DUONASE Nasal Spray (Azelastine hydrochloride + Fluticasone propionate)

Table of Content

For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only

Qualitative and Quantitative Composition

Each spray delivers:

Azelastine Hydrochloride IP …… 140 mcg

Fluticasone Propionate IP……… 50 mcg

Azelastine Hydrochloride IP ….0.14% w/w

Fluticasone Propionate IP ……. 0.05% w/w

Benzalkonium Chloride IP ……0.01% w/w (as preservative)

Dosage Form(s) and Strength(s)

Intranasal spray, Azelastine Hydrochloride/Fluticasone Propionate 140/50 mcg

Clinical Particulars

Therapeutic Indications

DUONASE Nasal Spray is indicated for the relief of symptoms of seasonal allergic rhinitis in patients 6 years of age and older who require treatment with both azelastine hydrochloride and fluticasone propionate for symptomatic relief.

Posology and Method of Administration

The recommended dosage of DUONASE nasal Spray is 1 spray in each nostril twice daily.

Administer DUONASE nasal Spray by the intranasal route only.

Shake the bottle gently before each use.

Priming: Prime DUONASE Nasal Spray before initial use by releasing 6 sprays or until a fine mist appears. When DUONASE Nasal Spray has not been used for 14 or more days, reprime with 1 spray or until a fine mist appears.

Avoid spraying DUONASE Nasal Spray into the eyes. If sprayed in the eyes, flush eyes with water for at least 10 minutes.

Contraindications

DUONASE Nasal Spray is contraindicated in patients with known hypersensitivity to azelastine hydrochloride or fluticasone propionate or any of the components of the preparation.

Special Warnings and Precautions for Use

Somnolence

In clinical trials, the occurrence of somnolence has been reported in some patients (6 of 853 patients and 2 of 416 children) taking azelastine hydrochloride and fluticasone propionate combination nasal spray in placebo controlled trials. 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 azelastine hydrochloride and fluticasone propionate combination nasal spray. Concurrent use of this combination with alcohol or other central nervous system (CNS) depressants or other antihistamines should be avoided as additional reductions in alertness and additional impairment of CNS performance may occur.

Local Nasal Effects

In clinical trials of 2 to 52 weeks’ duration, epistaxis was observed more frequently in patients treated with azelastine hydrochloride and fluticasone propionate combination nasal spray than those who received placebo.

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 trials with azelastine hydrochloride and fluticasone propionate combination nasal spray.

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 until healing has occurred.

In clinical trials with fluticasone propionate administered intranasally, the development of localized infections of the nose and pharynx with Candida albicans has occurred. When such an infection develops, it may require treatment with appropriate local therapy and discontinuation of treatment with the azelastine hydrochloride and fluticasone propionate combination. Patients using DUONASE over several months or longer should be examined periodically for evidence of Candida infection or other signs of adverse effects on the nasal mucosa.

Infections of the nasal airways should be treated with antibacterial or antimycotical therapy, but do not constitute a specific contraindication to treatment with DUONASE Nasal Spray.

Glaucoma and/or Cataracts

Nasal and inhaled corticosteroids may result in the development of glaucoma and/or cataracts. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts.

Glaucoma and cataract formation were evaluated with intraocular pressure measurements and slit lamp examinations in a controlled 12-month study in 612 adolescent and adult patients aged 12 years and older with perennial allergic or vasomotor rhinitis (VMR). Of the 612 patients enrolled in the study, 405 were randomized to receive azelastine hydrochloride and fluticasone propionate combination (1 spray per nostril twice daily) and 207 were randomized to receive fluticasone propionate nasal spray (2 sprays per nostril once daily). In the azelastine hydrochloride and fluticasone propionate group, one patient had increased intraocular pressure at month 6. In addition, three patients had evidence of posterior subcapsular cataract at month 6 and one at month 12 (end of treatment). In the fluticasone propionate group, three patients had evidence of posterior subcapsular cataract at month 12 (end of treatment).

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

Immunosuppression

Persons who are using drugs, such as corticosteroids, that suppress the immune system are more susceptible to infections than healthy individuals. Chicken pox and measles, for example, can take a more serious or even a fatal course in children or adults on immunosuppressant corticosteroids. In children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox or measles develops, treatment with antiviral agents may be considered.

Corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculous infections of the respiratory tract; untreated local or systemic fungal or bacterial infections; systemic viral or parasitic infections; or ocular herpes simplex because of the potential for worsening of these infections.

Hypothalamic-Pituitary-Adrenal (HPA) Axis Effects

When intranasal steroids are used at higher than recommended dosages or in susceptible individuals at recommended dosages, systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear. If such changes occur, the dosage of DUONASE Nasal Spray should be discontinued slowly, consistent with accepted procedures for discontinuing oral corticosteroid therapy. The concomitant use of an intranasal corticosteroid with other corticosteroids could increase the risk of signs or symptoms of hypercorticism and/or suppression of the HPA-axis.

The replacement of a systemic corticosteroid with a topical corticosteroid can be accompanied by signs of adrenal insufficiency. Some patients may experience symptoms of withdrawal, e.g., joint and/or muscular pain, lassitude, and depression. Patients previously treated for prolonged periods with systemic corticosteroids and transferred to topical corticosteroids should be carefully monitored for acute adrenal insufficiency in response to stress. In those patients who have asthma or other clinical conditions requiring long term systemic corticosteroid treatment, too rapid a decrease in systemic corticosteroids may cause a severe exacerbation of their symptoms.

Potential systemic effects may include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).

Treatment with higher than recommended doses of nasal corticosteroids may result in clinically significant adrenal suppression. If there is evidence for higher than recommended doses being used, then additional systemic corticosteroid cover should be considered during periods of stress or elective surgery.

Use of Cytochrome P450 3A4 Inhibitors

Ritonavir and other strong cytochrome P450 3A4 (CYP3A4) inhibitors can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations. During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing syndrome and adrenal suppression. Therefore, co-administration of azelastine hydrochloride and fluticasone propionate combination nasal spray and ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.

Use caution with the co-administration of azelastine hydrochloride and fluticasone propionate combination nasal spray and other potent CYP3A4 inhibitors, such as ketoconazole 

Effect on Growth

Corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. It is advised to monitor the growth routinely of pediatric patients receiving DUONASE Nasal Spray

Growth retardation has been reported in children receiving nasal corticosteroids at licensed doses. Since growing up is also given in adolescents it is recommended that the growth of adolescents receiving prolonged treatment with nasal corticosteroids is regularly monitored, too. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of nasal corticosteroid if possible, to the lowest dose at which effective control of symptoms is maintained.

