Spironolactone Ceva - patient leaflet, side effects, dosage

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• 16. MARKETING AUTHORISATION NUMBER(S)

EU/2/07/074/007

EU/2/07/074/008

EU/2/07/074/009

• 17. MANUFACTU­RER’S BATCH NUMBER

Lot: {number}

• 10. EXPIRY DATE

EXP: {month/year}

Partially used tablets to be used within 7 days.

• 11. SPECIAL STORAGE CONDITIONS

Store partially used tablets in the original blister.

• 12. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PROD WASTE MATERIALS, IF ANY

Disposal: read package leaflet.

• 13. THE WORDS “FOR ANIMAL TREATMENT ONLY” AND CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE, if ap plic able

For animal treatment only – to be supplied only on veterinary

EU/2/07/074/0j3 (3 blisters of 10 tablets)

EU/2/07/074/J04 (18 blisters of 10 tablets)

EU/2/07/G74/J05 (3 blisters of 10 tablets)

EU/2'07/074/006 (18 blisters of 10 tablets)

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGE

Bottle of 30 tablets

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Spironolactone Ceva 10 mg tablets for dogs

Spironolactone Ceva 40 mg tablets for dogs

Spironolactone Ceva 80 mg tablets for dogs spironolactone

PACKAGE LEAFLET

Spironolactone Ceva 10 mg tablets for dogs

Spironolactone Ceva 40 mg tablets for dogs

Spironolactone Ceva 80 mg tablets 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 :

Ceva Santé Animale 10, av. de La Ballastière 33500 Libourne

France

Tel: + 33 (0) 5 57 55 40 40

Fax : + 33 (0) 5 57 55 41 98

Manufacturers for batch release:

Ceva Santé Animale Z.I. Très le Bois 22600 Loudéac Fran­ce

Catalent Germany Schorndorf GmbH Steinbeistrasse 2 D-73614 Schorndorf Germany

• 2. NAME OF THE VETERINARY MEDICINAL PRODUCT

Spironolactone Ceva 10 mg tablets for dogs

Spironolactone Ceva 40 mg tablets for dogs

Spironolactone Ceva 80 mg tablets for dogs

Spironolactone Ceva 10 mg contains 10 mg spironolactone

Spironolactone Ceva 40 mg contains 40 mg spironolactone

Spironolactone Ceva 80 mg contains 80 mg spironolactone

ironolactone Ceva tablets are used in combination with standard therapy (including diuretic support, ere necessary) for the treatment of congestive heart failure caused by valvular regurgitation in dogs.

• 5. CONTRAINDI­CATIONS

Do not use in dogs suffering from hypoadrenocor­ticism, hyperkalaemia or hyponatraemia.

Do not use in conjunction with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in dogs with renal insufficiency (kidney impairment/dys­function).

Do not use during pregnancy or lactation.

Do not use in animals used for, or intended for use in breeding.

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• 6. ADVERSE REACTIONS

A reversible prostatic atrophy (reduction in size) is often observed in entire male dogs.

If you notice any serious effects or other effects not mentioned in this leaflet, please inform your veterinary surgeon.

• 7. TARGET SPECIES

  
  

Dogs.

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

Oral use.

Administer 2 mg/kg of body weight of spironolactone once daily.

Number of tablets

Bodyweight	Spironolacto ne Ceva 10 mg	Spironolactone Ceva 40 mg	Spironolactone Ceva 80 mg
1 to 2.5 kg
2.5 to 5 kg
5 to 10 kg
10 to 15 kg	2^ 3
15 to 20 kg		1
20 to 30 kg		1 + /
30 to 40 kg			1
40 to 50 kg			1 + %
50 to 60 kg			1 + /

• 9. ADVICE ON CORRECT ADMINISTRATION

The veterinary medicinal product should be administered with food. The tablet can either be mixed with a small amount of food offered prior to the main meal, or administered directly into the mouth after feeding. The tablets contain beef flavouring to improve palatability, and a study conducted in healthy dogs showed that they were voluntarily and fully consumed 75% of the time.

• 10. WITHDRAWAL PERIOD

  
  

• 11. SPECIAL STORAGE PRECAUTIONS

Keep out of the sight and reach of children.

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

Use within 2 months after first opening the bottle.

Partially used tablets should be stored in the original bottle.

Do not use after the expiry date which is stated on the carton after EXP.

