Dimista (Dimista)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Dosage form: & nbspnasal dosing spray
Composition:

One dose of the spray contains:

Active substances:

Azelastine hydrochloride 0.137 mg

Fluticasone propionate 0.050 mg

Excipients:

glycerol 3.151 mg; avicel CL-611 [cellulose microcrystalline, carmellose sodium] 2,740 mg; polysorbate - 80 0,007 mg; disodium edetate dihydrate 0.014 mg; benzalkonium chloride 0.014 mg; phenylethanol 0.343 mg; water purified 130.545 mg.
Description:White homogeneous redispersible suspension.
Pharmacotherapeutic group:Anti-allergic agent combined (H1-histamine receptor blocker + glucocorticosteroid for topical application)
ATX: & nbsp
  • Fluticasone in combination with other drugs
    • Pharmacodynamics:

    Dimista contains azelastine hydrochloride and fluticasone propionate, which have a different mechanism of action and show synergy with regard to alleviating the symptoms of allergic rhinitis and rhinoconjunctivitis.

    Fluticasone propionate is a synthetic trifluorinated glucocorticosteroid, which has a high affinity for glucocorticoid receptors, exhibits a powerful anti-inflammatory effect, which is 3-5 times that of dexamethasone.

    Azelastine hydrochloride, a derivative of phthalazinone, is known as an antiallergic long-acting compound that is an selective blocker of H1-histamine receptors,stabilizes mast cells and possesses

    anti-inflammatory properties. Research data in vivo and in vitro show that azelastine inhibits the synthesis and / or release of chemical mediators that participate in the early and late stages of allergic reactions, such as leukotrienes, histamine, platelet activating factor (PAP), and serotonin. Azelastine in the form of a nasal spray is characterized by a rapid onset of action compared with oral administration of antihistamines and glucocorticosteroids. Relief of nasal allergic symptoms is observed as early as 15 minutes after administration.

    The drug Dimist

    Compared with placebo and separately applied azelastine hydrochloride and fluticasone propionate, the use of Dimista in a single dose every nasal twice daily significantly alleviates nasal symptoms (including rhinorrhea, nasal congestion, sneezing and itching in the nose). There was also a significant relief of eye symptoms, such as itching, lacrimation and redness of the eyes.

    In comparison with the drug fluticasone propionate, significant relief of the main symptoms (50% reduction in severity of symptoms)was achieved much faster (for 3 days or more) with the use of Dimist.

    Pharmacokinetics:

    Suction

    After intranasal administration of fluticasone propionate (200 μg per day), the maximum concentration (CmOh) was 0.017 ng / ml. Absorption from the mucous membrane of the nasal cavity is negligible due to the low solubility of the drug in water, and most of the dose is probably swallowed. When administered orally, less than 1 % from the administered dose of the drug, which is associated with slow absorption and active metabolism immediately after ingestion. Thus, the total systemic absorption, which represents the aggregate of absorption from the nasal mucosa and absorption when ingested, is insignificant.

    After repeated administration of a daily dose of 0.56 mg of azelastine hydrochloride (corresponding to the administration of one dose in each nasal passage twice a day) CmOh in plasma was 0.027 ng / ml in healthy volunteers. Active metabolite level N- desmethylazelastine was at or below the lower detection threshold (0.12 ng / ml).

    In patients with allergic rhinitis after the administration of dailyof the dose of 0.56 mg of azelastine hydrochloride (two doses per nasal once a day), the azelastin concentration in the plasma 2 hours after the administration was about 0.65 ng / ml. Doubling the daily dose to 0.12 mg of azelastine hydrochloride (two injections in each nasal passage twice a day) resulted in an increase in the plasma azelastin concentration of up to 1.09 ng / ml, indicating a proportional increase in concentration as a function of the dose.

    Distribution

    Fluticasone propionate has a large volume of distribution in a stable state (approximately 318 liters). Binding to plasma proteins is 91%. The volume of distribution of azelastine indicates a preferential distribution in peripheral tissues. The level of binding to plasma proteins is 80-90%. Both substances have a wide therapeutic window.

    Metabolism

    Fluticasone propionate is rapidly excreted from the systemic blood stream, mainly through metabolism in the liver with the formation of an inactive metabolite - carboxylic acid via isoenzyme CYP3A4 cytochrome P450. Metabolism of the swallowed fraction of fluticasone propionate during the first passage through the liver occurs in the same way. Caution should be exercised in the simultaneous administration of potent inhibitors CYP3A4, such as ketoconazole and ritonavir, since it is possible to increase the concentration of fluticasone propionate in the blood.

    Azelastine is metabolized to A-desmethylazelastine using various isoenzymes CYP, mainly CYP3A4, CYP2D6 and CYP2C19.

    Excretion

    Elimination of fluticasone propionate is linear in the dose range from 250 to 1000 μg and is characterized by a high plasma clearance (1.1 l / min). The maximum plasma concentration is reduced by approximately 98% within 3-4 hours, and only at very low plasma concentrations a final half-life of 7.8 hours is observed. The renal clearance of fluticasone propionate is negligible (less than 0.2%), and the inactive metabolite - carboxylic acid - is less than 5%. Fluticasone propionate and its metabolites are mainly excreted with bile through the intestine.