Drug Interactions

No formal drug interaction studies have been performed with azelastine hydrochloride and fluticasone propionate combination nasal spray. The drug interactions of the combination are expected to reflect those of the individual components.

Erythromycin: Coadministration of orally administered azelastine (4 mg twice daily) with erythromycin (500 mg three times daily for 7 days) resulted in Cmax of 5.36 ± 2.6 ng/mL and AUC of 49.7 ± 24 ng•h/mL for azelastine, whereas, administration of azelastine alone resulted in Cmax of 5.57 ± 2.7 ng/mL and AUC of 48.4 ± 24 ng•h/mL for azelastine.

In another multiple-dose drug interaction study, coadministration of orally inhaled fluticasone propionate (500 mcg twice daily) and erythromycin (333 mg three times daily) did not affect fluticasone propionate pharmacokinetics.

Cimetidine and Ranitidine: In a multiple-dose, steady-state drug interaction trial in healthy subjects, cimetidine (400 mg twice daily) increased orally administered mean azelastine hydrochloride (4 mg twice daily) concentrations by approximately 65%. Coadministration of orally administered azelastine hydrochloride (4 mg twice daily) with ranitidine hydrochloride (150 mg twice daily) resulted in Cmax of 8.89 ± 3.28 ng/mL and AUC of 88.22 ± 40.43 ng•h/mL for azelastine hydrochloride, whereas, administration of azelastine hydrochloride alone resulted in Cmax of 7.83 ± 4.06 ng/mL and AUC of 80.09 ± 43.55 ng•h/mL for azelastine hydrochloride.

Theophylline: No significant pharmacokinetic interaction was observed with the coadministration of an oral 4 mg dose of azelastine hydrochloride twice daily and theophylline 300 mg or 400 mg twice daily. 

Ritonavir: Coadministration of fluticasone propionate and the strong CYP3A4 inhibitor, ritonavir, is not recommended based upon a multiple-dose, crossover drug interaction study in 18 healthy subjects. Fluticasone propionate aqueous nasal spray (200 mcg once daily) was coadministered for 7 days with ritonavir (100 mg twice daily). Plasma fluticasone propionate concentrations following fluticasone propionate aqueous nasal spray alone were undetectable (<10 pg/mL) in most subjects, and when concentrations were detectable, peak levels (Cmax) averaged 11.9 pg/mL (range, 10.8 to 14.1 pg/mL) and AUC(0-τ) averaged 8.43 pg•hr/mL (range,  4.2 to 18.8 pg•hr/mL). Fluticasone propionate Cmax and AUC(0-τ) increased to 318 pg/mL (range, 110 to 648 pg/mL) and 3,102.6 pg•hr/mL (range, 1,207.1 to 5,662.0 pg•hr/mL), respectively, after coadministration of ritonavir with fluticasone propionate aqueous nasal spray. This significant increase in plasma fluticasone propionate exposure resulted in a significant decrease (86%) in plasma cortisol area under the plasma concentration versus time curve (AUC).

Caution should be exercised when other strong CYP3A4 inhibitors are coadministered with fluticasone propionate. In a drug interaction study, coadministration of orally inhaled fluticasone propionate (1,000 mcg) and ketoconazole (200 mg once daily) resulted in increased fluticasone propionate exposure and reduced plasma cortisol AUC, but had no effect on urinary excretion of cortisol.

Fluticasone Propionate

Cytochrome P450 3A4

A drug interaction study in healthy subjects has shown that ritonavir (a strong CYP3A4 inhibitor) significantly increased plasma fluticasone propionate exposure following administration of fluticasone propionate aqueous nasal spray, resulting in significantly reduced serum cortisol concentrations. During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing syndrome and adrenal suppression. Therefore, co-administration of fluticasone propionate and ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.

Studies have shown that other inhibitors of cytochrome P450 3A4 produce negligible (erythromycin) and minor (ketoconazole) increases in systemic exposure to fluticasone propionate without notable reductions in serum cortisol concentrations. Nevertheless, care is advised when co-administering potent cytochrome P450 3A4 inhibitors (e.g. ketoconazole), as there is potential for increased systemic exposure to fluticasone propionate.

Ketoconazole (also a strong CYP3A4 inhibitor), administered in multiple 200 mg doses to steady-state, increased plasma exposure of fluticasone propionate, reduced plasma cortisol AUC, but had no effect on urinary excretion of cortisol, following administration of a single 1000 mcg dose of fluticasone propionate by oral inhalation route.

Caution should be exercised when DUONASE Nasal Spray is co-administered with ketoconazole and other known strong CYP3A4 inhibitors.

During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving intranasal or inhaled fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects. Co-treatment with other CYP 3A4 inhibitors, including cobicistat-containing products is also expected to increase the risk of systemic side effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side effects.

Central Nervous System Depressants

Concurrent use of DUONASE Nasal Spray with alcohol or other central nervous system depressants should be avoided because somnolence and impairment of central nervous system performance may occur.

Azelastine Hydrochloride

No specific interaction studies with azelastine hydrochloride nasal spray have been performed. Interaction studies at high oral doses have been performed. However, they bear no relevance to azelastine nasal spray as given recommended nasal doses result in much lower systemic exposure. Nevertheless, care should be taken when administering azelastine hydrochloride in patients taking concurrent sedative or central nervous medications because sedative effect may be enhanced. Alcohol may also enhance this effect

Use in Special Populations

Hepatic Impairment

Azelastine hydrochloride and fluticasone propionate combination nasal spray undergoes extensive first-pass metabolism, therefore the systemic exposure of intranasal fluticasone propionate in patients with severe liver disease is likely to be increased. This may result in a higher frequency of systemic adverse events. Caution is advised when treating these patients.

Pregnancy

Limited data from postmarketing experience with azelastine hydrochloride and fluticasone propionate combination nasal spray in pregnant women have not identified any drug associated risks of miscarriage, birth defects, or other adverse maternal or fetal outcomes. The individual components of azelastine hydrochloride and fluticasone propionate combination nasal spray have been marketed for decades.

While the data regarding the use of nasal preparations of fluticasone propionate in pregnancy are limited, data from clinical studies of inhaled fluticasone propionate do not indicate an increased risk of adverse maternal or fetal outcomes.

Animal reproduction studies with azelastine hydrochloride and fluticasone propionate combination nasal spray are not available; however, studies are available with its individual components, azelastine hydrochloride and fluticasone propionate. In animal reproduction studies, there was no evidence of fetal harm in animals at oral doses of azelastine hydrochloride approximately 10 times the clinical daily dose. Oral administration of azelastine hydrochloride to pregnant mice, rats, and rabbits, during the period of organogenesis, produced developmental toxicity that included structural abnormalities, decreased embryo-fetal survival, and decreased fetal body weights at doses 530 times and higher than the maximum recommended human daily intranasal dose (MRHDID) of 0.548 mg. However, the relevance of these findings in animals to pregnant women was considered questionable based upon the high animal to human dose multiple.

