Active ingredients: Azelastine (Azelastine hydrochloride), Fluticasone (Fluticasone propionate)
Dymista 137 micrograms / 50 micrograms per actuation
Indications Why is Dymista used? What is it for?
Dymista contains two active ingredients: azelastine hydrochloride and fluticasone propionate.
- Azelastine hydrochloride belongs to the pharmacotherapeutic group of antihistamines. Antihistamines work by blocking the effects of substances such as histamine, which the body produces as a result of an allergic reaction, thereby reducing the symptoms of allergic rhinitis.
- Fluticasone propionate belongs to the pharmacotherapeutic group of corticosteroids, which reduce inflammation.
Dymista is used to relieve the symptoms of moderate to severe seasonal and perennial allergic rhinitis when the use of the antihistamine alone or the intranasal corticosteroid alone is not considered sufficient.
Seasonal or perennial allergic rhinitis are allergic reactions to substances such as pollen (hay fever), dust mites, mold, dust, or pets.
Dymista relieves the symptoms of allergies, such as excessive nasal mucus production, runny nose, sneezing, itchy nose or stuffy nose.
Contraindications When Dymista should not be used
Do not use Dymista:
- if you are allergic to azelastine hydrochloride or fluticasone propionate or any of the other ingredients of this medicine (listed in section 6).
Precautions for use What you need to know before taking Dymista
Talk to your doctor or pharmacist before using Dymista:
- if you have recently had a nose operation
- if you have ever had a "nose infection. Nasal airway infections should be treated with an antibacterial or antifungal medicine. If you have been given a medicine for a" nose infection, you can continue to use Dymista to treat your allergies
- if you have tuberculosis or an "untreated infection."
- if you have had visual disturbances or if you have a history of raised eye pressure, glaucoma and / or cataracts. If these conditions apply to you, you will be closely monitored while using Dymista
- if you suffer from impaired adrenal function. Extreme care should be taken when switching from systemic corticosteroid treatment to Dymista
- if you have severe liver disease. Your risk of experiencing systemic side effects is higher.
In these cases, your doctor will decide whether you can use Dymista or not.
It is important that you take your dose as indicated in section 3 below or as advised by your doctor. Treatment with higher than recommended doses of inhaled corticosteroids can cause adrenal suppression, a condition that can cause weight loss, fatigue, muscle weakness, low blood sugar, craving for salty foods, joint pain, depression and dark coloring of the skin. If these conditions occur, your doctor may recommend another medicine during times of stress or in case of elective surgery.
To avoid adrenal suppression, your doctor will advise you to take the lowest dose that can effectively control your rhinitis symptoms.
When taken for long periods, inhaled glucocorticoids (such as Dymista) can cause growth slowdown in children and adolescents. Your doctor will check your child's height regularly and make sure he takes the lowest effective dose possible.
If you are not sure if any of the above conditions apply to you, talk to your doctor or pharmacist before using Dymista. Children The use of this medicine is not recommended in children under 12 years of age.
Interactions Which drugs or foods can modify the effect of Dymista
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Ask your doctor or pharmacist for advice:
- if you are taking medicines to treat the HIV virus, such as Ritonavir
- if you are taking medicines to treat fungal infections, such as ketoconazole.
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking Dymista.
Driving and using machines
Dymista has negligible influence on the ability to drive and use machines. Very rarely, fatigue or dizziness may occur due to both the disease itself and the use of Dymista. In these cases, avoid driving or operating machines. You should be aware that alcohol consumption may increase these effects.
Dymista contains benzalkonium chloride
It can cause irritation of the nasal mucosa and bronchospasm. Ask your doctor or pharmacist for advice if you feel unwell while using the spray
Dose, Method and Time of Administration How to use Dymista: Posology
Always use Dymista exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
It is essential to use Dymista regularly to achieve the full therapeutic benefit.
Avoid contact with eyes.
