Minirin免尿寧

Minirin

desmopressin

Manufacturer:

Ferring

Distributor:

DCH Auriga - Universal
/
Four Star
Full Prescribing Info
Contents
Desmopressin acetate.
Description
Each tablet contains desmopressin acetate 0.1 or 0.2 mg and excipients qs.
Each oral lyophilisate contains desmopressin (free base) 60 mcg or 120 mcg and excipients qs.
Each ampoule for injection contains desmopressin acetate 4 mcg, sodium chloride qs, hydrochloric acid (to adjust pH to 4) and water for injections.
Action
General: Desmopressin is 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.
Minirin injection in a high dosage, 0.3 mcg/kg body weight IV or SC, leads to a 2- to 4-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 mcg/kg body weight is reached after approximately 60 min and amounts to an average of 600 pg/mL. Plasma half-life (t½) ranges between 3 and 4 hrs. The duration of the haemostatic effect depends on the plasma t½ for VIII:C which is about 8-12 hrs.
Administration of desmospressin 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.
The pH of the solution is about 4.
Indications/Uses
Tablet/Melt Oral Lyophilisate/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.
Tablet/Melt Oral Lyophilisate: Primary Nocturnal Enuresis: Indicated for the treatment of primary nocturnal enuresis in patients ≥5 years who have normal ability to concentrate urine.
Nocturia: Symptomatic treatment of nocturia in adults associated with nocturnal polyuria ie, nocturnal urine production exceeding bladder capacity.
Injection: Renal Concentrating Capacity Test: Minirin injection 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: Minirin injection is indicated 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 IIB.
Dosage/Direction for Use
Central Diabetes Insipidus: Tablet: A suitable initial dose for children and adults is 0.1 mg 3 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 and 1.2 mg. For most patients, 0.1-0.2 mg 3 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. (Also see under Warnings.)
Melt Oral Lyophilisate: A suitable initial dose for children and adults is 60 mcg 3 times daily, administered sublingually. Dosage regimen can be adjusted in accordance with the patient's response. For most patients, the maintenance dose is 60 mcg to 120 mcg sublingually three times daily. Maximum daily dose varies between 120 mcg and 720 mcg sublingually. In the event of signs of water retention/hyponatraemia, treatment should be interrupted and the dose should be adjusted.
Injection: The dosage is determined for each patient and adjusted according to urine volume and serum sodium.
Normal Dosage: IV Injection: Adults: 1-4 mcg (0.25-1 mL). Children >1 year: 0.4-1 mcg (0.1-0.25 mL); <1 year: 0.2-0.4 mcg (0.05-0.1 mL). All doses to be taken 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.
Primary Nocturnal Enuresis: Tablet: 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 re-assessed after 3 months by means of a period of at least 1 week without Minirin treatment. A restricted water intake must be observed. (Also see under Warnings.)
Melt Oral Lyophilisate: A suitable initial dose is 120 mcg at bedtime, administered sublingually. The dose may be increased up to 240 mcg sublingually. Fluid restriction shall be enforced. In the event of signs or symptoms of water retention and/or hyponatraemia (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. Evaluation of continued need of treatment should be carried out after 3 months by means of at least 1 treatment-free week. (Also see under Warnings.)
Nocturia: Tablet: Initial dose: 0.1 mg at bedtime. If dose is not sufficiently effective after 1 week, it can be increased to 0.2 mg and then to 0.4 mg by means of weekly increases.
Melt Oral Lyophilisate: The recommended initial dose is 60 mcg at bedtime, administered sublingually. If this dose is not sufficiently effective after 1 week, the dose may be increased up to 120 mcg sublingually and subsequently 240 mcg sublingually by weekly dose escalations.
Tablet/Melt Oral Lyophilisate: Fluid restriction is to be enforced.
In nocturic patients, a frequency/volume chart should be used to diagnosed 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-hr urine production is regarded as nocturnal polyuria.
The initiation of treatment in the elderly (≥65 years) is not recommended. Should treatment of these patients 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 hyponatraemia (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 (see Precautions).
If adequate clinical effect is not achieved within 4 weeks following appropriate dose titration, Minirin should be discontinued.
Renal Concentrating Capacity Test: Injection: Normal adult dose by IM or SC injection is 4 mcg (1 mL). For children >12 months, the dose is 1-2 mcg (0.25-0.5 mL). For children <12 months, the dose is 0.4 mcg (0.1 mL). For children, it is recommended to use primarily the intranasal presentation. After administration of Minirin, possible urine within 1 hr is discarded. During the next 8 hrs, 2 portions of urine are collected for measurement of osmolality. A restricted water intake must be observed. (Also see under Warnings.)
The reference level for normal urine osmolality after Minirin administration is 800 mOsmol/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 IV infusion at a dose of 0.3 mcg/kg body weight diluted in sterile physiological saline and infused slowly over 15-30 min. In adults and children weighing ≥10 kg, 50 mL of diluent is used; in children weighing ≤10 kg, 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 hrs. 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 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 eg, 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.
