Amlotel Tablets

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: AMLOTEL is indicated in patients whose blood pressure is not adequately controlled on Amlodipine monotherapy.

AMLOTEL should be taken once daily. Replacement Therapy: Patients taking telmisartan and amlodipine as separate tablets can instead take AMLOTEL containing the same component doses in one tablet once daily. Add on therapy: AMLOTEL may be administered in patients whose blood pressure is not adequately controlled with amlodipine alone. The usual starting dose of AMLOTEL 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. AMLOTEL may be taken with or without food.

u2212 Hypersensitivity to telmisartan, amlodipine or any of the other components of AMLOTEL

u2212 Hypersensitivity to dihydropyridine derivatives

u2212 A history of angioedema related to previous therapy with ACE inhibitors or angiotensin receptor blockers (ARBs): These patients must never again be given these medicines

u2212 Hereditary or idiopathic angioedema

u2212 Hypertrophic obstructive cardiomyopathy (HOCM)

u2212 Severe renal function impairment (creatine clearance less than 30 mL / min)

u2212 Bilateral renal artery stenosis

u2212 Renal artery stenosis in patients with a single kidney

u2212 Aortic stenosis

u2212 Concomitant therapy with potassium sparing diuretics such as spironolactone, triamterene, amiloride (see INTERACTIONS).

u2212 Porphyria

u2212 The concomitant use of AMLOTEL with aliskiren-containing products is contraindicated (see WARNINGS AND SPECIAL PRECAUTIONS and INTERACTIONS)

u2212 Lithium therapy: concomitant administration with AMLOTEL may lead to toxic blood concentrations of lithium (see INTERACTIONS).

u2212 Pregnancy and lactation (see PREGNANCY AND LACTATION)

u2212 Biliary obstructive disorders

u2212 Severe hepatic impairment,

u2212 Cardiogenic shock

Pregnancy: Should a woman become pregnant while receiving AMLOTEL, the treatment should be stopped promptly and switched to a different class of antihypertensive medicine. (See CONTRAINDICATIONS and PREGNANCY AND LACTATION). AMLOTEL should not be initiated during pregnancy (see CONTRAINDICATIONS). Patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy.

Hepatic impairment: Telmisartan (ingredient of AMLOTEL) is mostly eliminated in the bile. Patients with biliary obstructive disorders or hepatic insufficiency can be expected to have reduced clearance. Amlodipineu2019s half-life is prolonged in patients with impaired liver functions and dosage recommendations have not been established. AMLOTEL 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 CONTRAINDICATIONS).

Renal impairment and kidney transplant: When AMLOTEL 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 AMLOTEL in patients with a recent kidney transplant. Telmisartan and amlodipine are not dialysable.

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 CONTRAINDICATONS).

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 restrictions, diarrhoea or vomiting. Such conditions should be corrected before the administration of AMLOTEL.

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 may increase the risk of hypotension, hyperkalaemia and decreases renal function (including acute renal failure). Dual blockade of RAAS through the combined use of AMLOTEL and aliskiren is therefore contraindicated (see CONTRAINDICATIONS).

Other conditions with stimulation of the renin-angiotensin-aldosterone systems: 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 AMLOTEL, that affects this system, has been associated with acute hypotension, hyperuremia, 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 AMLOTEL is not recommended.

Aortic and mitral valve stenosis, hypertrophic obstructive cardiomyopathy: AMLOTEL is contraindicated in patients suffering from aortic or mitral stenosis, or hypertrophic obstructive cardiomyopathy.

Unstable angina pectoris, acute myocardial infarction: There are no data to support the use of AMLOTEL in unstable angina pectoris and during or within one month of a myocardial infarction.

Heart failure: The use of amlodipine in patients with NYHA III and IIII heart failure of non-ischaemic aetiology is associated with pulmonary oedema.

Hyperkalaemia: During treatment with AMLOTEL, 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 AMLOTEL.

Other: Excessive reduction of blood pressure in patients with ischaemic cardiopathy or ischaemic cardiovascular disease may result in a myocardial infarction or stroke.