In animal reproduction studies, fluticasone propionate administered via nose-only inhalation to rats decreased fetal body weight, but did not induce teratogenicity at a maternal toxic dose less than the MRHDID on a mcg/m2 basis. Teratogenicity, characteristic of corticosteroids, decreased fetal body weight and/or skeletal variations, in rats, mice, and rabbits were observed with subcutaneously administered maternal toxic doses of fluticasone propionate less than the MRHDID of 200 mcg on a mcg/m2 basis (see Data). Experience with corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroids than humans. The estimated background risk of major birth defects and miscarriage for the indicated populations 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 2-4% and 15-20%, respectively.

Data

Animal Data

Azelastine hydrochloride: In an embryo-fetal development study in mice dosed during the period of organogenesis, azelastine hydrochloride caused embryo-fetal death, structural abnormalities (cleft palate; short or absent tail; fused, absent or branched ribs), delayed ossification, and decreased fetal weight at approximately 610 times the MRHDID in adults (on a mg/m2 basis at a maternal oral dose of 68.6 mg/kg/day), which also caused maternal toxicity as evidenced by decreased maternal body weight. Neither fetal nor maternal effects occurred in mice at approximately 25 times the MRHDID in adults (on a mg/m2 basis at a maternal oral dose of 3 mg/kg/day).

In an embryo-fetal development study in pregnant rats dosed during the period of organogenesis from gestation days 7 to 17, azelastine hydrochloride caused structural abnormalities (oligo-and brachydactylia), delayed ossification, and skeletal variations,  the absence of maternal toxicity, at approximately 530 times the MRHDID in adults (on a mg/m2 basis at a maternal oral dose of 30 mg/kg/day). Azelastine hydrochloride caused embryo-fetal death and decreased fetal weight and severe maternal toxicity at approximately 1200 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 68.6 mg/kg/day). Neither fetal nor maternal effects occurred at approximately 55 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 3 mg/kg/day).

In an embryo-fetal development study in pregnant rabbits dosed during the period of organogenesis from gestation days 6 to 18, azelastine hydrochloride caused abortion, delayed ossification and decreased fetal weight and severe maternal toxicity at approximately 1100 times the MRHDID in adults (on a mg/m2 basis at a maternal oral dose of 30 mg/kg/day). Neither fetal nor maternal effects occurred at approximately 10 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 0.3 mg/kg/day).

In a prenatal and postnatal development study in pregnant rats dosed from late in the gestation period and through the lactation period from gestation day 17 through lactation day 21, azelastine hydrochloride produced no adverse developmental effects on pups at maternal doses up to approximately 530 times the MRHDID (on mg/m2 basis at a maternal dose of 30 mg/kg/day).

Fluticasone propionate:

In embryofetal development studies with pregnant rats and mice dosed by the subcutaneous route throughout the period of organogenesis, fluticasone propionate was teratogenic in both species. Omphalocele, decreased body weight, and skeletal variations were observed in rat fetuses, in the presence of maternal toxicity, at a dose approximately 5 times the MRHDID (on a mg/m2 basis with a maternal subcutaneous dose of 100 mcg/kg/day). Neither fetal nor maternal effects occurred in rats at approximately 1 times the MRHDID (on a mg/m2 basis with a maternal subcutaneous dose of 30 mcg/kg/day). Cleft palate and fetal skeletal variations were observed in mouse fetuses at a dose approximately 1 times the MRHDID (on a mg/m2 basis with a maternal subcutaneous dose of 45 mcg/kg/day). Neither fetal nor maternal effects occurred in mice with a dose approximately 0.4 times the MRHDID (on a mg/m2 basis with a maternal subcutaneous dose of 15 mcg/kg/day).

In an embryofetal development study with pregnant rats dosed by the nose-only inhalation route throughout the period of organogenesis, fluticasone propionate produced decreased fetal body weights and skeletal variations, in the presence of maternal toxicity, at a dose approximately 1 times the MRHDID (on a mg/m2 basis with a maternal nose-only inhalation dose of 25.7 mcg/kg/day); however, there was no evidence of teratogenicity. Neither fetal nor maternal effects occurred in rats with a dose approximately 0.25 times the MRHDID (on a mg/m2 basis with a maternal nose-only inhalation dose of 5.5 mcg/kg/day).

In an embryofetal development study in pregnant rabbits that were dosed by the subcutaneous route throughout organogenesis, fluticasone propionate produced reductions of fetal body weights, in the presence of maternal toxicity, at doses approximately 0.06 times the MRHDID and higher (on a mg/m2 basis with a maternal subcutaneous dose of 0.57 mcg/kg/day). Teratogenicity was evident based upon a finding of cleft palate for 1 fetus at dose approximately 0.4 times the MRHDID (on a mg/m2 basis with a maternal subcutaneous dose of 4 mcg/kg/day). Neither fetal nor maternal effects occurred in rabbits with a dose approximately 0.01 times the MRHDID (on a mg/m2 basis with a maternal subcutaneous dose of 0.08 mcg/kg/day).

Fluticasone propionate crossed the placenta following subcutaneous administration to mice and rats and oral administration to rabbits.

In a pre-and post-natal development study in pregnant rats dosed from late gestation through delivery and lactation (Gestation Day 17 to Postpartum Day 22), fluticasone propionate was not associated with decreases in pup body weight, and had no effects on developmental landmarks, learning, memory, reflexes, or fertility at doses up to 2 times the MRHDID (on a mg/m2 basis with maternal subcutaneous doses up to 50 mcg/kg/day).

Lactation

There are no available data on the presence of azelastine hydrochloride or fluticasone propionate in human milk, the effects on the breastfed infant, or the effects on milk production. Breastfed infants should be monitored for signs of milk rejection during DUONASE Nasal Spray use by lactating women. Fluticasone propionate is present in rat milk. Other corticosteroids have been detected in human milk. However, fluticasone propionate concentrations in plasma after intranasal therapeutic doses are low and therefore concentrations in human breast milk are likely to be correspondingly low. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for DUONASE Nasal Spray and any potential adverse effects on the breastfed infant from DUONASE Nasal Spray or from the underlying maternal condition.

Clinical Considerations

Monitoring for Adverse Reactions

Breastfed infants of lactating women treated with DUONASE Nasal Spray should be monitored for possible signs of milk rejection related to the bitter taste of azelastine hydrochloride.

