Fixed Dose Combination: In clinical trials involving 2341 patients treated with olmesartan medoxomil/hydrochlorothiazide combinations and 466 patients treated with placebo for periods of up to 21 months, the overall frequency of adverse events on olmesartan medoxomil/hydrochlorothiazide combination therapy was similar to that on placebo. Discontinuations due to adverse events were also similar for olmesartan medoxomil/hydrochlorothiazide (2%) and placebo (3%). The frequency of adverse events on olmesartan medoxomil/hydrochlorothiazide relative to placebo appeared to be unrelated to age (<65 years vs ≥65 years), gender or race.
The only adverse event which was statistically significantly more frequent on olmesartan medoxomil/hydrochlorothiazide than on placebo was dizziness (3% vs 1%). The incidence of dizziness was not dose related.
Adverse events of potential clinical relevance are listed below by system organ class. Frequencies are defined as: Common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare ≥1/10,000).
Metabolism and Nutrition Disorders: Uncommon: Hyperuricaemia, hypertriglyceridaemia.
Nervous System Disorders: Common: Dizziness. Uncommon: Syncope.
Cardiac Disorders: Uncommon: Palpitations.
Vascular Disorders: Uncommon: Hypotension, orthostatic hypotension.
Skin and Subcutaneous Tissue Disorders: Uncommon: Rash, eczema.
General Disorders: Uncommon: Weakness.
Investigations: Uncommon: Decreased blood potassium, increased blood potassium, increased blood urea.
Laboratory Findings: In clinical trials, clinically important changes in standard laboratory parameters were rarely associated with olmesartan medoxomil/hydrochlorothiazide. Minor increases in mean uric acid, blood urea nitrogen and creatinine values, and minor decreases in mean haemoglobin and haematocrit values were observed during treatment with olmesartan medoxomil/hydrochlorothiazide.
Additional Information on Individual Components: Undesirable effects previously reported with either of the individual components may be potential undesirable effects with Olmetec Plus, even if not observed in clinical trials with Olmetec Plus.
Olmesartan Medoxomil: Market Experience: The following adverse reactions have been reported in post-marketing experience. They are listed by system organ class and ranked under headings of frequency using the following convention: Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000) including isolated reports: Blood and Lymphatic System Disorders: Very Rare: Thrombocytopenia.
Nervous System Disorders: Very Rare: Dizziness, headache.
Respiratory, Thoracic and Mediastinal Disorders: Very Rare: Cough.
Gastrointestinal Disorders: Very Rare: Abdominal pain, nausea, vomiting, diarrhea.
Skin and Subcutaneous Tissue Disorders: Pruritus, exanthem, rash, allergic conditions eg, angioneurotic oedema, allergic dermatitis, face oedema and urticaria, anaphylactic reaction.
Musculoskeletal and Connective Tissue Disorders: Very Rare: Muscle cramp, myalgia.
Renal and Urinary Disorders: Acute renal failure and renal insufficiency (see following texts under Investigations).
General Disorders and Administration Site: Very Rare: Asthenic conditions eg, asthenia, fatigue, lethargy, malaise, peripheral oedema.
Investigations: Very Rare: Abnormal renal function tests eg, increased blood creatinine and increased blood urea, increased hepatic enzymes.
Metabolic and Nutritional Disorders: Very Rare: Hyperkalaemia.
Clinical Trials: In double-blind, placebo-controlled monotherapy studies, the overall incidence of treatment-emergent adverse events was 42.4% on olmesartan medoxomil and 40.9% on placebo.
In placebo-controlled monotherapy studies, the only adverse drug reaction that was unequivocally related to treatment was dizziness (2.5% incidence on olmesartan medoxomil and 0.9% on placebo).
In long-term (2-year) treatment, the incidence of withdrawals due to adverse events on olmesartan medoxomil 10-20 mg once daily was 3.7%.
The following adverse events have been reported across all clinical trials with olmesartan medoxomil (including trials with active as well as placebo control), irrespective of causality or incidence relative to placebo. They are listed by body system and ranked under headings of frequency using the conventions previously mentioned: Central Nervous System Disorders: Common: Dizziness. Uncommon: Vertigo.
Cardiovascular Disorders: Rare: Hypotension. Uncommon: Vertigo.
Respiratory System Disorders: Common: Bronchitis, cough, pharyngitis, rhinitis. Gastrointestinal Disorders: Common: Abdominal pain, diarrhoea, dyspepsia, gastroenteritis, nausea.
Skin and Appendages Disorders: Uncommon: Rash.
Musculoskeletal Disorders: Common: Arthritis, back pain, skeletal pain.
Urinary System Disorders: Common: Haematuria, urinary tract infection.
General Disorders: Common: Chest pain, fatigue, influenza-like symptoms, peripheral oedema, pain.
Laboratory Findings: In placebo-controlled monotherapy studies the incidence was somewhat higher on olmesartan medoxomil compared with placebo for hypertriglyceridaemia (2% vs 1.1%) and for raised creatine phosphokinase (1.3% vs 0.7%).
Laboratory adverse events reported across all clinical trials with olmesartan medoxomil (including trials without a placebo control), irrespective of causality or incidence relative to placebo, included: Metabolic and Nutritional Disorders: Common: Increased creatine phosphokinase, hypertriglyceridaemia, hyperuricaemia; Rare: Hyperkalaemia.
Liver and Biliary Disorders: Common: Liver enzyme elevations.
Hydrochlorothiazide: Hydrochlorothiazide may cause or exacerbate volume depletion, which may lead to electrolyte imbalance (see Precautions).
Adverse events reported with the use of hydrochlorothiazide alone include: Gastrointestinal System Disorders: Anorexia, loss of appetite, gastric irritation, diarrhoea, constipation, sialadenitis, pancreatitis.
Hepatobiliary Disorders: Jaundice (intrahepatic cholestatic jaundice).
Eye Disorders: Xanthopsia, transient blurred vision.
Blood and Lymphatic System Disorders: Leukopenia, neutropenia/agranulocytosis, thrombocytopenia, aplastic anaemia, haemolytic anaemia, bone marrow depression.
Skin and Subcutaneous Tissue Disorders: Photosensitivity reactions, rash, cutaneous lupus erythematosus-like reactions, reactivation of cutaneous lupus, erythematosus, urticaria, necrotising angiitis (vasculitis, cutaneous vasculitis), anaphylactic reactions, toxic epidermal necrolysis.
General Disorders: Fever.
Respiratory System Disorders: Respiratory distress (including pneumonitis and pulmonary oedema).
Renal and Urinary Disorders: Renal dysfunction, interstitial nephritis.
Musculoskeletal Disorders: Muscle spasm, weakness.
Nervous System Disorders: Restlessness, lightheadedness, vertigo, paraesthesiae.
Vascular Disorders: Postural hypotension.
Cardiac Disorders: Cardiac arrhythmias.
Psychiatric Disorders: Sleep disturbances, depression.
Laboratory Findings: Hyperglycaemia, glycosuria, hyperuricaemia, electrolyte imbalance (including hyponatraemia and hypokalaemia), increases in cholesterol and triglycerides.