Fungitraxx - summary of medicine characteristics

ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

• 1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Fungitraxx 10 mg/ml oral solution for ornamental birds

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains:

Active substance:

Itraconazole      10 mg.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Oral solution.

Yellow to slightly amber, clear solution.

4. CLINICAL PARTICULARS4.1 Target species

Ornamental birds, particularly:

Psittaciformes (specifically cockatoos and true parrots: parakeets; budgerigars)

Falconiformes (falcons)

Accipitriformes (hawks)

Strigiformes (owls)

Anseriformes (specifically swans)

• 4.2 Indications for use, specifying the target species

Psittaciformes, Falconiformes, Accipitriformes, Strigiformes, and Anseriformes:

For the treatment of aspergillosis.

Psittaciformes (only):

Also for the treatment of candidiasis.

4.3 Contraindications

Do not use in birds intended for human consumption.

Do not use in case of hypersensitivity to the active substance or to any of the excipients.

• 4.4 Special warnings for each target species

None.

• 4.5 Special precautions for use

Special precautions for use in animals

Itraconazole is generally not well tolerated by African Grey Parrots and therefore the product should only be used with care in this species and if no alternative treatment is available and with the lowest recommended dose for the whole of the recommended treatment period.

Other Psittaciformes also appear less tolerant to itraconazole than other birds. Therefore if suspected adverse reactions such as emesis, anorexia or weight loss occur, the dose should be lowered, or treatment with the medicinal product should be discontinued.

Where there is more than one bird in the home/cage, all infected and treated birds should be separated from other birds.

In accordance with good animal husbandry, the cleaning and disinfection of the infected birds’ environment with an appropriate antifungal product should be recommended. An appropriate rate of air renewal in the environment of the treated bird(s) is also important.

Frequent and repeated use of antifungals from the same class may increase the risk of development of resistance to that class of antifungals.

The prevalence of such acquired resistance may vary geographically and over time for specific species, and therefore local information on antifungal/azole resistance is desirable, particularly when treating severe infections.

Special precautions to be taken by the person administering the veterinary medicinal product to animals

Wash hands and exposed skin after use.

In case of accidental contact with the eyes, rinse thoroughly with water.

In case of accidental ingestion, rinse the mouth with water and seek medical advice immediately and show the package leaflet or the label to the physician.

Some fungal infections of birds can be zoonotic diseases and infect humans. Because of the risk of transmission of aspergillosis to people, personal protective equipment consisting of latex gloves and a mask should therefore be worn when handling infected birds or when cleaning the syringe. If suspected lesions (such as the occurrence of cutaneous nodules or erythematous papules, respiratory symptoms such as coughing and wheezing) occur in humans, consult a physician.

• 4.6 Adverse reactions (frequency and seriousness)

Itraconazole generally has a narrow margin of safety in birds.

Emesis, anorexia and weight loss have commonly been observed in treated birds, however, these adverse reactions are usually mild and dose related. If emesis, anorexia or weight loss occurs, then in the first instance it is advisable to lower the dose (see section 4.5) or treatment with the veterinary medicinal product should be discontinued.

The frequency of adverse reactions is defined using the following convention:

• – very common (more than 1 in 10 animals treated displaying adverse reaction(s))

• – common (more than 1 but less than 10 animals in 100 animals treated)

• – uncommon (more than 1 but less than 10 animals in 1,000 animals treated)

• – rare (more than 1 but less than 10 animals in 10,000 animals treated)

• – very rare (less than 1 animal in 10,000 animals treated, including isolated reports).

• 4.7 Use during pregnancy, lactation or lay

Do not use in birds in lay and within 4 weeks before the start of the laying period.

Laboratory studies in rats have shown evidence of dose-related teratogenic, foetotoxic and maternotoxic effects at high dosages (40 and 160 mg/kg bodyweight administered daily for 10 days during their gestational period).

4.8 Interaction with other medicinal products and other forms of interaction

No information is available on the safety and efficacy of this veterinary medicinal product when used in the target species with any other veterinary medicinal product. Therefore co-administration of this product with other veterinary medicinal products should be avoided. The information below is indicative of the known interactions in humans, and in animals other than birds.

In humans it is known that itraconazole can inhibit the metabolism of medicinal products that are substrates for cytochrome 3A isoenzymes, for example, chloramphenicol, ivermectin or methylprednisolone. Although the relevance of this information for the target species is unknown, it would be prudent to avoid the concurrent use of such substances with this product because an increase and/or a prolongation of their pharmacological effects, including side effects, may occur.

The concomitant use of erythromycin can result in an increased plasma concentration of itraconazole.

Laboratory animal studies have shown that itraconazole used concomitantly with amphotericin B may be antagonistic against Aspergillus spp. or Candida spp.; the clinical importance of these findings is unclear.