Data

Subcutaneous administration of 10 mcg/kg of tritiated fluticasone propionate to lactating rats resulted in measurable radioactivity in the milk.

Pediatric Use

Use of azelastine hydrochloride and fluticasone propionate combination nasal spray for seasonal allergic rhinitis in pediatric patients 6 to 11 years of age is supported by safety and efficacy data from clinical studies (416 patients 6 to 11 years of age with allergic rhinitis were treated with azelastine hydrochloride and fluticasone propionate combination nasal spray in controlled clinical trials) and the established efficacy and safety of azelastine hydrochloride nasal spray and fluticasone propionate nasal spray in this age group.

Sixty-one patients ages 4-5 years of age were treated with azelastine hydrochloride and fluticasone propionate combination nasal spray in the pediatric studies described above. Safety findings in children 4-5 years of age were similar to those in children 6-11 years of age, but efficacy was not established.

Safety and effectiveness of azelastine hydrochloride and fluticasone propionate combination nasal spray has not been studied in pediatric patients below the age of 4 years.

Controlled clinical studies have shown that intranasal corticosteroids may cause a reduction in growth velocity in pediatric patients. This effect has been observed in the absence of laboratory evidence of HPA axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with intranasal corticosteroids, including the impact on final adult height, are unknown. The potential for “catch-up” growth following discontinuation of treatment with intranasal corticosteroids has not been adequately studied. The growth of pediatric patients receiving intranasal corticosteroids, including azelastine hydrochloride and fluticasone propionate combination nasal spray, should be monitored routinely (e.g., via stadiometry). The potential growth effects of prolonged treatment should be weighed against the clinical benefits obtained and the risks/benefits of treatment alternatives.

Geriatric Use

Clinical trials of azelastine hydrochloride and fluticasone propionate combination nasal spray did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Effects on Ability to Drive and Use Machines

Azelastine hydrochloride and fluticasone propionate combination nasal spray has minor influence on the ability to drive and use machines.

In isolated cases fatigue, weariness, exhaustion, dizziness or weakness that may also be caused by the disease itself, may occur when using azelastine hydrochloride and fluticasone propionate combination nasal spray. In these cases, the ability to drive and use machines may be impaired. Alcohol may enhance this effect.

Undesirable Effects

Systemic and local corticosteroid use may result in the following:

  • Somnolence
  • Local nasal effects, including epistaxis, nasal ulceration, nasal septal perforation, impaired wound healing, and Candida albicans infection.
  • Glaucoma and cataracts
  • Immunosuppression
  • Hypothalamic-pituitary-adrenal (HPA) axis effects, including growth reduction

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect rates observed in practice.

Adults and Adolescents 12 Years of Age and Older

The safety data described below in adults and adolescents 12 years of age and older reflect exposure to azelastine hydrochloride and fluticasone propionate combination nasal spray in 853 patients (12 years of age and older; 36% male and 64% female) with seasonal allergic rhinitis in 3 double-blind, placebo-controlled clinical trials of 2-week duration. The racial distribution for the 3 clinical trials was 80% white, 16% black, 2% Asian, and 1% other.

In the 3 placebo controlled clinical trials of 2-week duration, 3411 patients with seasonal allergic rhinitis were treated with 1 spray per nostril of azelastine hydrochloride and fluticasone propionate combination nasal spray, azelastine hydrochloride nasal spray, fluticasone propionate nasal spray, or placebo, twice daily. The azelastine hydrochloride and fluticasone propionate comparators use the same vehicle and device as azelastine hydrochloride and fluticasone propionate combination nasal spray and are not commercially marketed. Overall, adverse reactions were 16% in the azelastine hydrochloride and fluticasone propionate combination nasal spray treatment groups, 15% in the azelastine hydrochloride nasal spray groups, 13% in the fluticasone propionate nasal spray groups, and 12% in the placebo groups. Overall, 1% of patients in both the azelastine hydrochloride and fluticasone propionate combination nasal spray and placebo groups discontinued due to adverse reactions.

Table 1 contains adverse reactions reported with frequencies greater than or equal to 2% and more frequently than placebo in patients treated with azelastine hydrochloride and fluticasone propionate combination nasal spray in the seasonal allergic rhinitis controlled clinical trials.

Table 1. Adverse Reactions with ≥ 2% Incidence and More Frequently than Placebo in Placebo-Controlled Trials of 2 Weeks Duration with Azelastine hydrochloride and fluticasone propionate combination nasal spray in Adult and Adolescent Patients with Seasonal Allergic Rhinitis

1 spray per nostril twice daily

 

Azelastine Hydrochloride and Fluticasone Propionate Combination Nasal Spray (N=853)*

Azelastine Hydrochloride Nasal Spray

(N=851)

 

Fluticasone Propionate Nasal Spray

(N=846)

 

Vehicle Placebo

(N=861)

 

Dysgeusia

30(4%)

44(5%)

4(1%)

2(<1%)

Headache

18(2%)

20(2%)

20(2%)

10(1%)

Epistaxis

16(2%)

14(2%)

14(2%)

15(2%)

*Safety population N=853, intent-to-treat population N=848

Not commercially marketed

In the above trials, somnolence was reported in <1% of patients treated with azelastine hydrochloride and fluticasone propionate combination nasal spray (6 of 853) or vehicle placebo (1 of 861). 

Pediatric Patients 6-11 Years of Age

The safety data described below in children 6-11 years of age reflect exposure to azelastine hydrochloride and fluticasone propionate combination nasal spray in 152 patients (6-11 years of age; 57% male and 43% female) with seasonal allergic rhinitis in one double-blind, placebo-controlled clinical trial of 2-week duration. The racial distribution for the clinical trial was 69% white, 31% black, 2% Asian and 2% other.

In the placebo-controlled clinical trial of 2-week duration, patients with seasonal allergic rhinitis were treated with 1 spray per nostril of azelastine hydrochloride and fluticasone propionate combination nasal spray or placebo, twice daily. Overall, adverse reactions were 16% in the azelastine hydrochloride and fluticasone propionate combination nasal spray treatment group, and 12% in the placebo group. Overall, 1% of patients in both the azelastine hydrochloride and fluticasone propionate combination nasal spray and placebo groups discontinued due to adverse reactions.

Table 2 contains adverse reactions reported with frequencies greater than or equal to 2% and more frequently than placebo in patients treated with Azelastine hydrochloride and fluticasone propionate combination nasal spray in the seasonal allergic rhinitis controlled clinical trial.

