Kez 20 mg. Solution.

Replacement therapy: Treatment of essential hypertension in patients who have been stabilised on the two component medicines used at the same dose. Add on therapy: TESAMOLOT TM is indicated in patients whose blood pressure is not adequately controlled on amlodipine monotherapy.

Posology The recommended dose is one tablet once daily. Replacement therapy: Patients taking telmisartan and amlodipine as separate tablets can instead take TESAMOLOT TM containing the same component doses in one tablet once daily. Add on therapy: TESAMOLOT TM may be administered in patients whose blood pressure is not adequately controlled amlodipine alone. The usual starting TESAMOLOT TM is 40/5 mg once daily. If additional blood pressure lowering is needed after at least 2 weeks of therapy, the dose may be titrated up to a maximum of 80/10 mg once daily. Special populations: Renal impairment: No dosage adjustment is required for patients with mild to moderate renal impairment (see Section 4.4). Amlodipine and telmisartan are not dialysable. Hepatic impairment In patients with mild to moderate hepatic impairment telmisartan/amlodipine should be administered with caution. For telmisartan the dose should not exceed 40/5 mg or 40/10 mg once daily. TESAMOLOT TM is contraindicated in patients with severe hepatic impairment (see Section 4.3). Elderly (> 65 years) No dose adjustment is necessary for elderly patients. Children and adolescents (< 18 years old) TESAMOLOT TM is not recommended in children aged below 18 years, due to a lack of safety and efficacy studies. Method of administration TESAMOLOT TM is for oral administration. It is recommended to take TESAMOLOT TM with some liquid, with or without food. Administration of amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability may be increased in some patients resulting in increased blood pressure lowering effects (see Section 4.5).

TESAMOLOT TM is contraindicated in: u2022 Patients who have a known hypersensitivity to telmisartan and/ or amlodipine or to the other excipients of TESAMOLOT TM (see Section 6.1). u2022 Patients who have a hypersensitivity to dihydropyridine derivatives. u2022 Patients with a history of angioedema related to previous therapy with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs): These patients must never again be given these medicines. u2022 Patients being treated concomitantly with fluoroquinolones and Angiotensin-converting enzyme (ACE) inhibitors/Angiotensin receptor blockers (ARBs) is contraindicated in patients with moderate to severe renal impairment (Creatinine Clearance u2264 30 mL/min) and in elderly patients. u2022 Patients with hereditary or idiopathic angioedema. u2022 Patients with Hypertrophic Obstructive Cardiomyopathy (HOCM). u2022 Patients with severe renal function impairment (creatinine clearance less than 30 ml/min). u2022 Patients with bilateral renal artery stenosis. u2022 Patients with a single kidney with renal artery stenosis. u2022 Patients with aortic stenosis. u2022 Patients with concomitant therapy with potassium sparing diuretics such as spironolactone, triamterene and amiloride (see Section 4.4). u2022 Patients on lithium therapy: concomitant administration with TESAMOLOT TM may lead to toxic blood concentrations of lithium (see Section 4.5). u2022 Patients being treated concomitantly with aliskiren-containing medicines (see Sections 4.4 & 4.5). u2022 Patients with porphyria. u2022 Patients with biliary obstructive disorders. u2022 Patients with severe hepatic impairment (see Section 4.4). u2022 Patients suffering from cardiogenic shock. u2022 Pregnancy and lactation [women who are or may potentially be pregnant and women who are or planning to breast feed (see Section 4.6)].

