Vidalta® 10 mg prolonged-release tablets for cats Vidalta® 15 mg prolonged-release tablets for cats Species: Cats Therapeutic indication: Pharmaceuticals: Hormones and therapeutically related products: Others Active ingredient: Carbimazole Product:Vidalta® 10 mg prolonged-release tablets for cats Vidalta® 15 mg prolonged-release tablets for cats Product index: Vidalta® 10 mg and 15 mg tablets for cats Qualitative and quantitative composition Each 10 mg prolonged-release tablet contains: Active substance: Carbimazole 10.0 mg Excipients: Red ferric oxide (E172) 0.25 mg Each 15 mg prolonged-release tablet contains: Active substance: Carbimazole 15.00 mg Excipients: Red ferric oxide (E172) 0.75 mg For the full list of excipients see Section “Pharmaceutical particulars”. Pharmaceutical form Prolonged-release tablet. 10 mg prolonged-release tablets: Round pink tablet with little spots. 15 mg prolonged-release tablets: Round dark pink tablet with little spots. Clinical particulars Target species Cats. Indications for use Treatment of hyperthyroidism and hyperthyroidism-associated clinical signs in cats. Contraindications Do not use in cats suffering from concurrent systemic diseases, such as severe primary liver disease or diabetes mellitus. Do not use in cats showing signs of auto-immune diseases and/or altered red or white blood cell counts, such as anaemia, neutropaenia or lymphopaenia. Do not use in cats with platelet disorders (particularly thrombocytopaenia) or coagulopathies. Do not use in cats with hypersensitivity to mercaptoimidazoles (carbimazole or thiamazole (methimazole)). Please refer to section “Use during pregnancy or lactation”. Special warnings for each target species Thiamazole (methimazole), the active metabolite of carbimazole, inhibits thyroid hormone production and therefore cessation of treatment with carbimazole will result in a rapid (within 48 hours) return to pre-treatment thyroid hormone levels. Chronic administration is therefore necessary unless surgical or radiation-induced thyroidectomy is performed. A small proportion of cats with thyroid adenoma may fail to respond or have a poor response to treatment. Thyroid carcinoma is a rare cause of hyperthyroidism in the cat and medical management alone is not recommended in such cases as it is not curative. Special precautions for use Treatment should be adjusted according to a risk:benefit assessment by the responsible veterinarian for the individual case. Treatment of hyperthyroidism may result in a reduction in the glomerular filtration rate. This can lead to unmasking of pre-existent renal dysfunction. Treatment of hyperthyroidism may also induce an elevation of liver enzymes or a worsening of pre-existing hepatic disorders. Renal and liver function should therefore be monitored before and during treatment. Due to risk of leucopenia or haemolytic anaemia, haematology parameters should be monitored on a regular basis before and during treatment, preferably at each visit of the dose adjustment phase and maintenance phase (see section ‘Amounts to be administered and administration route’). Any animal that suddenly appears unwell during therapy, particularly if they are febrile, should have a blood sample taken for routine haematology and biochemistry. Neutropenic animals (neutrophil counts <2.5 x 109/L) should be treated prophylactically with bactericidal antibiotics and supportive therapy. Doses above 20 mg have only been trialled in a small number of cats. Therefore, careful monitoring is recommended and the dose should be adjusted according to the risk:benefit assessment for the individual case. Operator warnings Wash hands with soap and water after use and when handling litter used by treated animals. Do not handle this product if you are allergic to antithyroid products. If allergic symptoms develop, such as a skin rash, swelling of the face, lips or eyes or difficulty in breathing, you should seek medical attention immediately and show the package leaflet or label to the doctor. As carbimazole is a suspected human teratogen, women of child-bearing age should wear gloves when handling litter or vomit of treated cats. Pregnant women should wear gloves when handling the product. Do not break or crush tablets. Do not eat, drink or smoke while handling the tablet or used litter. In the case of accidental ingestion, seek medical advice immediately and show the package insert or the label to the physician. Carbimazole, as a prodrug of thiamazole (methimazole), may cause vomiting, epigastric distress, headache, fever, arthralgia, pruritus and pancytopaenia. Treatment is symptomatic. Adverse reactions Treatment of hyperthyroidism may result in a reduction of renal perfusion. Azotaemia has been reported in rare cases; depending on the severity, temporary or permanent discontinuation of treatment may be required. Polydipsia and polyuria have also been reported in rare (polydipsia) or very rare cases (polyuria). Weight loss, vomiting, lethargy, tachycardia, reduced appetite, diarrhoea and dehydration have been observed in rare cases. Increased liver enzymes have been reported in rare cases. Severe cases may require temporary or permanent discontinuation of treatment. However, these elevations are usually reversible when treatment is discontinued, although symptomatic therapy (nutritional and fluid support) may be required. Anaemia, increase or decrease in white blood cell count, neutrophilia, thrombocytopaenia, eosinophilia and/or lymphopaenia have been reported in rare cases, in particular during the first 