Mirataz - patient leaflet, side effects, dosage

2. NAME OF THE VETERINARY MEDICINAL PRODUCT

Mirataz 20 mg/g transdermal ointment for cats mirtazapine

3. STATEMENT OF THE ACTIVE SUBSTANCE(S) AND OTHER INGREDIENT(S)

Each dose of 0.1 g contains:

Active substance:

Mirtazapine (as hemihydrate) 2 mg

Excipients:

Butylhydroxytoluene (E321; as antioxidant) 0.01 mg

Non-greasy, homogeneous, white to off-white ointment.

4. INDICATION(S)

For body weight gain in cats experiencing poor appetite and weight loss resulting from chronic medical conditions (see “Other information”).

5. CONTRAINDICATIONS

Do not use in breeding, pregnant or lactating cats.

Do not use in animals less than 7.5 months of age or less than 2 kg body weight.

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

Do not use in cats treated with monoamine oxidase inhibitors (MAOIs) or treated with an MAOI within 14 days prior to treatment with the veterinary medicinal product due to an increased risk of serotonin syndrome (see also “Special warnings”).

6.

ADVERSE REACTIONS

Application site reaction(s) (erythema, crust/scab, residue, scaling/dryness, flaking, head shaking, dermatitis or irritation, alopecia, and pruritus) and behavioural changes (increased vocalisation, hyperactivity, disoriented state or ataxia, lethargy/weakness, attention seeking and aggression) occurred very commonly in safety and clinical studies.

Vomiting, polyuria associated with reduced urine specific gravity, elevated blood urea nitrogen (BUN) and dehydration were commonly observed in safety and clinical studies. Depending on the severity of vomiting, dehydration or behavioural changes, administration of the product may be discontinued according to the benefit-risk assessment of the veterinarian.

These adverse events, including local reactions, resolved at the end of treatment period with no specific treatment.

In rare occasions, hypersensitivity reactions can occur. In these cases, the treatment should be immediately withdrawn.

In case of oral ingestion, in addition to effects cited above (except local reactions), salivation and tremors may rarely occur.

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).

If you notice any side effects, even those not already listed in this package leaflet or you think that the medicine has not worked, please inform your veterinary surgeon.

7. TARGET SPECIES

Cats.

8. DOSAGE FOR EACH SPECIES, ROUTE(S) AND METHOD OF ADMINISTRATION

Transdermal use.

The veterinary medicinal product is applied topically to the inner pinna (inner surface of the ear) once daily for 14 days, at the dosage of 0.1 g ointment/cat (2 mg mirtazapine/cat). This corresponds to a 3.8 cm line of ointment (see below). Alternate the daily application between the left and right ears. If desired, the inner surface of the cat’s ear may be cleaned by wiping with a dry tissue or cloth immediately prior to the next scheduled dose. If a dose is missed, apply the veterinary medicinal product the following day and resume daily dosing.

The recommended fixed dose has been tested in cats weighing between 2.1 kg and 7.0 kg.

ADVICE ON CORRECT ADMINISTRATION

Step 3: Apply even pressure on tube and squeeze a 3.8 cm line of ointment onto your index finger using the measured line on the carton/bottle or in this leaflet as a guide.

Step 4: Using your finger, gently rub ointment on inside surface of cat’s ear (pinna) spreading it evenly over the surface. If contact with your skin occurs wash with soap and water.

The line below coincides with the appropriate length of ointment to be applied:

10. WITHDRAWAL PERIOD(S)

Not applicable.

11. SPECIAL STORAGE PRECAUTIONS

Keep out of the sight and reach of children.

This veterinary medicinal product does not require any special storage conditions.

The tube must be stored in the child resistant carton or bottle with cap, and returned to the carton or bottle and closed/capped immediately after every use.

Do not use this veterinary medicinal product after the expiry date which is stated on the carton or label. Shelf life after first opening the immediate packaging: 30 days.

12. SPECIAL WARNING(S)

Special warnings for each target species :

The efficacy of the veterinary medicinal product has not been established in cats less than 3 years of age.

The efficacy and safety of the veterinary medicinal product has not been established in cats with severe renal disease and/or neoplasia.

Proper diagnosis and treatment of the underlying disease is key to managing weight loss, and treatment options are dependent on the severity of weight loss and underlying disease(s). The management of any chronic disease associated with weight loss should include providing appropriate nutrition and monitoring body weight and appetite.

The therapy with mirtazapine should not replace necessary diagnostics and/or treatment regimens needed to manage the underlying disease(s) causing unintended weight loss.

The efficacy of the product was only demonstrated with a 14-day administration corresponding to the current recommendations. Repetition of the treatment has not been investigated and as such should only be done after benefit-risk balance assessment by the veterinarian. The efficacy and safety of the veterinary medicinal product has not been established in cats weighing less than 2.1 kg or more than 7.0 kg (see “Dosage for each species, route(s) and method of administration”).

Special precautions for use in animals :

The veterinary medicinal product should not be applied on damaged skin.

