Indications for use
Treatment of chronic manifestations of atopic dermatitis in dogs.
Do not use in cases of hypersensitivity to the active substance or any 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
Special precautions for use in animals and Interactions).
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, other allergies 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 tumours, 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. 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 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
Wash hands after administration.
In the case of accidental ingestion of the product, seek medical advice immediately and show the package leaflet or the label to the physician.
People with known hypersensitivity to ciclosporin should avoid contact with the product.
Avoid contact with the eyes. In case of contact, rinse thoroughly with clean water.
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. As for the subject of malignancy, please see Contraindications and Special precautions for use in animals.
Use during pregnancy and lactation
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 foetotoxic, 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.
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 such as erythromycin 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 CNS 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 Contraindications and Special precautions for use in animals).
Amounts to be administered and administration route
For oral use.
The mean recommended dose of ciclosporin is 5 mg per kg body weight (1 ml oral solution per 10 kg bodyweight). The veterinary medicinal product should be given at least 2 hours before or after feeding.
The product should be administered directly into the dog’s mouth on the back of the tongue using the graduated dosing syringe supplied. (1 ml oral solution contains 50 mg ciclosporin) and delivering the entire dose.
At first use: replace the original screw cap of the bottle with the separately delivered screw cap. Fill the dosing syringe by pulling the plunger until it reaches the graduation corresponding to the correct body weight of the dog.
The 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, 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.
No undesirable effects beyond those that were seen under recommended treatment have been observed in the dog with a single oral dose of up to 5 times of what is recommended.
In addition to what was seen under recommended dosage, the following adverse reactions were seen in case of overdose for 3 months or more at 4 times the mean recommended dosage: hyperkeratotic areas especially on the pinnae, callous-like lesions of the foot pads, weight loss or reduced weight gain, hypertrichosis, increased erythrocyte sedimentation rate, decreased eosinophil values. Frequency and severity of these signs are dose dependent.
There is no specific antidote and in case of signs of overdose the dog should be treated symptomatically. The signs are reversible within 2 months following cessation of treatment.