Should a woman become pregnant while receiving TESAMOLOT TM, the treatment should be stopped promptly and switched to a different class of antihypertensive medicine. (See Sections 4.3 & 4.6). Pregnancy: TESAMOLOT TM should not be initiated during pregnancy (see Section 4.3). Patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with TESAMOLOT TM should be stopped immediately, and, if appropriate, alternative therapy should be started (see Section 4.6). Dual blockade of the renin-angiotensin-aldosterone system (RAAS): There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is contraindicated. ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy. Hepatic impairment: Telmisartan (ingredient of TESAMOLOT TM is mostly eliminated in the bile. Patients with biliary obstructive disorders or hepatic insufficiency can be expected to have reduced clearance. Furthermore, as with all calcium antagonists, amlodipineu2019s (ingredient of TESAMOLOT TM) half-life is prolonged in patients with impaired liver function and dose recommendations have not been established. TESAMOLOT TM should therefore be used with caution in patients with mild to moderate impairment of liver function and should not be used in patients with severe liver impairment (see Section 4.3). 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 medicines that affect the renin-angiotensin-aldosterone system (RAAS) (see Section 4.3). Renal impairment and kidney transplant: When TESAMOLOT TM 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 TESAMOLOT TM in patients with a recent kidney transplant. Telmisartan and amlodipine are not dialysable. Intravascular hypovolaemia: Symptomatic hypotension, especially after the first dose, may occur in patients who are volume and/or sodium depleted by e.g., vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Such conditions should be corrected before the administration of TESAMOLOT TM. If hypotension occurs with TESAMOLOT TM, 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. Other conditions with stimulation of the renin-angiotensin-aldosterone system: In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with medicines that affect this system has been associated with acute hypotension, hyperazotaemia, oliguria, or rarely acute renal failure. Primary aldosteronism: Patients with primary aldosteronism generally will not respond to antihypertensive medicines acting through inhibition of the renin-angiotensin system. Therefore, the use of TESAMOLOT TM is not recommended. Concomitant use of fluoroquinolones: Concomitant use of fluoroquinolones and Angiotensin-converting enzyme (ACE) inhibitors/Angiotensin receptor blockers (ARBs) may precipitate acute kidney injury in patients, especially those with moderate to severe renal impairment and elderly patients. (See Section 4.3). Renal function should be assessed before initiating treatment and monitored during treatment with fluoroquinolones or Angiotensin-converting enzymes (ACE) inhibitors/Angiotensin receptor blockers (ARBs) whether used separately and/or concomitantly. Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy: TESAMOLOT TM is contraindicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy. Unstable angina pectoris, acute myocardial infarction: There are no data to support the use of TESAMOLOT TM in unstable angina pectoris and during or within one month of a myocardial infarction. Heart failure: In a long-term, placebo-controlled study (PRAISE-2) of amlodipine in patients with NYHA III and IV heart failure of non-ischaemic aetiology, amlodipine was associated with increased reports of pulmonary oedema. Hyperkalaemia: During treatment with TESAMOLOT TM hyperkalaemia may occur, especially in the presence of renal impairment and/or heart failure. Monitoring of serum potassium in patients at risk is recommended. Based on experience with the use of medicines that affect the renin-angiotensin system, concomitant use with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium or other medicines that may increase the potassium level (heparin, etc.) may lead to an increase in serum potassium and should therefore be co-administered cautiously with TESAMOLOT TM. Diabetic patients treated with insulin or antidiabetics: In diabetic patients with an additional cardiovascular risk, i.e., patients with diabetes mellitus and coexistent coronary artery disease (CAD), the risk of fatal myocardial infarction and unexpected cardiovascular death may be increased when treated with blood pressure lowering medicines such as ARBs or ACE-inhibitors. In patients with diabetes mellitus CAD may be asymptomatic and therefore undiagnosed. Patients with diabetes mellitus should undergo appropriate diagnostic evaluation, e.g., exercise stress testing, to detect and to treat CAD accordingly before initiating treatment with TESAMOLOT TM. Other: Excessive reduction of blood pressure in patients with ischaemic cardiopathy or ischaemic cardiovascular disease could result in a myocardial infarction or stroke. Important information about some of the excipients of TESAMOLOT TM: TESAMOLOT TM contains mannitol. May have a mild laxative effect.

