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Paediatric population
The safety and efficacy of Benetor Plus in children and adolescents below 18 years has not been established. No data are available. Method of administration:
The tablet should be swallowed with a sufficient amount of fluid (e.g. one glass of water). The tablet should not be chewed and should be taken at the same time each day.
4.7 Effects on ability to drive and use machines
Benetor Plus can have minor or moderate influence on the ability to drive and use machines. Dizziness or fatigue may occasionally occur in patients taking antihypertensive therapy, which may impair the ability to react.
4.8 Undesirable effects
The most commonly reported adverse reactions during treatment with Benetor Plus are headache (2.9%), dizziness (1.9%) and fatigue (1.0%).
Hydrochlorothiazide may cause or exacerbate volume depletion which may lead to electrolyte imbalance (see section 4.4).
In clinical trials involving 1155 patients treated with olmesartan medoxomil/hydrochlorothiazide combinations at dosages of 20/12.5 mg or 20/25 mg and 466 patients treated with placebo for periods of up to 21 months, the overall frequency of adverse reactions on olmesartan medoxomil/hydrochlorothiazide combination therapy was similar to that on placebo. Discontinuations due to adverse reactions were also similar for olmesartan medoxomil/hydrochlorothiazide 20/12.5 mg - 20/25 mg (2%) and placebo (3%). The frequency of adverse reactions on olmesartan medoxomil/hydrochlorothiazide overall relative to placebo appeared to be unrelated to age (< 65 years versus ³ 65 years), gender or race although the frequency of dizziness was somewhat increased in patients aged > 75 years.
In addition, the safety of Benetor Plus as a high dose combination was investigated in clinical trials in 3709 patients receiving olmesartan medoxomil in combination with hydrochlorothiazide in the dose strengths 40 mg/12.5 mg and 40 mg/25 mg.
Adverse reactions from Benetor Plus in clinical trials, post-authorisation safety studies and spontaneous reporting are summarised in the below table as well as adverse reactions from the individual components olmesartan medoxomil and hydrochlorothiazide based on the known safety profile of these substances.
The following terminologies have been used in order to classify the occurrence of adverse reactions: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). MedDRA System Organ Class Adverse reactions Frequency Benetor Plus Olmesartan HCTZ Infections and infestations Sialadenitis Rare Blood and lymphatic system disorders Aplastic anaemia Rare Bone marrow depression Rare Haemolytic anaemia Rare Leukopenia Rare Neutropenia/ Agranulocytosis Rare Thrombocytopenia Uncommon Rare Immune system disorders Anaphylactic reactions Uncommon Uncommon Metabolism and nutrition disorders Anorexia Uncommon Glykosuria Common Hypercalcaemia Common Hypercholesterolaemia Uncommon Very common Hyperglycaemia Common Hyperkalaemia Rare Hypertriglyceridaemia Uncommon Common Very common Hyperuricaemia Uncommon Common Very common Hypochloraemia Common Hypochloraemic alcalosis Very rare Hypokaliaemia Common Hypomagnesaemia Common Hyponatriaemia Common Hyperamylasaemia Common Psychiatric disorders Apathy Rare Depression Rare Restlessness Rare Sleep disturbances Rare Nervous system disorders Confusional state Common Convulsions Rare Disturbances in consciousness (such as loss of consciousness) Rare Dizziness/light-headedness Common Common Common Headache Common Common Rare Loss of appetite Uncommon Paraesthesia Rare Postural dizziness Uncommon Somnolence Uncommon Syncope Uncommon Eye disorders Lacrimation decreased Rare Transient blurred vision Rare Worsening of pre-existing myopia Uncommon Xanthopsia Rare Ear and labyrinth disorders Vertigo Uncommon Uncommon Rare Cardiac disorders