• 4.9 Amounts to be administered and administration route

Oral use.

Dose and treatment schedule:

Aspergillosis:     5 to 10 mg (0.5 ml to 1 ml) itraconazole per kg bodyweight per day for 8 weeks.

For the treatment of African Grey Parrots (see section 4.5) use no more than 5 mg (0.5 ml) itraconazole per kg bodyweight per day. If clinical signs show that the product is not well tolerated, then the treatment should be stopped.

In cases where, 8 weeks after the start of treatment, clinical signs are still present, or endoscopy indicates a fungal presence remains, the whole 8 weeks course of treatment should be repeated (using the same dose regimen).

Candidiasis (Psittaciformes only):

10 mg (1 ml) itraconazole per kg bodyweight per day for 14 days.

For the treatment of African Grey Parrots use no more than 5 mg (0.5 ml) itraconazole per kg bodyweight per day for 14 days (see section 4.5).

Method of administration:

To ensure the correct dose, and to avoid underdosing and overdosing, the bodyweight(s) of the bird(s) to be treated should be determined as accurately as possible.

The best method of administration of the oral solution is directly into the bird’s mouth. However, if direct oral administration is not feasible (for example, for raptors) the medicinal product can be administered with the bird’s food. (For example, for raptors a ‘spiked’ chick is generally used.) If the product has to be administered with the bird’s food, it should then be offered immediately to the bird(s), and discarded within 1 hour if it has not been consumed by then.

The 1 ml oral syringe has graduations for 0.05 ml solution (= 0.5 mg itraconazole).

The 5 ml oral syringe has graduations for 0.2 ml solution (= 2 mg itraconazole).

Remove the screw cap on the bottle. Using the oral syringe provided, place the syringe nozzle into the opening of the bottle and withdraw the necessary volume. Replace the screw cap after use.

Slowly and gently administer the oral solution into the mouth of the bird, allowing the bird to swallow it.

After dosing, the syringe should be washed with hot water and dried.

4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary

No information on overdose is currently available in the target species (see section 4.6.).

• 4.11 Withdrawal period(s)

Not applicable.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Antimycotics for systemic use, triazole derivatives.

ATCvet code: QJ02AC02.

5.1 Pharmacodynamic properties

The mode of action of itraconazole is based on its highly selective binding ability for fungal cytochrome P-450 isoenzymes. Itraconazole inhibits the synthesis of ergosterol. It also affects membrane-bound enzyme function and membrane permeability, and as this effect is irreversible it results in structural degeneration of the fungus.

The minimum inhibitory concentrations of itraconazole for different Aspergillus isolates in birds in Europe varies between 0.25 and >16 pg/ml.

Data were limited on the minimum inhibitory concentrations for different Candida isolates.

Resistance to azole antifungals is most commonly exhibited by modification of the cyp51A gene which encodes for the target enzyme 14-alpha-sterol demethylase. Cross-resistance amongst members of the azole class of drugs has been observed within Candida species, although resistance to one member of the class does not necessarily confer resistance to other azoles. Some resistant isolates have been identified from avian Aspergillus fumigatus.

• 5.2 Pharmacoki­netic particulars

In birds, itraconazole plasma concentrations vary with the type of bird. The different target species consume different types of food and exhibit differing metabolism. One metabolite, hydroxyitraco­nazole, has the same antifungal activity as the parent drug.

Itraconazole elimination may be a saturable process. Because of its long half-life, itraconazole does not reach steady state plasma levels for at least 6 days after the start of treatment.

6. PHARMACEUTICAL PARTICULARS6.1 List of excipients

Hydroxypropyl­betadex

Caramel flavour

Propylene glycol

Hydrochloric acid (for pH adjustment)

Sodium hydroxide (for pH adjustment) Purified water.

6.2 Major incompatibilities

In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products.

6.3 Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 18 months.

Shelf life after first opening the immediate packaging: 28 days.

6.4. Special precautions for storage

Do not store above 25 °C.

Do not refrigerate or freeze.

Keep the bottle in the outer carton in order to protect from light.

Keep the bottle tightly closed.

• 6.5 Nature and composition of immediate packaging

Cardboard box containing an amber glass (type III) bottle with a tamper-evident polypropylene screw cap and LDPE insert. A graduated polypropylene oral syringe is also included.

Box containing 1 bottle of 10 ml with one 1 ml oral syringe.

Box containing 1 bottle of 50 ml with one 5 ml oral syringe.

Not all pack sizes may be marketed.

• 6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products

7. MARKETING AUTHORISATION HOLDER

Avimedical B.V.

Abbinkdijk 1

7255 LX Hengelo (Gld)

THE NETHERLANDS

8. MARKETING AUTHORISATION NUMBER(S)

EU/2/13/160/001–002

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

DD/MM/YYYY