Summary of the safety profile: The safety and tolerability of TWYNSTA has been evaluated in five controlled clinical studies with over 3500 patients, over 2500 of whom received telmisartan in combination with amlodipine.
No additional adverse reactions were identified in clinical trials with the combination telmisartan plus amlodipine compared to the adverse reactions of the monocomponents. Peripheral oedema, a recognised dose dependent adverse reaction of the monocomponent amlodipine, was generally observed at a lower incidence in patients who received the telmisartan/amlodipine combination than in those who received amlodipine alone. Adverse reactions previously reported with one of the monocomponents (telmisartan or amlodipine) may be potential adverse reactions with TWYNSTA as well, even if not observed in clinical trials or during the post-marketing period. Therefore in addition to the reported adverse reactions during the TWYNSTA development programme all adverse reactions reported in patients who received telmisartan or amlodipine monotherapy, have been listed for TWYNSTA.
Tabulated summary of adverse reactions: The following adverse reactions derived from the use of the telmisartan/amlodipine combination or the use of the monocomponents (telmisartan or amlodipine) in clinical trials or from post-marketing experience are shown as follows classified by MedDRA System organ class and MedDRA Preferred terms.
Infections and infestations: Cystitis.
Psychiatric disorders: Depression, anxiety, insomnia.
Nervous system disorders: Dizziness, somnolence, migraine, headache, paraesthesia, syncope, neuropathy peripheral, hypoaesthesia, dysgeusia, tremor.
Ear and labyrinth disorders: Vertigo.
Cardiac disorders: Bradycardia, palpitations.
Vascular disorders: Hypotension, orthostatic hypotension, flushing.
Respiratory, thoracic and mediastinal disorders: Cough.
Gastrointestinal disorders: Abdominal pain, diarrhoea, nausea, vomiting, gingival hypertrophy, dyspepsia, dry mouth.
Skin and subcutaneous tissue disorders: Pruritus, eczema, erythema, rash.
Musculoskeletal and connective tissue disorders: Arthralgia, muscle spasms (cramps in legs), myalgia, back pain, pain in extremity (leg pain).
Renal and urinary disorders: Nocturia.
Reproductive system and breast disorders: Erectile dysfunction.
General disorders: Oedema Peripheral, asthenia (weakness), chest pain, fatigue, oedema, malaise.
Investigations: Hepatic enzyme increased, blood uric acid increased.
Telmisartan: Infections and infestations: Urinary tract infection, upper respiratory tract infection, sepsis including fatal outcome.
Blood and lymphatic system disorders: Anaemia, eosinophilia, thrombocytopenia.
Immune system disorders: Anaphylactic reaction, hypersensitivity.
Metabolism and nutrition disorders: Hyperkalaemia, hypoglycaemia (in diabetic patients).
Eye disorders: Visual impairment.
Cardiac disorders: Tachycardia.
Respiratory, thoracic and mediastinal disorders: Dyspnoea.
Gastrointestinal disorders: Flatulence, abdominal discomfort.
Hepatobiliary disorders: Hepatic function abnormal/liver disorder*.
*Most cases of hepatic function abnormal/liver disorder from post-marketing experience with telmisartan occurred in patients in Japan, who are more likely to experience these adverse reactions.
Skin and subcutaneous tissue disorders: Angioedema (with fatal outcome), hyperhidrosis, urticaria, drug eruption, toxic skin eruption.
Musculoskeletal and connective tissue disorders: Tendon pain (tendonitis like symptoms).
Renal and urinary disorders: Renal impairment including renal impairment (including acute kidney injury) (see also Precautions).
General disorders: Influenza like illness.
Investigations: Blood creatinine increased, haemoglobin decreased, blood creatine phosphokinase (CPK) increased.
Amlodipine: Blood and lymphatic system disorders: Leukopenia, thrombocytopenia.
Immune system disorders: Hypersensitivity.
Metabolism and nutrition disorders: Hyperglycaemia.
Psychiatric disorders: Mood altered, confusional state.
Nervous system disorders: Extrapyramidal disorder, Hypertonia.
Eye disorders: Visual impairment, Diplopia.
Ear and labyrinth disorders: Tinnitus.
Cardiac disorders: Myocardial infarction, arrhythmia, ventricular tachycardia, atrial fibrillation.
Vascular disorders: Vasculitis.
Respiratory, thoracic and mediastinal disorders: Dyspnoea, rhinitis.
Gastrointestinal disorders: Change of bowel habit, pancreatitis, gastritis, Constipation.
Hepatobiliary disorders: Hepatitis, jaundice, hepatic enzyme increase (mostly consistent with cholestasis).
Skin and subcutaneous tissue disorders: Hyperhidrosis, angioedema, urticaria, alopecia, purpura, skin discolouration, erythema multiforme, dermatitis exfoliative, Stevens-Johnson syndrome, photosensitivity reaction, Toxic epidermal necrolysis.
Renal and urinary disorders: Micturition disorder, pollakiuria.
Reproductive system and breast disorders: Gynaecomastia.
General disorders: Pain, weight increased, weight decreased.
Musculoskeletal and connective tissue disorders: Joint Swelling.