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LEO Pharma

LEO Pharma
Cashel Road, Dublin 12,
Telephone: +353 1 490 8924
Fax: +353 1 708 2054
Medical Information e-mail: medical-info.ie@leo-pharma.com
Medical Information Facsimile: +353 1 708 2089
Summary of Product Characteristics last updated on medicines.ie: 02/06/2011
SPC Low Centyl K

When a pharmaceutical company changes an SPC or PIL, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 02/06/2011 and displayed until Current
Reasons for adding or updating:
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   30-Apr-2011
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company



4.3 Contraindications

 

Hypersensitivity to the active substance or any of the excipients.

Severe electrolyte imbalance including hypercalcaemia, hyperchloraemia, hyperkalaemia or any situation which might lead to hyperkalaemia.

Severe renal impairment. 

Severe hepatic impairment.

Addison’s disease.  Established gout.  Ulcer or obstruction of the gastrointestinal tract. 

As with other diuretics, Low Centyl® K should not be administered concurrently to patients taking lithium.


To

4.3 Contraindications

 

  • Known hypersensitivity to the active substance or any of the excipients.
  • Severe electrolyte imbalance including hypercalcaemia, hyperchloraemia,  hyponatraemia, hypokalaemia, hyperkalaemia or any situation which might lead to hyperkalaemia.
  • Severe renal impairment. 
  • Severe hepatic impairment.
  • Addison’s disease. 
  • Established gout  
  • Ulcer or obstruction of the gastrointestinal tract.  
  •  As with other diuretics, Low Centyl® K should not be administered concurrently to patients taking lithium.

    4.4 Special warnings and special precautions for use

     

    Consideration should be given to fluid and electrolyte status to avoid inadequate potassium supplementation or excessive loss of fluid, especially in elderly patients or those on concomitant medication.

     

    Potassium chloride, alone or in combination with other medication may induce ulceration in the gastrointestinal tract in particular the lower oesophagus and small bowel.  This possibility is increased in patients with local disorders of the alimentary tract or on prolonged therapy. Mechanical or functional obstruction of the oesophagus or small bowel may delay passage of the dose form and increase the possibility of local ulceration.  Potassium chloride should be administered with caution to patients in whom passage through the gastro-intestinal tract may be delayed. Treatment should be discontinued if severe nausea, vomiting, or abdominal distress develops.

    Potassium chloride should be administered with considerable care to patients with cardiac disease or conditions predisposing to hyperkalaemia such as renal or adrenocortical insufficiency, acute dehydration, or extensive tissue destruction as occurs with severe burns. Serum potassium should be monitored in patients with cardiac or renal impairment. The tablets must be taken with at least ½ glass of fluid.

     

    Bendroflumethiazide may provoke hyperglycaemia and glycosuria in diabetic and other susceptible patients. In case of reduced glucose tolerance, adjustment of anti-diabetic medicines may be necessary.  Low dose bendroflumethiazide (1.25 mg daily) has been shown to have a much lower effect on blood glucose metabolism than higher doses.

     

    Thiazide diuretics should be used with caution in patients with renal or hepatic impairment and in patients with potential obstruction of the urinary tract.

     

    Thiazides may cause hyperuricaemia and precipitate or aggravate attacks of gout.

     

    Bendroflumethiazide may cause exacerbation or activating of systemic lupus erythematous.

     

    Bendroflumethiazide found in urine by doping test is cause for disqualification of athletes.

    To

    4.4 Special warnings and special precautions for use

     

    Thiazide diuretics should be used with caution in patients with renal or hepatic impairment and in patients with potential obstruction of the urinary tract.

     

    Consideration should be given to fluid and electrolyte status to avoid inadequate potassium supplementation or excessive loss of fluid, especially in elderly patients.

     

    Potassium chloride may induce ulceration in the gastrointestinal tract in particular the small bowel. Potassium chloride should be administered with caution to patients in whom passage through the gastro-intestinal tract may be delayed. Treatment should be discontinued if severe nausea, vomiting, or abdominal distress develops.

     

    Potassium chloride should be administered with considerable care to patients with cardiac disease or conditions predisposing to hyperkalaemia such as renal or adrenocortical insufficiency, acute dehydration, or extensive tissue destruction as occurs with severe burns. Serum potassium should be monitored in patients with cardiac or renal impairment. The tablets must be taken with at least ½ glass of fluid.