• 12. SPECIAL WARNING(S)

Special precautions for use in animals

Kidney function and serum potassium levels should be evaluated before initiating combined treatment with spironolactone and Angiotensin Converting Enzyme (ACE) inhibitors. Unlike in humans, an increased incidence of hyperkalaemia (raised blood potassium levels) was not observed in studies in dogs with this combination. However, in dogs with renal impairment regular monitoring of renal function and serum potassium levels is recommended as there may be an increased risk of hyperkalaemia.

Dogs treated concomitantly with spironolactone and NSAIDs should be correctly hydrated.

Monitoring of their renal function and plasma potassium levels is recommended before initiation and during treatment with combined therapy (see section „Contraindica­tions“).

As spironolactone has an antiandrogenic effect (acts against male hormones), it is not recommended to administer the veterinary medicinal product to growing dogs.

As spironolactone undergoes extensive hepatic (liver) biotransformation, care should be taken when using the veterinary medicinal product in dogs with liver dysfunction.

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

May cause skin sensitisation: people with known hypersensitivity to spironolactone should avoid contact with the veterinary medicinal product. Wash hands after use.

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

Use during pregnancy, lactation or lay

Do not use during pregnancy and lactation, laboratory studies in species (rat, mouse, rabbit and monkey) have shown evidence of developmental toxicity.

Interactions

Furosemide and pimobendan have been used together with Spironolactone Ceva in dogs with heart failure without any clinical evidence of adverse reactions.

Spironolactone decreases digoxin elimination and hence raises digoxin plasma concentration. As the therapeutic index for digoxin is very narrow, it is advisable to monitor closely dogs receiving both digoxin and spironolactone.

The administration of either deoxycorticosterone or NSAIDs with spironolactone may lead to a moderate reduction of the natriuretic effects (reduction of urinary sodium excretion) of spironolactone. Concomitant administration of spironolactone with ACE-inhibitors and other potassium-sparing drugs (as angiotensin receptor blockers, ß-blockers, calcium channels blockers, etc) may potentially lead to hyperkalaemia (see section „Special precautions for use in animals“).

Spironolactone may cause both induction and inhibition of cytochrome P450 enzymes and could therefore affect the metabolism of other drugs utilizing these metabolic pathways.

Overdose

After administration of up to 10 times the recommended dose (20 mg/kg) to healthy dogs, dosedependent adverse effects were noted (see section „Adverse Reactions“).

In case of an accidental massive ingestion by the dog, there is no specific antidote or treatment. It is therefore recommended to induce vomiting, gastric lavage (depending on risk assessment) and monitor electrolytes. Symptomatic treatment, e.g., fluid therapy, should be provided.

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

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 product is available on the website of the European Medicines Agency (EMA)

• 15. OTHER INFORMATION

  
  

Pack size:

Bottle containing 30 tablets packed in a cardboard box.

Not all pack sizes may be marketed.

Pharmacodynamic properties

Spironolactone and its active metabolites (including 7a-thiomethyl-spironolactone and canrenone) act as specific antagonists of aldosterone, and exert their effects by binding competitively to the mineralocorticoid receptor located in the kidneys, heart and blood vessels.

Spironolactone is a natriuretic drug (historically described as a soft diuretic). In the kidney, spironolactone inhibits the aldosterone-induced sodium retention leading to increase in sodium and subsequently water excretion, and potassium retention.

The renal effects of spironolactone and its metabolites lead to a decrease in extracellular volume and consequently in a decrease of cardiac preload and left atrial pressure. The result is an improvement in heart function.

In the cardiovascular system, spironolactone prevents the detrimental effects of aldosterone. Although the precise mechanism of action is not yet clearly defined, aldosterone promotes myocardial fibrosis, myocardial and vascular remodelling and endothelial dysfunction.

In experimental models in dogs, it was shown that long term therapy with an aldosterone antagonist prevents progressive left ventricle dysfunction and attenuates left ventricle remodelling in dogs with chronic heart failure.

In a clinical study investigating the survival time in dogs with congestive heart failure, there was a 65% reduction in the relative risk of mortality at 15 months in dogs treated with spironolactone in combination with standard therapy compared to dogs treated with standard therapy alone. (Mortality was classified as death or euthanasia due to heart failure).

When used in combination with ACE-inhibitors, spironolactone may counteract the effects of “aldosterone escape”.

A slight increase in aldosterone blood levels may be observed in animals on treatment. This is thought to be due to activation of feedback mechanisms without adverse clinical consequence.

There may be a dose related hypertrophy of the adrenal zona glomerulosa at high dose rates.

pironolactone Ceva tablets are used in combination with standard therapy (including diuretic support, here necessary) for the treatment of congestive heart failure caused by valvular regurgitation in dogs.

