Sign Out
Somnolence: In clinical studies, the occurrence of somnolence has been reported in some patients taking DYMISTA (see Adverse Reactions). The overall incidence of somnolence was much lower than that reported for oral antihistamines. Even so, patients should be cautioned against engaging in hazardous occupations requiring complete mental alertness and motor coordination such as operating machinery or driving a motor vehicle after administration of DYMISTA until they know how they react to the nasal spray. When administered orally in combination, azelastine hydrochloride 4.4 mg tablets and alcohol showed sedative effects. As no specific information is available with the nasal spray, caution is required if DYMISTA is used concomitantly with alcohol or other CNS depressants (see Effects on Ability to Drive and Operate Machinery as follows and Central Nervous System Depressants under Interactions).
Local Effects: Instances of nasal ulceration and nasal septal perforation have been reported in patients following the intranasal application of corticosteroids. There were no instances of nasal ulceration or nasal septal perforation observed in clinical studies with DYMISTA. Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal ulcers, nasal surgery, or nasal trauma should not use DYMISTA until healing has occurred.
Local infections of the nasal airways should be appropriately treated but do not constitute a specific contra-indication to treatment with DYMISTA. Candidiasis of the throat can occur in patients treated with intranasal steroids. Special care should be taken when treating patients who may be susceptible to candida infections (eg diabetics).
Glaucoma and Cataracts: Rare instances of glaucoma and increased intra-ocular pressure have been reported following administration of intranasal corticosteroids, as a class effect. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts.
Hypothalamic-Pituitary-Adrenal (HPA) Axis Effects: Intranasal steroid products are designed to deliver drug directly to the nasal mucosa in order to minimise overall systemic glucocorticoid exposure and side effects. Systemic effects such as HPA axis suppression, reduction of bone density and retardation of growth rate in children may occur with intranasal steroids, particularly at high doses prescribed for prolonged periods of time.
The lowest dose of fluticasone propionate nasal spray that causes suppression of the HPA axis or effects on bone mineral density or growth retardation has not yet been established. However, the systemic bioavailability of fluticasone propionate is low (estimated at 1.26% using high doses), when given as fluticasone propionate nasal spray, and this limits the potential for such systemic side effects. Measurement of serum cortisol and 24-hour urinary cortisol in the clinical studies in adults did not suggest any HPA axis suppression with recommended doses. Studies of effects on the HPA axis in children have not been conducted.
Care must be taken while transferring patients from systemic steroid treatment to DYMISTA if there is any reason to suppose that their adrenal function is impaired.
Use of Cytochrome P450 3A4 Inhibitors: Care should be taken when co-administering known, strong CYP3A4 inhibitors, eg. ritonavir and ketoconazole, as there is potential for increased systemic exposure to fluticasone propionate. (see Pharmacology: Pharmacokinetics: Metabolism under Actions and Interactions).
Effect on Growth: Retardation of growth rate in children may occur with intranasal steroids, particularly at high doses prescribed for prolonged periods of time. (see Use in Children and Adolescents under Precautions).
Effects on Laboratory Tests: No effects are known.
Effects on Ability to Drive or Operate Machinery: Due to the potential occurrence of somnolence (see Somnolence under Precautions), patients using DYMISTA should be cautioned against engaging in hazardous occupations requiring complete mental alertness and motor coordination such as driving or operating machinery after administration of DYMISTA until they know how they react to the nasal spray. Caution is required if DYMISTA is used concomitantly with alcohol or other CNS depressants (see Somnolence under Precautions and Central Nervous System Depressants under Interactions).
Carcinogenicity: No studies of carcinogenicity were conducted with DYMISTA; however, studies are available for the individual active components, azelastine and fluticasone propionate.
Azelastine demonstrated no carcinogenic potential in mice and rats at dietary doses up to 25 and 30 mg/kg/day respectively.
No evidence of a tumorigenic effect was observed in either a 2-year study in rats receiving doses of fluticasone propionate up to 57 μg /kg/day by inhalation or in an 18-month study in mice receiving oral doses of fluticasone propionate up to 1 mg/kg/day.
Genotoxicity: No studies of genotoxicity were conducted with DYMISTA. However, studies are available for the individual active components, azelastine and fluticasone propionate.
Azelastine demonstrated no genotoxic potential in standard assays for gene mutations, chromosomal damage and DNA damage.
Fluticasone propionate has no mutagenic effect in vivo or in vitro. There was no evidence of a mutagenic potential in a standard battery of mutagenicity assays.
Use in Patients with Renal Impairment: See Pharmacology: Pharmacokinetics: Special Populations: Renal Impairment under Actions.
Use in Patients with Hepatic Impairment: See Pharmacology: Pharmacokinetics: Special Populations: Hepatic Impairment under Actions.
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.
Use in Children and Adolescents: Safety and effectiveness of DYMISTA in pediatric patients below the age of 12 years have not been established.
Retardation of growth rate in children may occur with intranasal steroids, particularly at high doses prescribed for prolonged periods of time (see Effect on Growth under Precautions).
Use in Elderly: (See Pharmacology: Pharmacokinetics: Special Populations: Age under Actions).