No interactions between the two components of this fixed dose combinations have been observed in clinical studies. Interactions common to the combination: No medicine interaction studies have been performed with TESAMOLOT TM and other medicines. Concomitant use to be taken into account: Other antihypertensive medicines: The blood pressure lowering effect of TESAMOLOT TM can be increased by concomitant use of other antihypertensive medicines. Medicines with blood pressure lowering potential: Based on their pharmacological properties it can be expected that the following medicines may potentiate the hypotensive effects of all antihypertensives including TESAMOLOT TM, e.g., baclofen, amifostine, neuroleptics or antidepressants. Furthermore, orthostatic hypotension may be aggravated by alcohol, barbiturates, narcotics or antidepressants. Corticosteroids (systemic route): Reduction of the antihypertensive effect. Interactions linked to the telmisartan component of TESAMOLOT TM: Telmisartan may increase the hypotensive effect of other antihypertensive medicines. Other interactions of clinical significance have not been identified. Co-administration of telmisartan did not result in a clinically significant interaction with digoxin, warfarin, hydrochlorothiazide, glibenclamide, ibuprofen, paracetamol, simvastatin and amlodipine. For digoxin a 20 % increase in median plasma digoxin trough concentration has been observed (39 % in a single case); monitoring of plasma digoxin levels should be considered. In one study the co-administration of telmisartan and ramipril led to an increase of up to 2,5-fold in the AUC 0-24 and C max of ramipril and ramiprilat. The clinical relevance of this observation is not known. Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin-converting enzyme (ACE) inhibitors. Increased serum levels have also been reported with telmisartan. Treatment with NSAIDs (i.e., aspirin at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs) is associated with the potential for acute renal insufficiency in patients who are dehydrated. Compounds acting on the renin-angiotensin-system like telmisartan may have synergistic effects. Patients receiving NSAIDs and TESAMOLOT TM should be adequately hydrated and be monitored for renal function at the beginning of combined treatment. A reduced effect of antihypertensive medicines like TESAMOLOT TM by inhibition of vasodilating prostaglandins has been reported during combined treatment with NSAIDs. Dual blockade of the RAAS with ARBs, ACE inhibitors or aliskiren Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) through the combined use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (see Sections 4.3 & 4.4). Concomitant use of fluoroquinolones and Angiotensin-converting enzyme (ACE) inhibitors/Angiotensin receptor blockers (ARBs) may precipitate acute kidney injury. The mechanism of the possible interaction between the different classes of medicines, over and above different mechanisms of kidney damage, is unknown (see Section 4.3). Interactions linked to the amlodipine component of TESAMOLOT TM: Concomitant use requiring caution: Grapefruit and grapefruit juice Concomitant administration of 240 ml of grapefruit juice with a single oral dose of 10 mg amlodipine in 20 healthy volunteers did not show a significant effect on the pharmacokinetic properties of amlodipine. The concomitant use of amlodipine and grapefruit or grapefruit juice is still not recommended in patients as the bioavailability of amlodipine may increase in some and may result in increased hypotensive effects. CYP3A4 inhibitors: A study in elderly patients has shown that diltiazem inhibits the metabolism of amlodipine, probably via CYP3A4 (plasma concentration increases by approximately 50 % and the effect of amlodipine is increased). The possibility that more potent inhibitors of CYP3A4 (i.e., ketoconazole, itraconazole, ritonavir) may increase the plasma concentration of amlodipine to a greater extent than diltiazem cannot be excluded.

TESAMOLOT TM should not be used during pregnancy and lactation. Effects relating to the monotherapy components are described below. Pregnancy: Telmisartan: Safety in pregnancy and lactation has not been established. When pregnancy is planned or confirmed, TESAMOLOT TM should be discontinued as soon as possible (see Section 4.3 & 4.4). Medicines affecting the renin-angiotensin system, such as TESAMOLOT TM, can cause embryonal toxicity, foetal and neonatal morbidity and mortality when administered to pregnant women. Women of childbearing age should ensure effective contraception. Patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with TESAMOLOT TM should be stopped immediately, and, if appropriate, alternative therapy should be started. Should exposure to TESAMOLOT TM have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Infants whose mothers have taken TESAMOLOT TM should be closely observed for hypotension. Lactation: It is not known whether telmisartan (as in TESAMOLOT TM) is excreted in human milk. Animal studies have shown excretion of telmisartan in breastmilk. Amlodipine has been identified in breastfed infants of treated women. The effect of amlodipine on infants is unknown. Because of the potential adverse reactions in breastfed infants, TESAMOLOT TM should not be used by breastfeeding mothers (see Section 4.3).