Table 2. Adverse Reactions with ≥2% Incidence and More Frequently than Placebo in Placebo-Controlled Trials of 2 Weeks Duration with Azelastine hydrochloride and fluticasone propionate combination nasal spray in Children 6 to 11 Years of Age with Seasonal Allergic Rhinitis

 

1 spray per nostril twice daily

Azelastine hydrochloride and fluticasone propionate combination nasal spray (N=152)*

Vehicle Placebo (N=152)

Dysgeusia

6 (4%)

0 (0%)

Epistaxis

6 (4%)

4 (3%)

*Safety population N=152, intent-to-treat population N=152

In the above trial, somnolence was not reported

Long-Term (12-Month) Safety Trial in Adults and Adolescents 12 Years of Age and Older

In the 12-month open-label, active-controlled clinical trial, 404 Asian patients (240 males and 164 females) with perennial allergic rhinitis or vasomotor rhinitis were treated with azelastine hydrochloride and fluticasone propionate combination nasal spray, 1 spray per nostril twice daily.

In the 12-month, open-label, active-controlled, long-term safety trial in adults and adolescents 12 years of age and older, 404 patients with perennial allergic rhinitis or vasomotor rhinitis were treated with azelastine hydrochloride and fluticasone propionate combination nasal spray 1 spray per nostril twice daily and 207 patients were treated with fluticasone propionate nasal spray, 2 sprays per nostril once daily. Overall, adverse reactions were 47% in the azelastine hydrochloride and fluticasone propionate combination nasal spray treatment group and 44% in the fluticasone propionate nasal spray group.

The most frequently (≥ 2%) reported adverse reactions with azelastine hydrochloride and fluticasone propionate combination nasal spray were headache, pyrexia, cough, nasal congestion, rhinitis, dysgeusia, viral infection, upper respiratory tract infection, pharyngitis, pain, diarrhea, and epistaxis.

In the azelastine hydrochloride and fluticasone propionate combination nasal spray treatment group, 7 patients (2%) had mild epistaxis and 1 patient (<1%) had moderate epistaxis. In the fluticasone propionate nasal spray treatment group 1 patient (<1%) had mild epistaxis. No patients had reports of severe epistaxis. Focused nasal examinations were performed and no nasal ulcerations or septal perforations were observed. Eleven of 404 patients (3%) treated with azelastine hydrochloride and fluticasone propionate combination nasal spray and 6 of 207 patients (3%) treated with fluticasone propionate nasal spray discontinued from the trial due to adverse events.

Long-Term (3-Month) Safety Trial in Pediatric Patients 6-11 Years of Age

In the 3-month open label active-controlled clinical trial, 264 patients (60% male, 40% female) (80% white, 19% black, 4% Asian and 2% other) with allergic rhinitis were treated with azelastine hydrochloride and fluticasone propionate combination nasal spray , 1 spray per nostril twice daily.

In the 3-month, open label, active-controlled, safety trial in pediatric patients 6-11 years of age 264 patients (128 patients ≥6 to <9 years of age, and 136 patients ≥9 to <12 years of age) with allergic rhinitis (based on the Investigator’s assessment) were treated with azelastine hydrochloride and fluticasone propionate combination nasal spray , 1 spray per nostril twice daily and 89 patients (44 patients ≥6 to <9 years of age, and 45 patients ≥9 to <12 years of age) were treated with fluticasone propionate nasal spray, 1 spray per nostril twice daily. Overall, adverse reactions were 40% in the azelastine hydrochloride and fluticasone propionate combination nasal spray treatment group and 36% in the fluticasone propionate nasal spray group. The most frequently reported adverse reactions (≥2%) with azelastine hydrochloride and fluticasone propionate combination nasal spray were epistaxis, headache, oropharyngeal pain, vomiting, upper abdominal pain, cough, pyrexia, otitis media, upper respiratory tract infection, diarrhea, nausea, otitis externa, and urticaria. In the azelastine hydrochloride and fluticasone propionate combination nasal spray treatment group 23 patients (9%) had mild epistaxis and 3 patients (1%) had moderate epistaxis. In the fluticasone propionate nasal spray treatment group 8 patients (9%) had mild epistaxis. No patients had reports of severe epistaxis. Focused nasal examinations were performed and no ulcerations or septal perforations were observed. Four of 264 patients (2%) treated with azelastine hydrochloride and fluticasone propionate combination nasal spray and 3 of 89 (3%) treated with fluticasone propionate nasal spray discontinued from the trial due to adverse events. There were two reports of somnolence, one severe, among children taking azelastine hydrochloride and fluticasone propionate combination nasal spray.

Postmarketing Experience

The following spontaneous adverse events have been reported with azelastine hydrochloride and fluticasone propionate combination nasal spray or one of the components (azelastine and fluticasone). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiac disorders: atrial fibrillation, increased heart rate, palpitations

Eye disorder: blurred vision, cataracts, conjunctivitis, dryness and irritation, eye swelling, glaucoma, increased intraocular pressure, vision abnormal, xerophthalmia

Gastrointestinal disorders: nausea, vomiting, dry mouth

General disorders and administration site condition: aches and pain, application site irritation, chest pain, edema of face and tongue, fatigue, tolerance, weakness 

Immune system disorders: anaphylaxis/anaphylactoid reactions which in rare instances were severe, hypersensitivity reactions, angioedema (oedema of the face or tongue and skin rash), bronchospasm

Musculoskeletal and connective tissue disorders: growth suppression

Nervous system disorders: disturbance or loss of smell and/ or taste, dizziness, involuntary muscle contractions, paresthesia, parosmia, Headache, Dysgeusia, somnolence

Psychiatric disorders: anxiety, confusion, nervousness

Renal and urinary disorders: urinary retention

Respiratory, thoracic and mediastinal disorders: bronchospasm, cough, dysphonia, dyspnea, hoarseness, nasal septal perforation, nasal discomfort, nasal dryness, nasal sores, nasal ulcer, sore throat, throat dryness and irritation, voice changes, wheezing, sneezing, mucosal erosion, Nasal septal perforation, cough, epistaxis

Skin and subcutaneous tissue disorder: angioedema, erythema, face swelling, pruritus, rash, urticaria.

Vascular disorder: hypertension

Systemic effects of some nasal corticosteroids may occur, particularly when administered at high doses for prolonged periods.

Growth retardation has been reported in children receiving nasal corticosteroids. Growth retardation may be possible in adolescents

In rare cases osteoporosis was observed, if nasal glucocorticoids were administered long-term.

If you experience any side effects, talk to your doctor or write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024 or you can report to Cipla Ltd on 1800 267 7779.

By reporting side-effects, you can help provide more information on the safety of this product.

