Dymista Use In Pregnancy & Lactation

Effects on Fertility: No studies on impairment of fertility were conducted with DYMISTA 125/50. However, non- clinical studies are available for the individual active component, azelastine.
In male and female rats, azelastine at oral doses of 30 mg/kg/day and greater (resulting in plasma levels which were at least about 400 times above the plasma levels at the recommended therapeutic intranasal dose) caused a decrease in the fertility index, but in long term toxicity studies up to 2 years there were no drug-related alterations in reproductive organs either in males or in females in this species. A clinical study in 21 healthy human females using an intranasal dose of 1.12 mg/day found no effect on ovulation or sexual hormone pattern.
Use in Pregnancy: Category B3: There is no or insufficient evidence of safety of DYMISTA, azelastine or fluticasone propionate in human pregnancy. No studies on the effect on embryofetal development have been conducted with azelastine/fluticasone combination. Animal reproductive studies of azelastine and fluticasone propionate in mice and rats revealed evidence of teratogenicity as well as other developmental toxic effects. However, equivalent effects have not been reported when these individual compounds have been given to humans during pregnancy.
Direct intranasal application ensures minimal systemic exposure. As with other medicines, the use of DYMISTA during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.
In pregnant rats there was evidence of significant diapiacental transfer of the drug to the foetuses. Azelastine was embryo lethal and teratogenic in mice at oral doses greater than 30 mg/kg/day. In rats, azelastine was embryo-toxic at oral doses greater than 3 mg/kg/day, and teratogenicity and embryolethality were seen at doses greater than 30 mg/kg/day. In rabbits, azelastine was teratogenic at oral doses greater than 20 mg/kg/day. In pregnant rats, azelastine demonstrated no peri/ postnatal toxicity at oral doses up to 30 mg/kg/day.
In rats, the no effect doses resulted in plasma levels which were at least about 25 times above the plasma levels at the recommended therapeutic intranasal dose in humans. (The calculation of the safety factor is based on plasma levels derived from oral subchronic toxicity studies).
Reproductive toxicity studies with fluticasone propionate in mice and rats have shown the expected foetotoxic and teratogenic effects at subcutaneous doses of 100 to 150 μg /kg/day and above. As with previous compounds of this class, these effects are unlikely to be relevant to human therapy.
Use in Lactation: It is not known whether DYMISTA is excreted in human breast milk. Because many drugs are excreted in human milk, caution should be exercised when DYMISTA is administered to a nursing woman. Since there are no data from well-controlled human studies on the use of DYMISTA by nursing mothers, based on data from the individual components, a decision should be made whether to discontinue nursing or to discontinue DYMISTA, taking into account the importance of DYMISTA to the mother. No studies in lactating animals have been conducted with the combination azelastine/fluticasone.
It is not known if azelastine is excreted in human milk.
The excretion of fluticasone propionate into human breast milk has not been investigated. Subcutaneous administration of tritiated drug to lactating rats resulted in measurable radioactivity in both plasma and milk (levels in milk were 3-7 times plasma levels) 1-8 hours post-dosing. However, plasma levels in patients following intranasal application of fluticasone propionate at recommended doses are low and the amount of fluticasone ingested by the newborn is estimated to be very small as a consequence of very low maternal plasma concentration.