The problem
The vast majority of treated patients remain symptomatic¹

Dymista^® is a new class of treatment for AR, incorporates azelastine hydrochloride (AZE; 137 μg per spray) and fluticasone propionate (FP, 50 μg per spray), two potent drugs from different medication classes with complementary effects in a novel patented formulation Dymista^® is indicated for the relief of symptoms of moderate to severe seasonal AR (SAR) and perennial AR (PAR).

Dymista^® is indicated in patients 12 years and older (depending on the country) to relieve the symptoms of moderate to severe seasonal and perennial allergic rhinitis if the use of either intranasal antihistamine or corticosteroid alone is not considered sufficient.¹ Seasonal and perennial allergic rhinitis are allergic reactions to substances such as pollen, house mites, moulds, dust or pets.^2,3

Dymista^® – Mode of Action

The inflammatory response is split into an early and late phase, and induces all the symptoms associated with allergic rhinitis (Figure).^1–3

Adapted from Bjermer et al., 2019.

Pharmacotherapies (allergic rhinitis treatment) interact with the allergic rhinitis pathophysiological pathway at different points, reflecting their different modes of action and how effective they are at providing symptomatic relief.

Comprising both an intranasal corticosteroid (i.e. fluticasone propionate) and an intranasal anti-histamine (i.e. azelastine) in a patented formulation,⁶ Dymista not only benefits from the anti-inflammatory effect of fluticasone, but also from the anti-inflammatory, anti-histaminic, mast-cell stabilizing and anti-leukotriene activity of azelastine delivered in a single spray., thus providing better relief from allergic rhinitis symptoms compared to other treatments.^1,7–10

 

The value of Dymista^®1,2

Multiple components in Dymista^®
Multiple components contribute to the overall product effectiveness of Dymista^®: The two active ingredients and the formulation.

Superior Efficacy

Dymista^® has been shown to be more effective as fluticasone propionate or azelastine alone at treating the entire rhinitis symptom spectrum. In a randomised, double-blind, placebo-controlled, 2-week trial involving 779 patients with moderate-to-severe seasonal allergic rhinitis, Dymista^® administered as one spray to each nostril twice-daily provided greater nasal and ocular symptom improvement than azelastine (INAH) or fluticasone propionate (INS) administered alone (one spray to each nostril twice-daily).³

Real life symptom control

Dymista^®’s clinical efficacy has been confirmed in real life.⁴

Five-minute onset of action

Dymista^® provides a 5-minute onset of action,10 giving your patients rapid symptom relief. In a randomised, placebo-controlled, double-blind, double-dummy, 3-period crossover trial of 82 patients with a history of allergic rhinitis and a positive skin prick test to ragweed pollen, subjects had allergic rhinitis symptoms induced by ragweed pollen in an allergen environmental exposure chamber. Patients received single-dose Dymista^®, or the two medications oral loratadine and intranasal fluticasone propionate (FP + loratadine), or placebo, and were monitored for 4 hours.²

• Dymista^® reduced TNSS at 5 minutes and throughout the 4-hour assessment period (p<0.05 vs. placebo).² Loratadine plus FP was not significantly different from placebo until 150 minutes (p<0.05).²
• Dymista^® was superior over the entire assessment period compared with placebo (p<0.001).²

Dymista^® is suitable for long term use^1-3

For patients to get the full therapeutic benefit, regular usage of Dymista^® nasal spray is essential, and Dymista^® is suitable for long-term use.
Treatment should be continued for as long as the patient is exposed to the allergen(s).³
A 52-week open-label study showed Dymista^® has a large therapeutic spectrum, covering not only seasonal allergic rhinitis but also perennial allergic rhinitis with consistent superiority over an intranasal corticosteroid.

Dosage
Always use Dymista Nasal Spray exactly as your doctor has told you. Check with your doctor or pharmacist , if you are not sure. It is essential to use Dymista Nasal Spray regularly to gain the full therapeutic benefit. Contact with the eyes should be avoided.

Adults and adolescents (12 years and above)

The recommended dose is one spray into each nostril in the morning and evening.

Use in Children under 12 years

This medicine is not recommended for children under 12 years

Use in renal and hepatic impairment

There are no data in patients with renal and hepatic impairment.

Dymista ^® should only be administered via the nasal route.
INSTRUCTION FOR USE
Preparing the spray

1. Shake the bottle gently for 5 seconds by titling upwards and downwards and then remove the protective cap (see figure 1).
2. The first time the nasal spray is used, you must prime the pump by squirting it into the air.
   