Angina pectoris Uncommon Cardiac arrhythmias Rare Palpitations Uncommon Vascular disorders Embolism Rare Hypotension Uncommon Rare Necrotising angiitis (vasculitis, cutaneous vasculitis) Rare Orthostatic hypotension Uncommon Uncommon Thrombosis Rare Respiratory, thoracic and mediastinal disorders Bronchitis Common Cough Uncommon Common Dyspnoea Rare Interstitial pneumonia Rare Pharyngitis Common Pulmonary oedema Rare Respiratory distress Uncommon Rhinitis Common Gastrointestinal disorders Abdominal pain Uncommon Common Common Constipation Common Diarrhoea Uncommon Common Common Dyspepsia Uncommon Common Gastric irritation Common Gastroenteritis Common Meteorism Common Nausea Uncommon Common Common Pancreatitis Rare Paralytic ileus Very rare Vomiting Uncommon Uncommon Common Hepato-biliary disorders Acute cholecystitis Rare Jaundice (intrahepatic cholestasic icterus) Rare Skin and subcutaneous tissue disorders Allergic dermatitis Uncommon Anaphylactic skin reactions Rare Angioneurotic oedema Rare Rare Cutaneous lupus erythematodes-like reactions Rare Eczema Uncommon Erythema Uncommon Exanthem Uncommon Photosensitivity reactions Uncommon Pruritus Uncommon Uncommon Purpura Uncommon Rash Uncommon Uncommon Uncommon Reactivation of cutaneous lupus erythematodes Rare Toxic epidermal necrolysis Rare Urticaria Rare Uncommon Uncommon Musculoskeletal and connective tissue disorders Arthralgia Uncommon Arthritis Common Back pain Uncommon Common Muscle spasm Uncommon Rare Muscular weakness Rare Myalgia Uncommon Uncommon Pain in extremity Uncommon Paresis Rare Skeletal pain Common Renal and urinary disorders Acute renal failure Rare Rare Haematuria Uncommon Common Interstitial nephritis Rare Renal insufficiency Rare Renal dysfunction Rare Urinary tract infection Common Reproductive system and breast disorders Erectile dysfunction Uncommon Uncommon General disorders and administration site conditions Asthenia Common Uncommon Chest pain Common Common Face oedema Uncommon Fatigue Common Common Fever Rare Influenza-like symptoms Common Lethargy Rare Malaise Rare Uncommon Pain Common Peripheral oedema Common Common Weakness Uncommon Investigations Alanine aminotransferase increased Uncommon Aspartate aminotransferase increased Uncommon Blood calcium increased Uncommon Blood creatinine increased Uncommon Rare Common Blood creatine phosphokinase increased Common Blood glucose increased Uncommon Blood haematocrit decreased Rare Blood haemoglobin decreased Rare Blood lipids increased Uncommon Blood potassium decreased Uncommon Blood potassium increased Uncommon Blood urea increased Uncommon Common Common Blood urea nitrogen increased Rare Blood uric acid increased Rare Gamma glutamyl transferase increased Uncommon Hepatic enzymes increased Common
MedDRA
System Organ Class
Adverse reactions
Frequency
Benetor Plus
Olmesartan
HCTZ
Infections and infestations
Sialadenitis
Rare
Blood and lymphatic system disorders
Aplastic anaemia
Bone marrow depression
Haemolytic anaemia
Leukopenia
Neutropenia/ Agranulocytosis
Thrombocytopenia
Uncommon
Immune system disorders
Anaphylactic reactions
Metabolism and nutrition disorders
Anorexia
Glykosuria
Common
Hypercalcaemia
Hypercholesterolaemia
Very common
Hyperglycaemia
Hyperkalaemia
Hypertriglyceridaemia
Hyperuricaemia
Hypochloraemia
Hypochloraemic alcalosis
Very rare
Hypokaliaemia
Hypomagnesaemia
Hyponatriaemia
Hyperamylasaemia
Psychiatric disorders
Apathy
Depression
Restlessness
Sleep disturbances
Nervous system disorders
Confusional state
Convulsions
Disturbances in consciousness (such as loss of consciousness)
Dizziness/light-headedness
Headache
Loss of appetite
Paraesthesia
Postural dizziness
Somnolence
Syncope
Eye disorders
Lacrimation decreased
Transient blurred vision
Worsening of pre-existing myopia
Xanthopsia
Ear and labyrinth disorders
Vertigo
Cardiac disorders
