Marbogen

MARBOGEN survey 2017 – 01 What do practitioners consider important about medications used to treat otitis externa?

The place of Marbogen Complex ear drops in therapy

Last autumn, Alpha-Vet Kft. Conducted a survey among veterinarians engaged in pet practice about what aspects they consider important in connection with the medicines selected for the treatment of otitis externa?

After completing the questionnaire, it was returned by 40 colleagues who treat a total of about 220 external auditory canal inflammations per week in their office. The results of the survey can be summarized as follows:

95% of respondents consider it important to have an antifungal agent in the formulation used – the remaining 5% only consider it important if the presence of fungi is confirmed. Also, 95% of those consider it important to have the widest possible antibacterial spectrum of an agent. The rate for steroid anti-inflammatory drugs is lower: only 60 percent of veterinarians consider it essential, suggesting that effective treatment of the infection is considered more important than symptomatic anti-inflammatory treatment.

We also asked which of the ear drops available in Hungary are most preferred? It is noteworthy that 70 percent of respondents use at least three types of formulations in their practice, suggesting that the perfect, always effective ear drop has not yet been marketed. (Marbogen Complex ear drops were not included in the product list because they were not yet available at the time of the survey.)

To what extent does the composition of Marbogen Complex ear drops meet the expectations of colleagues?

Ketoconazole: the antimycotic is important for almost everyone: Marbogen Complex contains high concentrations of ketoconazole, which is a broad-spectrum and very effective antifungal agent.

Marbofloxacin + gentamicin for those who value antibacterial efficacy. The synergistic effect of the two drugs has been demonstrated against several bacterial strains, it also breaks through Pseudomonas resistance.

Prednisolone for those for whom steroid anti-inflammatory content also plays a significant role.

At first glance, it may seem strange, but in the case of medicines, we do not actually buy the product itself, but the confidence in the cure – and in veterinary medicine, this is accompanied by the trust in the treating veterinarian. Behind the parallel use of many different types of ear drops lies the unpleasant experience, the fact that one or the other ear drops did not cure the patient, the case became chronic, or perhaps recurred. In addition, the story has financial implications – regardless of the amount paid, the most expensive treatment that does not cure the patient.

With such a history, why try Marbogen Complex Ear Drops? Because in the studies done for the registration, 94 percent of the 165 dogs treated were cured of Marbogen Complex!

Don’t use four or five different preparations – use one, but it should be effective!

Marbogen Complex: Proven Efficacy!

MARBOGEN 2016 – 11

Marbogen Complex ear drops for dogs: when 1 + 1 is more than 2

Otitis externa: why is it so common in dogs?

Inflammation of the external auditory canal in dogs is one of the 10 most common diagnoses in pet practice. According to data from the American Banfield pet hospital chain, of the 2.5 million dogs they treated in 2015, 12.9% were diagnosed with the disease. Otitis externa is more common in hanging-eared varieties; 25% of golden retrievers and 20% of Labradors go to the vet for this reason. Causes include allergies, bacterial and fungal infections, foreign bodies (usually cochlea) in the ear canal when bathing, and sarcoptes. The affected area can be secondarily infected, the dog is very disturbed.

In terms of etiology, otitis externa is similar to dermatitis – ultimately the auditory canal here it is an inflammation of the skin in the auditory canal – the skin in the auditory canal is thinner and poorly ventilated. We distinguish several forms (erythematosus, ceruminous, purulent).

If the underlying cause cannot be eliminated, or the antimicrobial you choose is not sufficiently effective, you may relapse. According to a Hungarian study, the majority of otitis externa cases (55%) were mixed infections -Malassezia and some bacteria – usually the presence of Staphylococcus or Pseudomonas can be identified.

Figure 1: Species distribution of bacterial isolates in Hungary

Figure 2. Pattern of otitis externa isolates in Hungary

Marbogen Complex solution ear drops have been developed to treat inflammation of the external auditory canal in dogs. Its active ingredients are marbofloxacin, gentamicin, ketoconazole and prednisolone – these active ingredients are in an aqueous solution.

Marbofloxacin is a second-generation fluoroquinolone widely used in veterinary medicine for the treatment of dermatological and systemic bacterial infections. It is effective against a wide range of bacteria that cause dermatitis and otitis externa, especially Staphylococcus and Pseudomonas aeruginosa. Concentration-dependent, cid-acting antibiotic.

