Dymista

• Meda Pharmaceuticals, Inc.

Taking this medicine with other drugs that make you sleepy can worsen this effect. Ask your doctor before taking azelastine and fluticasone with a sleeping pill, narcotic pain medicine, muscle relaxer, or medicine for anxiety, depression, or seizures.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• ritonavir (Norvir, Kaletra); or

• antifungal medicine--fluconazole, itraconazole, ketoconazole.

This list is not complete. Other drugs may interact with azelastine and fluticasone, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

• If you have an allergy to azelastine, fluticasone, or any other part of Dymista (azelastine and fluticasone).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Very bad dizziness or passing out.
• Very upset stomach or throwing up.
• Feeling very tired or weak.
• Bad nose irritation.
• Crusting in the nose.
• Runny nose.
• Whistling sound when you breathe.
• Change in eyesight, eye pain, or very bad eye irritation.
• Bad nosebleeds.
• Redness or white patches in mouth or throat.
• Feeling sleepy.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Nosebleed.
• Nose irritation.
• Change in taste.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Seasonal Allergic Rhinitis

Dymista 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.

Dosing Information

The recommended dosage of Dymista is 1 spray in each nostril twice daily.

Important Administration Instructions

Administer Dymista by the intranasal route only.

Shake the bottle gently before each use.

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

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

Dymista is a nasal spray suspension. Each spray delivers a volume of 0.137 mL suspension containing 137 mcg of azelastine hydrochloride and 50 mcg of fluticasone propionate (137 mcg/50 mcg).

Systemic and local corticosteroid use may result in the following:

• Somnolence [see Warnings and Precautions (5.1)]
• Local nasal effects, including epistaxis, nasal ulceration, nasal septal perforation, impaired wound healing, and Candida albicans infection [see Warnings and Precautions (5.2)]
• Glaucoma and cataracts [see Warnings and Precautions (5.3)]
• Immunosuppression [see Warnings and Precautions (5.4)]
• Hypothalamic-pituitary-adrenal (HPA) axis effects, including growth reduction [see Warnings and Precautions (5.5 and 5.7), Use in Specific Populations (8.4)]

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 Dymista 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 Dymista, 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 Dymista and are not commercially marketed.  Overall, adverse reactions were 16% in the Dymista 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 Dymista 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 Dymista in the seasonal allergic rhinitis controlled clinical trials.

In the above trials, somnolence was reported in <1% of patients treated with Dymista (6 of 853) or vehicle placebo (1 of 861) [see Warnings and Precautions (5.1)].

Pediatric Patients 6-11 Years of Age

The safety data described below in children 6-11 years of age reflect exposure to Dymista 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 Dymista or placebo, twice daily. Overall, adverse reactions were 16% in the Dymista treatment group, and 12% in the placebo group. Overall, 1% of patients in both the Dymista 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 Dymista in the seasonal allergic rhinitis controlled clinical trial.

In the above trial, somnolence was not reported [see Warnings and Precautions (5.1)].

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 Dymista, 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 Dymista 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 Dymista treatment group and 44% in the fluticasone propionate nasal spray group. The most frequently reported adverse reactions (≥ 2%) with Dymista were headache, pyrexia, cough, nasal congestion, rhinitis, dysgeusia, viral infection, upper respiratory tract infection, pharyngitis, pain, diarrhea, and epistaxis. In the Dymista 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 Dymista 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 Dymista, 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 Dymista, 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 Dymista treatment group and 36% in the fluticasone propionate nasal spray group. The most frequently reported adverse reactions (≥2%) with Dymista 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 Dymista 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 Dymista 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 Dymista [see Warnings and Precautions (5.1)].

Postmarketing Experience

The following spontaneous adverse events have been reported with Dymista 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

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

Immune system disorders: anaphylaxis/anaphylactoid reactions which in rare instances were severe, hypersensitivity reactions

Musculoskeletal and connective tissue disorders: growth suppression [see Use in Specific Populations (8.4)]

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

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

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

Vascular disorder: hypertension

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

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, since one (1) 23 g bottle of Dymista contains approximately 23 mg of azelastine hydrochloride. 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 Dymista. Oral ingestion of antihistamines has the potential to cause serious adverse effects in children. Accordingly, Dymista should be kept out of the reach of children.

Fluticasone propionate: Chronic fluticasone propionate overdosage may result in signs/symptoms of hypercorticism [see Warnings and Precautions (5.5)]. 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 fluticasone propionate doses up to 16 mg have been studied in human volunteers with no acute toxic effects reported. Repeat oral doses up to 80 mg daily for 10 days in volunteers and repeat oral doses up to 10 mg daily for 14 days in patients were 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 since one (1) 23 g bottle of Dymista contains approximately 8.5 mg of fluticasone propionate.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.