ProZinc - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

PACKAGE LEAFLET:

ProZinc 40 IU/ml suspension for injection for cats and dogs

• 1. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER AND OF THE MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE, IF DIFFERENT

Marketing authorisation holder and manufacturer responsible for batch release:

Boehringer Ingelheim Vetmedica GmbH

Binger Strasse 173

55216 Ingelhe­im/Rhein

GERMANY

Manufacturer responsible for batch release:

KVP Pharma + Veterinär Produkte GmbH

Projensdorfer Str. 324

24106 Kiel

GERMANY

• 2. NAME OF THE VETERINARY MEDICINAL PRODUCT

ProZinc 40 IU/ml suspension for injection for cats and dogs insulin human

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

Each ml contains:

Active substance:

Insulin human* 40 IU as protamine zinc insulin.

One IU (International Unit) corresponds to 0.0347 mg of insulin human.

produced by recombinant DNA technology

Excipients:

Protamine sulfate 0.466 mg

Zinc oxide 0.088 mg

Phenol 2.5 mg

Cloudy, white, aqueous suspension.

For the treatment of diabetes mellitus in cats and dogs to achieve reduction of hyperglycaemia and improvement of associated clinical signs.

Do not use for the acute management of diabetic ketoacidosis.

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

• 6. ADVERSE REACTIONS

Hypoglycaemic reactions were very commonly reported in clinical studies: 13% (23 of 176) of treated cats and 26.5% (44 of 166) of treated dogs. These reactions were generally mild in nature. Clinical signs may include hunger, anxiety, unstable locomotion, muscle twitching, stumbling or sinking in the rear legs and disorientation.

In this case immediate administration of a glucose containing solution or gel and/or food is required.

Insulin administration should be temporarily stopped and the next dose of insulin adjusted appropriately.

Local injection site reactions were very rarely reported and resolved without cessation of therapy.

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).

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 and dogs

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

Subcutaneous use.

If the animal owner is to administer the product, suitable training/advice should be provided by the prescribing veterinarian before using for the first time.

Dosage:

The veterinarian should re-evaluate the animal at appropriate intervals and make adjustments to the treatment protocol, for instance dose and dosing regimen, until adequate glycaemic control has been attained.

Any dose adjustment (i.e. increase of dose) should be in general performed after several days (e.g. 1 week) since full action of insulin requires an equilibration phase. Dose reductions due to observed hypoglycaemia or suspected Somogyi effect (rebound hyperglycaemia) may be of 50% or higher (potentially including a temporary pause of insulin administration).

Once adequate glycaemic control is achieved intermittent glucose monitoring should be performed, especially when there is a change in clinical signs or diabetic remission is suspected, and further adjustments in the insulin dose might be necessary.

Cats:

The initial recommended dose is 0.2 to 0.4 IU insulin/kg bodyweight every 12 hours.

• – For cats previously controlled on insulin, a higher starting dose up to 0.7 IU insulin/kg bodyweight

may be appropriate.

• – Adjustments of insulin dose if required should usually be done between 0.5 to 1 IU insulin per

injection.

Cats can develop diabetic remission, in which case sufficient endogenous insulin production will be regained and exogenous insulin dose will need to be adjusted or ceased.

Dogs:

General guidance:

Dosing should be individualised and based on the clinical presentation of each patient. To achieve optimal control of diabetes mellitus, dose adjustments should primarily be based on clinical signs. Blood parameters such as fructosamine, maximum blood glucose and decrease of blood glucose concentrations in blood glucose curves conducted over a sufficient period of time to determine a blood glucose nadir should be used as supporting tools (see also section “Special precautions for use in dogs”).

Re-evaluation of clinical signs and laboratory parameters should be performed as recommended by the attending veterinarian.

Initiation

For initiation of treatment, the recommended dose is 0.5 to 1.0 IU insulin/kg bodyweight once daily every morning (approx. every 24 h).

For newly diagnosed diabetic dogs, a starting dose of 0.5 IU insulin/kg once daily is recommended.

Management

Adjustments of insulin dose on a once daily regimen, if required, should generally be done in a conservative and gradual manner, (e.g. up to 25% increase/decrease of the dose per injection).

If insufficient improvement in diabetic control is observed after an adequate dose adjustment period of 4 to 6 weeks on once daily treatment, the following options may be considered:

• - Further adjustments of insulin dose on once daily treatment may be necessary; in particular if dogs

undertake increased physical activity, have a change of their usual diet or during concomitant illness.