Adults and adolescents (from 12 years of age)
- The recommended dose is one "puff into each nostril in the morning and evening.
Use in children under 12 years of age
- The use of this medicine is not recommended in children under 12 years of age.
Use in patients with renal and hepatic insufficiency
- No data are available on patients with renal and hepatic insufficiency.
Method of administration
For inhalation use.
Read the information on this leaflet and follow the instructions.
INSTRUCTIONS FOR USE
Preparation of the spray
- Gently shake the vial for 5 seconds, tilting it down and up, then remove the protective cap (see Figure 1). Figure 1
- The first time you use the nasal spray, you must prime the pump by spraying the product into the air.
- Load the pump by placing two fingers on either side of the spray pump and place your thumb on the base of the vial.
- Press down and release the pump 6 times, until a fine mist comes out (see figure 2).
- The pump is now charged and ready for use.
- If the nasal spray has not been used for more than 7 days, you will need to refill the pump once by pressing and releasing the pump.
Use of the spray
- Gently shake the vial for about 5 seconds, tilting it down and up and then remove the protective cap (see figure 1)
- Blow your nose to clean your nostrils.
- Keep your head tilted down towards your feet. Don't lean your head back.
- Hold the vial upright and gently insert the spray tip into one nostril.
- Close the other nostril with one finger, quickly press down once and, at the same time, breathe in gently (see Figure 3).
- Breathe out of your mouth.
- Repeat the same procedure for the other nostril.
- Breathe in gently without tilting your head back after dispensing. This will prevent the medicine from going down your throat and making you taste unpleasant (see figure 4).
- After each use, wipe the tip of the spray dry with a paper towel or clean cloth and then put the protective cap back on.
It is important that you take your dose as advised by your doctor. Only use the amount recommended by your doctor.
Duration of treatment
Dymista is intended for long-term use. The duration of treatment must correspond to the period in which the symptoms of the allergy occur.
Overdose What to do if you have taken too much Dymista
If you use more Dymista than you should
If you squirt too much of this medicine into your nose, you are unlikely to have any problems. If you are concerned or if you have used higher than recommended doses for a long time, contact your doctor. In case of accidental ingestion of Dymista, especially by a child, contact your doctor or the nearest hospital emergency department as soon as possible.
If you forget to use Dymista
Use the nasal spray as soon as you remember, then take the next dose as usual. Do not take a double dose to make up for a forgotten dose.
If you stop taking Dymista
Do not stop using Dymista without asking your doctor, as this jeopardizes the success of the treatment.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Dymista
Like all medicines, Dymista can cause side effects, although not everybody gets them.
Very common side effects (may affect more than 1 in 10 patients):
- nosebleed
Common side effects (may affect up to 1 in 10 patients):
- headache
- bitter taste in your mouth, especially if you tilt your head back when using the nasal spray. It should go away quickly if you sip a soft drink for a few minutes after using this medicine
- unpleasant smell
Uncommon side effects (may affect up to 1 in 100 people):
- slight irritation of the inside of the nose. May cause mild burning, itching or sneezing
- dry nose, cough, dry throat or throat irritation
Rare side effects (may affect up to 1 in 1,000 people):
- dry mouth
Very rare side effects (may affect up to 1 in 10,000 patients):
- dizziness or sleepiness
- cataracts, glaucoma, or increased pressure in the eye, resulting in loss of vision and / or red, sore eyes. These side effects have been reported after prolonged treatment with fluticasone propionate nasal sprays.
- damage to the skin and mucous membrane of the nose
- feeling sick, tired, tired or weak
- rash, itchy or red skin, raised itchy bumps
- bronchospasm (narrowing of the airways in the lungs)
Get medical help immediately if you notice any of the following symptoms:
- swelling of the face, lips, tongue or throat which may cause difficulty in swallowing / breathing and sudden onset of skin rash. These could be signs of a severe allergic reaction. Note: This eventuality is very rare.
