Desmopressin Drug Information

Central Diabetes Insipidus The dosage of desmopressin acetate tablets must be determined for each individual patient and adjusted according to the diurnal pattern of response. Response should be estimated by two parameters: adequate duration of sleep and adequate, not excessive, water turnover. Patients previously on intranasal desmopressin acetate therapy should begin tablet therapy twelve hours after the last intranasal dose.

During the initial dose titration period, patients should be observed closely and appropriate safety parameters measured to assure adequate response. Patients should be monitored at regular intervals during the course of desmopressin acetate tablet therapy to assure adequate antidiuretic response. Modifications in dosage regimen should be implemented as necessary to assure adequate water turnover.

Fluid restriction should be observed. (See WARNINGS, PRECAUTIONS, Pediatric Use and Geriatric Use.) Adults and Children It is recommended that patients be started on doses of 0.05 mg (1/2 of the 0.1 mg tablet) two times a day and individually adjusted to their optimum therapeutic dose. Most patients in clinical trials found that the optimal dosage range is 0.1 mg to 0.8 mg daily, administered in divided doses. Each dose should be separately adjusted for an adequate diurnal rhythm of water turnover.

Total daily dosage should be increased or decreased in the range of 0.1 mg to 1.2 mg divided into two or three daily doses as needed to obtain adequate antidiuresis. See Pediatric Use subsection for special considerations when administering desmopressin acetate to pediatric diabetes insipidus patients. Geriatric Use This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. (See CLINCAL PHARMACOLOGY, Human Pharmacokinetics, CONTRAINDICATIONS, and PRECAUTIONS, Geriatric Use.) Primary Nocturnal Enuresis The dosage of desmopressin acetate tablets must be determined for each individual patient and adjusted according to response. Patients previously on intranasal desmopressin acetate therapy can begin tablet therapy the night following (24 hours after) the last intranasal dose. The recommended initial dose for patients age 6 years and older is 0.2 mg at bedtime.

The dose may be titrated up to 0.6 mg to achieve the desired response. Fluid restriction should be observed, and fluid intake should be limited to a minimum from 1 hour before desmopressin administration, until the next morning, or at least 8 hours after administration. (See WARNINGS, PRECAUTIONS, Pediatric Use and Geriatric Use.)

Infrequently, large doses of the intranasal formulations of desmopressin acetate tablets and injection have produced transient headache, nausea, flushing and mild abdominal cramps. These symptoms have disappeared with reduction in dosage. Central Diabetes Insipidus In long-term clinical studies in which patients with diabetes insipidus were followed for periods up to 44 months of desmopressin acetate tablet therapy, transient increases in AST (SGOT) no higher than 1.5 times the upper limit of normal were occasionally observed.

Elevated AST (SGOT) returned to the normal range despite continued use of desmopressin acetate tablets. Primary Nocturnal Enuresis The only adverse event occurring in ≥3% of patients in controlled clinical trials with desmopressin acetate tablets that was probably, possibly, or remotely related to study drug was headache (4% desmopressin acetate, 3% placebo). Other The following adverse events have been reported; however their relationship to desmopressin acetate has not been established: abnormal thinking, diarrhea, and edema-weight gain. See WARNINGS for the possibility of water intoxication and hyponatremia.

Post Marketing There have been rare reports of hyponatremic convulsions associated with concomitant use with the following medications: oxybutinin and imipramine.

Drug Interactions Although the pressor activity of desmopressin acetate is very low compared to its antidiuretic activity, large doses of desmopressin acetate tablets should be used with other pressor agents only with careful patient monitoring. The concomitant administration of drugs that may increase the risk of water intoxication with hyponatremia, (e.g. tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine, opiate analgesics, NSAIDs, lamotrigine and carbamazepine) should be performed with caution.

Pregnancy Category B Fertility studies have not been done. Teratology studies in rats and rabbits at doses from 0.05 to 10 mcg/kg/day (approximately 0.1 times the maximum systemic human exposure in rats and up to 38 times the maximum systemic human exposure in rabbits based on surface area, mg/m2) revealed no harm to the fetus due to desmopressin acetate. There are, however, no adequate and well-controlled studies in pregnant women.

Because animal studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Several publications where desmopressin acetate was used in the management of diabetes insipidus during pregnancy are available; these include a few anecdotal reports of congenital anomalies and low birth weight babies. However, no causal connection between these events and desmopressin acetate has been established.

A fifteen year Swedish epidemiologic study of the use of desmopressin acetate in pregnant women with diabetes insipidus found the rate of birth defects to be no greater than that in the general population; however, the statistical power of this study is low. As opposed to preparations containing natural hormones, desmopressin acetate in antidiuretic doses has no uterotonic action and the physician will have to weigh the possible therapeutic advantages against the possible risks in each case.

Pediatric Use Central Diabetes Insipidus Desmopressin acetate tablets have been used safely in pediatric patients, age 4 years and older, with diabetes insipidus for periods up to 44 months. In younger pediatric patients the dose must be individually adjusted in order to prevent an excessive decrease in plasma osmolality leading to hyponatremia and possible convulsions; dosing should start at 0.05 mg (1/2 of the 0.1 mg tablet). Use of desmopressin acetate tablets in pediatric patients requires careful fluid intake restrictions to prevent possible hyponatremia and water intoxication. Fluid restriction should be discussed with the patient and/or guardian. (See WARNINGS.) Primary Nocturnal Enuresis Desmopressin acetate tablets have been safely used in pediatric patients age 6 years and older with primary nocturnal enuresis for up to 6 months.

Some patients respond to a dose of 0.2 mg; however, increasing responses are seen at doses of 0.4 mg and 0.6 mg. No increase in the frequency or severity of adverse reactions or decrease in efficacy was seen with an increased dose or duration. The dose should be individually adjusted to achieve the best results.

Treatment with desmopressin for primary nocturnal enuresis should be interrupted during acute intercurrent illness characterized by fluid and/or electrolyte imbalance (e.g., systemic infections, fever, recurrent vomiting or diarrhea) or under conditions of extremely hot weather, vigorous exercise or other conditions associated with increased water intake.

Desmopressin acetate tablets are contraindicated in individuals with known hypersensitivity to desmopressin acetate or to any of the components of desmopressin acetate tablets. Desmopressin acetate tablets are contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50mL/min). Desmopressin acetate is contraindicated in patients with hyponatremia or a history of hyponatremia.

Signs of overdose may include confusion, drowsiness, continuing headache, problems with passing urine and rapid weight gain due to fluid retention. (See WARNINGS.) In case of overdose, the dose should be reduced, frequency of administration decreased, or the drug withdrawn according to the severity of the condition. There is no known specific antidote for desmopressin acetate. The patient should be observed and treated with appropriate symptomatic therapy.

An oral LD 50 has not been established. Oral doses up to 0.2 mg/kg/day have been administered to dogs and rats for 6 months without any significant drug-related toxicities reported. An intravenous dose of 2 mg/kg in mice demonstrated no effect.