SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Modulis 100 mg/ml oral solution for dogs

Modulis 100 mg/ml (FR)

Modulis vet 100 mg/ml oral solution for dogs(DK, SE, FI, NO)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains:

Active substance:

Ciclosporin 100 mg

Excipient(s):

all-rac--tocopherol (E-307) 1 mg

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Oral solution

Clear to slightly yellow opalescent solution.

4. CLINICAL PARTICULARS

4.1 Target species

Dogs

4.2 Indications for use, specifying the target species

Treatment of chronic manifestations of atopic dermatitis in dogs.

4.3 Contraindications

Do not use in cases of hypersensitivity to ciclosporin or one of the excipients.

Do not use in dogs less than six months of age or less than 2 kg in weight.

Do not use in cases with a history of malignant disorders or progressive malignant disorders.

Do not vaccinate with a live vaccine during treatment or within a two-week interval before or after treatment. (see also sections 4.5 “Special precautions for use” and 4.8 “Interaction with other medicinal products”)

4.4 Special warnings for each target species

None.

4.5 Special precautions for use

Special precautions for use in animals

Clinical signs of atopic dermatitis such as pruritus and skin inflammation are not specific for this disease and therefore other causes of dermatitis such as ectoparasitic infestations, otherallergies which cause dermatological signs (e.g. flea allergic dermatitis or food allergy) or bacterial and fungal infections should be ruled out before treatment is started. It is good practice to treat flea infestations before and during treatment of atopic dermatitis.

It is recommended to clear bacterial and fungal infections before administering the veterinary medicinal product. However, infections occurring during treatment are not necessarily a reason for drug withdrawal, unless the infection is severe.

A complete clinical examination should be performed before treatment. As ciclosporin inhibits T-lymphocytes and though it does not induce tumors, it may lead to increased incidences of clinically apparent malignancy. Lymphadenopathy observed on treatment with ciclosporin should be regularly monitored.

In laboratory animals, ciclosporin is liable to affect the circulating levels of insulin and to cause an increase in glycaemia. In the presence of suggestive signs of diabetes mellitus, the effect of treatment on glycaemia must be monitored. If signs of diabetes mellitus are observed following the use of the product, e.g. polyuria or polydipsia, the dose should be tapered or discontinued and veterinary care sought. The use of ciclosporin is not recommended in diabetic dogs.

Closely monitor creatinine levels in dogs with severe renal insufficiency.

Particular attention must be paid to vaccination. Treatment with the veterinary medicinal product may interfere with vaccination efficacy. In the case of inactivated vaccines, it is not recommended to vaccinate during treatment or within a two-week interval before or after administration of the product. For live vaccines see also section 4.3 “Contraindications”.

It is not recommended to use other immunosuppressive agents concomitantly.

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

People with known hypersensitivity to ciclosporin should avoid contact with the veterinary medicinal product

Wash hands after administration.

In the event of accidental contact of product with skin or eyes, the affected area should be washed with clean water.

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

4.6 Adverse reactions (frequency and seriousness)

The occurrence of adverse reactions is uncommon. The most frequently observed undesirable effects are gastrointestinal disturbances such as vomiting, mucoid or soft faeces and diarrhoea. They are mild and transient and generally do not require the cessation of the treatment.

Other undesirable effects may be observed infrequently: lethargy or hyperactivity, anorexia, mild to moderate gingival hyperplasia, skin lesions such as verruciform lesions or change of hair coat, red and swollen pinnae, muscle weakness or muscle cramps. These effects generally resolve spontaneously after treatment is stopped.

Very rarely diabetes mellitus has been observed, reported mainly in West Highland White Terriers.

As for the subject of malignancy, please see sections 4.3 “Contraindications” and 4.5 “Special precautions for use”.

4.7 Use during pregnancy, lactation or lay

In laboratory animals, at doses which induce maternal toxicity (rats at 30 mg/kg bw and rabbits at 100 mg/kg bw) ciclosporin was embryo- and fetotoxic, as indicated by increased pre- and postnatal mortality and reduced foetal weight together with skeletal retardations. In the well-tolerated dose range (rats at up to 17 mg/kg bw and rabbits at up to 30 mg/kg bw) ciclosporin was without embryolethal or teratogenic effects. The safety of the drug has neither been studied in breeding male dogs nor in pregnant or lactating female dogs. In the absence of such studies in the dog, it is recommended to use the drug in breeding dogs only upon a positive risk/benefit assessment by the veterinarian. Ciclosporin passes the placenta barrier and is excreted via milk. Therefore the treatment of lactating bitches is not recommended.

4.8 Interaction with other medicinal products and other forms of interaction

Various substances are known to competitively inhibit or induce the enzymes involved in the metabolism of ciclosporin, in particular cytochrome P450 (CYP 3A 4). In certain clinically justified cases, an adjustment of the dosage of the veterinary medicinal product may be required. Ketoconazole at 5-10 mg/kg is known to increase the blood concentration of ciclosporin in dogs up to five-fold, which is considered to be clinically relevant. During concomitant use of ketoconazole and ciclosporin the veterinarian should consider as a practical measure to double the treatment interval if the dog is on a daily treatment regime.

Macrolides may increase the plasma levels of ciclosporin up to twofold.

Certain inducers of cytochrome P450, anticonvulsants and antibiotics (e.g. trimethoprim/sulfadimidine) may lower the plasma concentration of ciclosporin.

Ciclosporin is a substrate and an inhibitor of the MDR1 P-glycoprotein transporter. Therefore, the co-administration of ciclosporin with P-glycoprotein substrates such as macrocyclic lactones (e.g. ivermectin and milbemycin) could decrease the efflux of such drugs from blood-brain barrier cells, potentially resulting in signs of Central nervous system toxicity.

Ciclosporin can increase the nephrotoxicity of aminoglycoside antibiotics and trimethoprim. The concomitant use of ciclosporin is not recommended with these active ingredients.

Particular attention must be paid to vaccination (see sections 4.3 “Contraindications” and 4.5 “Special precautions for use”).

4.9 Amounts to be administered and administration route

For oral use

The mean recommended dose of ciclosporin is 5 mg/kg body weight corresponding to 0.5 ml of solution for 10 kg of body weight.

The veterinary medicinal product will initially be given daily until a satisfactory clinical improvement is seen. This will generally be the case within 4 weeks. If no response is obtained within the first 8 weeks, the treatment should be stopped.

Once the clinical signs of atopic dermatitis are satisfactorily controlled, the preparation can then be given every other day as a maintenance dose. The veterinarian should perform a clinical assessment at regular intervals and adjust the frequency of administration to the clinical response obtained.

In some cases where the clinical signs are controlled with every-other-day dosing, the veterinarian can decide to give the veterinary medicinal product every 3 to 4 days.

Adjunct treatment (e.g. medicated shampoos, essential fatty acids) may be considered before reducing the dosing interval.

Treatment may be stopped when the clinical signs are controlled. Upon recurrence of clinical signs, treatment should be resumed at daily dosing, and in certain cases repeated treatment courses may be required.

The veterinary medicinal product should be given at least 2 hours before or after feeding.

The product is administered directly into the mouth.

Instructions for use

Push down and unscrew bottle top.

Insert the dosing syringe into the plastic adapter.