   
   
3. Prime the pump by putting two fingers on either side of the spray pump and place your thumb on the bottom of the bottle.
4. Press down and release the pump 6 times until a fine mist appears (see figure 2).
5. Now your pump is primed and ready to use.
6. 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

1. Shake the bottle gently for 5 seconds by tilting it upwards and downwards and then remove the protective cap (see figure 1).
2. Blow your nose to clear your nostrils.
3. Keep your head tilted downwards towards your toes. Do not tilt head backwards.
4. Hold the bottle upright and carefully insert the spray tip into one nostril.  
5. After each use wipe the spray tip with a clean tissue or cloth and then replace the protective cap

Contraindications
If you are allergic to azelastine hydrochloride or fluticasone propionate or any of the other ingredients of this medicine.
Warnings and Precautions
Talk to your doctor or pharmacist before using Dymista Nasal Spray if:

• You had an recent operation on your nose.
• You 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 Dymista Nasal Spray to treat your allergies.
• You have tuberculosis or an untreated infection.
• You have a change in vision or a history of increased ocular pressure, glaucoma and/or cataracts, if this applies to you, you will be closely monitored whilst using Dymista Nasal Spray.
• You suffered from impaired adrenal function. Care must be taken when transferring from systemic steroid treatment to Dymista Nasal Spray.
• Your suffer from a severe liver disease. You risk of suffering from systemic side-effects is increased.

In these cases your doctor will decide whether you can use Dymista Nasal Spray.
It is important that you take your dose as stated in section 3 below or as advised by your doctor. Treatment with higher than recommended doses of nasal corticosteroids may result in adrenal suppression, a condition that may produce weight loss, fatigue, muscle weakness, low blood sugar, salt cravings, joint pains, depression and darkening of the skin. If this happens your doctor may recommend another medicine during periods of stress or elective surgery.
To avoid adrenal suppression your doctor will advise you to take the lowest dose at which effective control of your symptoms of rhinitis is maintained.
Taking nasal glucocorticoids (such as Dymista) may when taken for a long time cause children and adolscents to grow more slowly. The doctor will check your child's height regularly, and make sure he or she is taking the lowest possible effective dose.
Contact your doctor if your experience blurred vision or other visual disturbances.
If you are unsure whether the above applies to you, talk to your doctor or pharmacist before using Dymista Nasal Spray.
Children
This medicine is not recommended for children under just 12 years.
Other medicines and Dymista Nasal Spray
Tell your doctor or pharmacist, if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.
Some medicines may increase the effects of Dymista Nasal Spray and your doctor may wish to monitor you carefully if you are taking these medicines (Including some medicines for HIV: ritonavir, Cobicistat and medicines for the treatment of fungal infections:Ketaconazole).
Pregnancy and breast-feeding
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 using Dymista Nasal Spray.

Dymista Nasal Spray contains benzalkonium chloride

It may cause irritation of the nasal mucosa and bronchospasm. Tell your doctor or pharmacist if you feel discomfort when using the spray. The preservative contained in Dymista (benzalkonium chloride) can cause swelling of the nasal mucosa, especially with prolonged use. If there is reason to suspect such a reaction (persistent blocked nose), a medicinal product that does not contain any preservative should be used in the nose if possible. If such preservative- free medicinal products for intranasal use are not available, a different pharmaceutical form should be considered.

Driving and using Machines
Dymista Nasal Spray has minor influence on the ability to drive and use machines.
Very rarely, you may experience fatigue or dizziness due to the disease itself or when using Dymista Nasal Spray. In these cases, do not drive or operate machinery, please be aware that drinking alcohol may enhance these effects.

Drug Interactions
Fluticasone propionate
Under normal circumstances, low plasma concentrations of fluticasone propionate are achieved after intranasal dosing, due to extensive first-pass metabolism and high systemic clearance mediated by cytochrome P450 3A4 in the gut and liver. Hence, clinically significant drug interactions mediated by fluticasone propionate are unlikely. A drug interaction study in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can greatly increase fluticasone propionate plasma concentrations, resulting in markedly reduced serum cortisol concentrations. During Post marketing 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. 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.
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 hydrochloride nasal spray, as the 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 the sedative effect may be strengthened. Alcohol may also enhance this effect

