WARNINGS
When DDAVP Tablets are administered, in particular and geriatric patients, fluid intake should be adjusted downward to decrease the potential occurrence of water intoxication and hyponatremia with accompanying signs and symptoms (headache, nausea/vomiting, decreased serum sodium and weight gain). 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.
PRECAUTIONS
General: Intranasal formulations of DDAVP at high doses and DDAVP Injection have infrequently produced a slight elevation of blood pressure which disappears with a reduction of dosage. Although this effect has not been observed when single oral doses up to 0.6 mg have been administered, the drug should be used with caution in patients with coronary artery insufficiency and/or hypertensive cardiovascular disease, because of a possible rise in blood pressure.
DDAVP should be used with caution in patients with conditions associated with fluid and electrolyte imbalance, such as cystic fibrosis, since these patients may develop hyponatremia.
Rare severe allergic reactions have been reported with DDAVP. Anaphylaxis has been reported with intravenous and intranasal administration of DDAVP Injection, but not with DDAVP Tablets. Laboratory Tests: Central Diabetes Insipidus: Laboratory tests for monitoring the patient with central diabetes insipidus or post-surgical or head trauma-related polyuria and polydipsia include urine volume and osmolality. In some cases, measurements of plasma osmolality may be useful. 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.
Carcinogenicity, Mutagenicity, Impairment of Fertility: Studies with DDAVP have not been performed to evaluate carcinogenic potential, mutagenic potential or effects on fertility.
Pregnancy: Category B: Fertility studies have not been done. Teratology studies in rats and rabbits at doses from 0.05 to 10 µg/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 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.
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. 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.
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.
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