Desmopressin

7 DRUG INTERACTIONS

7.1 Other Drugs that may Increase Risk of Hyponatremia Concomitant administration of DESMODA with other drugs that may increase the risk of water intoxication with hyponatremia, (e.g., tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine, opiate analgesics, thiazide diuretics, NSAIDs, lamotrigine, sulfonylureas, particularly chlorpropamide, oxybutynin and carbamazepine). Monitor serum sodium more frequently in patients taking DESMODA concomitantly with these drugs and when doses of these drugs are increased [see Warnings and Precautions (5.1), Adverse Reactions (6)].

7.2 Other Vasoconstrictors Desmopressin acetate can elevate blood pressure. Use of large doses of DESMODA with other vasoconstrictors may require a reduction of the DESMODA dosage [see Adverse Reactions (6)]. • Drugs that may Increase Risk of Hyponatremia: Requires more frequent monitoring of serum sodium. (7.1) • Other Vasoconstrictors : Concomitant use may elevate blood pressure and require a reduction in DESMODA dosage. (7.2)

8.1 Pregnancy Risk Summary Available data on the use of desmopressin acetate during pregnancy over decades of use have not identified a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks associated with untreated central diabetes insipidus during pregnancy (see Clinical Considerations). In vitro studies with human placenta demonstrate poor placental transfer of desmopressin.

No adverse developmental outcomes were observed in animal reproduction studies with administration of desmopressin during organogenesis to pregnant rats and rabbits at doses approximately <1 to 38 times, respectively, the maximum recommended human dose based on body surface areas (mg/m2) (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations Disease Associated Maternal and Embryo-Fetal Risk There are risks associated with untreated central diabetes insipidus during pregnancy such as dehydration, preterm birth and oligohydramnios. Pregnant patients with diabetes insipidus should be monitored for electrolyte imbalance, maternal hypotension, and low amniotic fluid levels. Data Animal Data In a developmental toxicity study in rats, desmopressin acetate was administered intravenously at doses of 9.68, 48.4, or 241 mcg/kg/day during the period of organogenesis (gestations days 7 to 17).

Laparohysterectomy for fetal examinations were conducted on gestation day 20 for twenty females in each group; the remaining 10 females were allowed to litter in order to determine any postnatal effects that might be attributable to pre-natal treatment. No effects were seen on maternal and fetal survival, growth and morphology or post-natal offspring survival, growth, development, behavior and reproductive performance up to 241 mcg/kg/day (4 times a 0.6 mg dose received by a 60 kg patient based on body surface area).

In an embryo-fetal development study and a pre- and postnatal development study in rabbits, desmopressin acetate was administered subcutaneously at doses of 2, 20 or 200 mcg/kg/day (embryo-fetal development) and 0.1, 1 or 10 mcg/kg/day (pre- and postnatal development) during the period of organogenesis (gestation days 6 to 18). No effects on maternal and fetal survival or morphology were…