Angina pectoris
Cardiac arrhythmias
Palpitations
Vascular disorders
Embolism
Hypotension
Necrotising angiitis (vasculitis, cutaneous vasculitis)
Orthostatic hypotension
Thrombosis
Respiratory, thoracic and mediastinal disorders
Bronchitis
Cough
Dyspnoea
Interstitial pneumonia
Pharyngitis
Pulmonary oedema
Respiratory distress
Rhinitis
Gastrointestinal disorders
Abdominal pain
Constipation
Diarrhoea
Dyspepsia
Gastric irritation
Gastroenteritis
Meteorism
Nausea
Pancreatitis
Paralytic ileus
Vomiting
Hepato-biliary disorders
Acute cholecystitis
Jaundice (intrahepatic cholestasic icterus)
Skin and subcutaneous tissue disorders
Allergic dermatitis
Anaphylactic skin reactions
Angioneurotic oedema
Cutaneous lupus erythematodes-like reactions
Eczema
Erythema
Exanthem
Photosensitivity reactions
Pruritus
Purpura
Rash
Reactivation of cutaneous lupus erythematodes
Toxic epidermal necrolysis
Urticaria
Musculoskeletal and connective tissue disorders
Arthralgia
Arthritis
Back pain
Muscle spasm
Muscular weakness
Myalgia
Pain in extremity
Paresis
Skeletal pain
Renal and urinary disorders
Acute renal failure
Haematuria
Interstitial nephritis
Renal insufficiency
Renal dysfunction
Urinary tract infection
Reproductive system and breast disorders
Erectile dysfunction
General disorders and administration site conditions
Asthenia
Chest pain
Face oedema
Fatigue
Fever
Influenza-like symptoms
Lethargy
Malaise
Pain
Peripheral oedema
Weakness
Investigations
Alanine aminotransferase increased
Aspartate aminotransferase increased
Blood calcium increased
Blood creatinine increased
Blood creatine phosphokinase increased
Blood glucose increased
Blood haematocrit decreased
Blood haemoglobin decreased
Blood lipids increased
Blood potassium decreased
Blood potassium increased
Blood urea increased
Blood urea nitrogen increased
Blood uric acid increased
Gamma glutamyl transferase increased
Hepatic enzymes increased
4.1 Therapeutic indications
Treatment of essential hypertension.
Benetor Plus fixed dose combination is indicated in adult patients whose blood pressure is not adequately controlled on olmesartan medoxomil alone. 4.2 Posology and method of administration Paediatric population The safety and efficacy of Benetor Plus in children and adolescents below 18 years has not been established. No data are available. Method of administration: The tablet should be swallowed with a sufficient amount of fluid (e.g. one glass of water). The tablet should not be chewed and should be taken at the same time each day. 4.7 Effects on ability to drive and use machines Benetor Plus can have minor or moderate influence on the ability to drive and use machines. Dizziness or fatigue may occasionally occur in patients taking antihypertensive therapy, which may impair the ability to react. 4.8 Undesirable effects The most commonly reported adverse reactions during treatment with Benetor Plus are headache (2.9%), dizziness (1.9%) and fatigue (1.0%). Hydrochlorothiazide may cause or exacerbate volume depletion which may lead to electrolyte imbalance (see section 4.4). In clinical trials involving 1155 patients treated with olmesartan medoxomil/hydrochlorothiazide combinations at dosages of 20/12.5 mg or 20/25 mg and 466 patients treated with placebo for periods of up to 21 months, the overall frequency of adverse reactions on olmesartan medoxomil/hydrochlorothiazide combination therapy was similar to that on placebo. Discontinuations due to adverse reactions were also similar for olmesartan medoxomil/hydrochlorothiazide 20/12.5 mg - 20/25 mg (2%) and placebo (3%). The frequency of adverse reactions on olmesartan medoxomil/hydrochlorothiazide overall relative to placebo appeared to be unrelated to age (< 65 years versus ³ 65 years), gender or race although the frequency of dizziness was somewhat increased in patients aged > 75 years. In addition, the safety