No studies on the effects on the ability to drive and use machines have been performed. However, patients should be advised that they may experience undesirable effects such as syncope (fainting), somnolence, dizziness, or vertigo during treatment. Therefore, caution should be recommended when driving a vehicle or operating machinery. If patients experience these adverse effects, they should avoid potentially hazardous tasks such as driving or operating machinery.

Infections and infestations u2022 Less frequent : cystitis. Psychiatric disorders u2022 Less frequent: depression, anxiety, insomnia. Nervous system disorders u2022 Frequent: dizziness. u2022 Less frequent: somnolence, migraine, headache, paraesthesia, syncope (fainting), peripheral neuropathy, hypoaesthesia, dysgeusia, tremor. Ear and labyrinth disorders u2022 Less frequent: vertigo. Cardiac disorders u2022 Less frequent: bradycardia, palpitations. Vascular disorders u2022 Less frequent : hypotension, orthostatic hypotension, flushing. Respiratory, thoracic and mediastinal disorders u2022 Less frequent: cough. Gastrointestinal disorders u2022 Less frequent: abdominal pain, diarrhoea, nausea, vomiting, gingival hypertrophy, dyspepsia, dry mouth. Skin and subcutaneous tissue disorders u2022 Less frequent: pruritus, eczema, erythema, rash. Musculoskeletal and connective tissue disorders u2022 Less frequent: arthralgia, muscle spasms, myalgia, back pain, pain in extremity. Renal and urinary disorders u2022 Less frequent: nocturia. Reproductive system and breast disorders: u2022 Less frequent: erectile dysfunction. General disorders and administration site conditions u2022 Less frequent: peripheral oedema, asthenia, chest pain, fatigue, oedema, malaise. Investigations u2022 Less frequent: increased hepatic enzymes, increased blood uric acid. The following side-effects have been observed and reported during treatment with telmisartan monotherapy: Infections and infestations u2022 Frequent : sepsis including fatal outcome, urinary tract infections including cystitis, upper respiratory tract infections including pharyngitis and sinusitis. Blood and lymphatic system disorders u2022 Less frequent: anaemia, eosinophilia, thrombocytopenia. Immune system disorders u2022 Less frequent: angioedema, anaphylactic reaction, hypersensitivity. Metabolism and nutrition disorders u2022 Less frequent: hyperkalaemia, hypoglycaemia (in diabetic patients). Eye disorders u2022 Less frequent: visual disturbance. Cardiac disorders u2022 Less frequent: tachycardia. Respiratory, thoracic and mediastinal disorders u2022 Less frequent: dyspnoea. Gastrointestinal disorders u2022 Less frequent: flatulence, stomach discomfort. Hepatobiliary disorders u2022 Less frequent: abnormal hepatic function, liver disorder. Skin and subcutaneous tissue disorders u2022 Less frequent: hyperhidrosis, urticaria, drug eruption, toxic skin eruption, angioedema. Musculoskeletal and connective tissue disorders u2022 Less frequent: tendon pain (tendinitis like symptoms). Renal and urinary disorders u2022 Less frequent: renal impairment including acute renal failure. General disorders and administration site conditions u2022 Less frequent: influenza-like illness. Investigations u2022 Less frequent: haemoglobin decreased, blood creatinine increased, blood creatinine phosphokinase (CPK) increased.

Symptoms: TESAMOLOT TM: There is no experience of overdose. Signs and symptoms of overdose are expected to be in line with exaggerated pharmacological effects. Telmisartan: The most likely manifestations of overdosage with telmisartan tablets would be hypotension, dizziness, and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Amlodipine: Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. Therapy: Supportive treatment should be instituted. Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. Telmisartan and amlodipine are not removed by haemodialysis.