    After a single application, the half-life of azelastine from the blood plasma is approximately 20-25 hours and about 45 hours for its therapeutically active metabolite N- desmethylazelastine. Excretion occurs mainly through the intestine. Prolonged excretion of small amounts through the intestine testifies to the possibility of the existence of intestinal-hepatic circulation.
    Indications:

    Symptomatic treatment of allergic rhinitis / rhinoconjunctivitis of moderate and severe severity.

    Contraindications:

    Hypersensitivity to the active ingredients or to any of the auxiliary components of the drug. Children under 12 years.

    Pregnancy and lactation:

    Pregnancy

    Data on the use of azelastine hydrochloride and fluticasone propionate in pregnant women are absent or limited. Thus, the drug Dimista can be used during pregnancy only if the expected benefit exceeds the possible risk.

    Breastfeeding period

    It is not known whether nasal administration of azelastine hydrochloride or its metabolites and fluticasone propionate or its metabolites into breast milk penetrates, therefore, Dimist should be prescribed to lactating women only if the expected benefit exceeds the possible risk to the child.

    Impact on fertility

    There were no studies of the effect of Dimist on fertility.

    There was no evidence of the effect of azelastine hydrochloride on the fertility of male and female rats when administered orally at doses up to 30 mg / kg (approximately 530 times the maximum recommended daily dose for an adult).When the drug was administered at a dose of 68.6 mg / kg, an increase in the duration of the estrous cycle was noted with a decrease in the copulatory activity of the animals and a decrease in the number of pregnancies. The number of yellow bodies in the ovaries and implantations decreased, but without raising the level of preimplantation losses.

    In studies on the reproductive toxicity of fluticasone propionate, conducted in male and female rats with subcutaneous administration of the drug at doses up to 50 μg / kg (approximately 2 times the recommended daily dose for an adult), no effect on the fertility of the animals was recorded. When subcutaneous administration of the drug at a dose of 50 mcg / kg, a significant reduction in the weight of the prostate gland was recorded.

    Dosing and Administration:

    Intranasally.

    Adults and adolescents (12 years and over) - one dose in each nasal passage twice a day (morning and evening).

    Elderly patients

    This age group does not require dose adjustment.

    Preparation and use of the spray

    1. Shake the bottle several times.

    2. Remove the protective cap.

    3. Before the first use, the nasal spray Dimist must be activated, i.e. Press and release the activator of the dispenser 6 times until the appearance of small sprays. If the spray has not been used for 7 days, it must be re-activated.

    4. Clean your nose, tilt your head down.

    Introduce the nebulizer into one nasal passage, closing the second with the finger. Press and inhale. Repeat the same with the second nasal passage.

    5. Wipe off the tip of the activator and wear a protective cap.

    Side effects:

    The incidence of side effects is determined as follows:

    Very often (≥1 / 10)

    Often (≥1 / 100 to <1/10)
    Infrequently (≥1 / 1000 to <1/100)
    Rarely (≥1 / 10000 to <1/1000)
    Very rarely (<1/10000)

    From the immune system: very rarely - hypersensitivity reactions, including anaphylactic reactions, angioedema, bronchospasm.

    From the nervous system: often - a headache, very rarely - dizziness, drowsiness, lethargy.

    From the sense organs: often - dysgeusia (perversion of taste), usually due to improper application, namely excessive tilt of the head back during the intake; very rarely - glaucoma, increased intraocular pressure, cataract.

    From the respiratory system, organs of the thorax and mediastinum: rarely - nosebleeds, nasal discomfort (burning, itching), sneezing, dry nasal mucosa, cough, dry throat, throat irritation; very rarely - perforations of the nasal septum, erosion of the mucous membrane of the nasal cavity; unpleasant odor.

    From the gastrointestinal tract: rarely dry mouth; very rarely - nausea.

    From the skin and subcutaneous tissue: very rarely - rash, itching, hives.

    General disorders and disorders at the site of administration: very rarely - fatigue, weakness.

    In applying intranasal glucocorticoids may develop systemic side effects, especially with prolonged use at high doses (see. The "Special instructions"). These effects are much less pronounced than with the oral administration of glucocorticosteroids. Possible systemic side effects may include: Cushing's syndrome, adrenal suppression, growth retardation in children, osteoporosis, development of long-term use.

    Overdose:

    With a nasal route of administration, an overdose is unlikely.

    There is no evidence of an acute and chronic overdose of fluticasone propionate.

    Nasal administration of 2 mg of fluticasone propionate (10 recommended daily doses) twice daily for 7 days in healthy volunteers had no effect on the hypothalamic-pituitary-adrenal system. The use of the drug in doses exceeding the recommended for a long period of time, can lead to a temporary suppression of the function of the adrenal glands. In this case, treatment should continue with the use of minimal doses sufficient to control the symptoms.

    In the case of an overdose due to accidental oral administration, there may be disorders of the nervous system (including drowsiness, confusion, coma, tachycardia or hypotension) caused by azelastine hydrochloride.