Overdosage

DUONASE Nasal Spray contains both azelastine hydrochloride and fluticasone propionate; therefore, the risks associated with overdosage for the individual components described below apply to DUONASE Nasal Spray.

Azelastine Hydrochloride

There have been no reported overdosages with azelastine hydrochloride. Acute azelastine hydrochloride overdosage by adults with this dosage form is unlikely to result in clinically significant adverse events, other than increased somnolence. Clinical trials in adults with single doses of the oral formulation of azelastine hydrochloride (up to 16 mg) have not resulted in increased incidence of serious adverse events. General supportive measures should be employed if overdosage occurs. There is no known antidote to azelastine hydrochloride and fluticasone propionate combination nasal spray. Oral ingestion of antihistamines has the potential to cause serious adverse effects in children. Accordingly, Duonase Nasal Spray should be kept out of the reach of children.

Fluticasone Propionate

Chronic fluticasone propionate overdosage may result in signs/symptoms of hypercorticism. Intranasal administration of 2 mg (10 times the recommended dose) of fluticasone propionate, twice daily for 7 days, to healthy human volunteers was well tolerated. Single oral doses of up to 16 mg have been studied in human volunteers with no acute toxic effects reported. Repeat oral doses of up to 80 mg daily for 10 days in volunteers and repeat oral doses of up to 10 mg daily for 14 days in patients were also well tolerated. Adverse reactions were of mild or moderate severity, and incidences were similar in active and placebo treatment groups. Acute overdosage with this dosage form is unlikely.

Administration of doses higher than those recommended over a long period of time may lead to temporary suppression of adrenal function. In these patients, treatment with DUONASE Nasal Spray should be continued at a dose sufficient to control symptoms; the adrenal function will recover in a few days and can be verified by measuring plasma cortisol.

In the event of overdose after incidental oral uptake, disturbances of the central nervous system (including drowsiness, confusion, coma, tachycardia and hypotension) caused by azelastine hydrochloride are to be expected based on the results of animal experiments. Treatment of these disorders must be symptomatic. Depending on the amount swallowed, gastric lavage is recommended. There is no known antidote.

Pharmacological Properties

As DUONASE Nasal Spray is a combination of azelastine hydrochloride and fluticasone propionate, the pharmacological properties of both the molecules are given separately.

Mechanism of Action

Azelastine hydrochloride:

Azelastine hydrochloride, a phthalazinone derivative, exhibits histamine H1-receptor antagonist activity in isolated tissues, animal models, and humans. Azelastine hydrochloride in DUONASE NASAL SPRAY is administered as a racemic mixture with no difference in pharmacologic activity noted between the enantiomers in in vitro studies. The major metabolite, desmethylazelastine, also possesses H1-receptor antagonist activity.

Fluticasone propionate:

Fluticasone propionate is a synthetic trifluorinated corticosteroid with anti-inflammatory activity. In vitro dose response studies on a cloned human glucocorticoid receptor system involving binding and gene expression afforded 50% responses at 1.25 and 0.17 nM concentrations, respectively. Fluticasone propionate was 3-fold to 5-fold more potent than dexamethasone in these assays. Data from the McKenzie vasoconstrictor assay in man also support its potent glucocorticoid activity. The clinical relevance of these findings is unknown.

The precise mechanism through which fluticasone propionate affects allergic rhinitis symptoms is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in inflammation.

Pharmacodynamic Properties

Cardiac Effects:

In a placebo-controlled trial (95 patients with allergic rhinitis), there was no evidence of an effect of azelastine hydrochloride nasal spray (2 sprays per nostril twice daily for 56 days) on cardiac repolarization as represented by the corrected QT interval (QTc) of the electrocardiogram. Following multiple dose oral administration of azelastine 4 mg or 8 mg twice daily, the mean change in QTc was 7.2 msec and 3.6 msec, respectively.

Interaction studies investigating the cardiac repolarization effects of concomitantly administered oral azelastine hydrochloride and erythromycin or ketoconazole were conducted. These drugs had no effect on QTc based on analysis of serial electrocardiograms.

Pharmacokinetic Properties

Absorption

After intranasal administration of two sprays per nostril (548 mcg of azelastine hydrochloride and 200 mcg of fluticasone) of azelastine hydrochloride and fluticasone propionate combination nasal spray, the mean (± standard deviation) peak plasma exposure (Cmax) was 194.5 ± 74.4 pg/mL for azelastine and 10.3±3.9 pg/mL for fluticasone propionate and the mean total exposure (AUC) was 4217 ± 2618 pg/mL*hr for azelastine and 97.7 ± 43.1 pg/mL*hr for fluticasone. The median time to peak exposure (tmax) from a single dose was 0.5 hours for azelastine and 1.0 hours for fluticasone.

Systemic bioavailability of azelastine from azelastine hydrochloride and fluticasone propionate combination nasal spray following intranasal administration was comparable with monotherapy azelastine hydrochloride nasal spray (i.e., approximately 40%). Systemic bioavailability of fluticasone from azelastine hydrochloride and fluticasone propionate combination nasal spray following intranasal administration was 44-61% higher than monotherapy fluticasone propionate (bioavailability for monotherapy fluticasone nasal spray was less than 2%). Due to the low intranasal bioavailability, pharmacokinetic data for fluticasone propionate were obtained via other routes of administration. Studies using oral dosing of radiolabeled fluticasone propionate showed negligible oral bioavailability and high extraction from plasma. The majority of the circulating radioactivity was due to an inactive metabolite.

Distribution

Based on intravenous and oral administration, the steady-state volume of distribution of azelastine hydrochloride is 14.5 L/kg. In vitro studies with human plasma indicate that the plasma protein binding of azelastine hydrochloride and its metabolite, desmethylazelastine, are approximately 88% and 97%, respectively.

Following intravenous administration, the initial disposition phase for fluticasone propionate was rapid and consistent with its high lipid solubility and tissue binding. The volume of distribution averaged 4.2 L/kg.

The percentage of fluticasone propionate bound to human plasma proteins averaged 91% with no obvious concentration relationship. Fluticasone propionate is weakly and reversibly bound to erythrocytes and freely equilibrates between erythrocytes and plasma. Fluticasone propionate is not significantly bound to human transcortin.

Metabolism

Azelastine hydrochloride is oxidatively metabolized to the principal active metabolite, desmethylazelastine, by the cytochrome P450 enzyme system. The specific P450 isoforms responsible for the biotransformation of azelastine have not been identified. The total clearance of azelastine is approximately 0.50 L/kg/hr.