Systemic side effects (side effects affecting the whole body) may occur when this medicine is used at high doses for a long time. These effects may vary in individual patients and between different corticosteroid preparations (see section 2) These effects are much less likely to occur if you use a corticosteroid nasal spray than if you take corticosteroids by mouth. Nasal corticosteroids can affect the normal production of hormones in the body, particularly if you use high doses for a long time. In children and adolescents, this side effect can cause a slowdown in growth.
In rare cases, a decrease in bone density (osteoporosis) has been observed when inhaled glucocorticoids have been administered for a long time.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the vial label and carton after "EXP". The expiry date refers to the last day of that month.
Do not refrigerate or freeze.
Shelf life after first opening: Dispose of unused medicine 6 months after first opening the nasal spray.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What Dymista contains
The active ingredients are: azelastine hydrochloride and fluticasone propionate.
Each gram of suspension contains 1,000 micrograms of azelastine hydrochloride and 365 micrograms of fluticasone propionate.
Each puff (0.14 g) delivers 137 micrograms of azelastine hydrochloride (= 125 micrograms of azelastine) and 50 micrograms of fluticasone propionate.
The other ingredients are: edetate disodium, glycerol, microcrystalline cellulose, sodium caramelose, polysorbate 80, benzalkonium chloride solution, phenylethyl alcohol and purified water.
Description of the appearance of Dymista and contents of the package
Dymista is a white, homogeneous suspension.
Dymista comes in an amber glass vial, equipped with a spray pump, applicator and protective cap.
The 10 ml vial contains 6.4 g of nasal spray suspension (at least 28 puffs). The 25 ml vial contains 23 g of nasal spray suspension (at least 120 puffs).
Dymista shows up in:
packs containing 1 vial with 6.4 g of nasal spray, suspension
packs containing 1 vial with 23 g of nasal spray, suspension
multipacks comprising 10 vials, each containing 6.4 g of nasal spray, suspension
multipacks comprising 3 vials, each containing 23 g of nasal spray, suspension
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
DYMISTA 137 MCG / 50 MCG FOR NASAL SPRAY DISPENSING, SUSPENSION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each gram of suspension contains 1,000 mcg of azelastine hydrochloride and 365 mcg of fluticasone propionate.
One delivery (0.14 g) administers 137 mcg of azelastine hydrochloride (= 125 mcg of azelastine) and 50 mcg of fluticasone propionate.
Excipients with known effects:
the dose delivered for a single application (0.14 g) administers 0.014 mg of benzalkonium chloride.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Nasal spray, suspension.
White, homogeneous suspension.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Relief of symptoms of moderate to severe seasonal and perennial allergic rhinitis when intranasal antihistamine or glucocorticoid monotherapy is not considered sufficient.
04.2 Posology and method of administration
Dosage
To achieve full therapeutic benefit, regular use is essential.
Avoid contact with eyes.
Adults and adolescents (from 12 years of age)
One "delivery in each nostril twice a day (morning and evening).
Children under 12 years old
The use of Dymista is not recommended in children below 12 years of age, as safety and efficacy in this patient population have not yet been established.
Senior citizens
In this patient population, no dose adjustment is required.
Renal and hepatic insufficiency
No data are available on patients with renal and hepatic insufficiency.
Duration of treatment
Dymista is intended for long-term use.
The duration of treatment must correspond to the period of exposure to allergens.
Method of administration
Dymista is intended for inhalation use only.
Instructions for Use
Preparation of the spray:
The vial should be shaken gently for approximately 5 seconds by tilting it down and up and then the protective cap removed. Before using Dymista for the first time, the pump must be pressed down and released six times. If Dymista has not been used for more than 7 days, the pump must be recharged once by pressing it down and releasing it.
Use of the spray:
The vial should be shaken gently for approximately 5 seconds by tilting it down and up and then the protective cap removed.