There are no interactions between the two components (telmisartan and amlodipine) of the fixed dose combination.

Interactions common to the combination: No interaction studies have been performed with AMLOTEL and other medicines.

Interactions to be taken into account with concomitant use: Other antihypertensive medicines: The blood pressure lowering effect of AMLOTEL 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 AMLOTEL e.g. baclofen, amifostine. Furthermore, orthostatic hypotension may be aggravated by alcohol, barbiturates, narcotics, or antidepressants.

Corticosteroids (systemic route): Concomitant use with corticosteroids causes a reduction of the antihypertensive effect.

Interactions linked to the telmisartan component of AMLOTEL: Telmisartan may increase the hypotensive effect of other antihypertensive medicines. Other interactions of clinical significance have not been identified. Co-administration of telmisartan does not result in a clinically significant interaction with digoxin, warfarin, hydrochlorothiazide, glibenclamide, ibuprofen, paracetamol, simvastatin and amlodipine. For digoxin in 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.

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 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 telmisartan should be adequately hydrated and be monitored for renal function at the beginning of combined treatment.

A reduced effect of antihypertensive medicines like telmisartan by inhibition of vasodilating prostaglandins occurs during combined treatment with NSAIDs.

Dual blockade of the RAAS with ARBu2019s ACE inhibitors or aliskiren: Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) through the combined use of 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 CONTRAINDICATIONS, WARNINGS AND SPECIAL PRECAUTIONS).

Interactions linked to the amlodipine component of AMLOTEL: Concomitant use requiring caution: CYP3A4 inhibitors: 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.

CYP3A4 inducers (anticonvulsant medicines [e.g. carbamazepine, phenobarbitone, phenytoin, fosphenytoin, primidone], rifampicin, Hypericum perforatum): Co-administration may lead to reduced plasma concentrations of amlodipine. Clinical monitoring is indicated, with possible dosage adjustment of amlodipine during the treatment with the inducer and after its withdrawal.

Concomitant use to be taken into account: Others: In monotherapy, amlodipine is safely administered with thiazide diuretics, beta blockers, ACE inhibitors, long-acting nitrates, sublingual nitroglycerin, non-steroidal anti-inflammatory medicines, antibiotics and oral hypoglycaemic combination. When amlodipine and sildenafil were used in combination, each medicine independently exerts its own blood pressure lowering effect.

Additional information: Concomitant administration of 240 mL of grapefruit juice with a single oral dose of 10 mg amlodipine does not show a significant effect on the pharmacokinetic properties of amlodipine.

Pregnancy: Safety in pregnancy has not been established (see Contraindications). When pregnancy is planned or confirmed, AMLOTEL should be discontinued (see WARNINGS and SPECIAL PRECAUTIONS). Medicines affecting the renin-angiotensin system, such as AMLOTEL, can cause embryonal toxicity, foetal and neonatal morbidity and mortality when administered to pregnant women. Patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. Should exposure to AMLOTEL have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Infants whose mothers have taken AMLOTEL should be closely observed for hypotension.

Women of Childbearing potential: Women of childbearing age should ensure adequate contraception.

Lactation: Safety in lactation has not been established (see CONTRAINDICATIONS). It is not known whether telmisartan and/or amlodipine (as in AMLOTEL) are excreted in human milk. Excretion of telmisartan in breast milk is shown in animal studies. Because of the potential adverse reactions in breastfed infants, AMLOTEL should not be used by breast feeding mothers.