• 5. CONTRAINDI­CATIONS

Do not use in dogs suffering from hypoadrenocor­ticism, hyperkalaemia or hyponatraemia.

Do not use in conjunction with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in dogs with renal insufficiency (kidney impairment/dys­function).

Do not use during pregnancy or lactation.

Do not use in animals used for, or intended for use in breeding.

. (

• 6. ADVERSE REACTIONS

A reversible prostatic atrophy (reduction in size) is often observed in entire male dogs.

If you notice any serious effects or other effects not mentioned in this leaflet, please inform your veterinary surgeon.

• 7. TARGET SPECIES

  
  

Dogs.

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

Oral use.

Administer 2 mg/kg of body weight of spironolactone once daily.

Number of # tablets

Bodyweight	Spironolacto ne Ceva 10 mg	Spironolactone Ceva 40 mg	Spironolactone Ceva 80 mg
1 to 2.5 kg
2.5 to 5 kg
5 to 10 kg
10 to 15 kg	2^ 3
15 to 20 kg		1
20 to 30 kg		1 + /
30 to 40 kg			1
40 to 50 kg			1 + %
50 to 60 kg			1 + /

• 9. ADVICE ON CORRECT ADMINISTRATION

The veterinary medicinal product should be administered with food. The tablet can either be mixed with a small amount of food offered prior to the main meal, or administered directly into the mouth after feeding.

• 10. WITHDRAWAL PERIOD

  bined treatment

  
  

• 11. SPECIAL STORAGE PRECAUTIONS

Keep out of the sight and reach of children.

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

Partially used tablets should be stored in the original blister and used within 7 days.

Do not use after the expiry date which is stated on the carton and blister label after EXP.

• 12. SPECIAL WARNING(S)

Special precautions for use in animals

Kidney function and serum potassium levels should be evaluated before initiati with spironolactone and Angiotensin Converting Enzyme (ACE) inhibitors. Unlike in humans, an increased incidence of hyperkalaemia (raised blood potassium levels) was not observed in studies in dogs with this combination. However, in dogs with renal impairment regular monitoring of renal function and serum potassium levels is recommended as there may be an increased risk of hyperkalaemia.

Dogs treated concomitantly with spironolactone and NSAIDs should be correctly hydrated.

Monitoring of their renal function and plasma potassium levels is recommended before initiation and during treatment with combined therapy (see section „Contraindica­tions“).

As spironolactone has an antiandrogenic effect (acts against male hormones), it is not recommended to administer the veterinary medicinal product to growing dogs.

As spironolactone undergoes extensive hepatic (liver) biotransformation, care should be taken when using the veterinary medicinal product in dogs with liver dysfunction.

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

May cause skin sensitisation: people with known hypersensitivity to spironolactone should avoid contact with the veterinary medicinal product. Wash hands after use.

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

Use during pregnancy, lactation or lay

Do not use during pregnancy and lactation, laboratory studies in species (rat, mouse, rabbit and monkey) have shown evidence of developmental toxicity.

Interactions

Furosemide and pimobendan have been used together with Spironolactone Ceva in dogs with heart failure without any clinical evidence of adverse reactions.

Spironolactone decreases digoxin elimination and hence raises digoxin plasma concentration. As the therapeutic index for digoxin is very narrow, it is advisable to monitor closely dogs receiving both digoxin and spironolactone.

The administration of either deoxycorticosterone or NSAIDs with spironolactone may lead to a moderate reduction of the natriuretic effects (reduction of urinary sodium excretion) of spironolactone. Concomitant administration of spironolactone with ACE-inhibitors and other potassium-sparing drugs (as angiotensin receptor blockers, ß-blockers, calcium channels blockers, etc) may potentially lead to hyperkalaemia (see section „Special precautions for use in animals“).

Spironolactone may cause both induction and inhibition of cytochrome P450 enzymes and could therefore affect the metabolism of other drugs utilizing these metabolic pathways.

Overdose

After administration of up to 10 times the recommended dose (20 mg/kg) to healthy dogs, dosedependent adverse effects were noted (see section „Adverse Reactions“).

In case of an accidental massive ingestion by the dog, there is no specific antidote or treatment. It is therefore recommended to induce vomiting, gastric lavage (depending on risk assessment) and monitor electrolytes. Symptomatic treatment, e.g., fluid therapy, should be provided.

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

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 product is available on the website of the European Medicines Agency (EMA)

• 15. OTHER INFORMATION