4-6 weeks of treatment. Discontinuation of treatment may be required in case of persistent and marked disorder. In most cases, the abnormality will resolve spontaneously within 1 month after the treatment has been discontinued. Dermatological signs (pruritus, dermatitis, erythema, alopecia) have been reported in rare cases. These clinical signs are usually mild, adequately controlled by symptomatic therapy and do not require discontinuation of treatment. However, if more severe clinical signs occur that do not respond to symptomatic therapy, the dose should be reduced or treatment stopped following a benefit-risk assessment by the responsible veterinarian. Signs of gastrointestinal bleeding such as bloody vomit, oral haemorrhage or dark faeces have been reported in rare cases. Ataxia, pyrexia, dyspnoea, disorientation ,aggressiveness, , and positive antinuclear antibody (ANA) have also been reported in very rare cases. In cases of serious adverse reactions, mortality, possibly due to the product, might occur if treatment is not discontinued. In many cases adverse reactions are reversible on cessation of treatment. The frequency of adverse reactions is defined using the following convention: − very common (more than 1 in 10 animals treated displaying adverse reactions) − 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). Use during pregnancy or lactation Laboratory studies in rats and mice have shown evidence of teratogenic and embryotoxic effects of thiamazole (methimazole). The safety of the product was not assessed in pregnant or lactating cats. Furthermore, thiamazole crosses the placenta, distributes into milk and reaches approximately the same concentration as in maternal serum. Do not use in pregnant or lactating females. Interactions Concomitant treatment with phenobarbital may reduce the clinical efficacy of carbimazole. Concomitant use of benzimidazole anthelmintics (fenbendazole or mebendazole) has been shown to reduce the hepatic oxidation of this therapeutic class and may therefore induce an increase in circulating levels. Accordingly, co-administration of carbimazole with a benzimidazole is not recommended. Thiamazole (methimazole) may display immunomodulating properties. This should be taken into account when considering vaccination of the cat. Amounts to be administered and administration route For oral use only. Administration with food enhances bioavailability. The timing of treatment and its relation to feeding should be kept consistent from day to day. Do not break or crush Vidalta tablets as this will affect the sustained release property. The aim of treatment is to maintain total thyroxine concentrations (TT4) in the lower end of the reference range. The following dose recommendations during the adjustment and maintenance phases are suggested. Dosing adjustment should primarily be based upon a clinical assessment of the individual cat. Monitoring of TT4, full haematology and liver and kidney parameters is recommended at each follow up visit (see sections Pharmacodynamic Properties and Adverse Reactions). Adjustment phase The starting dose is a single daily oral administration of one tablet of 15 mg carbimazole per cat. Consideration could be given to a starting dose of one 10 mg tablet daily where the TT4 concentration is only mildly increased, e.g. between 50 nmol/L and 100 nmol/L. With the recommended starting dose of one 15 mg tablet once daily, TT4 may decrease to within the euthyroid range (TT4<50 nmol/L) shortly after treatment initiation. A dose adjustment may be required as early as 10 days of treatment. Dose adjustment should be also performed 3, 5 and 8 weeks after initiation of treatment, depending on both clinical and hormonal responses to treatment. Maintenance phase Follow-up visits every 3 to 6 months are recommended. The dose should be adjusted individually based on clinical signs and TT4. It is advisable to check TT4 10-14 days after dose adjustment. The therapeutic dose ranges between 10 mg (one 10 mg tablet) and 25 mg (one 10 mg tablet and one 15 mg tablet) once daily. Some cats require doses of less than 10 mg carbimazole daily. Every other day dosing with 10 mg or 15 mg of carbimazole may be sufficient to control the disease. Dose increases should not be made in increments of greater than 5 mg. Doses above 20 mg have only been trialled in a small number of cats and should be used with caution. Overdose In case of an overdose, adverse effects that may appear include, but are not limited to, weight loss, inappetence, vomiting, lethargy and less frequently signs of gastrointestinal bleeding such as haematemesis, oral haemorrhage, or haemorrhage of the intestinal tract. Coat and skin abnormalities (erythema, alopecia), as well as as haematological/biochemical changes (eosinophilia, lymphocytosis, neutropaenia, lymphopaenia, slight leucopaenia, agranulocytosis, thrombocytopaenia or haemolytic anaemia) may also appear. Hepatitis and nephritis have been reported. These adverse effects may become severe in case of chronic overdosing. In most cases, adverse effects are reversible upon treatment discontinuation and appropriate veterinary care. TT4 below the lower limit of the reference range may be observed during treatment although this is rarely linked to overt clinical signs. Decreasing the dose will lead to an increase of the TT4. Dose adjustment should not be made based on TT4 only (see Section “Amounts to be administered and Administration Route”). Please also refer to section “Adverse Reactions”. Withdrawal period Not applicable.