Dymista^® – Clinical Information

Poorly controlled allergic rhinitis negatively affects asthma control to the same degree as smoking.¹

Asthma and rhinitis are linked on several levels (Figure),^2,3 a phenomenon termed ’one airway one disease.⁴ At the epidemiology level, up to 60% of patients with allergic rhinitis have clinical asthma;⁵ the prevalence of asthma is more than 6 times higher in subjects with rhinitis than in those without.⁶ Both diseases also share a common anatomy, triggers and the same inflammatory process (pathology of allergic rhinitis).^2,7 Furthermore, control of one affects control of the other.¹ For example, the presence of severe rhinitis is associated with asthma exacerbations in co-morbid patients,⁸ and those with both asthma and rhinitis also use more asthma medication,⁹ have more physician visits and more hospitalizations for asthma.¹⁰ Finally, although rare, the risk of developing asthma is approximately 3-times greater for allergic rhinitis patients.¹¹ Given this relationship between allergic rhinitis and asthma, it is likely that reducing inflammation in the nose will improve outcomes in the lungs for those patients with both diseases.

The allergic rhinitis treatment efficacy hierarchy hypothesis The allergic rhinitis treatment hierarchy hypothesis postulates that an allergic rhinitis treatment which provides more effective control of allergic rhinitis symptoms should, in turn, have a greater positive impact on co-morbid asthma control (Figure). Intranasal corticosteroids are more effective than oral antihistamines for the treatment of allergic rhinitis¹² Dymista^® is more effective than intranasal corticosteroids for the treatment of allergic rhinitis¹⁶


Achieving effective and rapid asthma control by virtue of effectively treating uncontrolled co-morbid allergic rhinitis may delay or defer the need to step-up asthma therapy

Dymista^®: Helping to improve asthma outcomes for allergic rhinitis patients with co-morbid asthma

Given the relationship between allergic rhinitis and asthma, it is likely that reducing inflammation in the nose will improve outcomes in the lungs for those patients with both diseases. It is, therefore, crucial to achieve rhinitis control in patients with co-morbid asthma.

Dymista^® improves asthma control: results from a non-interventional study

Patients with allergic rhinitis and asthma treated with Dymista^® experienced: 

• A rapid, statistically significant and sustained improvement in allergic rhinitis control, and a concomitant 46.2% improvement in asthma control, reaching the ARIA control zone in less than 3 days (Figure).²⁸
• A reduction in their asthma rescue medication use
• 69% of these co-morbid patients treated with Dymista^® were able to reduce or considerably reduce their asthma rescue medication use, a marker of improved asthma control (Figure).²⁸

 

Implications:
Achieving effective and rapid asthma control by virtue of effectively treating uncontrolled co-morbid allergic rhinitis with Dymista^® may delay or defer the need to step-up asthma therapy and is likely a more cost-effective approach. Don’t forget to assess your asthma patients for allergic rhinitis, since one reason for uncontrolled asthma is the presence of uncontrolled allergic rhinitis.¹

Adapted from Klimek, et al. 2019.

Did you know that poor rhinitis control impacts asthma control to the same degree as smoking!¹

Dymista^® may be considered the allergic rhinitis medication of choice for asthma co-morbid patients since it is the most effective and rapidly acting allergic rhinitis medication currently available.^25,26

Evidence to support Dymista^®’s position as the treatment of choice for allergic rhinitis and asthma co-morbid patients comes from real-life observational, pre-post cohort and socioeconomic studies.^27–30

Dymista^® for allergic rhinitis helps to improve asthma control by almost 50% in allergic rhinitis and asthma co-morbid patients.²⁸

Recognized by leading experts as the drug of choice

Dymista^® is the recommended AR therapy in next-generation guidelines¹

• Dymista^® is more effective vs. INS^1,2 
• Dymista^® is effective within minutes^1,3 
• Dymista^® is recommended for initiation and step-up treatment¹ 
• INS is recommended therapy vs. INS + OAH¹

Dymista^® can be considered the drug of choice for AR⁴

Allergic rhinitis is the most common chronic respiratory disease in the world; estimated to affect 400 million people globally.¹
Epidemiological studies estimate that allergic rhinitis affects 10-30% of adults and 40% of children.¹ In children, boys outnumber girls,² but this tendency reverses in puberty with both sexes equally affected by adulthood.² Globally, prevalence continues on an upward trajectory,¹ thought to be a consequence of increased urbanization and improved living standards, which contribute to an increased exposure to a variety of indoor and outdoor pollutants and allergens.⁴ The size of the allergic rhinitis population depends upon where you live in the world (Figure).⁴ When symptomatic, allergic rhinitis patients report a significant negative impact on their quality of life (severity of impact), can experience a worsening of co-morbid conditions (notably asthma; the link between rhinitis and asthma) and cost the economy billions every year due to lost productivity.^5–10

The allergic rhinitis world map

Adapted from Tong M, Lin J. 2015.