    Treatment is symptomatic. Depending on the amount swallowed, gastric lavage is recommended. There is no known antidote.

    Interaction:

    Fluticasone propionate

    The effects of other drugs on fluticasone propionate

    Caution should be given to fluticasone propionate in patients who simultaneously take medications that are inhibitors of the cytochrome P450 3A4 isoenzyme (eg, protease inhibitors such as ritonavir).In the study of interactions in healthy volunteers on the background of the appointment intranasal fluticasone propionate administration of 100 mg of ritonavir twice daily resulted in an increase in the concentration of fluticasone propionate in plasma is several hundred times, resulting in a significantly reduced level of hydrocortisone in serum. Post-registration use reported cases of clinically significant interactions in patients receiving fluticasone propionate and ritonavir, leading to systemic effects, including Itenko-Cushing syndrome and suppression of adrenal function. Simultaneous reception of these drugs should be avoided, unless the potential benefit to the patient's potential risk of systemic side effects of corticosteroids (see. Section "Special instructions").

    Inhibitors of cytochrome P450 isoenzyme ZA4 cause negligible (erythromycin) or insignificant (ketoconazole) an increase in the concentration of fluticasone propionate in the blood plasma, which does not entail any noticeable decrease in serum cortisol concentrations.Nevertheless, care should be taken when combining the use of inhibitors of the cytochrome P450 isoenzyme ZA4 (for example, ketoconazole) and fluticasone propionate because of a possible increase in the plasma concentration of the latter.

    Azelastine hydrochloride

    Special studies to study the interaction with other drugs with intranasal use of azelastine hydrochloride were not conducted. Studies have been conducted on the interaction of azelastine when ingested in high doses with other drugs, but the results of these studies can not be transferred to the intranasal use of the drug.

    In some cases, alcohol and sedatives can increase fatigue, dizziness, or weakness when taking Dimist.

    Special instructions:

    Possible manifestations of systemic action of nasal glucocorticosteroids, especially when assigning high doses and long-term treatment. The possibility of these phenomena is much lower than with oral administration of glucocorticosteroids, and they can vary in individual patients and between different glucocorticosteroid preparations.Possible manifestations of systemic action may include Itenko-Cushing syndrome, characteristic signs of cushingoid, oppression of adrenal function, growth retardation in children and adolescents, cataracts, glaucoma, and, significantly less often, changes in mental state and behavior, which is manifested by psychomotor hyperactivity, sleep disorders, anxiety , depression or aggression (especially in children). It is necessary to monitor patients receiving the drug for a long time. When identifying cases of growth retardation, it is necessary to reduce the dose of nasal glucocorticosteroid to the lowest, which allows to effectively control the symptoms. In addition, you should refer the patient to a consultation with the pediatrician. Patients with visual impairment or increased intraocular pressure, glaucoma and / or cataract in the anamnesis should be under constant supervision.

    If there is any suspicion of adrenal insufficiency, transfer of patients from systemic treatment with glucocorticosteroids to treatment with Dimist nasal spray should be done with caution.

    Treatment with glucocorticosteroids in doses higher than those recommended can lead to clinically significant suppression of adrenal function and if it is known that high doses of glucocorticosteroids were used, consideration should be given to the possibility of additional use of systemic glucocorticosteroids during periods of stress or planned surgical intervention.

    In patients with tuberculosis, any untreated infection, or a recent surgery or injury to the nose and mouth, the expected benefit of using Dimist should be compared with the possible risks.

    Infections of the nasal cavity or paranasal sinuses require appropriate treatment, but are not a contraindication to the use of Dimist.

    Ritonavir

    Post-registration use reported cases of clinically significant interactions in patients receiving fluticasone propionate and ritonavir, leading to systemic effects, including Itenko-Cushing syndrome and suppression of adrenal function. Simultaneous reception of these drugs should be avoided, except whenThe potential benefit to the patient exceeds the possible risk of systemic side effects of glucocorticosteroids.

    Effect on the ability to drive transp. cf. and fur:

    In some cases, when using the drug Dimist may be observed violations of the nervous system: headache, dizziness, drowsiness, lethargy.

    When these undesirable phenomena appear, one should refrain from driving and working with machinery.

    Form release / dosage:

    Spray nasal dosed with 137 μg / dose + 50 μg / dose.

    Packaging:

    For 4 ml (28 doses) or 17 ml (120 doses) of a spray in a vial of dark glass with a dispenser - dispenser in the crimping cap.

    1 bottle together with the instruction for use is placed in a cardboard box.

    Storage conditions:

    Store at a temperature of 8 - 25 ° C. Keep out of the reach of children.

    Shelf life:

    2 years

    Opened vials - 6 months

    Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-004072
    Date of registration:10.01.2017
    Expiration Date:10.01.2022
    The owner of the registration certificate:Meda Pharma GmbH & Co. KGMeda Pharma GmbH & Co. KG Germany
    Manufacturer: & nbsp
    Representation: & nbspMEDA PHARMA LLCMEDA PHARMA LLC
    Information update date: & nbsp26.01.2017
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