For fluticasone propionate, the only circulating metabolite detected in man is the 17_-carboxylic acid derivative, which is formed through the CYP3A4 pathway. This inactive metabolite had less affinity (approximately 1/2,000) than the parent drug for the glucocorticoid receptor of human lung cytosol in vitro and negligible pharmacological activity in animal studies. Other metabolites detected in vitro using cultured human hepatoma cells have not been detected in man. The average total clearance of fluticasone propionate is relatively high (approximately 66 L/hr).

Elimination

Following intranasal administration of azelastine hydrochloride and fluticasone propionate combination nasal spray, the elimination half-life of azelastine hydrochloride is approximately 25 hours. Approximately 75% of an oral dose of radiolabeled azelastine hydrochloride was excreted in the feces with less than 10% as unchanged azelastine.

Following intravenous dosing, fluticasone propionate showed polyexponential kinetics and had a terminal elimination half-life of approximately 7.8 hours. Less than 5% of a radiolabeled oral dose was excreted in the urine as metabolites, with the remainder excreted in the feces as parent drug and metabolites.

Special Populations

Azelastine hydrochloride and fluticasone propionate combination nasal spray was not studied in any special populations, and no gender-specific pharmacokinetic data have been obtained.

Hepatic Impairment

Following oral administration of azelastine hydrochloride, pharmacokinetic parameters were not influenced by hepatic impairment.

Renal Impairment

Based on oral, single-dose studies of azelastine hydrochloride, renal impairment (creatinine clearance <50 mL/min) resulted in a 70-75% higher Cmax and AUC compared to healthy subjects. Time to maximum concentration was unchanged.

Age

Following oral administration of azelastine hydrochloride, pharmacokinetic parameters were not influenced by age.

Gender

Following oral administration of azelastine hydrochloride, pharmacokinetic parameters were not influenced by gender.

Race

The effect of race has not been evaluated.

Non-Clinical Properties

Animal Toxicology or Pharmacology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No studies of carcinogenicity, mutagenicity, or impairment of fertility were conducted with DUONASE Nasal Spray; however, studies are available for the individual active components, azelastine hydrochloride and fluticasone propionate, as described below.

Azelastine hydrochloride:

Two-year carcinogenicity studies in Crl:CD(SD)BR rats and NMRI mice were conducted to assess the carcinogenic potential of azelastine hydrochloride. No evidence of tumorigenicity was observed in rats at doses up to 30 mg/kg/day (approximately 530 and 240 times the MRHDID for adults and children, respectively, on a mg/m2 basis). No evidence for tumorigenicity was observed in mice at doses up to 25 mg/kg (approximately 220 and 100 times the MRHDID for adults and children, respectively, on a mg/m2 basis).

Azelastine hydrochloride showed no genotoxic effects in the Ames test, DNA repair test, mouse lymphoma forward mutation assay, mouse micronucleus test, or chromosomal aberration test in rat bone marrow.

There were no effects on male or female fertility and reproductive in male and female rats at oral doses up to 30 mg/kg (approximately 530 times the MRHDID in adults on a mg/m2 basis). At 68.6 mg/kg (approximately 1200 times the MRHDID on a mg/m2 basis), the duration of estrous cycles was prolonged and copulatory activity and the number of pregnancies were decreased. The numbers of corpora lutea and implantations were decreased; however, pre-implantation loss was not increased.

Fluticasone propionate:

Fluticasone propionate demonstrated no tumorigenic potential in mice at oral doses up to 1,000 mcg/kg (approximately 25 and 10 times the MRHDID in adults and children, respectively, on a mcg/m2 basis) for 78 weeks or in rats at inhalation doses up to 57 mcg/kg (approximately 3 and 1 times the MRHDID in adults and children, respectively, on a mcg/m2 basis) for 104 weeks.

Fluticasone propionate did not induce gene mutation in prokaryotic or eukaryotic cells in vitro. No significant clastogenic effect was seen in cultured human peripheral lymphocytes in vitro or in the mouse micronucleus test.

Fertility and reproductive performance were unaffected in male and female rats at subcutaneous doses up to 50 mcg/kg (approximately 2 times the MRHDID for adults on a mcg/m2 basis).

Description

DUONASE Nasal Spray is an antihistamine-corticosteroid combination available as a nasal spray formulation for intranasal administration. It contains azelastine hydrochloride, which is a second generation H1 receptor-antagonist with potent topical activity, and fluticasone propionate, a synthetic corticosteroid with anti-inflammatory properties.

Azelastine hydrochloride

Azelastine hydrochloride active ingredient occurs as a white, odorless, crystalline powder with a bitter taste. It has a molecular weight of 418.37. It is sparingly soluble in water, methanol, and propylene glycol and slightly soluble in ethanol, octanol, and glycerin. It has a melting point of 225°C and the pH of 5.2. Its chemical name is (±)-1-(2H)-phthalazinone,4--2-(hexahydro-1-methyl-1H-azepin-4-yl)-, monohydrochloride. Its molecular formula is C22H24ClN3O•HCl with the following chemical structure:

Fluticasone propionate

Fluticasone propionate active ingredient is a white powder with a melting point of 273°C, a molecular weight of 500.6, and the empirical formula is C25H31F3O5S. It is practically insoluble in water, freely soluble in dimethyl sulfoxide and dimethylformamide, and slightly soluble in methanol and 95% ethanol. Fluticasone propionate is a synthetic corticosteroid having the chemical name S-(fluoromethyl)-6α,9-difluoro-11β-17-dihydroxy-16α-methyl-3-oxoandrosta1,4-diene-17β-carbothioate, 17-propionate, and the following chemical structure:

Pharmaceutical Particulars

Incompatibilities

Not applicable.

Shelf Life

See on the pack.

Packaging Information

DUONASE Nasal Spray

Sales pack contains 70 metered doses

Storage and Handling Instruction

Store below 30oC

Do not refrigerate

Protect from light

Patient Counselling Information

What is DUONASE Nasal Spray and what is it used for?

  • DUONASE Nasal Spray is a prescription medicine used to treat symptoms of seasonal allergic rhinitis in people 6 years of age and older, who need treatment with both azelastine hydrochloride and fluticasone propionate.
  • DUONASE Nasal Spray may help to reduce your nasal symptoms including stuffy nose, runny nose, itching, and sneezing.

It is not known if DUONASE Nasal Spray is safe or effective in children under 4 years of age.

What do you need to know before using DUONASE Nasal Spray?