     

    Thiazides may provoke hyperglycaemia and glycosuria in diabetic and other susceptible patients. In case of reduced glucose tolerance, adjustment of anti-diabetic medicines may be necessary. 

    Thiazides may cause hyperuricaemia and precipitate or aggravate attacks of gout.

     

    Bendroflumethiazide may cause exacerbation or activating of systemic lupus erythematous.

     

    Bendroflumethiazide found in urine by doping test is cause for disqualification of athletes.

    4.5 Interactions with other medicinal products and other forms of interaction

     

    Due to the content of potassium chloride, concomitant treatment with potassium-sparing diuretics or Angiotensin Converting Enzyme (ACE) inhibitors increases the risk of hyperkalaemia.

     

    Bendroflumethiazide may potentiate the effect of antihypertensive agents and drugs inducing postural hypotension e.g. tricyclic antidepressants.

     

    Bendroflumethiazide may impair control by hypoglycaemic agents in cases of diabetes mellitus (see section 4.4).

     

    Non-steroidal anti-inflammatory drugs (NSAID) inhibit the effect of bendroflumethiazide.

     

    Bendroflumethiazide reduces lithium clearance resulting in high serum levels of lithium, therefore concurrent use is contraindicated (see section 4.3).

     

    Probenecid inhibits the renal tubular secretion of bendroflumethiazide leading to a diminished natriuresis.

     

    Colestyramine and similar drugs reduces the absorption of thiazides.

     

    Co-administration of bendroflumethiazide and other drugs known to cause photosensitivity reactions may increase the severity of these reactions.

     

    Hypokalaemia (which may be induced by bendroflumethiazide) increases the sensitivity to digitalis glycosides and non-depolarising neuromuscular blocking agents.

     

    The urinary excretion of calcium is reduced.

    To

    4.5 Interactions with other medicinal products and other forms of interaction

     

    Due to the content of potassium chloride, concomitant treatment with potassium-sparing diuretics or Angiotensin Converting Enzyme (ACE) inhibitors increases the risk of hyperkalaemia.

     

    Bendroflumethiazide may potentiate the effect of antihypertensive agents and drugs inducing postural hypotension e.g. tricyclic antidepressants.

     

    Bendroflumethiazide may impair control by hypoglycaemic agents in cases of diabetes mellitus (see section 4.4).

     

    Non-steroidal anti-inflammatory drugs (NSAID) inhibit the effect of bendroflumethiazide.

     

    Bendroflumethiazide reduces lithium clearance resulting in high serum levels of lithium, therefore concomitant therapy should be avoided and if used requires close monitoring of serum lithium levels

     

    Probenecid inhibits the renal tubular secretion of bendroflumethiazide leading to a diminished natriuresis.

     

    Cholestyramine and similar drugs reduces the absorption of thiazides.

     

    Co-administration of bendroflumethiazide and other drugs known to cause photosensitivity reactions may increase the severity of these reactions.

     

    Hypokalaemia (which may be induced by bendroflumethiazide) increases the sensitivity to digitalis glycosides and non-depolarising neuromuscular blocking agents.

     

    The urinary excretion of calcium is reduced.

     

    4.8 Undesirable  effects

     

    The most frequent undesirable effects are headache, dizziness, fatigue, postural hypotension and gastrointestinal symptoms. Electrolyte disturbances can occur especially during long term treatment.

     

    Thiazide diuretics may cause a number of metabolic disturbances including reduced glucose tolerance and hyperuricaemia. Muscle cramps, various skin reactions, photosensitivity reactions and erectile dysfunction are less frequent. Vasculitis, blood dyscrasias, mainly affecting the platelets, and acute pancreatitis have been reported.

     

    Based on clinical trial data for Centyl® K undesirable effects occurred in approximately 15% and are dose dependant.

     

    Based on post-marketing data for both Centyl® and Centyl® K, the total ‘reporting rate’ of undesirable effects is very rare being approximately 2:100,000 treatment months.

     

    The undesirable effects are listed by MedDRA SOC and the individual undesirable effects are listed starting with the most frequently reported.