After blowing your nose, spray the suspension once in each nostril, keeping your head tilted down. After use it is necessary to dry the tip of the spray and put the protective cap back on.
04.3 Contraindications
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
04.4 Special warnings and appropriate precautions for use
Clinically significant drug interactions have been reported in patients administered fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects such as Cushing's syndrome and adrenal suppression. Consequently, co-administration of fluticasone propionate and ritonavir should be avoided unless the potential benefit to the patient outweighs the risk of systemic side effects of corticosteroids (see section 4.5).
The systemic effects of inhaled corticosteroids can occur especially when they are prescribed in high doses for prolonged periods. They may vary in individual patients and between different corticosteroid preparations but their occurrence is much less likely than oral corticostreroids. Potential systemic effects may include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataracts, glaucoma and more rarely, a range of psychological or behavioral effects, including psychomotor hyperactivity, sleep disturbances, anxiety, depression or aggression (especially in children).
Dymista undergoes extensive first pass metabolism, therefore systemic exposure of intranasal fluticasone propionate is likely to increase in patients with severe liver disease. This condition may result in an increased frequency of systemic adverse events.
Therefore, caution is recommended in the treatment of these patients.
Treatment with higher than recommended doses of inhaled corticosteroids may result in clinically significant adrenal suppression. If there is a need to use higher than recommended doses, additional coverage with systemic corticosteroids, during times of stress or in elective surgery should be considered.
In general, the dose of intranasal fluticasone should be reduced to the lowest dose that can effectively control the symptoms of rhinitis. Doses higher than recommended (see section 4.2) have not been studied with Dymista. As with all intranasal corticosteroids, the total systemic load of corticosteroids should be considered whenever other concomitant forms of corticosteroid treatment are prescribed.
Growth retardation has been reported in children treated with inhaled corticosteroids at licensed doses. Since growth also occurs in adolescents, it is recommended that adolescents receiving prolonged treatment with inhaled corticosteroids also be monitored regularly. If growth slows down, therapy should be re-examined with the aim, if possible, of reducing the dose to the lowest level that can effectively control symptoms.
Close monitoring is required in patients with impaired vision or with a history of increased ocular pressure, glaucoma and / or cataracts.
In the event that there is any reason to believe that adrenal function is impaired, care should be taken when switching patients from systemic steroid treatment to Dymista.
In patients with tuberculosis, any type of untreated infection, who have recently undergone surgery or have a recent injury to the nose or mouth, the possible benefits of treatment with Dymista should be weighed against the possible risks.
Nasal airway infections should be treated with antibacterial or antifungal therapy, but are not a specific contraindication to treatment with Dymista.
Dymista contains benzalkonium chloride which can cause irritation of the nasal mucosa and bronchospasm.
04.5 Interactions with other medicinal products and other forms of interaction
Fluticasone propionate
Under normal circumstances, low plasma concentrations of fluticasone propionate are achieved after intranasal administration due to extensive first pass metabolism and high clearance systemic, cytochrome P450 3A4 mediated in the gut and liver. Clinically significant fluticasone propionate mediated drug interactions are therefore unlikely.
A drug interaction study conducted in healthy subjects demonstrated that ritonavir (potent inhibitor of cytochrome P450 3A4) can significantly increase plasma concentrations of fluticasone propionate, resulting in markedly reduced concentrations of serum cortisol. Interactions have been reported. clinically significant pharmacological effects in patients treated with ritonavir and fluticasone propionate administered intranasally or by inhalation, resulting in systemic corticosteroid effects, such as Cushing's syndrome and adrenal suppression. Consequently, coadministration of fluticasone propionate and ritonavir should be avoided unless the benefit potential for the patient does not outweigh the risk of systemic side effects from corticosteroids.
Studies have shown that other inhibitors of cytochrome P450 3A4 generate negligible (erythromycin) and small (ketoconazole) increases in systemic exposure to fluticasone propionate, without significant reductions in serum cortisol concentrations. However, caution is recommended when co-administered. potent inhibitors of cytochrome P450 3A4 (eg, ketoconazole), as there is a potential risk of increased systemic exposure to fluticasone propionate.