Before using DUONASE Nasal Spray tell your healthcare provider if you:

  • have had recent nasal sores, nasal surgery, or nasal injury
  • have eye or vision problems, such as cataracts or glaucoma (increased pressure in your eye)
  • have an infection in your nose. Infections of the nasal airways should be treated with antibacterial or antifungal medication. If you are given medication for an infection in your nose you can continue to use DUONASE Nasal Spray to treat your allergies.
  • Suffer from impaired adrenal function. Care must be taken when transferring from systemic steroid treatment to DUONASE Nasal Spray.
  • Suffer from a severe liver disease. Your risk of suffering from systemic side effects is increased
  • have tuberculosis or any untreated fungal, bacterial, viral infections or eye infections caused by herpes
  • have been near someone who has chickenpox or measles
  • are not feeling well or have any other symptoms that you do not understand
  • have any other medical conditions
  • are pregnant or plan to become pregnant
  • are breastfeeding or plan to breastfeed. It is not known if DUONASE Nasal Spray passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby while using DUONASE Nasal Spray.

Before you use DUONASE, tell your doctor about the following:

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

DUONASE Nasal Spray and other medicines may affect each other, causing side effects.

Especially tell your healthcare provider if you take:

  • ritonavir (Norvir) or medicines that contain ritonavir, cobicistat (commonly used to treat HIV infection or AIDS)
  • ketoconazole, fluconazole, or itraconazole (for fungal infections)
  • DUONASE Nasal Spray contains benzalkonium chloride It may cause irritation of the nasal mucosa and bronchospasm. Tell your doctor if you feel discomfort when using the spray.

Ask your healthcare provider for a list of these medications, if you are not sure.

Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider when you get a new medicine.

How should you use DUONASE Nasal Spray?

  • Read the Instructions for Use at the end of this leaflet for information about the right way to use DUONASE Nasal Spray.
  • An adult should help a young child use DUONASE Nasal Spray.
  • DUONASE Nasal Spray is for use in your nose only. Do not spray it into your eyes or mouth. If you spray DUONASE Nasal Spray into your eyes, flush your eye(s) with large amounts of water for 10 minutes and then call your healthcare provider.
  • Use DUONASE Nasal Spray exactly as your healthcare provider tells you to use it. Your healthcare provider will tell you how much DUONASE Nasal Spray to use and when to use it.
  • If a child accidentally swallows DUONASE Nasal Spray or you use too much DUONASE Nasal Spray, call your healthcare provider or go to the nearest hospital emergency room right away.

Instruction for use

Preparing the spray

  • Shake the bottle gently for 5 seconds by tilting it upwards and downwards and then remove the protective cap (see figure).

 

  • The first time the nasal spray is used, you must prime the pump by squirting it into
  • Prime the pump by putting two fingers on either side of the spray pump and place your thumb on the bottom of the bottle.the air.
  • Press down and release the pump 6 times until a fine mist appears (see figure).

 

  • Now your pump is primed and ready to use.
  • If the nasal spray has not been used for more than 7 days, you will need to re-prime the pump once by pressing down and releasing the pump.

Using the spray:

  • Shake the bottle gently for 5 seconds by tilting it upwards and downwards and then remove the protective cap.
  • Blow your nose to clear your nostrils.
  • Keep your head tilted downwards towards your toes. Do not tilt head backwards.
  • Hold the bottle upright and carefully insert the spray tip into one nostril.
  • Close other nostril with your finger, rapidly press down once and sniff gently at the same time (see figure).

  • Breathe out through your mouth.
  • Repeat in your other nostril.
  • Breathe in gently, and do not tilt your head back after dosing. This will stop the medicine going into your throat and causing an unpleasant taste (see figure).

  • After each use wipe the spray tip with a clean tissue or cloth and then replace the protective cap.
  • Do not prick the nozzle in case spray is not obtained. Clean the actuator with water.

What should you avoid while using DUONASE Nasal Spray?

  • DUONASE Nasal Spray can cause sleepiness or drowsiness. Do not drive, operate machinery, or do anything that needs you to be alert until you know how DUONASE Nasal Spray affects you.
  • Do not drink alcohol or take any other medicines that may cause you to feel sleepy while using DUONASE Nasal Spray. It can increase your chances of having serious side effects.

What are the possible side effects of DUONASE Nasal Spray?

DUONASE Nasal Spray may cause serious side effects including:

  • Sleepiness or drowsiness.
  • Nasal Problems. Symptoms of nasal problems may include:
  • crusting in the nose
  • nosebleeds
  • runny nose
  • hole in the cartilage between your nose (nasal septal perforation). A whistling sound when you breathe may be a symptom of nasal septal perforation.
  • Slow wound healing. You should not use DUONASE Nasal Spray until your nose has healed if you have a sore in your nose, if you have had surgery on your nose, or if your nose has been injured.
  • Thrush (candida), a fungal infection in your nose and throat. Tell your healthcare provider if you have any redness or white colored patches in your nose or mouth.
  • Eye problems, such as glaucoma or cataracts. Some people may have eye problems, including glaucoma and cataracts. You should have regular eye exams when using DUONASE Nasal Spray.
  • Immune system problems that may increase your risk of infections DUONASE Nasal Spray may cause problems with the way your immune system protects your body against infection and increase your risk of infection. Avoid contact with people who have contagious diseases such as chickenpox or measles while you use DUONASE Nasal Spray. Symptoms of infection may include:
  • Fever
  • aches or pains
  • chills
  • feeling tired
  • Adrenal Insufficiency. Adrenal insufficiency is a condition in which the adrenal glands do not make enough steroid hormones. Symptoms of adrenal insufficiency may include:
  • Tiredness
  • Weakness
  • Nausea
  • Vomiting
  • low blood pressure
  • Slowed or delayed growth in children. A child's growth should be checked regularly while using DUONASE Nasal Spray.

Call your healthcare provider or get medical help right away if you have symptoms of any of the serious side effects listed above.

The most common side effects of DUONASE Nasal Spray Nasal Spray include:

  • changes in taste
  • nosebleeds
  • headache

If you experience any side effects, talk to your doctor or write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024 or you can report to Cipla Ltd on 1800 267 7779.

By reporting side-effects, you can help provide more information on the safety of this product.

How should you store DUONASE Nasal Spray?

  • Store below 30oC
  • Do not freeze or refrigerate DUONASE Nasal Spray.
  • Protect DUONASE Nasal Spray from light.

Keep DUONASE Nasal Spray and all medicines out of reach of children.

What are the ingredients in DUONASE Nasal Spray?

Active ingredients: azelastine hydrochloride and fluticasone propionate

Inactive ingredients: Benzalkonium Chloride

Details of Manufacturer

Cipla House, Peninsula Business Park, Ganpatrao Kadam Marg, Lower Parel, Mumbai, Maharashtra, INDIA

Details of Permission or Licence Number with Date

M/447/2007

16/09/2017

Date of Revision

06/08/2021