Dymista Special Precautions

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 Interactions and Pharmacology: Pharmacokinetics: Metabolism under Actions).
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 as follows).
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 as previously mentioned), 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 as previously mentioned and Central Nervous System Depressants under Interactions).
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.
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.
Effects on Fertility: See Use in Pregnancy & Lactation section for further information.
Use in Pregnancy: See Use in Pregnancy & Lactation section for further information.
Use in Lactation: See Use in Pregnancy & Lactation section for further information.
Use in Children and Adolescents: Safety and effectiveness of DYMISTA in pediatric patients below the age of 6 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 as previously mentioned).
Use in the Elderly: (See Pharmacology: Pharmacokinetics: Special Populations: Age under Actions).