DDAVP® Spray and Rhinyle Nasal Solutions
Ferring
Desmopressin Acetate
Antidiuretic
Action And Clinical Pharmacology: Desmopressin is a synthetic structural analogue of the antidiuretic hormone, arginine vasopressin, which alters the permeability of the renal tubule to increase resorption of water. The increase in the permeability of both the distal tubules and collecting ducts appears to be mediated by a stimulation of the adenylcyclase activity in the renal tubules.
Approximately 10 to 20% of the dose of desmopressin solution administered intranasally is absorbed through the nasal mucosa. Antidiuretic effects occur within 1 hour, peak in 1 to 5 hours, persist 8 to 20 hours and then abruptly end over a period of 60 to 90 minutes. Duration of action varies greatly among individuals and is dependent upon the rate of absorption from the nasal mucosa, persistence in plasma, and effect on renal tubules.
Indications And Clinical Uses: Diabetes Insipidus: Spray and Rhinyle: The management of vasopressin sensitive central diabetes insipidus and the control of temporary polyuria and polydipsia following head trauma, hypophysectomy or surgery in the pituitary region.
Nocturnal Enuresis: Spray only: The short-term management of nocturnal enuresis in patients 5 years of age and older who have normal ability to concentrate urine. Desmopressin should be used in conjunction with nonmedicinal therapy such as motivational counselling and bladder exercises.
Contra-Indications: Hypersensitivity to desmopressin or to any of the constituents.
Because of the risk of platelet aggregation and thrombocytopenia, desmopressin should not be used in patients with type IIB or platelet-type (pseudo) von Willebrand’s disease.
Manufacturers’ Warnings In Clinical States: For intranasal use only. Desmopressin is not effective in controlling polyuria caused by renal disease, nephrogenic diabetes insipidus, psychogenic diabetes insipidus, hypokalemia or hypercalcemia.
Fluid intake should be adjusted in order to reduce the possibility of water retention and hyponatremia especially in very young and elderly patients (see Dosage). Particular attention should be paid to the risk of an extreme decrease in plasma osmolality and resulting seizures in young children.
Changes in the nasal mucosa resulting from rhinitis, scarring, edema or other disease may cause erratic, unreliable absorption in which case intranasal desmopressin should not be used. In the case of temporary rhinitis, consideration should be given to using an injectable form of desmopressin, until the nasal mucosa returns to normal.
Precautions: General: Desmopressin at high dosage [40 g (0.4 mL) or more] has very occasionally produced a slight elevation of blood pressure, which disappeared with a reduction in dosage. The drug should be used with caution in patients with coronary artery insufficiency and/or hypertensive cardiovascular disease because of possible tachycardia and changes in blood pressure.
In the control of diabetes insipidus, the lowest effective dose should be used and the effective dosage, as determined by urine volume and osmolality and, in some cases, plasma osmolality, should be assessed periodically.
Desmopressin should not be administered to dehydrated patients until water balance has been adequately restored.
Desmopressin should be used with caution in patients with cystic fibrosis because these patients are prone to hyponatremia.
Children and geriatric patients should be closely observed for possible water retention due to over ingestion of fluids. When fluid intake is not excessive, there is little danger of water intoxication and hyponatremia with the usual intranasal doses of desmopressin used to control diabetes insipidus. Fluid intake should be carefully adjusted to prevent overhydration.
There are reports of changes in response over time, usually when the drug has been administered for periods longer than 6 months. Some patients may show decreased responsiveness, others a shortened duration of effect. There is no evidence that this effect is due to the development of binding antibodies, but may be due to local inactivation of the peptide.
For control of nocturnal enuresis a restricted fluid intake is recommended a few hours before administration.
Drug Interactions: Clofibrate, chlorpropamide and carbamazepine may potentiate the antidiuretic activity of desmopressin while demeclocycline, lithium and norepinephrine may decrease its activity.
Although the pressor activity of desmopressin is very low compared with the antidiuretic activity, use of large doses of desmopressin with other pressor agents should be done only with careful patient monitoring.
Pregnancy: Reproductive studies performed in rats and rabbits have revealed no evidence of harm to the fetus by desmopressin. Use in pregnant women with no harm to the fetus has been reported. However, no controlled studies in pregnant women have been carried out. Unlike preparations containing the natural hormone, desmopressin in antidiuretic doses has no uterotonic action, but the physician should weigh possible therapeutic advantages against potential risks in each case.
Lactation: There have been no controlled studies in nursing mothers. A single study on a postpartum woman demonstrated a marked change in maternal plasma desmopressin level following an intranasal dose of 10 µg (0.1 mL), but little desmopressin was detectable in breast milk.
Children: Desmopressin has been used in children with diabetes insipidus. The dose must be individually adjusted to the patient with attention in the very young to the danger of an extreme decrease of plasma osmolality with resulting convulsions. Dosage in infants younger than 3 months has not been established. Dose should start at 5 µg (0.05 mL) or less. Use of desmopressin in infants and children will require careful fluid intake restriction to prevent possible hyponatremia and water intoxication.
Laboratory Tests: Diagnosis of Central Diabetes Insipidus: Central diabetes insipidus may be demonstrated by the inability to produce urine of osmolality above 175 mOsm/kg with dehydration severe enough to cause a loss of greater than 2% of body weight.