of Benetor Plus as a high dose combination was investigated in clinical trials in 3709 patients receiving olmesartan medoxomil in combination with hydrochlorothiazide in the dose strengths 40 mg/12.5 mg and 40 mg/25 mg. Adverse reactions from Benetor Plus in clinical trials, post-authorisation safety studies and spontaneous reporting are summarised in the below table as well as adverse reactions from the individual components olmesartan medoxomil and hydrochlorothiazide based on the known safety profile of these substances. The following terminologies have been used in order to classify the occurrence of adverse reactions: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). MedDRA System Organ Class Adverse reactions Frequency Benetor Plus Olmesartan HCTZ Infections and infestations Sialadenitis Rare Blood and lymphatic system disorders Aplastic anaemia Rare Bone marrow depression Rare Haemolytic anaemia Rare Leukopenia Rare Neutropenia/ Agranulocytosis Rare Thrombocytopenia Uncommon Rare Immune system disorders Anaphylactic reactions Uncommon Uncommon Metabolism and nutrition disorders Anorexia Uncommon Glykosuria Common Hypercalcaemia Common Hypercholesterolaemia Uncommon Very common Hyperglycaemia Common Hyperkalaemia Rare Hypertriglyceridaemia Uncommon Common Very common Hyperuricaemia Uncommon Common Very common Hypochloraemia Common Hypochloraemic alcalosis Very rare Hypokaliaemia Common Hypomagnesaemia Common Hyponatriaemia Common Hyperamylasaemia Common Psychiatric disorders Apathy Rare Depression Rare Restlessness Rare Sleep disturbances Rare Nervous system disorders Confusional state Common Convulsions Rare Disturbances in consciousness (such as loss of consciousness) Rare Dizziness/light-headedness Common Common Common Headache Common Common Rare Loss of appetite Uncommon Paraesthesia Rare Postural dizziness Uncommon Somnolence Uncommon Syncope Uncommon Eye disorders Lacrimation decreased Rare Transient blurred vision Rare Worsening of pre-existing myopia Uncommon Xanthopsia Rare Ear and labyrinth disorders Vertigo Uncommon Uncommon Rare Cardiac disorders Angina pectoris Uncommon Cardiac arrhythmias Rare Palpitations Uncommon Vascular disorders Embolism Rare Hypotension Uncommon Rare Necrotising angiitis (vasculitis, cutaneous vasculitis) Rare Orthostatic hypotension Uncommon Uncommon Thrombosis Rare Respiratory, thoracic and mediastinal disorders Bronchitis Common Cough Uncommon Common Dyspnoea Rare Interstitial pneumonia Rare Pharyngitis Common Pulmonary oedema Rare Respiratory distress Uncommon Rhinitis Common Gastrointestinal disorders Abdominal pain Uncommon Common Common Constipation Common Diarrhoea Uncommon Common Common Dyspepsia Uncommon Common Gastric irritation Common Gastroenteritis Common Meteorism Common Nausea Uncommon Common Common Pancreatitis Rare Paralytic ileus Very rare Vomiting Uncommon Uncommon Common Hepato-biliary disorders Acute cholecystitis Rare Jaundice (intrahepatic cholestasic icterus) Rare Skin and subcutaneous tissue disorders Allergic dermatitis Uncommon Anaphylactic skin reactions Rare Angioneurotic oedema Rare Rare Cutaneous lupus erythematodes-like reactions Rare Eczema Uncommon Erythema Uncommon Exanthem Uncommon Photosensitivity reactions Uncommon Pruritus Uncommon Uncommon Purpura Uncommon Rash Uncommon Uncommon Uncommon Reactivation of cutaneous lupus erythematodes Rare Toxic epidermal necrolysis Rare Urticaria Rare Uncommon Uncommon Musculoskeletal and connective tissue disorders Arthralgia Uncommon Arthritis Common Back pain Uncommon Common Muscle spasm Uncommon Rare Muscular weakness Rare Myalgia Uncommon Uncommon Pain in extremity Uncommon Paresis Rare Skeletal pain Common Renal and urinary disorders Acute renal failure Rare Rare Haematuria Uncommon Common Interstitial nephritis Rare Renal insufficiency Rare Renal dysfunction Rare