• - Switching to twice daily dosing: In such cases, it is recommended to reduce the dose per injection by

one third (e.g. 12 kg dog being treated once daily with 12 IU insulin/injection may be switched to 8 IU insulin/injection administered twice daily). The product should be administered in the morning and in the evening, approx. 12 hours apart. Further adjustments of insulin dose on twice daily treatment may be necessary.

Depending on the underlying cause (e.g. dioestrus-induced diabetes mellitus), dogs can develop diabetic remission, although more seldom than in cats. In those cases sufficient endogenous insulin production will be regained and the exogenous insulin dose will need to be adjusted or ceased.

• 9. ADVICE ON CORRECT ADMINISTRATION

A U-40 syringe must be used.

The suspension should be mixed by gently rolling the vial prior to withdrawing each dose from the vial. Particular care should be taken with regard to the accuracy of dosing.

The veterinary medicinal product should be administered by subcutaneous injection.

The dose should be given concurrently with or immediately after a meal.

Avoid introduction of contamination during use.

After gently rolling the vial, ProZinc suspension has a white, cloudy appearance.

A white ring may be seen in the neck of some vials, but this does not affect the quality of the product. Agglomerates (e.g. clumps) can form in insulin suspensions: do not use the product if visible agglomerates persist after gently rolling the vial.

• 10. WITHDRAWAL PERIOD

Not applicable.

• 11. SPECIAL STORAGE PRECAUTIONS

Keep out of the sight and reach of children.

For unused and broached vials:

Store upright in a refrigerator (2 °C – 8 °C).

Do not freeze.

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

Shelf life after first opening the container: 60 days.

Do not use this veterinary medicinal product after the expiry date which is stated on the carton and the vial after EXP.

• 12. SPECIAL WARNING(S)

Special warnings for each target species:

Very stressful events, inappetance, concomitant treatment with gestagens and corticosteroids or other concomitant diseases (e.g. gastro-intestinal, infectious or inflammatory or endocrine diseases), might influence insulin effectiveness and therefore the insulin dose may need to be adjusted.

Special precautions for use in animals:

The insulin dose may need to be adjusted or discontinued in case of remission of the diabetic state in cats or after resolution of transient diabetic stages in dogs (e.g. dioestrus-induced diabetes mellitus, diabetes mellitus secondary to hyperadrenocor­ticism).

After the daily insulin dose is established, monitoring for diabetic control is recommended.

Treatment with insulin can cause hypoglycaemia, for clinical signs and appropriate treatment, please refer to section “Overdose”, below.

Special precautions for use in dogs

In cases where hypoglycaemia is suspected, blood glucose measurements should be taken at the time of occurrence (if possible) as well as shortly prior to the next feeding/injection (where applicable).

Stress and irregular exercise should be avoided. It is recommended to establish a regular twice daily feeding schedule with the owner whether injecting insulin once or twice daily.

In an experimental study in healthy dogs, median time to blood glucose nadir was approximately 16 and 12 hours following administration of 0.5 or 0.8 IU/kg bodyweight, respectively.

Under clinical field conditions in diabetic dogs, time to maximal effect in lowering blood glucose concentrations (i.e. blood glucose nadir) after subcutaneous administration was not observed within 9 hours after last injection in 67.9% of dogs overall. (73.5% on once daily and 59.3% on twice daily administration). Consequently, blood glucose curves should be conducted over a sufficient period to determine a blood glucose nadir.

Special precautions to be taken by the person administering the veterinary medicinal product to animals : Accidental self-injection can provoke clinical signs of hypoglycaemia which may be treated by oral administration of sugar. There is a low possibility of an allergic reaction in sensitised individuals.

In case of accidental self-injection seek medical advice immediately and show the package leaflet to the physician.

Pregnancy and lactation:

The safety and efficacy of ProZinc in breeding, pregnant and lactating animals has not been evaluated. Use only according to the benefit-risk assessment by the responsible veterinarian.

In general, insulin requirements during pregnancy and lactation might be different due to a change in the metabolic state. Therefore, close glucose monitoring and veterinary supervision is advised.

Interaction with other medicinal products and other forms of interaction:

Changes in insulin requirements may result from administration of substances which alter glucose tolerance (e.g. corticosteroids and gestagens). Monitoring of glucose concentrations should be performed to adjust the dose accordingly. Similarly, feeding cats with a high protein/low carbohydrate diet and changing the diet of any given cat or dog may alter insulin requirements and necessitate a change of insulin dose.

Overdose (symptoms, emergency procedures, antidotes) :

An overdose of insulin can result in hypoglycaemia in which case immediate administration of a glucose containing solution or gel and/or food is required.

Clinical signs may include hunger, increasing anxiety, unstable locomotion, muscle twitching, stumbling or sinking in the rear legs and disorientation.