Patients are selected for therapy by establishing a diagnosis by means of a water deprivation test, the hypertonic saline infusion test, and/or response to 5 units arginine vasopressin given s.c. after dehydration. Continued response to desmopressin can be monitored by urine volume and osmolality. In cases of severe dehydration, plasma osmolality determination may be required.
Adverse Reactions: Infrequently, high doses of desmopressin have produced transient headache and nausea. Nasal congestion, rhinitis, flushing and mild abdominal cramps have been reported. These symptoms disappeared with reduction in dosage.
Side effects reported from controlled clinical trials involving 638 subjects included headache (2%) and rhinitis (1%), nasal discomfort (1%), epistaxis (1%) and abdominal pain (1%). Other effects, reported at a frequency of less than 1%, included dizziness, chills, wheezing, rash, edema of face and hands, nausea, constipation, anorexia, increased appetite, conjunctivitis and after taste in the mouth. These symptoms disappeared with reduction of dosage or withdrawal of drug. Adverse effects rarely necessitate discontinuance of the drug.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: Overdose symptoms include headaches, abdominal cramps, nausea and facial flushing. There is no known antidote. Dosage and frequency of administration should be reduced, or the drug withdrawn according to the severity of the condition.
Water retention can be controlled by decreasing the dosage of desmopressin; severe water retention caused by overdosage may be treated with a diuretic such as furosemide.
Dosage And Administration: Diabetes Insipidus: Central diabetes insipidus may be demonstrated by the inability to produce urine of osmolality above 175 mOsm/kg with dehydration severe enough to cause a loss of greater than 2% of body weight.
Dosage in children up to 3 months of age has not been established.
Dosage must be individualized but clinical experience has shown that the average daily dose for adults is 10 to 40 g (0.1 to 0.4 mL) desmopressin and for children 3 months to 12 years of age, 5 to 30 g (0.05 to 0.3 mL). This may be given as a single dose or divided into 2 or 3 doses. About 33% of patients can be treated with a single daily dose. Geriatric patients may be more sensitive to the antidiuretic effect of the usual adult dose of desmopressin.
In those children who require less than 10 g (0.1 mL), the rhinyle presentation should be used since the spray will only deliver a minimum of 10 µg. In some patients, better control of polyuria is attained with smaller doses given at 6 to 8 hour intervals.
Most adults require 20 g (0.2 mL) daily, administered in 2 divided doses (in the morning and the evening). Initially, therapy should be directed to control nocturia with a single evening dose. Response to therapy can be measured by the volume and frequency of urination and duration of uninterrupted sleep. The dosage of desmopressin should be adjusted according to the diurnal pattern of response, with the morning and evening doses being adjusted separately. Patients being switched from parenteral to intranasal administration generally require 10 times their maintenance i.v. dose intranasally.
To institute therapy with desmopressin patients should be withdrawn from previous medication and allowed to establish a baseline polyuria to permit determination of the magnitude and duration of the response to medication. In less severe cases, prior water loading may be desirable to establish a vigorous flow of urine. When the urine osmolality reaches a plateau at low level (in most cases, less than 100 mOsm/kg), the first oral dose of desmopressin [10 g (0.1 mL)] is administered intranasally. A urine sample is obtained after 2 hours and hourly thereafter following desmopressin administration. Urine volume and osmolality is measured. When the patient has reached the previous baseline urine osmolality and urine flow, the drug effect has ceased and the next dose is administered. The cycle is then repeated until the patient has reached a stable condition.
Nocturnal Enuresis: Dosage must be individualized by the physician. The clinically effective intranasal dose varies between patients and ranges between 10 and 40 µg desmopressin daily. A suitable starting dose for adults and children is 20 µg given 1 hour before sleep. A restricted fluid intake is recommended a few hours before administration.
For the method of administering desmopressin by the nasal spray pump refer to Information for the Patient.
Changes in the nasal mucosa resulting from rhinitis, scarring, edema or other disease may cause erratic, unreliable absorption in which case intranasal desmopressin should not be used. In the case of temporary rhinitis, consideration should be given to using an injectable form of desmopressin, until the nasal mucosa returns to normal.
Rarely, patients may develop tolerance to the drug during long-term intranasal use, and require cautious increase in dosage to achieve an adequate therapeutic response.
Availability And Storage: Rhinyle: Each bottle contains: desmopressin acetate 250 g (equivalent to 225 g free base) in 2.5 mL of isotonic water, clear, colorless solution, with 1 calibrated rhinyle tube for intranasal administration. Keep in refrigerator at 2 to 8°C but do not freeze. Store out of reach of children.
Spray: Each pre-compression metered dose spray pump contains: desmopressin acetate 0.1 mg/mL in a buffered isotonic aqueous solution. Also contains benzalkonium chloride as a preservative. Each depression delivers desmopressin acetate 10 g. Spray bottles of 2.5 mL containing 25 doses and 5 mL containing 50 doses. Store at room temperature 15 to 30°C. Do not freeze. Store out of reach of children.
DDAVP® Spray and Rhinyle Nasal Solutions Ferring Desmopressin Acetate Antidiuretic
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