DDAVP 0.2 MG Oral Tablet
WARNINGS
1.
Very rare cases of hyponatremia have been reported from world-wide postmarketing experience in patients treated with DDAVP (desmopressin acetate).
DDAVP is a potent antidiuretic which, when administered, may lead to water intoxication and/or hyponatremia.
Unless properly diagnosed and treated hyponatremia can be fatal.
Therefore, fluid restriction is recommended and should be discussed with the patient and/or guardian.
Careful medical supervision is required.
2.
When DDAVP Tablets are administered, in particular in pediatric and geriatric patients, fluid intake should be adjusted downward to decrease the potential occurrence of water intoxication and hyponatremia.(See PRECAUTIONS, Pediatric Use and Geriatric Use .) All patients receiving DDAVP therapy should be observed for the following signs or symptoms associated with hyponatremia: headache, nausea/vomiting, decreased serum sodium, weight gain, restlessness, fatigue, lethargy, disorientation, depressed reflexes, loss of appetite, irritability, muscle weakness, muscle spasms or cramps and abnormal mental status such as hallucinations, decreased consciousness and confusion.
Severe symptoms may include one or a combination of the following: seizure, coma and/or respiratory arrest.
Particular attention should be paid to the possibility of the rare occurrence of an extreme decrease in plasma osmolality that may result in seizures which could lead to coma.
3.
DDAVP should be used with caution in patients with habitual or psychogenic polydipsia who may be more likely to drink excessive amounts of water, putting them at greater risk of hyponatremia.
DRUG INTERACTIONS
Drug Interactions Although the pressor activity of DDAVP is very low compared to its antidiuretic activity, large doses of DDAVP 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.
OVERDOSAGE
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 In case of overdose, the dose should be reduced, frequency of administration decreased, or the drug withdrawn according to the severity of the condition.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 DDAVP.
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.
DESCRIPTION
DDAVP ® Tablets (desmopressin acetate) are a synthetic analogue of the natural pituitary hormone 8-arginine vasopressin (ADH), an antidiuretic hormone affecting renal water conservation.
It is chemically defined as follows: Mol.
Wt.
1183.34 Empirical Formula: C 46 H 64 N 14 O 12 S 2 • C 2 H 4 O 2 • 3H 2 O 1-(3-mercaptopropionic acid)-8-D-arginine vasopressin monoacetate (salt) trihydrate.
DDAVP Tablets contain either 0.1 or 0.2 mg desmopressin acetate.
Inactive ingredients include: lactose, potato starch, magnesium stearate and povidone.
Chemical Structure
HOW SUPPLIED
Strength Size NDC 0075- Color Markings 0.1 mg Bottle of 100 0016-00 White 0.2 mg Bottle of 100 0026-00 White Store at Controlled Room Temperature 20 to 25°C (68 to 77°F) [see USP].
Avoid exposure to excessive heat or light.
This product should be dispensed in a container with a child-resistant cap.
Keep out of the reach of children.
U.S.
Patent Nos.
5,500,413; 5,596,078; 5,674,850; 5,047,398; 5,763,407 Figure Figure
GERIATRIC USE
Geriatric Use Clinical studies of DDAVP Tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
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.
DDAVP is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50ml/min).
(See CLINICAL PHARMACOLOGY, Human Pharmacokinetics and CONTRAINDICATIONS .) Use of DDAVP Tablets in geriatric patients requires careful fluid intake restrictions to prevent possible hyponatremia and water intoxication.
Fluid restriction should be discussed with the patient.
(See WARNINGS .)
INDICATIONS AND USAGE
Central Diabetes Insipidus DDAVP Tablets are indicated as antidiuretic replacement therapy in the management of central diabetes insipidus and for the management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region.
DDAVP is ineffective for the treatment of nephrogenic diabetes insipidus.
Patients were selected for therapy based on the diagnosis by means of the water deprivation test, the hypertonic saline infusion test, and/or response to antidiuretic hormone.
Continued response to DDAVP can be monitored by measuring urine volume and osmolality.
Primary Nocturnal Enuresis DDAVP Tablets are indicated for the management of primary nocturnal enuresis.
DDAVP may be used alone or as an adjunct to behavioral conditioning or other non-pharmacologic intervention.
PEDIATRIC USE
Pediatric Use Central Diabetes Insipidus DDAVP Tablets (desmopressin acetate) 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 DDAVP 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 DDAVP 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.
PREGNANCY
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/m 2 ) revealed no harm to the fetus due to DDAVP ® (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.
NUSRING MOTHERS
Nursing Mothers There have been no controlled studies in nursing mothers.
A single study in postpartum women demonstrated a marked change in plasma, but little if any change in assayable DDAVP in breast milk following an intranasal dose of 0.01 mg.
It is not known whether the drug is excreted in human milk.
Because many drugs are excreted in human milk, caution should be exercised when DDAVP is administered to nursing mothers.
DOSAGE AND ADMINISTRATION
Central Diabetes Insipidus The dosage of DDAVP 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 DDAVP 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 DDAVP 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 CLINICAL PHARMACOLOGY, Human Pharmacokinetics , CONTRAINDICATIONS , and PRECAUTIONS, Geriatric Use .) Primary Nocturnal Enuresis The dosage of DDAVP Tablets must be determined for each individual patient and adjusted according to response.
Patients previously on intranasal DDAVP 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 .)