     

    Nervous system disorders

    Headache

    Dizziness

    Vertigo

    Syncope

    Postural hypotension

     

    General disorders and application site conditions

    Fatigue

    Asthenia

    Dry mouth

    Thirst

    Paraesthesia

     

    Gastrointestinal disorders

    Nausea

    Gastric irritation

    Vomiting

    Diarrhoea

    Constipation

     

    Metabolism and nutrition disorder

    Dehydration

    Hyponatraemia

    Hypokalaemia

    Hyperkalaemia

    Gout

    Hyperuricaemia

    Hyperglycaemia

    Diabetes Mellitus

    Metabolic alkalosis

    Hypochloraemia

    Hypocalcaemia

    Hypomagnesaemia

     

    Musculoskeletal and connective tissue disorders

    Myalgia

    Muscle cramp

     

    Skin and subcutaneous tissue reactions

    Rash

    Photosensitivity reactions

    Pruritus

     

    Reproductive system and breast disorder

    Erectile dysfunction

     

    Vascular Disorders

    Hypotension

    Vasculitis

     

    Blood and lymphatic system disorder

    Thrombocytopenia

    Granulocytopenia

    To

    4.8 Undesirable  effects

     

     

    Very common >1/10

    Common >1/100 and <1/10

    Uncommon >1/1,000 and <1/100

    Rare >1/10,000 and <1/1,000

    Very rare <1/10,000

     

    The most frequently reported undesirable effects are headache, dizziness, fatigue, gastrointestinal symptoms including nausea, and postural hypotension/orthostatic reactions. Electrolyte disturbances can occur especially during long term treatment.

     

    Thiazide diuretics may cause a number of metabolic disturbances including reduced glucose tolerance and hyperuricaemia. Muscle cramps, various skin reactions and erectile dysfunction are less frequent.

     

    Based on clinical trial data for Centyl® K, 16% of the patients can be expected to experience an undesirable effect, mainly non-serious and dose-dependent.

     

    Based on post-marketing data for both Centyl® and Centyl® K, the total ‘reporting rate’ of undesirable effects is very rare being approximately 2:100,000 treatment months.

     

    Renal failure and abnormal hepatic function have been reported in post-marketing safety surveillance.

     

    The undesirable effects are listed by MedDRA SOC and the individual undesirable effects are listed starting with the most frequently reported.

     

    • Blood and the lymphatic system disorders

    Frequency unknown*:

    Thrombocytopenia

    Granulocytopenia

     

    • Endocrine disorders

    Uncommon:

    Hyperparathyroidism

     

    • Metabolism and nutrition disorders**

    Very common:

    Hypomagnesaemia

    Hypokalaemia

     

    Uncommon:

    Hyperuricaemia

    Gout

    Increased creatinine

     

    Rare:

    Glucose metabolism disorders

     

    Frequency unknown:

    Hyponatraemia

    Dehydration

    Hyperkalaemia

    Metabolic alkalosis

    Hypochloraemia

    Hypocalcaemia

     

    • Psychiatric disorders

    Uncommon:

    Depression

    Sleep disturbance

     

    • Nervous system disorders

    Common:

    Headache

    Dizziness

     

    Uncommon:

    Vertigo

     

    Rare:

    Syncope

    Dysgeusia

    Ataxia

    Disorientation

     

    • Eye disorders

    Uncommon:

    Eye irritation

     

    Rare:

    Blurred vision

     

    • Cardiac disorders

    Uncommon:

    Palpitations

    Cardiovascular disturbance

     

    • Vascular disorders

    Common:

    Orthostatic reactions

    Hypotension or postural hypotension

     

    Uncommon:

    Flushing

    Cold extremities

     

    Rare:

    Vasodilation

     

    Frequency unknown:

    Vasculitis

     

    • Respiratory, thoracic and mediastinal disorders

    Uncommon:

    Respiratory disorder

    Cough

    Dyspnoea

     

    • Gastrointestinal disorders

    Common:

    Nausea

    Gastrointestinal disturbance

    Dry mouth

    Constipation

     

    Uncommon:

    Diarrhoea

    Abdominal pain

    Flatulence

    Vomiting

     

    Frequency unknown:

    Gastric irritation

     

    • Skin and subcutaneous tissue disorders

    Uncommon:

    Skin disorders

    Rash

    Pruritus

    Sweating

    Urticaria

     

    Rare:

    Face oedema

     

    Frequency unknown:

    Photosensitivity reactions

     

    • Musculoskeletal, connective tissue and bone disorders

    Uncommon:

    Arthralgia

    Muscle cramp

    Pain in the extremities

     

    Not known:

