Twynsta

Posology The recommended dose of this medicinal product is one tablet per day. The maximum recommended dose is one tablet 80 mg telmisartan/10 mg amlodipine per day. This medicinal product is indicated for long term treatment. 5). Add on therapy Twynsta 40 mg/5 mg may be administered in patients whose blood pressure is not adequately controlled on amlodipine 5 mg alone.

e. amlodipine and telmisartan) is recommended before changing to the fixed dose combination. When clinically appropriate, direct change from monotherapy to the fixed combination may be considered. 3 Patients treated with 10 mg amlodipine who experience any dose limiting adverse reactions such as oedema, may be switched to Twynsta 40 mg/5 mg once daily, reducing the dose of amlodipine without reducing the overall expected antihypertensive response.

Replacement therapy Patients receiving telmisartan and amlodipine from separate tablets can instead receive tablets of Twynsta containing the same component doses in one tablet once daily. Elderly (> 65 years) No dose adjustment is necessary for elderly patients.

Little information is available in the very elderly patients. 4). Renal impairment Limited experience is available in patients with severe renal impairment or haemodialysis. 4). No posology adjustment is required for patients with mild to moderate renal impairment.

3). In patients with mild to moderate hepatic impairment telmisartan/amlodipine should be administered with caution. 4). Paediatric population The safety and efficacy of telmisartan/amlodipine in children aged below 18 years have not been established.

No data are available. Method of administration Oral use. Twynsta can be taken with or without food. It is recommended to take Twynsta with some liquid. Twynsta should be kept in the sealed blister due to the hygroscopic property of the tablets.

6).

Summary of the safety profile The most common adverse reactions include dizziness and peripheral oedema. Serious syncope may occur rarely (less than 1 case per 1,000 patients). Adverse reactions previously reported with one of the individual components (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.

Tabulated list of adverse reactions The safety and tolerability of Twynsta has been evaluated in five controlled clinical studies with over 3,500 patients, over 2,500 of whom received telmisartan in combination with amlodipine. Adverse reactions have been ranked under headings of frequency using the following convention: 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), not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. System Organ Class Twynsta Telmisartan Amlodipine Infections and infestations Uncommon upper respiratory tract infection including pharyngitis and sinusitis, urinary tract infection including cystitis Rare cystitis sepsis including fatal outcome1 Blood and lymphatic system disorders: 10 Uncommon anaemia Rare thrombocytopenia, eosinophilia Very rare leukocytopenia, thrombocytopenia Immune system disorders: Rare hypersensitivity, anaphylactic reaction Very rare hypersensitivity Metabolism and nutrition disorders Uncommon hyperkalaemia Rare hypoglycaemia (in diabetic patients), hyponatraemia Very rare hyperglycaemia Psychiatric disorders Uncommon mood change Rare depression, anxiety, insomnia confusion Nervous system disorders Common dizziness Uncommon somnolence, migraine, headache, paraesthesia Rare syncope, peripheral neuropathy, hypoaesthesia, dysgeusia, tremor Very rare extrapyramidal syndrome, hypertonia Eye disorders Common visual disturbance (including diplopia) Uncommon visual impairment Rare visual disturbance 11 Ear and labyrinth disorders Uncommon vertigo tinnitus Cardiac disorders Uncommon bradycardia, palpitations Rare tachycardia Very rare myocardial infarction, arrhythmia, ventricular tachycardia, atrial fibrillation Vascular disorders Uncommon hypotension, orthostatic hypotension, flushing Very rare vasculitis Respiratory, thoracic and mediastinal disorders Uncommon cough dyspnoea dyspnoea, rhinitis Very rare interstitial lung disease3 Gastrointestinal disorder Common altered bowel habits (including diarrhoea and constipation) Uncommon abdominal pain, diarrhoea, nausea flatulence Rare vomiting, gingival hypertrophy, dyspepsia, dry mouth stomach discomfort Very rare pancreatitis, gastritis Hepato-biliary disorders Rare hepatic function abnormal, liver disorder2 Very rare hepatitis, jaundice, hepatic enzyme elevations (mostly consistent with cholestasis) Skin and subcutaneous tissue disorders Uncommon pruritus hyperhidrosis alopecia, purpura, skin discolouration, hyperhidrosis 12 Rare eczema, erythema, rash angioedema (including fatal outcome), drug eruption, toxic skin eruption, urticaria Very rare angioedema, erythema multiforme, urticaria, exfoliative dermatitis, Stevens-Johnson syndrome, photosensitivity Not known toxic epidermal necrolysis Musculoskeletal and connective tissue disorders Common ankle swelling Uncommon arthralgia, muscle spasms (cramps in legs), myalgia Rare back pain, pain in extremity (leg pain) tendon pain (tendinitis like symptoms) Renal and urinary disorders Uncommon renal impairment including acute renal failure micturition disorder, pollakiuria Rare nocturia Reproductive system and breast disorders Uncommon erectile dysfunction gynaecomastia General disorders and administration site condition Common peripheral oedema Uncommon asthenia, chest pain, fatigue, oedema pain Rare malaise influenza-like illness Investigations Uncommon hepatic enzymes increased blood creatinine increased weight increased, weight decreased Rare blood uric acid increased blood creatine phosphokinase 13 increased, haemoglobin decreased 1: the event may be a chance finding or related to a mechanism currently not known 2: most cases of hepatic function abnormal / liver disorder from post-marketing experience with telmisartan occurred in Japanese patients.

Pregnancy Angiotensin II receptor blockers should not be initiated during pregnancy. Unless continued angiotensin II receptor blocker therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy.

6). Hepatic impairment Telmisartan is mostly eliminated in the bile. Patients with biliary obstructive disorders or hepatic insufficiency can be expected to have reduced clearance. The half-life of amlodipine is prolonged and AUC values are higher in patients with impaired liver function; dose recommendations have not been established.

Amlodipine should therefore be initiated at the lower end of the dosing range and caution should be used, both on initial treatment and when increasing the dose. Telmisartan/amlodipine should therefore be used with caution in these patients.

Renovascular hypertension There is an increased risk of severe hypotension and renal insufficiency when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with medicinal products that affect the renin-angiotensin-aldosterone system (RAAS).

Renal impairment and kidney transplantation When telmisartan/amlodipine is used in patients with impaired renal function, a periodic monitoring of potassium and creatinine serum levels is recommended. There is no experience regarding the administration of telmisartan/amlodipine in patients with a recent kidney transplant.

Amlodipine is not dialysable and telmisartan is not removed from blood by haemofiltration and not dialysable. g. vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Such conditions should be corrected before the administration of telmisartan.

If hypotension occurs with telmisartan/amlodipine, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. Treatment can be continued once blood pressure has been stabilised.

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