Azelastine hydrochloride
No specific interaction studies have been performed with azelastine hydrochloride nasal spray. Dose interaction studies have been performed oral high. However, they have no relevance for azelastine nasal spray, as recommended inhalation doses result in significantly lower "systemic exposure. However, caution should be exercised when administering azelastine hydrochloride to patients taking concomitant sedatives or central nervous system medications, since the sedative effect may be enhanced. Alcohol may also exacerbate this effect (see section 4.7).
04.6 Pregnancy and lactation
Fertility
There is a limited amount of fertility data (see section 5.3).
Pregnancy
There are no or limited data from the use of azelastine hydrochloride and fluticasone propionate in pregnant women. Dymista should therefore only be used during pregnancy if the potential benefit justifies the potential risk to the fetus (see section 5.3).
Feeding time
It is unknown whether azelastine hydrochloride, fluticasone propionate or their metabolites are excreted in human breast milk following inhalation administration. Dymista should only be used during breastfeeding if the potential benefit justifies the potential risk to the newborn / infant (see section 5.3).
04.7 Effects on ability to drive and use machines
Dymista has negligible influence on the ability to drive and use machines.
In isolated cases, fatigue, tiredness, exhaustion, dizziness or weakness, also caused by the disease itself, may occur while using Dymista. In these cases, the ability to drive and use machines may be impaired. Alcohol may potentiate this effect.
04.8 Undesirable effects
Usually, after administration, dysgeusia, an unpleasant taste typical of the drug, may occur (often due to an incorrect method of application, i.e. tilting the head too far back during administration).
Adverse reactions by system organ class and frequency are listed below. Frequencies are defined as follows:
Very common (≥1 / 10)
Common (≥1 / 100,
Uncommon (≥1 / 1,000 to
Rare (≥1 / 10,000,
Very rare (
Not known (frequency cannot be estimated from the available data)
* After prolonged treatment with intranasal fluticasone propionate, a very small number of spontaneous reports have been identified.
** Nasal septal perforation has been reported after use of intranasal corticosteroids.
The systemic effects of some inhaled corticosteroids may occur especially when prescribed at high doses for prolonged periods (see section 4.4).
In children treated with inhaled corticosteroids, growth retardation has been reported. Growth retardation is also possible in adolescents (see section 4.4).
In rare cases, osteoporosis has been observed when inhaled glucocorticoids have been administered for prolonged periods.
04.9 Overdose
No overdose reactions are expected with the nasal route of administration.
No patient data are available on the effects of acute or chronic overdose with intranasal fluticasone propionate.
Intranasal administration of 2 milligrams of fluticasone propionate (10 times the recommended daily dose), twice daily for seven days in healthy volunteers, had no effect on hypothalamic-pituitary-adrenal (HPA) axis function.
Administration of higher than recommended doses over a long period of time may result in temporary suppression of adrenal function.
In these patients, Dymista treatment should be continued at a dose sufficient to control symptoms. Adrenal function will resume after a few days and can be checked by measuring the plasma cortisol level.
In case of overdose after accidental oral intake, based on the results from animal studies it is possible for central nervous system disorders caused by azelastine hydrochloride (including sleep, confusion, coma, tachycardia and hypotension).
Treatment of these disorders must be symptomatic. Gastric lavage is recommended, based on the amount of substance ingested. There is no known antidote.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: decongestants and other nasal preparations for topical use, combinations of corticosteroids / fluticasone.
ATC code: R01AD58.
Mechanism of action and pharmacodynamic effects
Dymista contains azelastine hydrochloride and fluticasone propionate, which have different mechanisms of action and show synergistic effects in terms of improving the symptoms of allergic rhinitis and rhinoconjunctivitis.