Insulin administration should be temporarily stopped and the next dose of insulin adjusted appropriately.

The owner is advised to have glucose containing products (e.g. honey, dextrose gel) in the household.

Major incompatibilities:

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

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

Medicines should not be disposed via wastewater or household waste. Ask your veterinary surgeon 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

Pack size of 1 clear glass vial of 10 ml. The vial is closed with a butyl rubber stopper and sealed with a plastic flip-off cap.

PACKAGE LEAFLET:

ProZinc 40 IU/ml suspension for injection for dogs

• 1. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER AND OF THE MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE, IF DIFFERENT

Marketing authorisation holder and manufacturer responsible for batch release:

Boehringer Ingelheim Vetmedica GmbH

Binger Strasse 173

55216 Ingelhe­im/Rhein

GERMANY

Manufacturer responsible for batch release:

KVP Pharma + Veterinär Produkte GmbH

Projensdorfer Str. 324

24106 Kiel

GERMANY

• 2. NAME OF THE VETERINARY MEDICINAL PRODUCT

ProZinc 40 IU/ml suspension for injection for dogs insulin human

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

Each ml contains:

Active substance:

Insulin human 40 IU as protamine zinc insulin.

One IU (International Unit) corresponds to 0.0347 mg of insulin human.

*produced by recombinant DNA technology

Excipients:

Protamine sulfate 0.466 mg

Zinc oxide 0.088 mg

Phenol 2.5 mg

Cloudy, white, aqueous suspension.

For the treatment of diabetes mellitus in dogs to achieve reduction of hyperglycaemia and improvement of associated clinical signs.

Do not use for the acute management of diabetic ketoacidosis.

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

• 6. ADVERSE REACTIONS

Hypoglycaemic reactions were very commonly reported in a clinical study: 26.5% (44 of 166) of treated dogs. These reactions were generally mild in nature. Clinical signs may include hunger, anxiety, unstable locomotion, muscle twitching, stumbling or sinking in the rear legs and disorientation.

In this case immediate administration of a glucose containing solution or gel and/or food is required.

Insulin administration should be temporarily stopped and the next dose of insulin adjusted appropriately.

Local injection site reactions were very rarely reported and resolved without cessation of therapy.

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).

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

Dogs

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

Subcutaneous use.

If the animal owner is to administer the product, suitable training/advice should be provided by the prescribing veterinarian before using for the first time.

Dosage:

The veterinarian should re-evaluate the animal at appropriate intervals and make adjustments to the treatment protocol, for instance dose and dosing regimen, until adequate glycaemic control has been attained.

Any dose adjustment (i.e. increase of dose) should be in general performed after several days (e.g. 1 week) since full action of insulin requires an equilibration phase. Dose reductions due to observed hypoglycaemia or suspected Somogyi effect (rebound hyperglycaemia) may be of 50% or higher (potentially including a temporary pause of insulin administration).

Once adequate glycaemic control is achieved intermittent glucose monitoring should be performed, especially when there is a change in clinical signs, and further adjustments in the insulin dose might be necessary.

General guidance:

Dosing should be individualised and based on the clinical presentation of each patient. To achieve optimal control of diabetes mellitus, dose adjustments should primarily be based on clinical signs. Blood parameters such as fructosamine, maximum blood glucose and decrease of blood glucose concentrations in blood glucose curves conducted over a sufficient period of time to determine a blood glucose nadir should be used as supporting tools (see also section “Special precautions for use in animals”).

Re-evaluation of clinical signs and laboratory parameters should be performed as recommended by the attending veterinarian.

Initiation

For initiation of treatment, the recommended dose is 0.5 to 1.0 IU insulin/kg bodyweight once daily every morning (approx. every 24 h).

For newly diagnosed diabetic dogs, a starting dose of 0.5 IU insulin/kg once daily is recommended.

Management

Adjustments of insulin dose on a once daily regimen, if required, should generally be done in a conservative and gradual manner, (e.g. up to 25% increase/decrease of the dose per injection).

If insufficient improvement in diabetic control is observed after an adequate dose adjustment period of 4 to

• 6 weeks on once daily treatment, the following options may be considered:

• - Further adjustments of insulin dose on once daily treatment may be necessary; in particular if dogs

undertake increased physical activity, have a change of their usual diet or during concomitant illness.

• - Switching to twice daily dosing: In such cases, it is recommended to reduce the dose per injection by

one third (e.g. 12 kg dog being treated once daily with 12 IU insulin/injection may be switched to 8 IU insulin/injection administered twice daily). The product should be administered in the morning and in the evening, approx. 12 hours apart. Further adjustments of insulin dose on twice daily treatment may be necessary.