There is very little inter-racial variation in allergic rhinitis prevalence implying that environmental factors have a greater influence than genetic differences. Indeed, climate change is measurably altering the timing, distribution, quality and quantity of allergenic plants and aeroallergens, so that the season starts earlier, lasts longer, and is more intense (i.e. higher pollen load).^11,12 These changes may affect the global distribution of allergic rhinitis incidence and prevalence, as well as symptom severity.¹³

Which of my patients are more at risk of developing allergic rhinitis?
Risk factors for the development of allergic rhinitis include:^2,14–16

• Presence of other allergic disease (e.g. asthma, eczema)
• A family history of atopic diseases
• Parental rhinitis
  • 3 times more likely if one parent has rhinitis
  • 4 times more likely if both parents have rhinitis
• Increased total serum IgE before 6 years of age,
• Allergenic sensitivity to common household aeroallergens and
• higher socio-economic class

What are my patients allergic to?

Allergic rhinitis may be triggered by several different allergens. It is important to link allergen exposure and symptoms when making a diagnosis. Allergens or triggers are commonly divided into seasonal triggers (i.e. those present during a specific time of the year or season – e.g. pollen) and perennial triggers (i.e. those present during the whole year – e.g. house dust mite) (classification of allergic rhinitis).¹⁴ The relative prevalence of seasonal AR (SAR) and perennial AR (PAR) also varies by country, depending upon the most common prevailing allergens.¹⁴

Seasonal triggers

The duration of the pollen season varies from year to year and from country to country.¹⁷ The season is usually divided into different periods, since different types of pollen are released at different times (Table).
Table: temporal trends for common seasonal triggers

Individuals may be sensitized to many different types of allergen (i.e. poly-sensitized) and in this instance can experience a very prolonged hay fever season.
Perennial triggers
The most common perennial triggers are house dust mite (HDM), pet dander and indoor mould (Table).¹⁴ Patients with perennial allergic rhinitis present to clinic throughout the year.
Table: common perennial triggers

On average, 3 out of every 10 of your patients could have allergic rhinitis, and this number is set to rise in the future¹
Climate change and urbanization means that more and more people are developing allergic rhintis. Are you ready to meet the challenge? ^2-3
The scale of the allergy epidemic means that symptoms cannot be avoided, but they can be treated!

Patient’s Material

How to use a Nasal Spray
 

What does uncontrolled AR mean?

Current AR guidelines define uncontrolled AR as--≥5.^1-3

What does uncontrolled mean?

New guidelines state VAS as a useful tool to assess symptom control in AR.²

Patients’ AR symptom control status^1,*

Dymista^® recommended first-line treatment for AR patients with a VAS ≥5^1,*

[Dymista]^® abbreviated prescribing information

PRESENTATION: Bottle Nasal Spray, with 23g (17ml) of suspension in 25 mL bottles (at least 120 actuations).

One actuation (0.14 g) delivers 137 micrograms azelastine hydrochloride (= 125 micrograms azelastine) and 50 micrograms fluticasone propionate.

INDICATIONS: Relief of symptoms of moderately severe to severe seasonal and perennial allergic rhinitis if monotherapy with either intranasal antihistamine or glucocorticoid is not considered sufficient.