Fluticasone propionate
Fluticasone propionate is a synthetic trifluorinated corticosteroid that possesses a particularly high affinity for the glucocorticoid receptor and has a potent anti-inflammatory action, 3-5 times more potent than that of dexamethasone based on gene expression and binding studies on the human glucocorticoid receptor cloned.
Azelastine hydrochloride
Azelastine, a derivative of phthalazinone, is classified as a potent and long-acting antiallergic agent with selective H1-antagonist activity and anti-inflammatory and mast cell stabilizing properties. Data obtained from studies in vivo (preclinical) e in vitro, show that azelastine inhibits the synthesis or release of chemical mediators responsible for early and late allergic reactions, such as leukotrienes, histamine, platelet activating factor (platelet-activating factor - PAF) and serotonin.
Relief of nasal allergy symptoms was observed within 15 minutes of administration.
Dymista
In 4 clinical studies conducted in adults and adolescents with allergic rhinitis, a "delivery of Dymista into each nostril twice daily reduced nasal symptoms significantly (including runny nose, nasal congestion, sneezing and nasal itching), compared to placebo. azelastine hydrochloride and fluticasone propionate once administered. Dymista significantly reduced ocular symptoms (including itching, tear / tearing and redness) and improved patient-related quality of life (Rhinoconjunctivitis Quality of Life Questionnaire - RQLQ) in all 4 studies.
Substantial improvement in symptomatology (50% reduction in severity of nasal symptoms) was achieved with Dymista within a significantly shorter period of time (3 or more days) than a commercially available fluticasone propionate nasal spray. The greater efficacy of Dymista compared to the fluticasone propionate nasal spray was maintained over a full one-year study in patients with chronic persistent allergic rhinitis and non-allergic / vasomotor rhinitis.
05.2 Pharmacokinetic properties
Absorption
After intranasal administration of two puffs per nostril (548 μg of azelastine hydrochloride and 200 μg of fluticasone) of Dymista, the mean peak plasma concentration (± standard deviation) (Cmax) was 194.5 ± 74.4 pg / mL for azelastine and 10.3 ± 3.9 pg / mL for fluticasone propionate and the area under the curve (AUC) was 4217 ± 2618 pg / mL * hr for azelastine and 97.7 ± 43.1 pg / mL * hr for fluticasone The mean time to reach maximum concentration (tmax) after single dose was 0.5 hours for azelastine and 1.0 hours for fluticasone.
Systemic exposure to fluticasone was increased by 50% with Dymista compared to commercial nasal spray containing fluticasone. Systemic exposure to azelastine with Dymista was equivalent to that of a commercial nasal spray containing azelastine. There was no evidence of pharmacokinetic interactions between azelastine hydrochloride and fluticasone propionate.
Distribution
Fluticasone propionate exhibits a large volume of distribution at steady-state (approximately 318 liters). The plasma protein binding is 91%.
The volume of distribution of azelastine is high and highly suggestive of a prevalent distribution in peripheral tissues. The protein binding is 80-90%. Both drugs also have a "wide therapeutic window: it is therefore unlikely that drug displacement reactions will develop.
Biotransformation
Fluticasone propionate is rapidly cleared from the systemic circulation, primarily by hepatic metabolism, by the cytochrome P450 enzyme CYP3A4 to an inactive carboxylic acid metabolite. Orally administered fluticasone propionate also undergoes extensive first pass metabolism. Azelastine is metabolised. to No.-desmethylazelastine through various CYP isoenzymes, mainly CYP3A4, CYP2D6 and CYP2C19.
Elimination
The rate of elimination of fluticasone propionate, administered intravenously, is linear over the dose range of 250 to 1,000 micrograms and is characterized by a clearance elevated plasma (CL = 1.1 l / min). Peak plasma concentrations are reduced by approximately 98% within 3-4 hours and only low plasma concentrations have been associated with the terminal half-life of 7.8 hours. clearance renal fluticasone propionate is negligible (bile.
