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2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 2.5 mg of Bendroflumethiazide and 573 mg of Potassium Chloride.
For full list of excipients, see section 6.1
To 2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 2.5 mg of bendroflumethiazide and 573 mg of potassium chloride.
3. PHARMACEUTICAL FORM
Modified release tablet.
Green, filmcoated, oval tablets.
To 3. PHARMACEUTICAL FORM
Green, film-coated, oval tablets.
4.3 Contraindications
Hypersensitivity to the active ingredient or to 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, Centyl® K should not be administered concurrently to patients taking lithium. To 4.3 Contraindications Known hypersensitivity to the active ingredient or to 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, 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 glucosuria 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 glucosuria 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 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 effect 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: Pollakisuria 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 bendroflumethizide 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. 10. DATE OF (PARTIAL) REVISION OF THE TEXT February 2009 To 10. DATE OF (PARTIAL) REVISION OF THE TEXT April 2011.
To
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 glucosuria 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.
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.
Thiazides may provoke hyperglycaemia and glucosuria in diabetic and other susceptible patients. In case of reduced glucose tolerance, adjustment of anti-diabetic medicines may be necessary.
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
Bendroflumethiazide reduces lithium clearance resulting in high serum levels of lithium, therefore concomitant therapy requires close monitoring of serum lithium levels.
Cholestyramine and similar drugs reduces the absorption of thiazides.
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 effect 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: Pollakisuria 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 bendroflumethizide 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. 10. DATE OF (PARTIAL) REVISION OF THE TEXT February 2009 To 10. DATE OF (PARTIAL) REVISION OF THE TEXT April 2011.
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 effect 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: Pollakisuria 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 bendroflumethizide 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. 10. DATE OF (PARTIAL) REVISION OF THE TEXT February 2009 To 10. DATE OF (PARTIAL) REVISION OF THE TEXT April 2011.
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.
Frequency unknown*:
Granulocytopenia
Uncommon:
Hyperparathyroidism
Very common:
Hyperuricaemia
Gout
Increased creatinine
Rare:
Glucose metabolism disorders
Frequency unknown:
Hyperkalaemia
Depression
Sleep disturbance
Common:
Headache
Dizziness
Vertigo
Syncope
Dysgeusia
Ataxia
Disorientation
Eye irritation
Blurred vision
Palpitations
Cardiovascular disturbance
Orthostatic reactions
Hypotension or postural hypotension
Flushing
Cold extremities
Vasodilation
Vasculitis
Respiratory disorder
Cough
Dyspnoea
Nausea
Gastrointestinal disturbance
Dry mouth
Abdominal pain
Flatulence
Skin disorders
Rash
Pruritus
Sweating
Urticaria
Face oedema
Photosensitivity reactions
Arthralgia
Muscle cramp
Pain in the extremities
Not known:
Myalgia
Pollakisuria
Bladder tension
Erectile dysfunction
Fatigue/asthenia
Pain
Flu-like symptoms
Oedema
Weakness
Thirst
Paraesthesia
Sputum increased
* Not known: cannot be estimated from the available data
** The table includes data on bendroflumethizide 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. 10. DATE OF (PARTIAL) REVISION OF THE TEXT
February 2009
To 10. DATE OF (PARTIAL) REVISION OF THE TEXT
April 2011.