Fixed dose combination: Infections and infestations: Less frequent: Cystitis

Psychiatric disorders: Less frequent: depression, anxiety, insomnia

Nervous system disorders: Frequent: Dizziness Less frequent: Somnolence, migraine, headache, paraesthesia, syncope (fainting), peripheral neuropathy, hypoaesthesia, dysgeusia, tremor

Ear and labyrinth disorders: Less frequent: Vertigo

Cardiac disorders: Less frequent: Bradycardia, palpitation

Vascular disorders: Less frequent: Hypotension, orthostatic hypotension, flushing

Respiratory, thoracic and mediastinal disorders: Less frequent: Cough

Gastro-intestinal disorders: Less frequent: Abdominal pain, diarrhoea, nausea, vomiting, gingival, hypertrophy, dyspepsia, dry mouth

Skin and subcutaneous tissue disorders: Less frequent: Pruritus, eczema, erythema, rash

Musculoskeletal, connective tissue and bone disorders: Less frequent: Arthralgia, muscle spasms, myalgia, back pain, pain in extremity

Renal and urinary disorders: Less frequent: Nocturia

Reproductive system and breast disorders: Less frequent: Erectile dysfunction

General disorders: Frequent: Oedema, peripheral Less frequent: Asthenia, chest pain, fatigue, oedema, malaise

Investigations: Less frequent: Hepatic enzymes increased, blood uric acid increased

The following side effects are expected based on experience with telmisartan monotherapy, but the frequencies are not determined: Infections and infestations: Frequency not known: Sepsis including fatal outcome, urinary tract infections, upper respiratory tract infections

Blood and the lymphatic system disorders: Frequency not known: Anaemia, eosinophilia, thrombocytopenia

Immune system disorders: Frequency not known: Angioedema, anaphylactic reaction, hypersensitivity

Metabolism and nutritional disorders: Frequency not known: Hyperkalaemia

Eye disorders: Frequency not known: Visual disturbance

Cardiac disorders: Frequency not known: Tachycardia

Respiratory, thoracic, mediastinal disorders: Frequency not known: Dyspnoea

Gastrointestinal disorders: Frequency not known: Flatulence, stomach discomfort

Hepato-biliary disorders: Frequency not known: Hepatic function abnormal, liver disorder

Skin and subcutaneous tissue disorders: Frequency not known: Hyperhidrosis, urticaria, medicine eruption, toxic skin eruption

Musculoskeletal, connective tissue and bone disorders: Frequency not known: Tendon pain

Renal and urinary disorders: Frequency not known: Renal impairment

General disorders: Frequency not known: Influenza-like illness

Investigations: Frequency not known: haemoglobin decreased, blood creatinine increased, blood creatinine phosphokinase (CPK) increased.

The following side effects are expected based on experience with amlodipine monotherapy, but the frequencies are not determined: Blood and the lymphatic system disorders: Frequency not known: Thrombocytopenia

Immune system disorders: Frequency not known: Angioedema, hypersensitivity

Metabolism and nutritional disorders: Frequency not known: Hyperglycaemia

Psychiatric disorders: Frequency not known: Mood change

Eye disorders: Frequency not known: Visual impairment

Ear and labyrinth disorders: Frequency not known: Tinnitus

Cardiac disorders: Frequency not known: Myocardial infarction, dysrhythmia, ventricular tachycardia, atrial fibrillation

Vascular disorders: Frequency not known: Vasculitis

Respiratory, thoracic and mediastinal disorders: Frequency not known: Dyspnoea, rhinitis

Gastrointestinal disorders: Frequency not known: Change of bowel habit, pancreatitis, gastritis

Hepato-biliary disorders: Frequency not known: Hepatitis, jaundice, hepatic enzyme elevations (mostly consistent with cholestasis)

Skin and subcutaneous tissue disorders: Frequency not known: Hyperhidrosis, urticaria, alopecia, purpura, skin discolouration, erythema multiforme

Renal and urinary disorders: Frequency not known: Micturition disorder, pollakiuria

Reproductive and breast-feeding disorders: Frequency not known: Gynaecomastia

General disorders: Frequency not known: Pain, weight increased, weight decreased

Signs and symptoms of overdosage are expected to be in line with exaggerated pharmacological effects. Available data for amlodipine suggest that gross overdosage could result in excessive peripheral vasodilatation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal outcome have been reported. Non-cardiogenic pulmonary oedema has rarely been reported as a consequence of amlodipine overdose that may manifest with a delayed onset (24-48 hours post-ingestion) and require ventilatory support. Early resuscitative measures (including fluid overload) to maintain perfusion and cardiac output may be precipitating factors.

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.