Urinary tract infection Common Reproductive system and breast disorders Erectile dysfunction Uncommon Uncommon General disorders and administration site conditions Asthenia Common Uncommon Chest pain Common Common Face oedema Uncommon Fatigue Common Common Fever Rare Influenza-like symptoms Common Lethargy Rare Malaise Rare Uncommon Pain Common Peripheral oedema Common Common Weakness Uncommon Investigations Alanine aminotransferase increased Uncommon Aspartate aminotransferase increased Uncommon Blood calcium increased Uncommon Blood creatinine increased Uncommon Rare Common Blood creatine phosphokinase increased Common Blood glucose increased Uncommon Blood haematocrit decreased Rare Blood haemoglobin decreased Rare Blood lipids increased Uncommon Blood potassium decreased Uncommon Blood potassium increased Uncommon Blood urea increased Uncommon Common Common Blood urea nitrogen increased Rare Blood uric acid increased Rare Gamma glutamyl transferase increased Uncommon Hepatic enzymes increased Common 10. DATE OF REVISION OF THE TEXT November 2011
4.2 Posology and method of administration
The safety and efficacy of Benetor Plus in children and adolescents below 18 years has not been established. No data are available.
Method of administration:
Benetor Plus can have minor or moderate influence on the ability to drive and use machines. Dizziness or fatigue may occasionally occur in patients taking antihypertensive therapy, which may impair the ability to react. 4.8 Undesirable effects The most commonly reported adverse reactions during treatment with Benetor Plus are headache (2.9%), dizziness (1.9%) and fatigue (1.0%). Hydrochlorothiazide may cause or exacerbate volume depletion which may lead to electrolyte imbalance (see section 4.4). In clinical trials involving 1155 patients treated with olmesartan medoxomil/hydrochlorothiazide combinations at dosages of 20/12.5 mg or 20/25 mg and 466 patients treated with placebo for periods of up to 21 months, the overall frequency of adverse reactions on olmesartan medoxomil/hydrochlorothiazide combination therapy was similar to that on placebo. Discontinuations due to adverse reactions were also similar for olmesartan medoxomil/hydrochlorothiazide 20/12.5 mg - 20/25 mg (2%) and placebo (3%). The frequency of adverse reactions on olmesartan medoxomil/hydrochlorothiazide overall relative to placebo appeared to be unrelated to age (< 65 years versus ³ 65 years), gender or race although the frequency of dizziness was somewhat increased in patients aged > 75 years. In addition, the safety of Benetor Plus as a high dose combination was investigated in clinical trials in 3709 patients receiving olmesartan medoxomil in combination with hydrochlorothiazide in the dose strengths 40 mg/12.5 mg and 40 mg/25 mg. Adverse reactions from Benetor Plus in clinical trials, post-authorisation safety studies and spontaneous reporting are summarised in the below table as well as adverse reactions from the individual components olmesartan medoxomil and hydrochlorothiazide based on the known safety profile of these substances. The following terminologies have been used in order to classify the occurrence of adverse reactions: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). MedDRA System Organ Class Adverse reactions Frequency Benetor Plus Olmesartan HCTZ Infections and infestations Sialadenitis Rare Blood and lymphatic system disorders Aplastic anaemia Rare Bone marrow depression Rare Haemolytic anaemia Rare Leukopenia Rare Neutropenia/ Agranulocytosis Rare Thrombocytopenia Uncommon Rare Immune system disorders Anaphylactic reactions Uncommon Uncommon Metabolism and nutrition disorders Anorexia Uncommon Glykosuria Common Hypercalcaemia Common Hypercholesterolaemia Uncommon Very common Hyperglycaemia Common Hyperkalaemia Rare Hypertriglyceridaemia Uncommon Common Very