In the case of hepatic disease, elevated hepatic enzyme levels may be observed. Kidney disease may cause reduced clearance of mirtazapine, which may result in higher drug exposure. In these special cases, biochemical hepatic and renal parameters should be regularly monitored during the treatment.

The effects of mirtazapine on glucose regulation have not been evaluated. In the case of use in cats with diabetes mellitus, glycaemia should be regularly monitored.

When used in hypovolemic cats, supportive treatment (fluid therapy) should be implemented.

Care should be taken that other animals in the household do not come in contact with the application site until it is dry.

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

The product can be absorbed via the cutaneous or oral route and can cause drowsiness or sedation.

Avoid direct contact with the product. Avoid contact with the treated animal for the first 12 hours after each daily application and until the application site is dry. It is therefore recommended to treat the animal in the evening. Treated animals should not be allowed to sleep with owners, especially children and pregnant women during all the period of the treatment.

Impermeable disposable protective gloves should be provided at the point of sale with the product and must be worn when handling and administering the veterinary medicinal product.

Thoroughly wash hands immediately after administration of the veterinary medicinal product or in case of skin contact with the product or the treated cat.

Limited data are available on the reproductive toxicity of mirtazapine. Given that pregnant women are considered a more sensitive population, it is recommended that pregnant women or women trying to conceive should avoid handling the product and avoid contact with treated animals throughout the treatment period.

The product may be harmful after ingestion.

Do not leave the tube out of its child resistant container except during the application phase.

Children must not be present when applying the treatment to the cat.

The tube must be placed in the child resistant container after application, which must be closed immediately.

Do not eat, drink or smoke while handling the veterinary medicinal product.

The veterinary medicinal product is a skin sensitiser. People with known hypersensitivity to mirtazapine should not handle the veterinary medicinal product.

This veterinary medicinal product may cause eye and skin irritation. Avoid hand to mouth and hand to eye contact until hands have been thoroughly washed. In the case of contact with eyes, rinse the eyes thoroughly with clean water. In the case of contact with the skin, wash thoroughly with soap and warm water. If skin or eye irritation occurs or in case of accidental ingestion, seek medical advice immediately and show the label to the physician.

Pregnancy and lactation :

Do not use in pregnant or lactating cats.

Fertility :

Do not use in breeding animals.

Interaction with other medicinal products and other forms of interaction :

Do not use in cats treated with cyproheptadine, tramadol or monoamine oxidase inhibitors (MAOIs) or treated with an MAOI within 14 days prior to treatment with the veterinary medicinal product as there may be an increased risk of serotonin syndrome (see “Contraindica­tions”).

Mirtazapine may increase sedative properties of benzodiazepines and of other substances with sedative properties (antihistamines H1, opiates). The plasma concentrations of mirtazapine may be also increased when used concomitantly with ketoconazole or cimetidine.

Overdose (symptoms, emergency procedures, antidotes) :

The known symptoms of a mirtazapine overdose of > 2.5 mg/kg in cats include: vocalisation and behavioural changes, vomiting, ataxia, restlessness and tremors. In case of an overdose, symptomatic/sup­portive treatment should be instituted if needed.

In the case of overdose, the same effects as those observed at the recommended therapeutic dose were noted but with a higher incidence.

Transient increased hepatic alanine transferase can be observed uncommonly. It is not associated with clinical signs.

Incompatibilities :

Not applicable.

13. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCT OR WASTE MATERIALS, IF ANY

Medicines should not be disposed of via wastewater or household waste.

Ask your veterinary surgeon or pharmacist how to dispose of medicines no longer required. These measures should help to protect the environment.

14. DATE ON WHICH THE PACKAGE LEAFLET WAS LAST APPROVED

Detailed information on this veterinary medicinal product is available on the website of the European Medicines Agency.

15. OTHER INFORMATION

Pharmacodynamic properties

Mirtazapine is an a2-adrenergic receptor antagonist noradrenergic and serotonergic antidepressant drug. The exact mechanism by which mirtazapine induces weight gain appears to be multifactorial. Mirtazapine is a potent antagonist of 5-HT2 and 5-HT3 receptors in the central nervous system (CNS), and a potent inhibitor of histamine H1 receptors. Inhibition of 5-HT2 and histamine H1 receptors may account for the orexigenic effects of the molecule. Mirtazapine-induced weight gain may be secondary to changes in leptin and the tumour necrosis factor (TNF).

The product has an expected positive effect on feed intake by stimulating the appetite but this effect was not measured in the pivotal field trial. The only effect tested under field practice was on body weight: client-owned cats presented with a weight loss > 5%, deemed clinically significant by the investigator, gained a statistically significant (p<0.0001) amount of weight, after 14 days of product administration (3.39% weight gain or average of 130 grams) compared to those cats administered placebo (0.09% weight gain or average of 10 grams).

Pack size

5 gram coated aluminium tube (coat: lacquer (internal)/enamel (external)) with a low-density polyethylene (LDPE) screw cap and crimp sealant.

Each child resistant cardboard carton or plastic bottle with a child resistant cap contains 1 tube (5 g).

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