Depending on the underlying cause (e.g. dioestrus-induced diabetes mellitus), dogs can develop diabetic remission, although seldom. In those cases sufficient endogenous insulin production will be regained and the exogenous insulin dose will need to be adjusted or ceased.

• 9. ADVICE ON CORRECT ADMINISTRATION

A U-40 syringe must be used.

The suspension should be mixed by gently rolling the vial prior to withdrawing each dose from the vial. Particular care should be taken with regard to the accuracy of dosing.

The veterinary medicinal product should be administered by subcutaneous injection.

The dose should be given concurrently with or immediately after a meal.

Avoid introduction of contamination during use.

After gently rolling the vial, ProZinc suspension has a white, cloudy appearance.

A white ring may be seen in the neck of some vials, but this does not affect the quality of the product. Agglomerates (e.g. clumps) can form in insulin suspensions: do not use the product if visible agglomerates persist after gently rolling the vial.

• 10. WITHDRAWAL PERIOD

Not applicable.

• 11. SPECIAL STORAGE PRECAUTIONS

Keep out of the sight and reach of children.

For unused and broached vials:

Store upright in a refrigerator (2 °C – 8 °C).

Do not freeze.

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

Shelf life after first opening the container: 60 days.

Do not use this veterinary medicinal product after the expiry date which is stated on the carton and the vial

after EXP.

• 12. SPECIAL WARNING(S)

Special warnings for each target species:

Very stressful events, inappetance, concomitant treatment with gestagens and corticosteroids or other concomitant diseases (e.g. gastro-intestinal, infectious or inflammatory or endocrine diseases), might influence insulin effectiveness and therefore the insulin dose may need to be adjusted.

Special precautions for use in animals:

The insulin dose may need to be adjusted or discontinued after resolution of transient diabetic stages (e.g. dioestrus-induced diabetes mellitus, diabetes mellitus secondary to hyperadrenocor­ticism).

After the daily insulin dose is established, monitoring for diabetic control is recommended.

Treatment with insulin can cause hypoglycaemia, for clinical signs and appropriate treatment, please refer to section “Overdose”, below.

In cases where hypoglycaemia is suspected, blood glucose measurements should be taken at the time of occurrence (if possible) as well as shortly prior to the next feeding/injection (where applicable).

Stress and irregular exercise should be avoided. It is recommended to establish a regular twice daily feeding schedule with the owner whether injecting insulin once or twice daily.

In an experimental study in healthy dogs, median time to blood glucose nadir was approximately 16 and 12 hours following administration of 0.5 or 0.8 IU/kg bodyweight, respectively.

Under clinical field conditions in diabetic dogs, time to maximal effect in lowering blood glucose concentrations (i.e. blood glucose nadir) after subcutaneous administration was not observed within 9 hours after last injection in 67.9% of dogs overall. (73.5% on once daily and 59.3% on twice daily administration). Consequently, blood glucose curves should be conducted over a sufficient period to determine a blood glucose nadir.

Special precautions to be taken by the person administering the veterinary medicinal product to animals : Accidental self-injection can provoke clinical signs of hypoglycaemia which may be treated by oral administration of sugar. There is a low possibility of an allergic reaction in sensitised individuals.

In case of accidental self-injection seek medical advice immediately and show the package leaflet to the physician.

Pregnancy and lactation:

The safety and efficacy of ProZinc in breeding, pregnant and lactating animals has not been evaluated.

Use only according to the benefit-risk assessment by the responsible veterinarian.

In general, insulin requirements during pregnancy and lactation might be different due to a change in the metabolic state. Therefore, close glucose monitoring and veterinary supervision is advised.

Interaction with other medicinal products and other forms of interaction:

Changes in insulin requirements may result from administration of substances which alter glucose tolerance (e.g. corticosteroids and gestagens). Monitoring of glucose concentrations should be performed to adjust the dose accordingly. Similarly, changing the diet may alter insulin requirements and necessitate a change of insulin dose.

Overdose (symptoms, emergency procedures, antidotes) :

An overdose of insulin can result in hypoglycaemia in which case immediate administration of a glucose containing solution or gel and/or food is required.

Clinical signs may include hunger, increasing anxiety, unstable locomotion, muscle twitching, stumbling or sinking in the rear legs and disorientation.

Insulin administration should be temporarily stopped and the next dose of insulin adjusted appropriately.

The owner is advised to have glucose containing products (e.g. honey, dextrose gel) in the household.

Major incompatibilities:

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

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

Medicines should not be disposed via wastewater or household waste. Ask your veterinary surgeon 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