Figure 1: Marbofloxacin acts by inhibiting topoisomerase enzymes.

Gentamicin is an aminoglycoside antibiotic that is also used for both topical and systemic treatment in veterinary medicine.

It is against the principles of modern antibiotic use to use a combination of antibiotics to broaden the antibacterial spectrum of a preparation, but this is not the case with Marbogen Complex. It contains two types of antibiotics because of the synergistic effect between marbofloxacin and gentamicin. This has also been demonstrated against several pathogens, P. aeruginosa, and several strains of Staphylococcus and Streptococcus canis. As a result, clinical efficacy is improved and the chances of developing resistance in these variable pathogens are reduced.

Keeping inhibitory concentrations low is especially important for P. aeruginosa, as a significant proportion of strains produce biofilm, which reduces the efficacy of agents used against them.

Ketoconazole is one of the most potent broad-spectrum antifungal imidazole derivatives. Its spectrum includes a number of yeasts and dermatophytes that cause dermatitis in animals: Malassezia species, Candida albicans, Trichophyton, and Microsporum species are generally very sensitive.

Certain yeast species produce biofilm in their natural environment, which makes it difficult for the drug to enter the cell, resulting in significant differences of up to thousands of times between the in vitro and in vivo inhibitory effects of each drug. Based on our own studies, biofilm-producing strains isolated from Malassezia pachydermatis dogs did not grow in the absence of biofilm in the presence of 0.008 µg / ml ketoconazole, while in the presence of biofilm 0.2-1.0 µg / ml was required for the inhibitory effect. In view of this result, a dose much higher than the MIC 90 values in dermatological preparations is recommended if M. pachydermatis infection is suspected. In this way, biofilm-producing strains are also killed and the development of resistance can be prevented.

The active substance content of topically applied antimicrobials should be determined based on the results of several studies in such a way that the concentration exceeds the inhibitory values against the least sensitive strains by at least ten to twelve times. In contrast to the 1: 1 gentamicin / marbofloxacin combination, P. aeruginosa strains isolated from the area were approximately 10% fell into the moderately sensitive category, corresponding to the active substance content of Marbogen.

The in vitro activity of Marbogen Complex has been tested on pathogens isolated from the auditory canal of dogs. Pseudomonas aeruginosa strains proved to be the most resistant, but even in their case, 100% of the strains were killed by Marbogen Complex even at 64x dilution.

Figure 1. In vitro activity of Marbogen Complex against pathogens isolated from the auditory canal of dogs at different dilutions

Marbogen Complex contains prednisolone in addition to antimicrobials. Prednisolone is a well-proven corticosteroid anti-inflammatory. By inhibiting the enzyme phospholipase A2, it reduces the synthesis of eicosanoid molecules and rapidly reduces the pain and irritation caused by inflammation. DMSO, which is used as a carrier for the composition, is also preferred for reducing pain.

When determining the concentration of the active ingredients in the Marbogen Complex, it was also necessary to take into account the need to cut the hair from the surface when treating an infected skin surface, but this is limited in the auditory canal, making it difficult for the product to reach the skin surface.

Clinical results: The efficacy of Marbogen Complex was studied in Hungary in a multicenter, active-controlled trial. As a control, a commercial paraffin vehicle containing miconazole, polymyxin-B and prednisolone was used for the treatment. 94% of the 143 dogs treated with Marbogen Complex recovered. The average healing time for the right and left ears was 8.75 and 8.44 days, compared to 9.87 and 10.14 days for the control product. The healing time of more than one day is due to the unique, water-soluble formula of Marbogen Complex and the synergistic effect of marbofloxacin-gentamicin.

Scratching time was also measured in the study – dogs treated with Marbogen Complex scratched on average for less, more than a day, which is very important because scratching is the most common cause of re-infection.

The treated animals tolerated the product well, and no treatment had to be discontinued due to side effects.

Marbogen Complex features:

Composition – 1 ml contains:

Marbofloxacin: 2.041 mg

Gentamicin sulfate 2.044 mg

Ketoconazole 4,081 mg

Prednisolone 1, 850 mg

Therapeutic indication: For the treatment of acute otitis media caused by Staphylococcus pseudointermedius, Pseudomonas aeruginosa and ketoconazole susceptible Malassezia pachydermatis in dogs.