The plasma elimination half-lives after a single dose of azelastine are approximately 20-25 hours for azelastine and 45 hours for the therapeutically active metabolite. No.-desmethyl azelastine. Excretion occurs primarily via the faeces. Prolonged excretion of small amounts of the dose in the faeces indicates the possibility of some degree of enterohepatic circulation.
05.3 Preclinical safety data
Fluticasone propionate
The results of general toxicology studies are similar to those observed with other glucocorticoids and are associated with exacerbated pharmacological activity. These results are unlikely to be relevant to humans, given the recommended inhalation doses, which result in minimal systemic exposure. No genotoxic effects of fluticasone propionate were observed in conventional genotoxicity tests. In addition, no drug-related increases in tumor incidence were reported in two-year inhalation studies in rats and mice.
In animal studies, glucocorticoids have been shown to induce malformations, including cleft palate and intrauterine growth retardation. These results are also unlikely to be relevant to humans, given the recommended inhalation doses, which result in minimal systemic exposure (see section 5.2).
Azelastine hydrochloride
Azelastine hydrochloride did not show any sensitization potential in guinea pigs. Azelastine showed no genotoxicity in a series of tests in vitro And in vivonor any carcinogenic potential in rats or mice. In male and female rats, azelastine administered at oral doses greater than 3 mg / kg /die caused a dose-related reduction in the fertility index. No drug-related alterations were detected in the reproductive organs of male or female specimens during chronic toxicity studies; however, embryotoxic and teratogenic effects occurred in rats, mice and rabbits , only at maternally toxic doses (e.g. skeletal malformations were observed in rats and mice at doses of 68.6 mg / kg /die).
Dymista
Repeated dose intranasal toxicity studies in rats for up to 90 days and in dogs for 14 days with Dymista did not reveal any new adverse events with respect to the individual components.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Disodium edetate
Glycerol
Microcrystalline cellulose
Carmellose sodium
Polysorbate 80
Benzalkonium chloride solution
Phenylethyl alcohol
Purified water
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
Shelf life in use (after first administration): 6 months.
06.4 Special precautions for storage
Do not refrigerate or freeze.
06.5 Nature of the immediate packaging and contents of the package
Type I amber glass vial, equipped with a spray pump, a polypropylene nasal applicator (dispenser) and a protective dust cap, containing a suspension of 6.4 g (at least 28 puffs) and 23 g (at least 120 disbursements).
Pack sizes:
1 vial with suspension of 6.4 g in vials of 10 ml (at least 28 actuations), 1 vial with suspension of 23 g in vials of 25 ml (at least 120 actuations)
Multipacks containing 64 g (10 vials with 6.4 g) of nasal spray, suspension, multipacks containing 69 g (3 vials with 23 g) of nasal spray, suspension
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions for disposal.
07.0 MARKETING AUTHORIZATION HOLDER
Meda Pharma S.p.A.
Viale Brenta 18
20139 Milan
08.0 MARKETING AUTHORIZATION NUMBER
041808015 - "137 mcg / 50 mcg / DISPENSING NASAL SPRAY, SUSPENSION" 1 GLASS BOTTLE WITH 6.4 G / 28 DISPENSES
041808027 - "137 mcg / 50 mcg / DISPENSING NASAL SPRAY, SUSPENSION" 10 GLASS BOTTLES WITH 6.4 G / 28 DISPENSES
041808039 - "137 mcg / 50 mcg / DISPENSING NASAL SPRAY, SUSPENSION" 1 GLASS BOTTLE WITH 23 G / 120 DISPENSES
041808041 - "137 mcg / 50 mcg / DISPENSING NASAL SPRAY, SUSPENSION" 3 GLASS BOTTLES WITH 23 G / 120 DISPENSES
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 27 May 2013
10.0 DATE OF REVISION OF THE TEXT
May 2013