common Hyperuricaemia Uncommon Common Very common Hypochloraemia Common Hypochloraemic alcalosis Very rare Hypokaliaemia Common Hypomagnesaemia Common Hyponatriaemia Common Hyperamylasaemia Common Psychiatric disorders Apathy Rare Depression Rare Restlessness Rare Sleep disturbances Rare Nervous system disorders Confusional state Common Convulsions Rare Disturbances in consciousness (such as loss of consciousness) Rare Dizziness/light-headedness Common Common Common Headache Common Common Rare Loss of appetite Uncommon Paraesthesia Rare Postural dizziness Uncommon Somnolence Uncommon Syncope Uncommon Eye disorders Lacrimation decreased Rare Transient blurred vision Rare Worsening of pre-existing myopia Uncommon Xanthopsia Rare Ear and labyrinth disorders Vertigo Uncommon Uncommon Rare Cardiac disorders Angina pectoris Uncommon Cardiac arrhythmias Rare Palpitations Uncommon Vascular disorders Embolism Rare Hypotension Uncommon Rare Necrotising angiitis (vasculitis, cutaneous vasculitis) Rare Orthostatic hypotension Uncommon Uncommon Thrombosis Rare Respiratory, thoracic and mediastinal disorders Bronchitis Common Cough Uncommon Common Dyspnoea Rare Interstitial pneumonia Rare Pharyngitis Common Pulmonary oedema Rare Respiratory distress Uncommon Rhinitis Common Gastrointestinal disorders Abdominal pain Uncommon Common Common Constipation Common Diarrhoea Uncommon Common Common Dyspepsia Uncommon Common Gastric irritation Common Gastroenteritis Common Meteorism Common Nausea Uncommon Common Common Pancreatitis Rare Paralytic ileus Very rare Vomiting Uncommon Uncommon Common Hepato-biliary disorders Acute cholecystitis Rare Jaundice (intrahepatic cholestasic icterus) Rare Skin and subcutaneous tissue disorders Allergic dermatitis Uncommon Anaphylactic skin reactions Rare Angioneurotic oedema Rare Rare Cutaneous lupus erythematodes-like reactions Rare Eczema Uncommon Erythema Uncommon Exanthem Uncommon Photosensitivity reactions Uncommon Pruritus Uncommon Uncommon Purpura Uncommon Rash Uncommon Uncommon Uncommon Reactivation of cutaneous lupus erythematodes Rare Toxic epidermal necrolysis Rare Urticaria Rare Uncommon Uncommon Musculoskeletal and connective tissue disorders Arthralgia Uncommon Arthritis Common Back pain Uncommon Common Muscle spasm Uncommon Rare Muscular weakness Rare Myalgia Uncommon Uncommon Pain in extremity Uncommon Paresis Rare Skeletal pain Common Renal and urinary disorders Acute renal failure Rare Rare Haematuria Uncommon Common Interstitial nephritis Rare Renal insufficiency Rare Renal dysfunction Rare Urinary tract infection Common Reproductive system and breast disorders Erectile dysfunction Uncommon Uncommon General disorders and administration site conditions Asthenia Common Uncommon Chest pain Common Common Face oedema Uncommon Fatigue Common Common Fever Rare Influenza-like symptoms Common Lethargy Rare Malaise Rare Uncommon Pain Common Peripheral oedema Common Common Weakness Uncommon Investigations Alanine aminotransferase increased Uncommon Aspartate aminotransferase increased Uncommon Blood calcium increased Uncommon Blood creatinine increased Uncommon Rare Common Blood creatine phosphokinase increased Common Blood glucose increased Uncommon Blood haematocrit decreased Rare Blood haemoglobin decreased Rare Blood lipids increased Uncommon Blood potassium decreased Uncommon Blood potassium increased Uncommon Blood urea increased Uncommon Common Common Blood urea nitrogen increased Rare Blood uric acid increased Rare Gamma glutamyl transferase increased Uncommon Hepatic enzymes increased Common 10. DATE OF REVISION OF THE TEXT November 2011
The following terminologies have been used in order to classify the occurrence of adverse reactions: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).
10. DATE OF REVISION OF THE TEXT November 2011
PA 1595/2/1
PA 1595/2/1-2