    Myalgia

     

    • Renal and urinary disorders

    Uncommon:

    Polyuria

     

    Rare:

    Bladder tension

     

    • Reproductive system and breast disorders

    Common:

    Erectile dysfunction

     

    • General disorders and administration site conditions

    Common:

    Fatigue/asthenia

     

    Uncommon:

    Pain

    Flu-like symptoms

    Oedema

    Weakness

    Thirst

     

    Rare:

    Paraesthesia

     

    • Investigations

    Uncommon:

    Sputum increased

     

    * Not known: cannot be estimated from the available data

    ** The table includes data on bendroflumethiazide products both with and without potassium. The frequency of hypokalaemia can be expected to be lower in patients receiving Centyl K® .

    Centyl® and Centyl K® have been extensively used in the elderly and no safety information was specifically observed for the elderly.

    5.2 Pharmacokinetic properties

    Bendroflumethiazide is well absorbed from the gastrointestinal tract after oral administration and the absorption is not affected by food.  Plasma protein binding, as with most thiazides, is high.  The plasma half-life averaged 3.9 hours after a 5 mg dose.

    To

    5.2 Pharmacokinetic properties 

    Bendroflumethiazide is well absorbed from the gastrointestinal tract after oral administration and the absorption is not affected by food.  Plasma protein binding, as with most thiazides, is high.  The plasma half-life averaged 3.9 hours after a 5 mg dose. There is evidence that bendroflumethiazide is fairly extensively metabolised; about 30% is excreted unchanged in the urine.

    10. DATE OF REVISION OF THE TEXT

    February 2009

    To

    10. DATE OF REVISION OF THE TEXT

    April 2011

Updated on 01/10/2009 and displayed until 02/06/2011
Reasons for adding or updating:
  • Change to section 3 - Pharmaceutical form
  • Change to section 6.1 - List of excipients
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   16-Feb-2009
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company

Section 3 - Updated as tablet has changed from sugar coated tablet to film coated tablet.
Section 6.1 - List of excipients updated.
Section 10 - Date revised to Feb 2009.
Updated on 12/02/2009 and displayed until 01/10/2009
Reasons for adding or updating:
  • Addition of legal category
  • Correction of spelling/typing errors
Date of revision of text on the SPC:   02/2008
Legal Category:   prescription only

Free-text change information supplied by the pharmaceutical company

Legal category amended to reflect PA
Updated on 07/03/2008 and displayed until 12/02/2009
Reasons for adding or updating:
  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 6.1 - List of excipients
  • Change to section 6.5 - Nature and contents of container
Date of revision of text on the SPC:   02/2008
Legal Category:   prescription only

Free-text change information supplied by the pharmaceutical company

Section 1 - Trade name changed to include strength
Section 2 - Excipeints added
Section 6.1 - Changed to include 'E numbers'
Section 6.5 - Pack size of 100's deleted
Updated on 04/10/2006 and displayed until 07/03/2008
Reasons for adding or updating:
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   08/2005
Legal Category:   prescription only

Free-text change information supplied by the pharmaceutical company

 Section 10 - Date updated
 
 
Updated on 16/08/2005 and displayed until 04/10/2006
Reasons for adding or updating:
  • Change to section 4 - Clinical particulars
  • Change to section 6 - Pharmaceutical particulars
Updated on 05/11/2003 and displayed until 16/08/2005
Reasons for adding or updating:
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 6.4 - Special precautions for storage
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 6.1 - List of excipients
Updated on 26/06/2003 and displayed until 05/11/2003
Reasons for adding or updating:
  • Addition of legal category
Updated on 26/06/2003 and displayed until 26/06/2003
Reasons for adding or updating:
  • New SPC for medicines.ie

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Active Ingredients

 
   Potassium Chloride
   Bendroflumethiazide

Versions

 
02/06/2011 to Current
01/10/2009 to 02/06/2011
12/02/2009 to 01/10/2009
07/03/2008 to 12/02/2009
04/10/2006 to 07/03/2008
16/08/2005 to 04/10/2006
05/11/2003 to 16/08/2005
26/06/2003 to 05/11/2003
26/06/2003 to 26/06/2003
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Registered Address: Franklin House, 140 Pembroke Road, Dublin 4, Ireland
Registered Number: 254776
Tel: (353 1) 6603350 Fax: (353 1) 6686672 Email: info@ipha.ie

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