DOSAGE AND ADMINISTRATION: Adults and adolescents (12 years and older): One actuation in each nostril twice daily (morning and evening). Children below 12 years: Dymista Nasal Spray is not recommended for use in children below 12 years of age, as safety and efficacy has not been established in this age group. Elderly patients: No dose adjustment is required in this population. Patients with renal and hepatic impairment: There are no data on patients with renal or hepatic impairment. Duration of treatment: Dymista Nasal Spray is suitable for long-term use. The duration of treatment should correspond to the period of allergenic exposure. Pregnancy: There are no, or only limited, data from the use of azelastine hydrochloride and fluticasone propionate in pregnant women. Therefore, Dymista Nasal Spray should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. Breast-feeding: It is unknown whether nasally administered azelastine hydrochloride/metabolites or fluticasone propionate/metabolites are excreted in human breast milk. Dymista Nasal Spray should be used during lactation only if the potential benefit for the mother is higher than the potential risk to the newborn/infant. Method of administration: Dymista Nasal Spray is for nasal use only. Instruction for use Preparing the spray:The bottle should be shaken well before use for about 5 seconds by tilting it upwards and downwards. Then remove the protective cap. Prior to first use, Dymista Nasal Spray must be primed by pressing down and releasing the pump 6 times. If Dymista Nasal Spray has not been used for more than 7 days it must be reprimed by pressing down and releasing the pump once. Using the spray: The bottle should be shaken well before use for about 5 seconds by tilting it upwards and downwards. Then remove the protective cap. After blowing one's nose the suspension is sprayed once into each nostril keeping the head tilted downward . After use, wipe the spray tip and replace the protective cap.

CONTRAINDICATIONS: Hypersensitivity to the active substances or to any of the excipients.

WARNING AND PRECAUTIONS: Clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided, unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side- effects. Systemic effects of nasal corticosteroids may occur, particularly when prescribed at high doses for prolonged periods. 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). Dymista Nasal Spray undergoes extensive first-pass metabolism, therefore the systemic exposure of intranasal fluticasone propionate is likely to be increased in patients with severe liver disease. This may result in a higher frequency of systemic adverse events. Caution is advised when treating these patients. 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. In general the dose of intranasal fluticasone formulations should be reduced to the lowest level at which effective control of the symptoms of rhinitis is maintained. Higher doses than the recommended one have not been tested for Dymista. As with all intranasal corticosteroids, the total systemic burden of corticosteroids should be considered whenever other forms of corticosteroid treatment are prescribed concurrently. Growth retardation has been reported in children receiving nasal corticosteroids at licensed doses. Since adolescents may also still be growing, 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. 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. Close monitoring is required in patients with a change in vision or with a history of increased ocular pressure, glaucoma and/or cataracts. If there is any reason to believe that adrenal function is impaired, care must be taken when transferring patients from systemic steroid treatment to Dymista Nasal Spray. In patients who have tuberculosis or any other type of untreated infection, or have had a recent surgical operation or injury to the nose or mouth, the possible benefits of the treatment with Dymista Nasal Spray should be weighed against possible risk. Upper respiratory tract infections should be treated with antibacterial or antimycotic drugs, but do not constitute a specific contraindication to treatment with Dymista Nasal Spray. Dymista contains benzalkonium chloride. It may cause irritation of the nasal mucosa and bronchospasm. The preservative contained in Dymista (benzalkonium chloride) can cause swelling of the nasal mucosa, especially with prolonged use. If there is reason to suspect such a reaction (persistent blocked nose), a medicinal product that does not contain any preservative should be used in the nose if possible. If such preservative-free medicinal products for intranasal use are not available, a different pharmaceutical form should be considered.

INTERACTIONS: Fluticasone propionate: Under normal circumstances, low plasma concentrations of fluticasone propionate are achieved after intranasal dosing. Co-treatment with other CYP 3A4 inhibitors, including cobicistat-containing products is also expected to increase the risk of systemic side- effects. 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. Azelastine hydrochloride: No specific interaction studies with azelastine hydrochloride nasal spray have been performed. Nevertheless, care should be taken when administering azelastine hydrochloride in patients taking concurrent sedative or central nervous medications because the sedative effect may be strengthened. Alcohol may also enhance this effect.

OVERDOSING: With the nasal route of administration, overdose reactions are not anticipated. 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 Dymista Nasal Spray should be continued at a dose that is just 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 accidental 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.

ADVERSE REACTION: Very Common adverse reactions (≥1/10): Epistaxis. Common adverse reactions (≥1/100 to <1/10): Headache, dysgeusia (unpleasant taste), unpleasant smell

PHARMACEUTICAL PRECAUTIONS: Shelf life: 24 months.

Special precautions for storage: Store below 30°C Do not refrigerate or freeze.

Special precautions for disposal and other handling: No special requirements for disposal.

REFERENCE: Dymista [SmPC]. MEDA Pharma GmbH & Co. KG; Bad Homburg. January 2019

Date of This Document: 22 August 2021

FULL PRESCRIBING INFORMATION IS AVAILABLE UPON REQUEST

DYM-2022-0248