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.
Although the bioavailability of orally ingested desmopressin is low, reported as being about 1 to 5%, it is sufficient to induce an antidiuresis (urine osmolality greater than 400 mOsm/kg) lasting 7 to 9 hours in healthy subjects and in patients with diabetes insipidus. Onset of action, as determined by decreased urine volume and increased urine osmolality, is within 1 hour. In both adults and children, there is a log linear relationship between desmopressin doses and maximal urine osmolality and duration of antidiuresis within the dose range 12.5 to 400 Âµg. Measurements of plasma desmopressin concentrations after peroral desmopressin administration show a linear relationship between amounts of desmopressin absorbed and dose, but with great interindividual differences.
Indications And Clinical Uses: For the management of vasopressin sensitive central diabetes insipidus, and for the control of temporary polyuria and polydipsia following head trauma, hypophysectomy or surgery in the pituitary region.
Contra-Indications: Hypersensitivity to desmopressin or any of the tablet’s constituents. Because of the risk of platelet aggregation and thrombocytopenia, the drug should not be used in patients with type IIB or platelet-type (pseudo) von Willebrand’s disease. tag_WarningWarnings
Manufacturers’ Warnings In Clinical States: 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 to reduce the possibility of water intoxication and hyponatremia especially in the 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.
Keep this medication, as well as all medication out of reach of children.
Precautions: Desmopressin at high dosage (40 Âµg or more) has 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.
Lack of therapeutic response to oral desmopressin may be noted in some patients even at the maximum recommended dosage. These patients should be switched to the intranasal or injectable dosage form of desmopressin.
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.
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. 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.
Drug Interactions: Clofibrate, chlorpropamide and carbamazapine 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. The use of desmopressin 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 Âµg, 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 100 Âµg 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 and by means of Minirin test. 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.
Serum AST levels were elevated in 4/16 patients 6 months after commencing oral desmopressin therapy (200 to 600 Âµg/day). Two of these patients had exhibited baseline levels of AST that were above the normal range and all 4 patients had normal AST levels on repeat test at 9 months, even though desmopressin administration was continued. The possibility that desmopressin has an adverse effect on serum enzymes is therefore remote.
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 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: Desmopressin dosage must be determined for each patient and adjusted according to the pattern of response. Response should be estimated by adequate duration of sleep and adequate, not excessive, water turnover and maintenance of urine osmolality at levels of 400 mOsm/kg or greater.
To institute desmopressin therapy, patients should be withdrawn from previous medication and allowed to establish a baseline polyuria and polydipsia. The stable polyuria is used as a baseline to determine 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 the low level (in most cases, less than 100 mOsm/kg), the first oral dose (e.g., 100 Âµg) of desmopressin is administered. A urine sample is obtained after 2 hours and hourly thereafter; urine volume is measured and urine osmolality determined. When the patient has reached the previous baseline urine osmolality and urine flow, the drug effect has ceased and the next desmopressin dose is administered. The cycle is then repeated until the patient has reached a stable condition.
Dosage must be individualized. A suitable starting dose for adults and children is 100 Âµg (0.1 mg desmopressin) 3 times daily. This dosage regimen should then be adjusted in accordance with the patient’s response in order to ensure an optimum dose. For patients who have been controlled on intranasal desmopressin and who are to be switched to the oral form, the oral dose producing comparable antidiuresis is about 10 to 20 times greater than the established intranasal dose. Geriatric patients may be more sensitive to the antidiuretic effect of the usual adult dose of desmopressin.
In children, the evening dose is usually 2x higher than the morning and midday dose to ensure sufficient antidiuresis during sleep. This is generally not a requirement for adult patients, presumably because adults sleep for shorter periods of time.
The maximum recommended dosage for both adults and children is 1.2 mg/day (400 Âµg t.i.d.). Although there is no evidence that potentially serious adverse reactions would occur at daily doses greater than 1.2 mg, a maximum of 1.2 mg is being recommended at the present time since clinical experiences with daily dosages exceeding 1.2 mg is limited. The lowest effective dosage should be given. Rarely, during long-term use, patients may develop tolerance to the drug and require cautious increase in dosage to achieve adequate therapeutic response.
Availability And Storage: 0.1 mg: Each white, uncoated tablet contains: desmopressin acetate 0.1 mg. Nonmedicinal ingredients: lactose, magnesium stearate, potato starch and povidone. Strip of 30 per carton.
0.2 mg: Each white, uncoated tablet contains: desmopressin acetate 0.2 mg. Nonmedicinal ingredients: lactose, magnesium stearate, potato starch and povidone. Strip of 30 per carton.
Store below 25Â°C in a dry place.
DDAVPÂ® Tablets Ferring Desmopressin Acetate Antidiuretic
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