Dosage: Five drops should be instilled into the ear canal twice a day for 14 days.

Packaging: 10 ml

Please read the instructions for use before use!

Sources used:

1. Banfield: State of Pet Health®2016 Report

2. Zoltán Lajos: OTITIS EXTERNA IN A DIFFERENT WAY: MICROBIOLOGY AND ANTIBIOTICS TREATMENT Faculty of Dermatology 09.05.2014.

3. Jerzsele és Gál: Activity of Ketoconazole Against biofilm producing and planctonic Malassezia pachydermati s strains – a comparative study. Sudy code: AU-04/2014

4. Jerzsele and Gál: Pharmacokinetics-pharmacodynamics (PK / PD) analysis for topical products containing marbofloxacin, gentamicin and marbofloxacin: gentamicin in a 1: 1 ratio. Study code: AU-05/2014

5. Vandeputte P. et al. Antifungal resistance and new strategies to control fungal infections. International Journal of Microbiology. 2012th

6. Kroemer et al .: Antibiotic susceptibility of bacteria isolated from infections in cats and dogs throughout Europe (2002–2009). Comparative Immunology, Microbiology and Infectious Diseases 37 (2014) 97–108

7. István Csere: Final study report. Study No: 001 / ED / A003

8. Marbogen Complex Solution Ear Drops for Dogs A.U.V. – a summary of the product characteristics

CHART: Inhibitory dilution Bactericidal / fungicidal dilution

Staphylococci 50% OF THE STRAINS

90% OF THE STRAINS

Streptococci 50%…

90%…

P. aeruginosa 50% …

90%…

M. pachydermatis 50%…

90%…

Costumer experience 2016 – 04- AD

AlphaDerm Plus spray in daily practice – the experience of practicing colleagues with the product

It is well known that data collection on a medicinal product does not end with registration. In connection with the newly introduced product, companies are collecting not only side effects but also therapeutic experiences.

AlphaDerm Plus spray is still under trial, with a significant number of colleagues just starting to try it – but there are already some who already have substantial experience with it. We are now sharing these with our dear Readers.

Dr. Edina Rőber, Veszprém: So far I have used it on three patients – including my own dog. The effect of the preparation is extremely spectacular, in one case the wound healed in a few days, in the other case a 10-day treatment was required. In the third case, the owner treated the dog, no feedback was received, so he was probably satisfied with the result.

Dr. Sándor Kovács Tiszabercel: I have used it in many cases of bacterial and fungal superinfections. In all cases, I saw a spectacular improvement, often even after a few days of treatment. I can also say this because if the keeper does the treatment, I will always go back in a few days and check the patient’s condition.

Dr. József Pelbát, Dombóvár: I used it in some cases, the treatment was performed by the animal owners. So far, in no case have the animal been brought back, no complaints have been made, suggesting that they were satisfied with the effectiveness of the preparation.

Dr. Attila Kovács Miskolc: I have used it in several cases, in superinfected, purulent dermatitis and pyoderma. The preparation works very well, I am satisfied with the therapeutic effect experienced.

Dr Vecsera ErvinTapolca: The preparation has worked well. I consider it a special advantage that it is not a propellant, but a pump. Dogs are very afraid of hissing propellant aerosols, while AlphaDerm spray is quiet and tolerates treatment well.

Dr. Zoltán Keleti, Vértesszőlős: I used it on a couple of patients, the treatment is done by the owners. So far no one has brought their dog back, there have been no complaints about it, which is a clear indication that its clinical effectiveness is adequate.

Dr. Gábor Zayzon, Izsák: I used it in about 10 dogs, its effect is extremely fast, I am very satisfied with it. I experienced an unexpected effect in one case, but it may not be due to the product: one of the animals developed a hypersensitivity reaction during the treatment and developed allergic skin symptoms all over the body. I advised the owner to discontinue treatment and try to start again after the symptoms had gone to determine if there was a causal relationship? I don’t know the end result because the owner hasn’t applied since.

Dr. László Boa, Nagykanizsa: I used AlphaDerm plus spray in different types of dermatitis, where there was also a bacterial / fungal infection. I am satisfied with its efficiency. Compared to products with similar active ingredients, the advantage is the spray form, because this way we can conveniently apply the active ingredients to the more difficult-to-reach body and skin surfaces.

ALPHADERM 2015-15

Ketoconazole: Are skin infections treated orally or topically?