Overdosage
Overdosage increases the risk of fluid retention and hyponatremia. 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.
Contraindications
Habitual or psychogenic polydipsia (urine production exceeding 40 mL/kg/24 hrs). Known or suspected cardiac insufficiency and other conditions that require treatment with diuretics. Moderate to severe renal insufficiency (creatinine clearance <50 mL/min). Syndrome of inappropriate ADH secretion (SIADH). Known hyponatraemia. And hypersensitivity to desmopressin or to any of the excipients (contain fish gelatine).
For Hemostatic Use: Unstable angina pectoris, decompensated cardiac insufficiency and von Willebrand's disease type IIB.
Warnings
Special attention must be paid to the risk of water retention. The fluid intake should be restricted to the least possible and the body weight should be checked regularly. When used for diagnostic purposes, the fluid intake must not exceed 0.5 L from 1 hr before until 8 hrs after administration.
In patients with urgency/urge incontinence, organic causes for increased micturition frequency or nocturia, polydipsia and poorly adjusted diabetes mellitus, the specific cause should be treated. Elderly patients, patients with low serum sodium levels and patients with a high 24-hr urine volume (>2.8-3 L) may have an increased risk for hyponatraemia. Treatment with desmopressin should be interrupted during acute intercurrent illnesses, characterized by fluid and/or electrolyte imbalance eg, systemic infections, fever, gastroenteritis.
Should there be a gradual increase of the body weight, decrease of serum sodium to <130 mmol/L or plasma osmolality to <270 mOsmol/kg body weight, the fluid intake must be reduced drastically and the administration of Minirin interrupted.
In connection with the infusion of Minirin for hemostatic use, the patient's blood pressure must be monitored continuously.
Minirin does not reduce prolonged bleeding time in thrombocytopenia.
Special Precautions
General: Particular precautions to prevent fluid overload must be taken in very young and elderly patients, other conditions characterized by fluid and/or electrolyte imbalance and patients at risk for increased intracranial pressure.
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 NSAIDs and with drugs which are known to induce SIADH eg, tricyclic antidepressants, chlorpromazine, selective serotonin reuptake inhibitors and carbamazepine.
For Renal Concentration Capacity Testing: Testing in children <1 year should only be performed under carefully supervised conditions in hospital.
For Hemostatic Use: Measures to prevent fluid overload must be taken in patients with conditions requiring treatment with diuretic agents.
Use in pregnancy: Injection: Reproduction studies performed in rats and rabbits with doses >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 >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.
Tablet/Melt Oral Lyophilisate: 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 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.
Use in lactation: Results from analyses of milk from nursing mothers receiving high dose desmopressin (300 mcg 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.
Use In Pregnancy & Lactation
Use in pregnancy: Injection: Reproduction studies performed in rats and rabbits with doses >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 >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.
Tablet/Melt Oral Lyophilisate: 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 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.
Use in lactation: Results from analyses of milk from nursing mothers receiving high dose desmopressin (300 mcg 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.
Adverse Reactions
A few percent of treated patients can be expected to experience side effects eg, headache, nausea and stomach pain, nasal congestion/rhinitis, epistaxis.
Common (>1/100): General: Headache. At high doses: Fatigue. Circulation: At high doses: Transient fall in blood pressure with a reflex tachycardia and facial flushing at the time of administration. Gastrointestinal: Stomach pain, nausea.
Rare (<1/1,000): General: At high doses: Dizziness.
Treatment without concomitant restriction of water intake may lead to water retention with or without accompanying signs and symptoms (reduced serum sodium, weight gain and in serious cases, convulsions).
Tablet: Peripheral oedema, more frequent need of urinating during daytime, dry mouth, weight gain.
Drug Interactions
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.
Melt and Tablet: Loperamide, 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 may result in a decrease of absorption.
Storage
Minirin tablets should be stored at room temperature (maximum 25°C) and in a dry place.
Minirin Melt oral lyophilisate should be stored below 25°C in the original package (sensitive to moisture).
Minirin injection should be stored at 2-8°C.
ATC Classification
H01BA02 - desmopressin ; Belongs to the class of vasopressin and analogues. Used in posterior pituitary lobe hormone preparations.
Presentation/Packing
Tab 0.1 mg x 30's. 0.2 mg x 30's. Melt oral lyophilisate 60 mcg x 30's. 120 mcg x 30's. Inj 4 mcg/mL x 1 mL x 10's.
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