients with known hyponatraemia.
Patients with a history of known or suspected cardiac insufficiency and other conditions requiring treatment with diuretics.
Patients with moderate and severe renal insufficiency (creatinine clearance below 50 ml/min).
Patients with hypersensitivity to desmopressin or to any of the excipients;
Patients with patients over the age of 65 for the treatment of primary nocturnal enuresis.
Patients with patients over the age of 65 for the treatment of nocturia.
Before prescribing Minirin tablets the diagnosis of psychogenic polydipsia and alcohol abuse should be excluded.

Special warnings:
When used for primary nocturnal enuresis and nocturia indications, the fluid intake must be limited to a minimum from 1 hour before until the next morning (at least 8 hours) after administration. Treatment without concomitant reduction of fluid intake may lead to water retention and/or hyponatraemia with or without accompanying warning signs and symptoms (headache, nausea/vomiting, weight gain, and, in severe cases, convulsions). All patients and, when applicable, their guardians should be carefully instructed to adhere to the fluid restrictions.
This product contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.
Use of the product should be under specialist supervision with appropriate facilities available for monitoring and interpretation of response.
All patients on desmopressin therapy should be observed for the signs of symptoms associated with hyponatraemia (headache, nausea/vomiting, weight increased and, in severe cases, convulsions).
Care should be taken with patients who have reduced renal function  and/or cardiovascular disease or cystic fibrosis.
Patients being treated for primary nocturnal enuresis or nocturia should discontinue Minirin Tablets during an episode of vomiting and/or diarrhoea until their fluid balance is once again normal.
Precautions
Severe bladder dysfunction and outlet obstruction should be considered before starting treatment.
Older patients and patients with low serum sodium levels may have an increased risk of hyponatraemia therefore Minirin Tablets are contraindicated in patients being treated for primary nocturnal enuresis and nocturia.
Treatment with desmopressin should be interrupted during acute intercurrent illnesses characterised by fluid and/or electrolyte imbalance (such as systemic infections, fever, and gastroenteritis).
Precautions must be taken in patients at risk for increased intracranial pressure.
Desmopressin should be used with caution in patients with conditions characterized by fluid and/or electrolyte imbalance.
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 serotonine reuptake inhibitors, chlorpromazine and carbamazepine, case of concomitant treatment with NSAIDs

Treatment without concomitant reduction of fluid intake may lead to water retention/hyponatraemia with accompanying signs and symptoms (headache, nausea/vomiting, decreased serum sodium, weight gain, decreased serum sodium and in serious cases, convulsions). Primary nocturnal enuresis & diabetes insipidus.
For full details see prescribing information

Substances, which are known to induce SIADH, e.g. tricyclic antidepressants, selective serotonine reuptake inhibitors, chlorpromazine and carbamazepine, as well as some antidiabetics of the sulfonylurea group particularly Chlorpropamide, may cause an additive antidiuretic effect leading to an increased risk of water retention/hyponatraemia.
NSAIDs may induce water retention/hyponatraemia.
Concomitant treatment with loperamide may result in a 3-fold increase of desmopressin plasma concentrations, which may lead to an increased risk of water retention/hyponatraemia. Although not investigated, other drugs
slowing intestinal transport might have the same effect.
It is unlikely that desmopressin will interact with drugs affecting hepatic metabolism, since desmopressin has been shown not to undergo significant liver metabolism in in vitro studies with human microsomes. However,
formal in vivo interaction studies have not been performed. The concomitant use of food decreases the rate and extent of absorption of Nordurine tablets by 40%. No significant effect was observed with respect to pharmacodynamics (urine production or osmolality).
Food intake may reduce the intensity and duration of the antidiuretic effect at low oral doses of desmopressin.

Pregnancy: Published data on a limited number (n = 53) of exposed pregnancies in women with diabetes insipidus  indicate rare cases of malformations in children treated during pregnancy. 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. Blood pressure monitoring is recommended due to the increased risk of pre-eclampsia.
Lactation: Results from analyses of milk from nursing mothers receiving high dose desmopressin (300 µg intranasal), indicate that the amounts of desmopressin that may be transferred to the child are considerably less than the amounts required to influence diuresis.

Overdose of Minirin tablets leads to a prolonged duration of action with an increased risk of water retention and hyponatraemia.
Treatment:
Although the treatment of hyponatraemia should be individualised, the following general recommendations can be given – discontinue the desmopressin treatment and institute fluid restriction, and symptomatic treatment if needed.