In the treatment of fungal skin infections, topical treatment is also preferred over Malassezia, because oral or parenteral administration of imidazole derivatives requires twenty to thirty times the dose used for topical treatment, so special attention should be paid to side effects. For oral treatment, 5-10 mg / kg twice daily is required for 3 weeks. (1) This means administering a total of 4-6 g of ketoconazole to an average-sized dog, whereas a bottle of AlphaDerm Plus Spray contains only 0.2 g of total active ingredient, which is often enough to treat several patients. This is explained by the fact that the bioavailability of orally administered ketoconazole is low, but locally high drug concentrations can be achieved, and efficacy can be ensured with a fractional dose.

Imidazole derivatives may affect hepatic and adrenal function at high doses and may interact metabolically with other drugs. Imidazole derivatives are metabolised by the microsomal CYP3A4 enzyme and may affect the kinetics of other co-administered drugs, resulting in higher plasma concentrations and longer duration of action. (2)

Ketoconazole also has potent antifungal activity against dermatophytons as well as budding fungi. In the form of a cream, ketoconazole usually has a very rapid effect in pruritus, which usually occurs after dermatophyton or budding fungal infection. This symptomatic improvement can be observed even before the first signs of recovery appear. (3)

Ketoconazole has not been used for oral treatment in human medicine in Hungary since 2013. A group property of imidazole-type drugs is hepatotoxicity (4), which is also true for ketoconazole. As a result, the marketing of ketoconazole tablets for human use has also been suspended in the European Union and the United States (5, 6). In veterinary medicine, such a restriction does not yet exist, but it warns against caution with oral treatment.

However, it is still free for topical treatment – ketoconazole can be used because it is not absorbed through the skin to the extent that it causes harmful side effects in the treated dog. In our own study, the maximum plasma level of ketoconazole was 2.8 ng / l during treatment, which decreased rapidly after therapy – but its therapeutic effect was extremely good.

Sources used:

1. Veterinary Dermatology Volume 16, Issue 3, pp. 171–176

2. http://www.drugs.com/monograph/ketoconazole.html

3. https://hu.wikipedia.org/wiki/Ketokonazolhttp://www.ogyei.gov.hu/dynamic/ketokonazol.pdf

4. http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/07/news_detail_001855.jsp&mid=WC0b01ac058004d5c1

5. http://www.fda.gov/drugs/drugsafety/ucm362415.htm

ALPHADERM questions from foreigner 2015 – 09

Austrian questions about using AlphaDerm Plus Spray

AlphaDerm Plus Spray has already been registered by Alpha-Vet Kft in several EU member states. During its use, foreign colleagues asked us several questions that may be of interest to our Hungarian colleagues. The following questions were received from Austrian colleagues practicing in Austria:

Ð Is it possible to use AlphaDerm Plus Spray at a higher dose than specified in the instructions for use?

Answer: The attending veterinarian may in principle deviate from the instructions for use, but this is not required for AlphaDerm Plus Spray. Based on the clinical trials performed with the approved dosage in the package leaflet, 96% of treated dogs improved symptoms after up to 14 days of treatment to the extent that the animal was declared cured by the treating veterinarian.

Based on this, it is not necessary to increase the dose, it is unnecessary to use a higher dose – this is why the authority approved the given dosage.

At the same time, we need to draw attention to performing a proper wound toilet before treatments. The hair must be trimmed from the surface of the wound, and the wound exudate must be removed from the wound surface so that the medicine can reach the skin surface and exert its effect.

A higher dose is unnecessarily sprayed on the covered wound surface – if the product does not reach the skin surface, it will not be able to exert the expected therapeutic effect.

Ð If a dog develops a skin lesion in several places at the same time (Hot Spot), can the entire body surface of the animal be treated at once or should the local lesions be treated individually?

Answer: If several isolated skin lesions are found in a patient at the same time, they can be treated at the same time according to the approved dosage of the product.

However, if the allergic lesions cover a large part of the body, systemic treatment is also required. AlphaDerm Plus Spray is not indicated for topical, full body treatment.

In the case of large-scale and deep-acting lesions and infections, AlphaDerm Plus treatment should be supplemented with systemic therapy for maximum efficacy.

Sources used:

AlphaDerm Clinical Study (registration documentation)

AlphaDerm Plus Spray SPC

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