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

Transcription

1 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 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 hours. C max and AUC do not increase in proportion to the administered dose. The distribution volume is 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

2 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

3 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

4 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, 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

5 MINIRIN tablets should be stored below 30 o C. 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